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Conserved domains on  [gi|1039797231|ref|XP_017173968|]
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adhesion G-protein coupled receptor G2 isoform X10 [Mus musculus]

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 ...
624-893 1.06e-168

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: 494.34  E-value: 1.06e-168
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  624 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNT-RGFCIAVAVFLHY 702
Cdd:cd15444      1 MLILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKDiVGLCISVAVFLHY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  703 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIGSYGKFPNGTPDDFCWINSN 782
Cdd:cd15444     81 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYGLGSYGKSPNGSTDDFCWINNN 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  783 VVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYL 862
Cdd:cd15444    161 IVFYITVVGYFCVIFLLNISMFIVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFAWGPVNLAFMYL 240
                          250       260       270
                   ....*....|....*....|....*....|.
gi 1039797231  863 FAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15444    241 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 271
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
560-611 2.77e-13

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: 65.02  E-value: 2.77e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1039797231  560 VKCVFWDLGRNdtalvptgGKGGWSSDGCSVKDKRMNETICTCSHLTSFGIL 611
Cdd:pfam01825    1 PQCVFWDFTNS--------TTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
PHA03247 super family cl33720
large tegument protein UL36; Provisional
242-382 3.08e-05

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.40  E-value: 3.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  242 PHGPPLSSSSKPVVPQATIishvasdfSLAEPLDhALMTPSTPSLTQEsnlPSPQPTIPLASSPATDLPVQSvvvssLPQ 321
Cdd:PHA03247  2878 PARPPVRRLARPAVSRSTE--------SFALPPD-QPERPPQPQAPPP---PQPQPQPPPPPQPQPPPPPPP-----RPQ 2940
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  322 TDLSHTLSPVQSSIPSPTTPAP----------SVPTELVTISTPPGET-VVNTSTVSDLEA-QVSQMEKALSL 382
Cdd:PHA03247  2941 PPLAPTTDPAGAGEPSGAVPQPwlgalvpgrvAVPRFRVPQPAPSREApASSTPPLTGHSLsRVSSWASSLAL 3013
PRK12323 super family cl46901
DNA polymerase III subunit gamma/tau;
292-483 7.85e-05

DNA polymerase III subunit gamma/tau;


The actual alignment was detected with superfamily member PRK14948:

Pssm-ID: 481241 [Multi-domain]  Cd Length: 620  Bit Score: 46.49  E-value: 7.85e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  292 LPSPQPTIPLASSPATDLPVQSVV----VSSLPQTDLSHTLSPVQSSIP-SPTTPAPSVPTELVTISTPPgETVVNTSTV 366
Cdd:PRK14948   360 LPSAFISEIANASAPANPTPAPNPspppAPIQPSAPKTKQAATTPSPPPaKASPPIPVPAEPTEPSPTPP-ANAANAPPS 438
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  367 SDLEAQVSQMekalsLGSLEPNLAGEMVNRVSKL--LHSPPALLApLAQRLLKVV--------DAI------GLQLNFSS 430
Cdd:PRK14948   439 LNLEELWQQI-----LAKLELPSTRMLLSQQAELvsLDSNRAVIA-VSPNWLGMVqsrkplleQAFakvlgrSIKLNLES 512
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  431 TTISLTSPSLALAVIRVNASNFNTTTFAAQDPTNLQVSLETPPPENSIGAITL 483
Cdd:PRK14948   513 QSGSASNTAKTPPPPQKSPPPPAPTPPLPQPTATAPPPTPPPPPPTATQASSN 565
 
Name Accession Description Interval E-value
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
624-893 1.06e-168

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: 494.34  E-value: 1.06e-168
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  624 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNT-RGFCIAVAVFLHY 702
Cdd:cd15444      1 MLILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKDiVGLCISVAVFLHY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  703 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIGSYGKFPNGTPDDFCWINSN 782
Cdd:cd15444     81 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYGLGSYGKSPNGSTDDFCWINNN 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  783 VVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYL 862
Cdd:cd15444    161 IVFYITVVGYFCVIFLLNISMFIVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFAWGPVNLAFMYL 240
                          250       260       270
                   ....*....|....*....|....*....|.
gi 1039797231  863 FAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15444    241 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 271
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
624-874 1.80e-64

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: 217.92  E-value: 1.80e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  624 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDyPSKILIQLCAALLLLNLIFLLDSWIALYNTRGF------CIAVA 697
Cdd:pfam00002    1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCT-RNYIHLNLFASFILRALLFLVGDAVLFNKQDLDhcswvgCKVVA 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  698 VFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGIPAVVVSIVLTISPDNYGigsygkfpngtPDDFC 777
Cdd:pfam00002   80 VFLHYFFLANFFWMLVEGLYLYTLLVEVFFSE-RKYFWWYLLIGWGVPALVVGIWAGVDPKGYG-----------EDDGC 147
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  778 WINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSI-QDLRSIAGLTFLLGITWGFAFFAWGPVN 856
Cdd:pfam00002  148 WLSNENGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYrRLAKSTLLLLPLLGITWVFGLFAFNPEN 227
                          250       260
                   ....*....|....*....|.
gi 1039797231  857 ---VTFMYLFAIFNTLQGFFI 874
Cdd:pfam00002  228 tlrVVFLYLFLILNSFQGFFV 248
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
560-611 2.77e-13

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: 65.02  E-value: 2.77e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1039797231  560 VKCVFWDLGRNdtalvptgGKGGWSSDGCSVKDKRMNETICTCSHLTSFGIL 611
Cdd:pfam01825    1 PQCVFWDFTNS--------TTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
559-616 9.99e-13

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: 63.56  E-value: 9.99e-13
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039797231   559 TVKCVFWDLGRndtalvptggkGGWSSDGCSVKDKRMNETICTCSHLTSFGILLDLSR 616
Cdd:smart00303    2 NPICVFWDESS-----------GEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPP 48
PHA03247 PHA03247
large tegument protein UL36; Provisional
242-382 3.08e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.40  E-value: 3.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  242 PHGPPLSSSSKPVVPQATIishvasdfSLAEPLDhALMTPSTPSLTQEsnlPSPQPTIPLASSPATDLPVQSvvvssLPQ 321
Cdd:PHA03247  2878 PARPPVRRLARPAVSRSTE--------SFALPPD-QPERPPQPQAPPP---PQPQPQPPPPPQPQPPPPPPP-----RPQ 2940
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  322 TDLSHTLSPVQSSIPSPTTPAP----------SVPTELVTISTPPGET-VVNTSTVSDLEA-QVSQMEKALSL 382
Cdd:PHA03247  2941 PPLAPTTDPAGAGEPSGAVPQPwlgalvpgrvAVPRFRVPQPAPSREApASSTPPLTGHSLsRVSSWASSLAL 3013
PRK14948 PRK14948
DNA polymerase III subunit gamma/tau;
292-483 7.85e-05

DNA polymerase III subunit gamma/tau;


Pssm-ID: 237862 [Multi-domain]  Cd Length: 620  Bit Score: 46.49  E-value: 7.85e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  292 LPSPQPTIPLASSPATDLPVQSVV----VSSLPQTDLSHTLSPVQSSIP-SPTTPAPSVPTELVTISTPPgETVVNTSTV 366
Cdd:PRK14948   360 LPSAFISEIANASAPANPTPAPNPspppAPIQPSAPKTKQAATTPSPPPaKASPPIPVPAEPTEPSPTPP-ANAANAPPS 438
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  367 SDLEAQVSQMekalsLGSLEPNLAGEMVNRVSKL--LHSPPALLApLAQRLLKVV--------DAI------GLQLNFSS 430
Cdd:PRK14948   439 LNLEELWQQI-----LAKLELPSTRMLLSQQAELvsLDSNRAVIA-VSPNWLGMVqsrkplleQAFakvlgrSIKLNLES 512
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  431 TTISLTSPSLALAVIRVNASNFNTTTFAAQDPTNLQVSLETPPPENSIGAITL 483
Cdd:PRK14948   513 QSGSASNTAKTPPPPQKSPPPPAPTPPLPQPTATAPPPTPPPPPPTATQASSN 565
KLF8_12_N cd21093
N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins; Kruppel-like ...
265-343 4.64e-03

N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins; Kruppel-like transcription factors (also known as Krueppel-like transcription factors, KLFs) belong to a family of proteins called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Although these factors bind to similar elements in vitro, they have distinct activities in vivo depending on their expression profile and the sequence of the N-terminal activation/repression domain, which differ between members. This model represents the related N-terminal activation/repression domains of KLF8 and KLF12.


Pssm-ID: 410606 [Multi-domain]  Cd Length: 172  Bit Score: 38.99  E-value: 4.64e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  265 ASDFSL--AEPLDHALMTPSTPSLTQESNLPSPQPTIPLASSPAtdlPVQSVVVSSLpqtdlshTLSPVQSSIPSPTTPA 342
Cdd:cd21093     29 SSDHSQpqTEPVDLSINKARTSPTAVSSSPVSMSSSISSSSSSS---PRPASSPTVI-------TSVSSASAIPTVLSPG 98

                   .
gi 1039797231  343 P 343
Cdd:cd21093     99 S 99
 
Name Accession Description Interval E-value
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
624-893 1.06e-168

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: 494.34  E-value: 1.06e-168
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  624 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNT-RGFCIAVAVFLHY 702
Cdd:cd15444      1 MLILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKDiVGLCISVAVFLHY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  703 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIGSYGKFPNGTPDDFCWINSN 782
Cdd:cd15444     81 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYGLGSYGKSPNGSTDDFCWINNN 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  783 VVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYL 862
Cdd:cd15444    161 IVFYITVVGYFCVIFLLNISMFIVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFAWGPVNLAFMYL 240
                          250       260       270
                   ....*....|....*....|....*....|.
gi 1039797231  863 FAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15444    241 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 271
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
627-893 1.08e-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: 424.46  E-value: 1.08e-141
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  627 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYFLLV 706
Cdd:cd15997      4 LTLITYLGCGISSIFLGITLVTYLAFEKLRRDYPSKILINLCTALLMLNLVFLLNSWLSSFNNYGLCITVAAFLHYFLLA 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  707 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIGSYGKFPNGTpDDFCWINSNVVFY 786
Cdd:cd15997     84 SFTWMGLEAVHMYFALVKVFNIYIPNYILKFCIAGWGIPAVVVALVLAINKDFYGNELSSDSLHPS-TPFCWIQDDVVFY 162
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  787 ITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLFAIF 866
Cdd:cd15997    163 ISVVAYFCLIFLCNISMFITVLIQIRSMKAKKPSRNWKQGFLHDLKSVASLTFLLGLTWGFAFFAWGPVRIFFLYLFSIC 242
                          250       260
                   ....*....|....*....|....*..
gi 1039797231  867 NTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15997    243 NTLQGFFIFVFHCLMKENVRKQWRIHL 269
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
624-891 1.24e-140

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: 421.82  E-value: 1.24e-140
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  624 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYF 703
Cdd:cd15258      1 LHILTFISYVGCGISAIFLAITILTYIAFRKLRRDYPSKIHMNLCAALLLLNLAFLLSSWIASFGSDGLCIAVAVALHYF 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  704 LLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIGSYGKFPNGTPDDFCWINSNV 783
Cdd:cd15258     81 LLACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLCLVGWGLPALLVTLVLSVRSDNYGPITIPNGEGFQNDSFCWIRDPV 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  784 VFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLgAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLF 863
Cdd:cd15258    161 VFYITVVGYFGLTFLFNMVMLATVLVQICRLREKAQA-TPRKRALHDLLTLLGLTFLLGLTWGLAFFAWGPFNLPFLYLF 239
                          250       260
                   ....*....|....*....|....*...
gi 1039797231  864 AIFNTLQGFFIFIFYCAAKENVRKQWRR 891
Cdd:cd15258    240 AIFNSLQGFFIFIWYCSMKENVRKQWRA 267
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
627-893 5.12e-126

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: 383.85  E-value: 5.12e-126
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  627 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYFLLV 706
Cdd:cd15996      4 LTFITYIGCGISAIFSAATLLTYIAFEKLRRDYPSKILMNLSTALLFLNLVFLLDGWIASFEIDELCITVAVLLHFFLLA 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  707 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIGSYGKFPNGTP-DDFCWINSNVVF 785
Cdd:cd15996     84 TFTWMGLEAIHMYIALVKVFNTYIRRYILKFCIIGWGLPALIVSIVLASTNDNYGYGYYGKDKDGQGgDEFCWIKNPVVF 163
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  786 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLFAI 865
Cdd:cd15996    164 YVTCAAYFGIMFLMNVAMFIVVMVQICGRNGKRSNRTLREEILRNLRSVVSLTFLLGMTWGFAFFAWGPVNLAFMYLFTI 243
                          250       260
                   ....*....|....*....|....*...
gi 1039797231  866 FNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15996    244 FNSLQGLFIFVFHCALKENVQKQWRRHL 271
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
626-889 2.57e-89

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: 286.01  E-value: 2.57e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  626 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWiaLYNTRGFCIAVAVFLHYFLL 705
Cdd:cd15040      3 ALSIITYIGCGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFLFGIN--STDNPVLCTAVAALLHYFLL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  706 VSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYgigsygkfpnGTPDDFCWINSNVVF 785
Cdd:cd15040     81 ASFMWMLVEALLLYLRLVKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSY----------GNSSGYCWLSNGNGL 150
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  786 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQdLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLFAI 865
Cdd:cd15040    151 YYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQ-LRAAVSLFFLLGLTWIFGILAIFGARVVFQYLFAI 229
                          250       260
                   ....*....|....*....|....
gi 1039797231  866 FNTLQGFFIFIFYCAAKENVRKQW 889
Cdd:cd15040    230 FNSLQGFFIFIFHCLRNKEVRKAW 253
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
626-889 1.12e-72

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: 241.35  E-value: 1.12e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  626 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRdYPSKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYFLL 705
Cdd:cd13952      3 ALSIITYIGCSLSLVGLLLTIITYLLFPKLRN-LRGKILINLCLSLLLAQLLFLIGQLLTSSDRPVLCKALAILLHYFLL 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  706 VSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIGSYGKfpngtpDDFCWINSNVVF 785
Cdd:cd13952     82 ASFFWMLVEAFDLYRTFVKVFGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSPGYG------GEYCWLSNGNAL 155
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  786 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAW-GPVNVTFMYLFA 864
Cdd:cd13952    156 LWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKSDRKQLRAYLKLFPLMGLTWIFGILAPfVGGSLVFWYLFD 235
                          250       260
                   ....*....|....*....|....*
gi 1039797231  865 IFNTLQGFFIFIFYCAAKENVRKQW 889
Cdd:cd13952    236 ILNSLQGFFIFLIFCLKNKEVRRLL 260
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
624-874 1.80e-64

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: 217.92  E-value: 1.80e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  624 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDyPSKILIQLCAALLLLNLIFLLDSWIALYNTRGF------CIAVA 697
Cdd:pfam00002    1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCT-RNYIHLNLFASFILRALLFLVGDAVLFNKQDLDhcswvgCKVVA 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  698 VFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGIPAVVVSIVLTISPDNYGigsygkfpngtPDDFC 777
Cdd:pfam00002   80 VFLHYFFLANFFWMLVEGLYLYTLLVEVFFSE-RKYFWWYLLIGWGVPALVVGIWAGVDPKGYG-----------EDDGC 147
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  778 WINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSI-QDLRSIAGLTFLLGITWGFAFFAWGPVN 856
Cdd:pfam00002  148 WLSNENGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYrRLAKSTLLLLPLLGITWVFGLFAFNPEN 227
                          250       260
                   ....*....|....*....|.
gi 1039797231  857 ---VTFMYLFAIFNTLQGFFI 874
Cdd:pfam00002  228 tlrVVFLYLFLILNSFQGFFV 248
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
627-886 4.55e-58

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: 200.75  E-value: 4.55e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  627 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYFLLV 706
Cdd:cd15443      4 LTYISIVGCSISAAASLLTILLHFFSRKQPKDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQSTWLCRAAAALLHYSLLC 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  707 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYG---IGSYGKFPNGTpddFCWINSNV 783
Cdd:cd15443     84 CLTWMAIEGFHLYLLLVKVYNIYIRRYVLKLCVLGWGLPALIVLLVLIFKREAYGphtIPTGTGYQNAS---MCWITSSK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  784 VFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRktSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLF 863
Cdd:cd15443    161 VHYVLVLGYAGLTSLFNLVVLAWVVRMLRRLRSRKQELGER--ARRDWVTVLGLTCLLGTTWALAFFSFGVFLIPQLFLF 238
                          250       260
                   ....*....|....*....|...
gi 1039797231  864 AIFNTLQGFFIFIFYCAAKENVR 886
Cdd:cd15443    239 TIINSLYGFFICLWYCTQRRRSD 261
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
627-878 2.22e-57

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: 199.25  E-value: 2.22e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  627 LTFITYIGCGLSSIFLSVTLVTYIA----FEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHY 702
Cdd:cd15442      4 LVTISSAGCGVSMVFLIFTIILYFFlrftYQKFKSEDAPKIHVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKALGGVTHY 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  703 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTispdnygIGSYGKF-----PNGTPDDFC 777
Cdd:cd15442     84 FLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKLCLVGWGFPALVVTITGS-------INSYGAYtimdmANRTTLHLC 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  778 WINSN--VVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLrSIAGLTFLLGITWGFAFFAWGPV 855
Cdd:cd15442    157 WINSKhlTVHYITVCGYFGLTFLFNTVVLGLVAWKIFHLQSATAGKEKCQAWKGGL-TVLGLSCLLGVTWGLAFFTYGSM 235
                          250       260
                   ....*....|....*....|...
gi 1039797231  856 NVTFMYLFAIFNTLQGFFIFIFY 878
Cdd:cd15442    236 SVPTVYIFALLNSLQGLFIFIWF 258
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
626-893 1.95e-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: 170.14  E-value: 1.95e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  626 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDypsKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYFLL 705
Cdd:cd15440      3 ALTFITYIGCIISIVCLLLAFITFTCFRNLQCD---RNTIHKNLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  706 VSFTWMGLEAFHMYLALVKVFNTYIRKyILKFCIVGWGIPAVVVSIVLTISPDNYGIgsygkfpngtpDDFCWINSNVVF 785
Cdd:cd15440     80 AAFSWMLLEGFQLYVMLVEVFEPEKSR-IKWYYLFGYGLPALIVAVSAGVDPTGYGT-----------EDHCWLSTENGF 147
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  786 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKK--KKQLGAQRKTSIQD-LRSIAGLTFLLGITWGFAFFAWGPVNVTFMYL 862
Cdd:cd15440    148 IWSFVGPVIVVLLANLVFLGMAIYVMCRHSSrsASKKDASKLKNIRGwLKGSIVLVVLLGLTWTFGLLFINQESIVMAYI 227
                          250       260       270
                   ....*....|....*....|....*....|.
gi 1039797231  863 FAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15440    228 FTILNSLQGLFIFIFHCVLNEKVRKELRRWL 258
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
627-887 3.82e-45

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: 163.85  E-value: 3.82e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  627 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYFLLV 706
Cdd:cd15995      4 LTILTYVGCIISALASVFTIAFYLCSRRKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAACRAGGMFLHFSLLA 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  707 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIGSYGKF--PNG-TPDDFCWINSNV 783
Cdd:cd15995     84 CLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVTLIFLVDQDNYGPIILAVHrsPEKvTYATICWITDSL 163
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  784 VFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQlgaqrktSIQDLRSIAGLTFLLGITWGFAFFAW--GPVNVTFMY 861
Cdd:cd15995    164 ISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTH-------KWSHVLTLLGLSLVLGIPWALAFFSFasGTFQLVIVY 236
                          250       260
                   ....*....|....*....|....*.
gi 1039797231  862 LFAIFNTLQGFFIFIFYCAAKENVRK 887
Cdd:cd15995    237 LFTIINSLQGFLIFLWYWSMVLQARG 262
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
625-889 6.63e-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: 157.10  E-value: 6.63e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  625 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYpSKILIQLCAALLLLNLIFLLDSWIALYNTrgFCIAVAVFLHYFL 704
Cdd:cd15933      2 RALSIISYIGCGISIACLALTLIIFLVLRVLSSDR-FQIHKNLCVALLLAQILLLAGEWAEGNKV--ACKVVAILLHFFF 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  705 LVSFTWMGLEAFHMYLALVKVFNTYIRKYIlkFCIVGWGIPAVVVSIVLTISPDNYGigsygkfpngtPDDFCWINSNVV 784
Cdd:cd15933     79 MAAFSWMLVEGLHLYLMIVKVFNYKSKMRY--YYFIGWGLPAIIVAISLAILFDDYG-----------SPNVCWLSLDDG 145
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  785 FYITVVGyfCVIFLLNVSMFIVVLV-----QLCRIKKKKQLG--AQRKTSIqdlRSIAGLTFLLGITWGFAFFAWGPVNV 857
Cdd:cd15933    146 LIWAFVG--PVIFIITVNTVILILVvkitvSLSTNDAKKSQGtlAQIKSTA---KASVVLLPILGLTWLFGVLVVNSQTI 220
                          250       260       270
                   ....*....|....*....|....*....|..
gi 1039797231  858 TFMYLFAIFNTLQGFFIFIFYCAAKENVRKQW 889
Cdd:cd15933    221 VFQYIFVILNSLQGLMIFLFHCVLNSEVRSAF 252
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
692-894 9.09e-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: 9.09e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  692 FCIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNtyIRKYILKFC-IVGWGIPAVVVSIVLTISPDNYGigsygkfpn 770
Cdd:cd15441     66 PCKLIAILLHYFYLSAFSWLLVESLHLYRMLTEPRD--INHGHMRFYyLLGYGIPAIIVGLSVGLRPDGYG--------- 134
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  771 gtPDDFCWINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQlgaqRKTSIQ-DLRSIAGLTFLLGITWGFAF 849
Cdd:cd15441    135 --NPDFCWLSVNETLIWSFAGPIAFVIVITLIIFILALRASCTLKRHVL----EKASVRtDLRSSFLLLPLLGATWVFGL 208
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1039797231  850 FAwgpVN---VTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYLC 894
Cdd:cd15441    209 LA---VNedsELLHYLFAGLNFLQGLFIFLFYCIFNKKVRRELKNALL 253
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
626-895 3.16e-37

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: 140.94  E-value: 3.16e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  626 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLdswIALYNTRGFCIAVAVFLHYFLL 705
Cdd:cd15439      3 ALTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQLSLCLFLADLLFLVG---IDRTDNKVLCSIIAGFLHYLFL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  706 VSFTWMGLEAFHMYLAL--VKVFN-TYIRKYILKF-CIVGWGIPAVVVSIVLTISPDNYGIGSYgkfpngtpddfCWINS 781
Cdd:cd15439     80 ACFAWMFLEAVHLFLTVrnLKVVNyFSSHRFKKRFmYPVGYGLPAVIVAISAAVNPQGYGTPKH-----------CWLSM 148
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  782 NVVFYITVVGYFCVIFLLNVSMFIVVLVQLcriKKK-----KQLGAQRKTSIQDLRSIAGLtFLLGITWGFAFFAWGPVN 856
Cdd:cd15439    149 EKGFIWSFLGPVCVIIVINLVLFCLTLWIL---REKlsslnAEVSTLKNTRLLTFKAIAQL-FILGCTWILGLFQVGPVA 224
                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1039797231  857 VTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYLCC 895
Cdd:cd15439    225 TVMAYLFTITNSLQGVFIFLVHCLLNRQVREEYRRWITG 263
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
625-893 4.12e-37

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: 140.33  E-value: 4.12e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  625 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDypsKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYFL 704
Cdd:cd15252      2 NILTRITQVGIIISLVCLAICIFTFWFFRGLQSD---RTTIHKNLCISLFLAELVFLIGINTTTNKIFCSVIAGLLHYFF 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  705 LVSFTWMGLEAFHMYLALVKVFNT--YIRKYilkFCIVGWGIPAVVVSIVLTISPDNYGIgsygkfpngtpDDFCWINSN 782
Cdd:cd15252     79 LAAFAWMFIEGIQLYLMLVEVFENegSRHKN---FYIFGYGSPAVIVGVSAALGYRYYGT-----------TKVCWLSTE 144
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  783 VVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQD-LRSIAGLTFLLGITWGFAFFAWGPVNVTFMY 861
Cdd:cd15252    145 NYFIWSFIGPATLIILLNLIFLGVAIYKMFRHTAGLKPEVSCLENIRSwARGAIALLFLLGLTWIFGVLHINHASVVMAY 224
                          250       260       270
                   ....*....|....*....|....*....|..
gi 1039797231  862 LFAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15252    225 LFTVSNSLQGMFIFLFHCVLSRKVRKEYYKLF 256
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
630-891 5.44e-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: 140.44  E-value: 5.44e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  630 ITYIGCGLSSIFLSVTLVTYIAFEKIRrDYPSKILIQLCAALLLLNLIFLLDSWIALYNTRgFCIAVAVFLHYFLLVSFT 709
Cdd:cd15039      7 LTLIGLIISLVFLLLTLAVYALLPELR-NLHGKCLMCLVLSLFVAYLLLLIGQLLSSGDST-LCVALGILLHFFFLAAFF 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  710 WMGLEAFHMYLAL----VKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTIS---PDNYGIGSYGkfpngtpDDFCWINSN 782
Cdd:cd15039     85 WLNVMSFDIWRTFrgkrSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDfspNTDSLRPGYG-------EGSCWISNP 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  783 VVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKK-KQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAW-GPVNVTFM 860
Cdd:cd15039    158 WALLLYFYGPVALLLLFNIILFILTAIRIRKVKKEtAKVQSRLRSDKQRFRLYLKLFVIMGVTWILEIISWfVGGSSVLW 237
                          250       260       270
                   ....*....|....*....|....*....|..
gi 1039797231  861 YLFAIFNTLQGFFIF-IFYCaaKENVRKQWRR 891
Cdd:cd15039    238 YIFDILNGLQGVFIFlIFVC--KRRVLRLLKK 267
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
627-894 3.38e-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: 3.38e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  627 LTFITYIGCGLSSIFLSVTLVTYIAfekIRRDYPSKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYFLLV 706
Cdd:cd15438      4 LTLITKVGLSVSLFCLFLCILTFLF---CRSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNNQVACAVVAGLLHYFFLA 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  707 SFTWMGLEAFHMYLALVKVFNTYIRKYiLKFCIVGWGIPAVVVSIVLTISPDNYGigsygkfpngtPDDFCWINSNVVFY 786
Cdd:cd15438     81 AFCWMSLEGVELYLMVVQVFNTQSLKK-RYLLLIGYGVPLVIVAISAAVNSKGYG-----------TQRHCWLSLERGFL 148
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  787 ITVVGYFCVIFLLNVSMFIVVLVQLCR--IKKKKQLGAQRKTSIQDLRSIAGLtFLLGITWGFAFFAWGPVNVTFMYLFA 864
Cdd:cd15438    149 WSFLGPVCLIILVNAIIFVITVWKLAEkfSSINPDMEKLRKIRALTITAIAQL-CILGCTWIFGFFQFSDSTLVMSYLFT 227
                          250       260       270
                   ....*....|....*....|....*....|
gi 1039797231  865 IFNTLQGFFIFIFYCAAKENVRKQWRRYLC 894
Cdd:cd15438    228 ILNSLQGLFIFLLHCLLSKQVREEYSRWLC 257
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
626-887 4.15e-31

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: 124.60  E-value: 4.15e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  626 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKI-----------------------LIQLCAALLLLNLIFLLDS 682
Cdd:cd15257      3 TLDIISTIGCVLSIAGLVITIIFHLHTRKLRKSSVTWVllnlcsslllfniiftsgventnNDYEISTVPDRETNTVLLS 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  683 WIALYNTRGFCIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGIPAVVVSIVLTISpdnygI 762
Cdd:cd15257     83 EEYVEPDTDVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQASAIGWGIPAVVVAITLGAT-----Y 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  763 GSYGKFPNGTPD----DFCWI---NSNVVF-------YITVVGyfcVIFLLNVSMFIVVLVQLCriKKKKQLGAQRKTSI 828
Cdd:cd15257    158 RFPTSLPVFTRTyrqeEFCWLaalDKNFDIkkpllwgFLLPVG---LILITNVILFIMTSQKVL--KKNNKKLTTKKRSY 232
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  829 QDLRSIA-GLTFLLGITWGFAFFAW---GPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRK 887
Cdd:cd15257    233 MKKIYITvSVAVVFGITWILGYLMLvnnDLSKLVFSYIFCITNTTQGVQIFILYTWRTPEFRK 295
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
693-893 6.77e-30

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: 119.64  E-value: 6.77e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYILKFCivGWGIPAVVVSIVLTISPDNYGIgsygkfpng 771
Cdd:cd16007     67 CPIFAGLLHFFFLAAFSWLCLEGVQLYLMLVEVFESeYSRKKYYYLC--GYCFPALVVGISAAIDYRSYGT--------- 135
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  772 tpDDFCWINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQD--LRSIAgLTFLLGITWGFAF 849
Cdd:cd16007    136 --EKACWLRVDNYFIWSFIGPVSFVIVVNLVFLMVTLHKMIRSSSVLKPDSSRLDNIKSwaLGAIT-LLFLLGLTWAFGL 212
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1039797231  850 FAWGPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd16007    213 LFINKESVVMAYLFTTFNAFQGMFIFIFHCALQKKVHKEYSKCL 256
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
625-890 6.63e-29

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: 116.95  E-value: 6.63e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  625 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIrrdypSKILIQLCAALLLLNLIFLLDSWIALYNTRGF-----CIAVAVF 699
Cdd:cd15256      2 VALSSITYVGCSLSIFCLAITLVTFAVLSSV-----STIRNQRYHIHANLSFAVLVAQILLLISFRFEpgtlpCKIMAIL 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  700 LHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIvGWGIPAVVVSIVLTISPDNYGigsygkfpngtPDDFCWI 779
Cdd:cd15256     77 LHFFFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYGI-GWGSPLLICIISLTSALDSYG-----------ESDNCWL 144
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  780 N-SNVVFYITVVGYFCVIfLLNVSMFIVVLVQLCRIKKKkQLGAQRKTSIQDL--RSIAGLTFLLGITWGFAFFAWGPVN 856
Cdd:cd15256    145 SlENGAIWAFVAPALFVI-VVNIGILIAVTRVISRISAD-NYKVHGDANAFKLtaKAVAVLLPILGSSWVFGVLAVNTHA 222
                          250       260       270
                   ....*....|....*....|....*....|....
gi 1039797231  857 VTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWR 890
Cdd:cd15256    223 LVFQYMFAIFNSLQGFFIFLFHCLLNSEVRAAFK 256
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
693-893 1.15e-27

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: 112.96  E-value: 1.15e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYI--RKYilkFCIVGWGIPAVVVSIVLTISPDNYGigsygkfpn 770
Cdd:cd15436     67 CPIFAGLLHFFFLAAFCWLCLEGVQLYLLLVEVFESEYsrRKY---FYLCGYSFPALVVAVSAAIDYRSYG--------- 134
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  771 gtPDDFCWINSNVVFYITVVGYFCVIFLLNVsmfIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIA----GLTFLLGITWG 846
Cdd:cd15436    135 --TEKACWLRVDNYFIWSFIGPVTFVITLNL---VFLVITLHKMVSHSDLLKPDSSRLDNIKSWAlgaiALLFLLGLTWS 209
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1039797231  847 FAFFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15436    210 FGLMFINEESVVMAYLFTIFNAFQGVFIFIFHCALQKKVRKEYSKCL 256
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
693-893 2.29e-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: 112.25  E-value: 2.29e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT---YIRKYIlkfcIVGWGIPAVVVSIVLTISPDNYGigsygkfp 769
Cdd:cd15991     67 CTVVAILLHYFYMSTFAWMFVEGLHIYRMLTEVRNIntgHMRFYY----VVGWGIPAIITGLAVGLDPQGYG-------- 134
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  770 ngTPDdFCWINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRikkKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAF 849
Cdd:cd15991    135 --NPD-FCWLSVQDTLIWSFAGPIGIVVIINTVIFVLAAKASCG---RRQRYFEKSGVISMLRTAFLLLLLISATWLLGL 208
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1039797231  850 FAWGPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15991    209 MAVNSDTLSFHYLFAIFSCLQGIFIFFFHCIFNKEVRKHLKNVL 252
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
625-893 6.35e-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: 110.80  E-value: 6.35e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  625 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRD----YPSKILIQLCAALLLLNLIFLLDSWIAlyntrgfCIAVAVFL 700
Cdd:cd16005      2 LLLDVITWVGILLSLVCLLICIFTFCFFRGLQSDrntiHKNLCISLFVAELLFLIGINRTDQPIA-------CAVFAALL 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  701 HYFLLVSFTWMGLEAFHMYLALVKVFNT--YIRKYilkFCIVGWGIPAVVVSIVLTISPDNYGIgsygkfpngtpDDFCW 778
Cdd:cd16005     75 HFFFLAAFTWMFLEGVQLYIMLVEVFESehSRRKY---FYLVGYGMPALIVAVSAAVDYRSYGT-----------DKVCW 140
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  779 INSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKK--KKQLGAQRKTSIQDLRSIAgLTFLLGITWGFAFFAWGPVN 856
Cdd:cd16005    141 LRLDTYFIWSFIGPATLIIMLNVIFLGIALYKMFHHTAilKPESGCLDNIKSWVIGAIA-LLCLLGLTWAFGLMYINEST 219
                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1039797231  857 VTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd16005    220 VIMAYLFTIFNSLQGMFIFIFHCVLQKKVRKEYGKCL 256
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
627-891 7.82e-27

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: 110.74  E-value: 7.82e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  627 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRdypSKILIQLCAALLLLNLIFLLDSWIALYNTRGFCIAVAVFLHYFLLV 706
Cdd:cd15437      4 LTRITQLGIIISLICLSMCIFTFWFFSEIQS---TRTTIHKNLCCSLFLAELIFLIGINMNANKLFCSIIAGLLHYFFLA 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  707 SFTWMGLEAFHMYLALVKVFntYIRKYILK-FCIVGWGIPAVVVSIVLTISPDNYGIgsygkfpngtpDDFCWINSNVVF 785
Cdd:cd15437     81 AFAWMCIEGIHLYLIVVGVI--YNKGFLHKnFYIFGYGSPAVVVGISAALGYKYYGT-----------TKVCWLSTENNF 147
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  786 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQlgaQRKTSIQDLRSIA----GLTFLLGITWGFAFFAWGPVNVTFMY 861
Cdd:cd15437    148 IWSFIGPACLIILVNLLAFGVIIYKVFRHTAMLK---PEVSCYENIRSCArgalALLFLLGATWIFGVLHVVYGSVVTAY 224
                          250       260       270
                   ....*....|....*....|....*....|
gi 1039797231  862 LFAIFNTLQGFFIFIFYCAAKENVRKQWRR 891
Cdd:cd15437    225 LFTISNAFQGMFIFIFLCVLSRKIQEEYYR 254
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
625-891 8.22e-27

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: 110.78  E-value: 8.22e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  625 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLdswIALYNTRGFCIAVAVFLHYFL 704
Cdd:cd16006      2 LLLTVITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIG---IDKTEYKIACPIFAGLLHFFF 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  705 LVSFTWMGLEAFHMYLALVKVFNTYI--RKYilkFCIVGWGIPAVVVSIVLTISPDNYGIgsygkfpngtpDDFCWINSN 782
Cdd:cd16006     79 LAAFAWMCLEGVQLYLMLVEVFESEYsrKKY---YYVAGYLFPATVVGVSAAIDYKSYGT-----------EKACWLRVD 144
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  783 VVFYITVVGYFCVIFLLNVsmfIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTF----LLGITWGFAFFAWGPVNVT 858
Cdd:cd16006    145 NYFIWSFIGPVTFIILLNL---IFLVITLCKMVKHSNTLKPDSSRLENIKSWVLGAFallcLLGLTWSFGLLFINEETIV 221
                          250       260       270
                   ....*....|....*....|....*....|...
gi 1039797231  859 FMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRR 891
Cdd:cd16006    222 MAYLFTIFNAFQGMFIFIFHCALQKKVRKEYSK 254
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
693-894 1.84e-26

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: 109.91  E-value: 1.84e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYILK---FCIVGWGIPAVVVSIVLTISPDNYGIGSYgkf 768
Cdd:cd15931     67 CTVMAGLLHYLFLASFVWMLLEALQLHLLVRRLTKVqVIQRDGLPrplLCLIGYGVPFLIVGVSALVYSDGYGEAKM--- 143
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  769 pngtpddfCWINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRI--KKKKQLGAQRKTSIQDLRSIAGLtFLLGITWG 846
Cdd:cd15931    144 --------CWLSQERGFNWSFLGPVIAIIGINWILFCATLWCLRQTlsNMNSDISQLKDTRLLTFKAVAQL-FILGCTWV 214
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1039797231  847 FAFFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYLC 894
Cdd:cd15931    215 LGLFQTNPVALVFQYLFTILNSLQGAFLFLVHCLLNKEVREEYIKWLT 262
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
626-886 4.02e-23

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: 100.08  E-value: 4.02e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  626 ALTFITYIGCGLSSIFLSVTLVTYIAFEK-IRRDYPSKILIQLCAALLLLNLIFllDSW----IALYNTRGF---CIAVA 697
Cdd:cd15932      3 ALDYITYVGLGISILSLVLCLIIEALVWKsVTKNKTSYMRHVCLVNIALSLLIA--DIWfiigAAISTPPNPspaCTAAT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  698 VFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILK--FCiVGWGIPAV--VVSIVLTISPDNYgigsygkfpngTP 773
Cdd:cd15932     81 FFIHFFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAiaFS-LGYGCPLIiaIITVAATAPQGGY-----------TR 148
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  774 DDFCWINSN-----VVFYITVVgyfcVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTS-IQDLRSIAGLTFLLGITWGF 847
Cdd:cd15932    149 KGVCWLNWDktkalLAFVIPAL----AIVVVNFIILIVVIFKLLRPSVGERPSKDEKNAlVQIGKSVAILTPLLGLTWGF 224
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1039797231  848 AFF-AWGPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVR 886
Cdd:cd15932    225 GLGtMIDPKSLAFHIIFAILNSFQGFFILVFGTLLDSKVR 264
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
630-895 4.41e-23

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: 99.76  E-value: 4.41e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  630 ITYIGCGLSSIFLSVTLVTYIAFEKIRRdYPSKILIQLCAALLLLNLIFLLDSW-IALYNTRGFCIAVAVFLHYFLLVSF 708
Cdd:cd15259      7 VVYAGAALCLLCLLATIITYIVFHRLIR-ISRKGRHMLVNLCLHLLLTCVVFVGgINRTANQLVCQAVGILLHYSTLCTL 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  709 TWMGLEAFHMYLALVKVFNT--------YIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIgsygkfpngtpDDFCWIN 780
Cdd:cd15259     86 LWVGVTARNMYKQVTKTAKPpqdedqppRPPKPMLRFYLIGWGIPLIICGITAAVNLDNYST-----------YDYCWLA 154
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  781 SNV---VFYITVvgyfCVIFLLNVSMFIVVLVQLcrikkkkqlgAQRKTSIQD-LRSIAGLTFLLGITWGFAFFA---WG 853
Cdd:cd15259    155 WDPslgAFYGPA----ALIVLVNCIYFLRIYCQL----------KGAPVSFQSqLRGAVITLFLYVAMWACGALAvsqRY 220
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1039797231  854 PVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRylCC 895
Cdd:cd15259    221 FLDLVFSCLYGATCSSLGLFVLIHHCLSREDVRQSWRQ--CC 260
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
692-890 4.83e-23

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: 99.53  E-value: 4.83e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  692 FCIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIvGWGIPAVVVSIVLTISPDNYGigsygkfpng 771
Cdd:cd15993     66 LCTVVAILLHYFFLSTFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAI-GWGVPAIITGLAVGLDPEGYG---------- 134
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  772 TPDdFCWINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKqlgAQRKTSIQDLRSIAGLTFLLGITWGFAFFA 851
Cdd:cd15993    135 NPD-FCWISIHDKLVWSFAGPIVVVIVMNGVMFLLVARMSCSPGQKE---TKKTSVLMTLRSSFLLLLLISATWLFGLLA 210
                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1039797231  852 WGPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWR 890
Cdd:cd15993    211 VNNSVLAFHYLHAILCCLQGLAVLLLFCVLNEEVQEAWK 249
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
624-891 1.36e-21

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: 95.75  E-value: 1.36e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  624 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIR--RDYPSK----------ILIQLCAALLLLNLIFLLDSWIALYNTRG 691
Cdd:cd15041      1 LLVVYYIYLVGYSLSLVALLPAIVIFLYFRSLRctRIRLHInlflsfilraVFWIIWDLLVVYDRLTSSGVETVLMQNPV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  692 FCIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFnTYIRKYILKFCIVGWGIPAVVVSIvltispdnYGIGSYgkfpnG 771
Cdd:cd15041     81 GCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAF-FSEPSSLKLYYAIGWGLPLVIVVI--------WAIVRA-----L 146
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  772 TPDDFCWINSNV-----VFYITVVgyFC----VIFLLNVsmfIVVLVQlcrikkkkQLGAQRKTSIQDLRSIAGLTF--- 839
Cdd:cd15041    147 LSNESCWISYNNghyewILYGPNL--LAllvnLFFLINI---LRILLT--------KLRSHPNAEPSNYRKAVKATLili 213
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039797231  840 -LLGITwgFAFFAWGP-----VNVTFMYLFAIFNTLQGFFIFIFYCAA----KENVRKQWRR 891
Cdd:cd15041    214 pLFGIQ--YLLTIYRPpdgseGELVYEYFNAILNSSQGFFVAVIYCFLngevQSELKRKWSR 273
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
693-897 3.64e-21

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: 94.12  E-value: 3.64e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTY---IRKYILkfciVGWGIPAVVVSIVLTISPDNYGigsygkfp 769
Cdd:cd15992     67 CTVIAILLHFFYLCTFSWLFLEGLHIYRMLSEVRDINygpMRFYYL----IGWGVPAFITGLAVGLDPEGYG-------- 134
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  770 ngTPDdFCWINsnvvFYITVVGYFC--VIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGF 847
Cdd:cd15992    135 --NPD-FCWLS----IYDTLIWSFAgpVAFAVSMNVFLYILSSRASCSAQQQSFEKKKGPVSGLRTAFTVLLLVSVTCLL 207
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1039797231  848 AFFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRryLCCGK 897
Cdd:cd15992    208 ALLSVNSDVILFHYLFAGFNCLQGPFIFLSHVVLLKEVRKALK--TLCGP 255
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
633-890 2.84e-19

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: 88.47  E-value: 2.84e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  633 IGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALynTRGFCIAVAVFLHYFLLVSFTWMG 712
Cdd:cd15251     10 VGCGVSCLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNILILVGQTQTL--NKGVCTMTAAFLHFFFLSSFCWVL 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  713 LEAFHMYLALV-KVFNTYIRKyilKFCIVGWGIPAVVVSIVLTIS-PDNYGIGSYgkfpngtpddfCWINSNVVFYITVV 790
Cdd:cd15251     88 TEAWQSYMAVTgRMRTRLIRK---RFLCLGWGLPALVVAVSVGFTrTKGYGTSSY-----------CWLSLEGGLLYAFV 153
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  791 GYFCVIFLLNVSMFIVVLVQLCrikkkkqlgaqRKTSIQDlRSIAGL------TFLLGITWGFAFFAWGPV-NVTFMYLF 863
Cdd:cd15251    154 GPAAAVVLVNMVIGILVFNKLV-----------SRDGISD-NAMASLwsscvvLPLLALTWMSAVLAMTDRrSVLFQILF 221
                          250       260
                   ....*....|....*....|....*..
gi 1039797231  864 AIFNTLQGFFIFIFYCAAKENVRKQWR 890
Cdd:cd15251    222 AVFDSLQGFVIVMVHCILRREVQDAVK 248
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
633-886 3.33e-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: 89.24  E-value: 3.33e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  633 IGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIALynTRGFCIAVAVFLHYFLLVSFTWMG 712
Cdd:cd15988     10 IGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNILILVGQSQTL--SKGVCTMTAAFLHFFFLSSFCWVL 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  713 LEAFHMYLALV-KVFNTYIRKyilKFCIVGWGIPAVVVSIVLTIS-PDNYGIGSYgkfpngtpddfCWINSNVVFYITVV 790
Cdd:cd15988     88 TEAWQSYLAVIgRMRTRLVRK---RFLCLGWGLPALVVAVSVGFTrTKGYGTASY-----------CWLSLEGGLLYAFV 153
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  791 GYFCVIFLLNVSMFIVVLVQLCR------IKKKKQLGAQR--------------------------KTSIQDLRSIAGLT 838
Cdd:cd15988    154 GPAAVIVLVNMLIGIIVFNKLMSrdgisdKSKKQRAGSEAepcsslllkcskcgvvssaamssataSSAMASLWSSCVVL 233
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1039797231  839 FLLGITWGFAFFAWGP-VNVTFMYLFAIFNTLQGFFIFIFYCAAKENVR 886
Cdd:cd15988    234 PLLALTWMSAVLAMTDrRSILFQVLFAVFNSVQGFVIITVHCFLRREVQ 282
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
626-895 8.42e-19

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: 87.51  E-value: 8.42e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  626 ALTFITYIGCGLSSIFLSVTLVTY-IAFEKIRRDYPSKILIQLCAALLLLNLIFLL----DSWIALYNTRGFCIAVAVFL 700
Cdd:cd15253      3 WLDFLSQVGLGASILALLLCLGIYrLVWRSVVRNKISYFRHMTLVNIAFSLLLADTcflgATFLSAGHESPLCLAAAFLC 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  701 HYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCI-VGWGIPAVVVSIVLTISpdnygigsygkFPNGT--PDDFC 777
Cdd:cd15253     83 HFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMVtLGYLCPLLIAAATVAYY-----------YPKRQylHEGAC 151
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  778 WINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIK-KKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAW-GPV 855
Cdd:cd15253    152 WLNGESGAIYAFSIPVLAIVLVNLLVLFVVLMKLMRPSvSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVATLtGES 231
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1039797231  856 NVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYLCC 895
Cdd:cd15253    232 SQVSHYGFAILNAFQGVFILLFGCLMDKKVREALLKRLCK 271
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
693-893 3.71e-18

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: 85.40  E-value: 3.71e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFntyIRKYILK--FCIVGWGIPAVVVSIvltispdnygigsYGKFPN 770
Cdd:cd15260     75 CQALHVLLQYFMVCNYFWMFCEGLYLHTVLVVAF---ISEKSLMrwFIAIGWGVPLVITAI-------------YAGVRA 138
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  771 GTPDD--FCWINSNVVFYITVVGYFC-----VIFLLNVsmfIVVLVqlcriKKKKQLGAQRKTSI--QDLRSIAGLTFLL 841
Cdd:cd15260    139 SLPDDteRCWMEESSYQWILIVPVVLsllinLIFLINI---VRVLL-----TKLRATSPNPAPAGlrKAVRATLILIPLL 210
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1039797231  842 GITWGFAFF---AWGPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15260    211 GLQFLLIPFrpePGAPLETIYQYVSALLTSLQGLCVAVLFCFCNGEVIAAIKRKW 265
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
627-891 1.55e-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: 83.75  E-value: 1.55e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  627 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYpSKILIQLCAALLLLNLIFLLDSWIAlyNTRGFCIAVAVFLHYFLLV 706
Cdd:cd15255      4 LRTLSFIGCGVSLCALIVTFILFLAVGVPKSER-TTVHKNLIFALAAAEFLLMFSEWAK--GNQVACWAVTALLHLFFLA 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  707 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFcIVGWGIPAVVVSIVLTISPDNYgigsygkfpngTPDDFCWINSNVVFY 786
Cdd:cd15255     81 AFSWMLVEGLLLWSKVVAVNMSEDRRMKFYY-VTGWGLPVVIVAVTLATSFNKY-----------VADQHCWLNVQTDII 148
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  787 ITVVGyfCVIFLLNVSMFI---VVLVQLCRIKKKKQL-----GAQRKTSIQ---DLRSIAGLTFLLGITWGFAFFAwgPV 855
Cdd:cd15255    149 WAFVG--PVLFVLTVNTFVlfrVVMVTVSSARRRAKMltpssDLEKQIGIQiwaTAKPVLVLLPVLGLTWLCGVLV--HL 224
                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1039797231  856 NVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRR 891
Cdd:cd15255    225 SDVWAYVFITLNSFQGLYIFLVYAIYNSEVRNAIQR 260
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
627-879 2.52e-17

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: 83.32  E-value: 2.52e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  627 LTFITYIGCGLSSIFLSVTLV----TYIAFEKIRRDYPSKILIQLCAALLLLNlifllDSWI----ALYNTR-----GFC 693
Cdd:cd15254      4 LDYITYIGLSISILSLAICIVieslVWKSVTKNRTSYMRHVCILNIAVSLLIA-----DIWFivvaAIQDQNyavngNVC 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  694 IAVAVFLHYFLLVSFTWM---GLEAFHMYLALVKVFNTYIRKYIlKFCIvGWGIPAV--VVSIVLTISPDNYgigsygkf 768
Cdd:cd15254     79 VAATFFIHFFYLCVFFWMlalGLMLFYRLVFILHDTSKTIQKAV-AFCL-GYGCPLIisVITIAVTLPRDSY-------- 148
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  769 pngTPDDFCWIN-SNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIK-KKKQLGAQRKTSIQDLRSIAGLTFLLGITWG 846
Cdd:cd15254    149 ---TRKKVCWLNwEDSKALLAFVIPALIIVAVNSIITVVVIVKILRPSiGEKPSKQERSSLFQIIKSIGVLTPLLGLTWG 225
                          250       260       270
                   ....*....|....*....|....*....|....
gi 1039797231  847 FAFFAWGP-VNVTFMYLFAIFNTLQGFFIFIFYC 879
Cdd:cd15254    226 FGLATVIKgSSIVFHILFTLLNAFQGLFILVFGT 259
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
693-895 1.74e-16

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: 80.77  E-value: 1.74e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVK----VFNT----YIRKYILKFCIVGWGIPAVVVSIVLTISPDNYGIGS 764
Cdd:cd16000     70 CQAVGIVLHYSTLSTMLWIGVTARNIYKQVTKkphlCQDTdqppYPKQPLLRFYLVSGGVPFIICGITAATNINNYGTED 149
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  765 YgkfpnGTPddFCWIN---SNVVFYitvvGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLL 841
Cdd:cd16000    150 E-----DTP--YCWMAwepSLGAFY----GPVAFIVLVTCIYFLCTYVQLRRHPERKYELKNEHSFKAQLRAAAFTLFLF 218
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039797231  842 GITWGFAFFA--WGP-VNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWrrYLCC 895
Cdd:cd16000    219 TATWAFGALAvsQGHfLDMIFSCLYGAFCVTLGLFILIHHCAKRDDVWHCW--WSCC 273
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
693-886 5.65e-15

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: 76.25  E-value: 5.65e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIvGWGIPAVVVSIVLTISPDNYGIGSYGKFPNGT 772
Cdd:cd15263     71 CIILVVLLHYFHLTNFFWMFVEGLYLYMLVVETFSGENIKLRVYAFI-GWGIPAVVIVIWAIVKALAPTAPNTALDPNGL 149
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  773 PDDFCWINSNVV--FYITVVgyfCVIFLLNV---SMFIVVLVQLCRIKKKKQLGAQRKTSiqdlRSIAGLTFLLGITwgF 847
Cdd:cd15263    150 LKHCPWMAEHIVdwIFQGPA---ILVLAVNLvflVRIMWVLITKLRSANTVETQQYRKAA----KALLVLIPLLGIT--Y 220
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1039797231  848 AFFAWGP----VNVTFMYLFAIFNTLQGFFIFIFYCAAKENVR 886
Cdd:cd15263    221 ILVIAGPtegiAANIFEYVRAVLLSTQGFTVALFYCFLNTEVR 263
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
633-887 6.11e-15

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: 76.18  E-value: 6.11e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  633 IGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLIFLLDSWIAlyNTRGFCIAVAVFLHYFLLVSFTWMG 712
Cdd:cd15990     13 VGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQT--RNKVVCTLVAAFLHFFFLSSFCWVL 90
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  713 LEAFHMYLALV-KVFNTYIRKyilKFCIVGWGIPAVVVSIVLTISPDNygigSYGKFpngtpdDFCWINSNVVFYITVVG 791
Cdd:cd15990     91 TEAWQSYMAVTgRLRNRIIRK---RFLCLGWGLPALVVAISVGFTKAK----GYGTV------NYCWLSLEGGLLYAFVG 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  792 YFCVIFLLNVSMFIVVLVQLCR------IKKKKQLGAQRKTSIQDLRsiagltfLLGITWGFAFFAWGP-VNVTFMYLFA 864
Cdd:cd15990    158 PAAAVVLVNMVIGILVFNKLVSkdgitdKKLKERAGASLWSSCVVLP-------LLALTWMSAVLAITDrRSALFQILFA 230
                          250       260
                   ....*....|....*....|...
gi 1039797231  865 IFNTLQGFFIFIFYCAAKENVRK 887
Cdd:cd15990    231 VFDSLEGFVIVMVHCILRREVQD 253
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
693-890 2.63e-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: 71.15  E-value: 2.63e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGIPAVVVSI--VLTISPDNYGigsygkfpn 770
Cdd:cd15987     77 CKAVMVFFHYCVMSNYFWLFIEGLYLFTLLVETFFPE-RRYFYWYTIIGWGTPTICVTVwaVLRLHFDDTG--------- 146
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  771 gtpddfCW-INSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKT-SIQDLRSIAGLTFLLGITwgFA 848
Cdd:cd15987    147 ------CWdMNDNTALWWVIKGPVVGSIMINFVLFIGIIIILVQKLQSPDIGGNESSiYLRLARSTLLLIPLFGIH--YT 218
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1039797231  849 FFAWGPVNVTF--MYLFAI-FNTLQGFFIFIFYC----AAKENVRKQWR 890
Cdd:cd15987    219 VFAFSPENVSKreRLVFELgLGSFQGFVVAVLYCflngEVQSEIKRKWR 267
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
560-611 2.77e-13

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: 65.02  E-value: 2.77e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1039797231  560 VKCVFWDLGRNdtalvptgGKGGWSSDGCSVKDKRMNETICTCSHLTSFGIL 611
Cdd:pfam01825    1 PQCVFWDFTNS--------TTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
559-616 9.99e-13

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: 63.56  E-value: 9.99e-13
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039797231   559 TVKCVFWDLGRndtalvptggkGGWSSDGCSVKDKRMNETICTCSHLTSFGILLDLSR 616
Cdd:smart00303    2 NPICVFWDESS-----------GEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPP 48
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
630-891 1.67e-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: 68.98  E-value: 1.67e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  630 ITYIGCGLSSIFLSVTLVTYIAFEKIRrdypskILIQLCAALLLLNLIFLLDSWIALYNT---------RGFC-IAVAVF 699
Cdd:cd15264      7 IYYLGFSISLVALAVALIIFLYFRSLR------CLRNNIHCNLIVTFILRNVTWFIMQNTlteihhqsnQWVCrLIVTVY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  700 lHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYIlkFCIVGWGIPAVVVsIVLTISPdNYGIGSYGKFPNGTPDDFCW 778
Cdd:cd15264     81 -NYFQVTNFFWMFVEGLYLHTMIVWAYSAdKIRFWY--YIVIGWCIPCPFV-LAWAIVK-LLYENEHCWLPKSENSYYDY 155
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  779 INSNVVFYITVVGyfcVIFLLNVsmfIVVLVQLCRIKKKKQLGAQRKTsiqdLRSIAGLTFLLGITWGFAFFAWGP---V 855
Cdd:cd15264    156 IYQGPILLVLLIN---FIFLFNI---VWVLITKLRASNTLETIQYRKA----VKATLVLLPLLGITYMLFFINPGDdktS 225
                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1039797231  856 NVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRR 891
Cdd:cd15264    226 RLVFIYFNTFLQSFQGLFVAVFYCFLNGEVRSAIRK 261
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
693-891 4.16e-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: 67.84  E-value: 4.16e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFnTYIRKYILKFCIVGWGIPAVVVS--IVLTISPDNYGigsygkfpn 770
Cdd:cd15930     77 CKASMVFFQYCVMANFFWLLVEGLYLHTLLVISF-FSERRYFWWYVLIGWGAPTVFVTvwIVARLYFEDTG--------- 146
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  771 gtpddfCW-INSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDL-RSIAGLTFLLGITWG-F 847
Cdd:cd15930    147 ------CWdINDESPYWWIIKGPILISILVNFVLFINIIRILLQKLRSPDIGGNESSQYKRLaRSTLLLIPLFGIHYIvF 220
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1039797231  848 AFFawgPVNVTF---MYLFAIFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15930    221 AFF---PENISLgirLYFELCLGSFQGFVVAVLYCflngEVQAEIKRKWRS 268
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
691-891 4.23e-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: 67.65  E-value: 4.23e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  691 GFCIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYIlkFCIVGWGIPAVVVsIVLTISPDNYGigsygkfp 769
Cdd:cd15445     71 VWCRLVTAAYNYFHVTNFFWMFGEGCYLHTAIVLTYSTdKLRKWM--FICIGWCIPFPII-VAWAIGKLYYD-------- 139
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  770 ngtpDDFCWINSNVVFYITVV--GYFCVIFLLNvsmfIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAG---LTFLLGIT 844
Cdd:cd15445    140 ----NEKCWFGKRAGVYTDYIyqGPMILVLLIN----FIFLFNIVRILMTKLRASTTSETIQYRKAVKAtlvLLPLLGIT 211
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1039797231  845 WGFAFFAWGPVNVT---FMYLFAIFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15445    212 YMLFFVNPGEDEISrivFIYFNSFLESFQGFFVSVFYCflnsEVRSAVRKRWHR 265
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
688-890 6.57e-12

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: 67.40  E-value: 6.57e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  688 NTRGFCIAVAVFLHYFLLVSFTWMGLEAFHMYLALV-KVFNTYIRKyilKFCIVGWGIPAVVVSIVLTISPDNygigSYG 766
Cdd:cd15989     65 HNKGICTMTTAFLHFFFLASFCWVLTEAWQSYMAVTgKIRTRLIRK---RFLCLGWGLPALVVAISMGFTKAK----GYG 137
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  767 KfpngtpDDFCWINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQL-------------------------------CRIK 815
Cdd:cd15989    138 T------PHYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLvsrdgildkklkhragqmsephsgltlkcakCGVV 211
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039797231  816 KKKQLGAQRKT-SIQDLRSIAGLTFLLGITWGFAFFAW-GPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWR 890
Cdd:cd15989    212 STTALSATTASnAMASLWSSCVVLPLLALTWMSAVLAMtDKRSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFR 288
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
692-891 9.46e-12

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: 66.52  E-value: 9.46e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  692 FCIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYIlkFCIVGWGIPAVVVsIVLTISPDNYgigsygkfpn 770
Cdd:cd15446     71 WCRCITTIYNYFVVTNFFWMFVEGCYLHTAIVMTYSTdKLRKWV--FLFIGWCIPCPII-VAWAIGKLYY---------- 137
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  771 gtPDDFCWINSNVVFYITVVGYFCVIFLLNVSMfiVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAG---LTFLLGITWGF 847
Cdd:cd15446    138 --ENEQCWFGKEPGKYIDYIYQGPVILVLLINF--VFLFNIVRILMTKLRASTTSETIQYRKAVKAtlvLLPLLGITYML 213
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1039797231  848 AFFAWGPVNVT---FMYLFAIFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15446    214 FFVNPGEDDISqivFIYFNSFLQSFQGFFVSVFYCflngEVRSAARKRWHR 264
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
693-877 3.67e-11

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: 64.86  E-value: 3.67e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIR-KYILKFCIVGWGIPAVVVSIVLTISPDNYGIGSYGKfpng 771
Cdd:cd15994     76 CVAATFFLHFFYLSLFFWMLTKALLILYGILLVFFKITKsVFIATAFSIGYGCPLVIAVLTVAITEPKKGYLRPEA---- 151
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  772 tpddfCWIN-SNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFF 850
Cdd:cd15994    152 -----CWLNwDETKALLAFIIPALSIVVVNLIVVGVVVVKTQRSSIGESCKQDVSNIIRISKNVAILTPLLGLTWGFGLA 226
                          170       180
                   ....*....|....*....|....*...
gi 1039797231  851 AW-GPVNVTFMYLFAIFNTLQGFFIFIF 877
Cdd:cd15994    227 TIiDSRSLPFHIIFALLNAFQGFFILLF 254
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
693-894 7.48e-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: 63.98  E-value: 7.48e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFnTYIRKYILKFCIVGWGIPAVVVSI-VLT-ISPDNYGigsygkfpn 770
Cdd:cd15271     77 CKAAVTFFQFCVLANFFWLLVEGMYLQTLLLLTF-TSDRKYFWWYILIGWGAPSVTVTVwVLTrLQYDNRG--------- 146
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  771 gtpddfCWINSNVVFYITVVGYFCVIFLLNVSMFIVV---LVQlcRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWG- 846
Cdd:cd15271    147 ------CWDDLESRIWWIIKTPILLSVFVNFLIFINViriLVQ--KLKSPDVGGNDTSHYMRLAKSTLLLIPLFGVHYVv 218
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1039797231  847 FAFFawgPVNVTF---MYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRYLC 894
Cdd:cd15271    219 FAFF---PEHVGVearLYFELVLGSFQGFIVALLYCFLNGEVQAEIKKRLG 266
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
693-891 7.49e-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: 7.49e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGIPAVVVSIVLTISPDnygigsygkfpngT 772
Cdd:cd15984     95 CKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSE-KKYLWGFTLFGWGLPAVFVTIWASVRAT-------------L 160
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  773 PDDFCW-INSNVVFYITVVGYFCVIfLLNVSMFIVVLVQLCriKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWG----- 846
Cdd:cd15984    161 ADTGCWdLSAGNLKWIIQVPILAAI-VVNFILFINIVRVLA--TKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGvhyiv 237
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  847 FAFFAWGPVNVTF----MYLFAIFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15984    238 FMAMPYTEVSGILwqvqMHYEMLFNSFQGFFVAIIYCfcngEVQAEIKKSWSR 290
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
682-891 1.71e-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: 63.16  E-value: 1.71e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  682 SWIALYNTRGFCIAVAVFLHYFLLVSFTWMGLEAFHMY-LALVKVFNTyiRKYILKFCIVGWGIPAVVVSIVLTISPDNY 760
Cdd:cd15261     77 EGRTINSTPILCEGFYVLLEYAKTVMFMWMFIEGLYLHnIIVVSVFSG--KPNYLFYYILGWGIPIVHTSAWAIVTLIKM 154
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  761 GIGSYGKFPNGTPddFCWINSNVVFYITVVGYFcviFLLNVsmfIVVLVQLCRIKKKKQLGAQRKTsiqdLRSIAGLTFL 840
Cdd:cd15261    155 KVNRCWFGYYLTP--YYWILEGPRLAVILINLF---FLLNI---IRVLVSKLRESHSREIEQVRKA----VKAAIVLLPL 222
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1039797231  841 LGIT--------------WGFAFFAWGpvnVTFMYLFaifntlQGFFIFIFYCAAKENVR----KQWRR 891
Cdd:cd15261    223 LGITnilqmipppltsviVGFAVWSYS---THFLTSF------QGFFVALIYCFLNGEVKnvlkKFWRR 282
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
684-893 9.16e-10

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: 60.85  E-value: 9.16e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  684 IALYNTRGFCIAVAVFLHYFLLVSFTWMGLEAFHMY-LALVKVF--NTYIRKYIlkfcIVGWGIPAVVVS--IVLTISPD 758
Cdd:cd15273     82 IANIGSNWVCKAITSLWQYFIIANYSWILMEGLYLHnLIFLALFsdENNIILYI----LLGWGLPLIFVVpwIVARILFE 157
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  759 NygigsygkfpngtpdDFCWI-NSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLcrIKKKKQLGAQRKTSIQDL-RSIAG 836
Cdd:cd15273    158 N---------------SLCWTtNSNLLNFLIIRIPIMISVLINFILFLNIVRVL--LVKLRSSVNEDSRRYKKWaKSTLV 220
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  837 LTFLLGITW----GFAFFAWGPVNVTFMYLF--AIFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15273    221 LVPLFGVHYtiflILSYLDDTNEAVELIWLFcdQLFASFQGFFVALLYCFLNGEVRAEIQRKW 283
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
681-891 1.62e-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: 60.14  E-value: 1.62e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  681 DSWIALYN--TRGFCIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGIPA--VVVSIVLTIS 756
Cdd:cd15266     73 TGWISYLSeeSSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSE-RRLLKKYMLIGWGTPVlfVVPWGVAKIL 151
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  757 PDNYGigsygkfpngtpddfCW-INSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLgAQRKTSIQDLRSIA 835
Cdd:cd15266    152 LENTG---------------CWgRNENMGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQM-RFTDYKYRLARSTL 215
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039797231  836 GLTFLLGI------------TWGFAFFAWGPVNVTfmylfaiFNTLQGFFIFIFYCAA----KENVRKQWRR 891
Cdd:cd15266    216 VLIPLLGIhevvfsfitdeqVEGFSRHIRLFIQLT-------LSSFQGFLVAVLYCFAngevKAELKKRWQL 280
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
693-891 1.98e-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: 59.48  E-value: 1.98e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGIPAVVVSI--VLTISPDNYGigsygkfpn 770
Cdd:cd15269     77 CKAAMVFFQYCIMANFFWLLVEGLYLHTLLAVSFFSE-RKYFWWYILIGWGAPSVFITAwsVARIYFEDVG--------- 146
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  771 gtpddfCW--INSNVVFYITVVGYFCVIfLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDL-RSIAGLTFLLGITwgF 847
Cdd:cd15269    147 ------CWdtIIESLLWWIIKTPILVSI-LVNFILFICIIRILVQKLHSPDIGRNESSQYSRLaKSTLLLIPLFGIH--Y 217
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1039797231  848 AFFAWGPVNVTF---MYLFAIFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15269    218 IMFAFFPDNFKAevkLVFELILGSFQGFVVAVLYCflngEVQAELKRKWRR 268
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
694-891 7.39e-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: 7.39e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  694 IAVAVFLhYFLLVSFTWMGLEAFHMY-LALVKVFNTyiRKYILKFCIVGWGIPAVVVSIVLTISPDnygigsygkfpngT 772
Cdd:cd15982     97 IAVVMFI-YFLATNYYWILVEGLYLHsLIFVAFFSD--TKYLWGFTLIGWGFPAVFVAAWAVVRAT-------------L 160
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  773 PDDFCW-INSNVVFYITVVGYFCVIFLlNVSMFI-VVLVQLCRIKKKKQLGAQRKtsiQDLRSIAGLTFLLGITWGFAFF 850
Cdd:cd15982    161 ADARCWeLSAGDIKWIYQAPILAAIGL-NFILFLnTVRVLATKIWETNAVGYDTR---KQYRKLAKSTLVLVLVFGVHYI 236
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  851 AWGPVNVTF--------MYLFAIFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15982    237 VFVCLPHTFtglgweirMHCELFFNSFQGFFVSIIYCycngEVQTEIKKTWTR 289
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
684-895 1.49e-08

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: 56.89  E-value: 1.49e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  684 IALYNTRGFCIAVAVFLHYFLLVSFTWMGLEAFHMYLALV---------KVFNTYIRKyILKFCIVGWGIPAVVVSIVLT 754
Cdd:cd15998     61 ITLTNYQMVCQAVGITLHYSSLSTLLWMGVKARVLHKELTwrapppqegDPALPTPRP-MLRFYLIAGGIPLIICGITAA 139
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  755 ISPDNYgigsygkfPNGTPddFCWI---NSNVVFYITVVgyfcVIFLLNVSMFIVVLVQL-CRIKKKKQLGAQRktsiQD 830
Cdd:cd15998    140 VNIHNY--------RDHSP--YCWLvwrPSLGAFYIPVA----LILLVTWIYFLCAGLHLrGPSADGDSVYSPG----VQ 201
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1039797231  831 LRSIAGLTFLLGITWGFAFFA----WGPvNVTFMYLFAIFNTLQGFFIFIFYCAAKENVRKQWRRylCC 895
Cdd:cd15998    202 LGALVTTHFLYLAMWACGALAvsqrWLP-RVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRA--CC 267
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
693-891 2.01e-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: 53.80  E-value: 2.01e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVkvFNTYIRKYILK-FCIVGWGIPAVVVSIvltispdnYGIGSYGkfpng 771
Cdd:cd15268     86 CRLVFLLMQYCVAANYYWLLVEGVYLYTLLA--FSVFSEQRIFRlYLSIGWGVPLLFVIP--------WGIVKYL----- 150
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  772 TPDDFCWI-NSNVVFYITVvgYFCVIFLLNVSMFIVVLVqLCRIKKKKQLGAQRKTSIQDLRSIAGLTF--LLG---ITW 845
Cdd:cd15268    151 YEDEGCWTrNSNMNYWLII--RLPILFAIGVNFLIFIRV-ICIVVSKLKANLMCKTDIKCRLAKSTLTLipLLGtheVIF 227
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1039797231  846 GFAFFAWGPVNVTFMYLFA--IFNTLQGFFIFIFYCAAKENV----RKQWRR 891
Cdd:cd15268    228 AFVMDEHARGTLRFVKLFTelSFTSFQGLMVAILYCFVNNEVqmefRKSWER 279
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
693-891 3.27e-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: 53.15  E-value: 3.27e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMY-LALVKVFNTyiRKYILKFCIVGWGIPAVVVSIVLTIspdnygigsygkfpNG 771
Cdd:cd15265     95 CKVAVTLFLYFLATNYYWILVEGLYLHsLIFMAFFSD--KKYLWGFTLIGWGFPAVFVIPWASV--------------RA 158
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  772 TPDDF-CWINSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLcrIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWG--FA 848
Cdd:cd15265    159 TLADTrCWDLSAGNYKWIYQVPILAAIVVNFILFLNIVRVL--ATKLRETNAGRCDTRQQYRKLAKSTLVLIPLFGvhYI 236
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  849 FFAWGPVNVTF------MYLFAIFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15265    237 VFMGMPYTEVGllwqirMHYELFFNSFQGFFVAIIYCfcngEVQAEIKKRWER 289
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
694-891 4.75e-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: 52.62  E-value: 4.75e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  694 IAVAVFLhYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGIPAVVVSIVLTISPDnygigsygkfpngTP 773
Cdd:cd15983     92 VTVTLFL-YFLATNHYWILVEGLYLHSLIFMAFLSD-KNYLWALTIIGWGLPAVFVSVWASVRVS-------------LA 156
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  774 DDFCWI----NSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIqdLRSIAGLTFLLGITWgFAF 849
Cdd:cd15983    157 DTQCWDlsagNLKWIYQVPILAAILVNFFLFLNIVRVLASKLWETNTGKLDPRQQYRKL--LKSTLVLMPLFGVHY-VLF 233
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1039797231  850 FAWGPVNVTF------MYLFAIFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15983    234 MAMPYTDVTGllwqiqMHYEMLFNSSQGFFVAFIYCfcngEVQAEIKKAWLR 285
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
701-891 1.07e-06

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: 1.07e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  701 HYFLLVSFTWMGLEAFHMY-LALVKVFNtyIRKYILKFCIVGWG------IPAVVVSIVLTispdnygigsygkfpngtp 773
Cdd:cd15272     98 NYILGANYMWIFVEGLYLHmLIFVAVFS--ENSRVKWYILLGWLspllfvLPWVFVRATLE------------------- 156
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  774 DDFCW-INSNVVFYITVVGYFCVIFLLNVSMFI-VVLVQLCRIKKkkqlGAQRKTSIQDLRSIAGLTFLLGITWG--FAF 849
Cdd:cd15272    157 DTLCWnTNTNKGYFWIIRGPIVISIAINFLFFInIVRVLFTKLKA----SNTQESRPFRYRKLAKSTLVLIPLFGvhYMV 232
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  850 FAWGPVNVTF-------MYLFAIFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15272    233 FVVLPDSMSSdeaelvwLYFEMFFNSFQGFIVALLFCflngEVQSEIKKKWQR 285
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
633-891 2.36e-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: 50.51  E-value: 2.36e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  633 IGCGLSSIFLSVTLVTYIAFEKIR--RDY------PSKILIQLCAALLLLNLIFLLDSWIALYNTRGfCIAVAVFLHYFL 704
Cdd:cd15275     10 VGYSVSLVSLAIALAILCSFRRLHctRNYihmqlfLSFILRAISIFIKDAVLFSSEDDNHCDIYTVG-CKVAMVFSNYCI 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  705 LVSFTWMGLEAFHMYLALVKVFNTyIRKYILKFCIVGWGIPAVVVSivltispdNYGIGSYgkfpnGTPDDFCW-INSNV 783
Cdd:cd15275     89 MANYSWLLVEGLYLHSLLSISFFS-ERKHLWWYIALGWGSPLIFII--------SWAIARY-----LHENEGCWdTRRNA 154
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  784 VFYITVVGYFCVIFLLNVSMFIVVLVQLcrIKKKKQLGAQRKTSIQdLRSIAGLTFLLGITWG-----FAFFAWGPVNVT 858
Cdd:cd15275    155 WIWWIIRGPVILSIFVNFILFLNILRIL--MRKLRAPDMRGNEFSQ-YKRLAKSTLLLIPLFGlhyilFAFFPEDVSSGT 231
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1039797231  859 F-MYLFA--IFNTLQGFFIFIFYC----AAKENVRKQWRR 891
Cdd:cd15275    232 MeIWLFFelALGSFQGFVVAVLYCflngEVQLEIQRKWRR 271
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
696-892 3.14e-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: 50.16  E-value: 3.14e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  696 VAVFLHYFLLVS-FTWMGLEAFHMY-LALVKVFNTyiRKYILKFCIVGWGIPAVVVSIvltispdnYGIGSYGKFpngtp 773
Cdd:cd15274     77 ILHFIHQYMMGCnYFWMLCEGIYLHtLIVVAVFAE--KQRLMWYYLLGWGFPLIPTTI--------HAITRAVYY----- 141
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  774 DDFCWINSNVVFYITVVGYFCVIFLLNVsMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITwgFAFFAWG 853
Cdd:cd15274    142 NDNCWLSSETHLLYIIHGPIMAALVVNF-FFLLNIVRVLVTKLRETHEAESHMYLKAVKATLILVPLLGIQ--FVLFPWR 218
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1039797231  854 P----VNVTFMYLFAIFNTLQGFFIFIFYCAAKENV----RKQWRRY 892
Cdd:cd15274    219 PsgkiLGKIYDYVMHSLIHFQGFFVATIFCFCNGEVqatlKRQWNQY 265
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
693-894 5.39e-06

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: 49.48  E-value: 5.39e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIR--------KYILKFCIVGWGIPAVVVSIVLTISpdnygIGS 764
Cdd:cd15999     70 CQAVGIILHYSTLATVLWVGVTARNIYKQVTRKAKRCQDpdepppppRPMLRFYLIGGGIPIIVCGITAAAN-----IKN 144
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  765 YGKFPNGTpddFCWIN---SNVVFYitvvGYFCVIFLLNVSMFIVVLVQLCRIKKKK-------------------QLGA 822
Cdd:cd15999    145 YGSRPNAP---YCWMAwepSLGAFY----GPAGFIIFVNCMYFLSIFIQLKRHPERKyelkepteeqqrlaasehgELNH 217
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  823 QRKTSIQDLRSI------------------AGLT-FLLGITWGFAFFA---WGPVNVTFMYLFAIFNTLQGFFIFIFYCA 880
Cdd:cd15999    218 QDSGSSSASCSLvstsalenehsfqaqllgASLAlFLYVALWIFGALAvslYYPMDLVFSCLFGATCLSLGAFLVVHHCV 297
                          250
                   ....*....|....
gi 1039797231  881 AKENVRKQWRRYLC 894
Cdd:cd15999    298 NREDVRRAWIATCC 311
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
693-893 8.25e-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: 48.58  E-value: 8.25e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALvkVFNTYIRKYILK-FCIVGWGIPavvvsiVLTISPdnYGIGSYGKfpng 771
Cdd:cd15929     86 CRVAQVLMQYCVAANYYWLLVEGLYLHTLL--VLAVFSERSIFRlYLLLGWGAP------VLFVVP--WGIVKYLY---- 151
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  772 tPDDFCW-INSNVVFYITVVGYFCVIFLLNVSMFIVVLvQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWG-FAF 849
Cdd:cd15929    152 -ENTGCWtRNDNMAYWWIIRLPILLAILINFFIFVRIL-KILVSKLRANQMCKTDYKFRLAKSTLTLIPLLGVHEVvFAF 229
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1039797231  850 F----AWGpvNVTFMYLFA--IFNTLQGFFIFIFYCAAKENVRKQWRRYL 893
Cdd:cd15929    230 VtdeqARG--TLRFIKLFFelFLSSFQGLLVAVLYCFANKEVQSELRKKW 277
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
693-890 1.57e-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: 48.00  E-value: 1.57e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIvGWGIPAVVVSIVLTISpdnygigsYGKfpngt 772
Cdd:cd15985     87 CRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYL-GWGTPVLFVVPWMLAK--------YLK----- 152
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  773 PDDFCW-INSNVVFYITVVGYFCVIFLLNVSMFIVVL-VQLCRIKKKKQLGAQRKTSIQdlRSIAGLTFLLGITWGFAFF 850
Cdd:cd15985    153 ENKECWaLNENMAYWWIIRIPILLASLINLLIFMRILkVILSKLRANQKGYADYKLRLA--KATLTLIPLFGIHEVVFIF 230
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1039797231  851 AWGPVNVTFMYLFAIF-----NTLQGFFIFIFYCAAKENVR----KQWR 890
Cdd:cd15985    231 ATDEQTTGILRYIKVFftlflNSFQGFLVAVLYCFANKEVKsellKKWR 279
PHA03247 PHA03247
large tegument protein UL36; Provisional
242-382 3.08e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.40  E-value: 3.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  242 PHGPPLSSSSKPVVPQATIishvasdfSLAEPLDhALMTPSTPSLTQEsnlPSPQPTIPLASSPATDLPVQSvvvssLPQ 321
Cdd:PHA03247  2878 PARPPVRRLARPAVSRSTE--------SFALPPD-QPERPPQPQAPPP---PQPQPQPPPPPQPQPPPPPPP-----RPQ 2940
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  322 TDLSHTLSPVQSSIPSPTTPAP----------SVPTELVTISTPPGET-VVNTSTVSDLEA-QVSQMEKALSL 382
Cdd:PHA03247  2941 PPLAPTTDPAGAGEPSGAVPQPwlgalvpgrvAVPRFRVPQPAPSREApASSTPPLTGHSLsRVSSWASSLAL 3013
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
693-891 3.86e-05

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: 46.71  E-value: 3.86e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFnTYIRKYILKFCIVGWGIPavVVSIVLTISPDNYgigsygkfpngT 772
Cdd:cd15270     77 CKVSVVFCHYCVMTNFFWLLVEAVYLNCLLASSF-PRGKRYFWWLVLLGWGLP--TLCTGTWILCKLY-----------F 142
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  773 PDDFCW-INSNVVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDL-RSIAGLTFLLGITWGFAFF 850
Cdd:cd15270    143 EDTECWdINNDSPYWWIIKGPIVISVGVNFLLFLNIIRILLKKLDPRQINFNNSAQYRRLsKSTLLLIPLFGTHYIIFNF 222
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1039797231  851 AWGPVNVTF-MYLFAIFNTLQGFFIFIFYCAAKENVRKQWRR 891
Cdd:cd15270    223 LPDYAGLGIrLYLELCLGSFQGFIVAVLYCFLNQEVQTEISR 264
PRK14948 PRK14948
DNA polymerase III subunit gamma/tau;
292-483 7.85e-05

DNA polymerase III subunit gamma/tau;


Pssm-ID: 237862 [Multi-domain]  Cd Length: 620  Bit Score: 46.49  E-value: 7.85e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  292 LPSPQPTIPLASSPATDLPVQSVV----VSSLPQTDLSHTLSPVQSSIP-SPTTPAPSVPTELVTISTPPgETVVNTSTV 366
Cdd:PRK14948   360 LPSAFISEIANASAPANPTPAPNPspppAPIQPSAPKTKQAATTPSPPPaKASPPIPVPAEPTEPSPTPP-ANAANAPPS 438
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  367 SDLEAQVSQMekalsLGSLEPNLAGEMVNRVSKL--LHSPPALLApLAQRLLKVV--------DAI------GLQLNFSS 430
Cdd:PRK14948   439 LNLEELWQQI-----LAKLELPSTRMLLSQQAELvsLDSNRAVIA-VSPNWLGMVqsrkplleQAFakvlgrSIKLNLES 512
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1039797231  431 TTISLTSPSLALAVIRVNASNFNTTTFAAQDPTNLQVSLETPPPENSIGAITL 483
Cdd:PRK14948   513 QSGSASNTAKTPPPPQKSPPPPAPTPPLPQPTATAPPPTPPPPPPTATQASSN 565
PHA03369 PHA03369
capsid maturational protease; Provisional
250-560 1.73e-04

capsid maturational protease; Provisional


Pssm-ID: 223061 [Multi-domain]  Cd Length: 663  Bit Score: 45.38  E-value: 1.73e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  250 SSKPVVPQATIISHVASDFSLAEPldhalMTPSTPSLTQESNLPSPQPTIPLASSPATDLPVQSVVVSSLPQTDLSHTLS 329
Cdd:PHA03369   349 KTASLTAPSRVLAAAAKVAVIAAP-----QTHTGPADRQRPQRPDGIPYSVPARSPMTAYPPVPQFCGDPGLVSPYNPQS 423
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  330 PVQSSIPSPTTPAPSVPTELVTISTPPGETVVNTstvsdLEAQVSQMEKALSLGSLEPNLAgEMVNRVSKLLHSPPALLA 409
Cdd:PHA03369   424 PGTSYGPEPVGPVPPQPTNPYVMPISMANMVYPG-----HPQEHGHERKRKRGGELKEELI-ETLKLVKKLKEEQESLAK 497
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  410 PLAQRLLKvvdaiGLQLNFSSTTISLTSPSLALAVIRVNASnfntttfAAQDPTNLQvsleTPPPEnsigaitlpsslmn 489
Cdd:PHA03369   498 ELEATAHK-----SEIKKIAESEFKNAGAKTAAANIEPNCS-------ADAAAPATK----RARPE-------------- 547
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1039797231  490 nlPANDVELASRI--QFNFFETPALFQDPSLENLTLISYVISSSVTNMT--IKNLTRNVTValkhiNPSPDDLTV 560
Cdd:PHA03369   548 --TKTELEAVVRFpyQIRNMESPAFVHSFTSTTLAAAAGQGSDTAEALAgaIETLLTQASA-----QPAGLSLPA 615
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
693-890 6.64e-04

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: 42.87  E-value: 6.64e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTyiRKYILKFCIVGWGIPAVVVS--IVLTISPDNygIGSYGKFPN 770
Cdd:cd15986     79 CKVSLVILQYCIMANFYWLLVEGLYLHTLLVVIFSE--NRHFIVYLLIGWGIPTVFIIawIVARIYLED--TGCWDTNDH 154
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  771 GTPddfcWINSNVVFYITVVgyfcviflLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDL-RSIAGLTFLLGITWG-FA 848
Cdd:cd15986    155 SVP----WWVIRIPIIISII--------LNFILFISIIRILLQKLRSPDVGGNDQSQYKRLaKSTLLLIPLFGVHYIvFV 222
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1039797231  849 FFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCAAKENV----RKQWR 890
Cdd:cd15986    223 YFPDSSSSNYQIFFELCLGSFQGLVVAILYCFLNSEVqgelKRKWR 268
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
693-868 1.25e-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: 42.31  E-value: 1.25e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  693 CIAVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYILKFCIVGWGIPAVVVSIVLT---ISPDNY-GIgsygk 767
Cdd:cd13951     94 CAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSSeAIEKKSSYFHLVAWGLPAVLTIAVLVlrkVDGDELtGI----- 168
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  768 fpngtpddfCWI-NSNVVFYIT-VVGYFCViFLLNVSMFIVV-LVQLCRIKKKKQlGAQRKTSIQDLRSIagltfLLGIt 844
Cdd:cd13951    169 ---------CFVgNQNLDALRGfVLAPLFL-YLILGTVFLLCgFLSLFRIRSILS-NDGKKTDKLEKLML-----RIGI- 231
                          170       180
                   ....*....|....*....|....*
gi 1039797231  845 wgFAFFAWGPVNVTF-MYLFAIFNT 868
Cdd:cd13951    232 --FAVLYTLPALIVIaCYFYEYANR 254
KLF8_12_N cd21093
N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins; Kruppel-like ...
265-343 4.64e-03

N-terminal domain of Kruppel-like factor (KLF) 8, KLF12, and similar proteins; Kruppel-like transcription factors (also known as Krueppel-like transcription factors, KLFs) belong to a family of proteins called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Although these factors bind to similar elements in vitro, they have distinct activities in vivo depending on their expression profile and the sequence of the N-terminal activation/repression domain, which differ between members. This model represents the related N-terminal activation/repression domains of KLF8 and KLF12.


Pssm-ID: 410606 [Multi-domain]  Cd Length: 172  Bit Score: 38.99  E-value: 4.64e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039797231  265 ASDFSL--AEPLDHALMTPSTPSLTQESNLPSPQPTIPLASSPAtdlPVQSVVVSSLpqtdlshTLSPVQSSIPSPTTPA 342
Cdd:cd21093     29 SSDHSQpqTEPVDLSINKARTSPTAVSSSPVSMSSSISSSSSSS---PRPASSPTVI-------TSVSSASAIPTVLSPG 98

                   .
gi 1039797231  343 P 343
Cdd:cd21093     99 S 99
 
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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