NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|568991003|ref|XP_006520333|]
View 

adhesion G protein-coupled receptor B1 isoform X2 [Mus musculus]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

Name Accession Description Interval E-value
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
944-1233 2.29e-155

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: 472.89  E-value: 2.29e-155
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  944 TVPSVTLIVGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLS 1023
Cdd:cd15251     2 GSPSVTLIVGCGVSCLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNILILVGQTQTLNKGVCTMTAAFLHFFFLS 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1024 SFCWVLTEAWQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVL 1103
Cdd:cd15251    82 SFCWVLTEAWQSYMAVTGRMRTRLIRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAFVGPAAAVVL 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1104 VNMVIGILVFNKLVSKDGITDkklkeragqlpvpplgraltcaecgvlsaaeansdatsNAMASLWSSCVVLPLLALTWM 1183
Cdd:cd15251   162 VNMVIGILVFNKLVSRDGISD--------------------------------------NAMASLWSSCVVLPLLALTWM 203
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 568991003 1184 SAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVVD 1233
Cdd:cd15251   204 SAVLAMTDRRSVLFQILFAVFDSLQGFVIVMVHCILRREVQDAVKCRMGV 253
AGRB_N pfam19188
Adhesion GPCR B N-terminal region; This region is found at the N-terminus of various adhesion ...
43-218 4.23e-88

Adhesion GPCR B N-terminal region; This region is found at the N-terminus of various adhesion G-protein coupled receptor B proteins. This region contains 10 cysteine residues that probably form disulphide bonds.


:

Pssm-ID: 465991  Cd Length: 177  Bit Score: 284.37  E-value: 4.23e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003    43 CTTLVQGKFFGYFSAAAVFPANASRCSWTLRNPDPRRYTLYMKVAKAPAPCSgPGRVRTYQFDSFLES-TRTYLGVESFD 121
Cdd:pfam19188    3 CSTLVQGVLYGSFSLRDLFPTNASGCSWTLENPDPTKYTLYLKFTKPTQSCL-PFSPRLLQFDHYLENtTRTYLGRESFD 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   122 EVLRLCDSSAPLAFLQASKQFLQMQRQQPPQDgdLGPQGEfPSSSDDFSVEYLVVGNRNPSHAACQMLCRWLDACLAGSR 201
Cdd:pfam19188   82 EVVELCDASSPFSFLEFDKNFVQLCLLAEPRG--DPESVV-PGPSGDFKVEVLVINNENPSQFTCGVLCRWLEECLSAST 158
                          170
                   ....*....|....*..
gi 568991003   202 SSHPCGIMQTPCACLGG 218
Cdd:pfam19188  159 SSRPCGIMQTPCICPGT 175
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
661-858 2.75e-53

GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and beta-strands that is found in cell-adhesion GPCRs and precedes the GPS motif where the autoproteolysis occurs, family, pfam01825. The full GAIN domain, comprises the GPS and the GAIN, in cell-adhesion GPCRs, and is the functional unit for autoproteolysis. The GPS motif at the end of the GAIN domain is an ancient domain that exists in primitive ancestor organizms, and the full GAIN + GPS is conserved in all cell-adhesion GPCRs and all PKD1-related proteins.


:

Pssm-ID: 465137  Cd Length: 205  Bit Score: 185.55  E-value: 2.75e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   661 GVSEVIQTLLEISQDGTSYSGDLLSTIDVLRNMTEIFRRAYYSPTPGDVQNFVQIISNLLAEENRDKWEEAQLMGPNAKE 740
Cdd:pfam16489    1 GAKELARELRNATRHGPLYGGDVLTAVELLSQLFDLLATQDATLSNAFLENFVQTVSNLLDPENRESWEDLQQTERGTAA 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   741 --LFRLVEDFVDVIGFRMKDLRDAYQVTDNLVLSIHKLPAS---GATDISFPMKGWRATGdwakvpEDRVTVSKSVFStg 815
Cdd:pfam16489   81 tkLLRTLEEYALLLAQNMKYLTPFTIVTPNIVLSVDRLDTHnfkGARFPRFPMKGERPKD------EDSVKLPPKAFK-- 152
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 568991003   816 lAADDSSVFVVGTVLYRNLGSFLALQRN-----------TTVLNSKVISVTVKP 858
Cdd:pfam16489  153 -PPDSNGTVVVVFILYRNLGSLLPPSSRydpdrrslrlpRRVVNSPVVSASVHS 205
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
412-462 5.17e-16

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


:

Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 73.39  E-value: 5.17e-16
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 568991003    412 WDEWSPWSLCSSTCGRGFRDRTRTC--RPPQFGGNPCEGPEKQTKFCNIALCP 462
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCcsPPPQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
470-520 2.17e-15

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


:

Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 71.85  E-value: 2.17e-15
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 568991003    470 WNEWSSWSTCSASCSQGRQQRTRECNGP--SYGGAECQGHWVETRDCFLQQCP 520
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
525-575 1.17e-14

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


:

Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 69.54  E-value: 1.17e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 568991003    525 WQAWASWGSCSVTCGGGSQRRERVCSGP--FFGGAACQGPQDEYRQCGAQRCP 575
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
879-937 3.76e-12

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: 62.40  E-value: 3.76e-12
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 568991003    879 TNQTCILWDETDGPsssappqlgpWSWRGCRTVPLDALRTRCLCDRLSTFAILAQLSAD 937
Cdd:smart00303    1 FNPICVFWDESSGE----------WSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPPI 49
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
359-407 6.64e-12

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


:

Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 61.83  E-value: 6.64e-12
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 568991003    359 EWSPWSVCSSTCGEGWQTRTRFCVSSSYS---TQCSGPLREQRLCNNSAvCP 407
Cdd:smart00209    3 EWSEWSPCSVTCGGGVQTRTRSCCSPPPQnggGPCTGEDVETRACNEQP-CP 53
HormR smart00008
Domain present in hormone receptors;
577-643 2.10e-10

Domain present in hormone receptors;


:

Pssm-ID: 214468  Cd Length: 70  Bit Score: 57.91  E-value: 2.10e-10
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568991003    577 PHEICDEDNFGAVVWKETPAGEVAAVRCPRNATGL-----ILRRCELDEegiaFWEP--PTYIRCVSIDYRNIQ 643
Cdd:smart00008    1 TDLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFsyktgASRNCTENG----GWSPpfPNYSNCTSNDYEELK 70
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
264-314 7.53e-07

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


:

Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 47.58  E-value: 7.53e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 568991003    264 WKLWSLWGECTRDCGGGLQTRTRTC-LPTLGVEGGGCEGVLEEGRLCNRKAC 314
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCcSPPPQNGGGPCTGEDVETRACNEQPC 52
 
Name Accession Description Interval E-value
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
944-1233 2.29e-155

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: 472.89  E-value: 2.29e-155
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  944 TVPSVTLIVGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLS 1023
Cdd:cd15251     2 GSPSVTLIVGCGVSCLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNILILVGQTQTLNKGVCTMTAAFLHFFFLS 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1024 SFCWVLTEAWQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVL 1103
Cdd:cd15251    82 SFCWVLTEAWQSYMAVTGRMRTRLIRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAFVGPAAAVVL 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1104 VNMVIGILVFNKLVSKDGITDkklkeragqlpvpplgraltcaecgvlsaaeansdatsNAMASLWSSCVVLPLLALTWM 1183
Cdd:cd15251   162 VNMVIGILVFNKLVSRDGISD--------------------------------------NAMASLWSSCVVLPLLALTWM 203
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 568991003 1184 SAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVVD 1233
Cdd:cd15251   204 SAVLAMTDRRSVLFQILFAVFDSLQGFVIVMVHCILRREVQDAVKCRMGV 253
AGRB_N pfam19188
Adhesion GPCR B N-terminal region; This region is found at the N-terminus of various adhesion ...
43-218 4.23e-88

Adhesion GPCR B N-terminal region; This region is found at the N-terminus of various adhesion G-protein coupled receptor B proteins. This region contains 10 cysteine residues that probably form disulphide bonds.


Pssm-ID: 465991  Cd Length: 177  Bit Score: 284.37  E-value: 4.23e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003    43 CTTLVQGKFFGYFSAAAVFPANASRCSWTLRNPDPRRYTLYMKVAKAPAPCSgPGRVRTYQFDSFLES-TRTYLGVESFD 121
Cdd:pfam19188    3 CSTLVQGVLYGSFSLRDLFPTNASGCSWTLENPDPTKYTLYLKFTKPTQSCL-PFSPRLLQFDHYLENtTRTYLGRESFD 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   122 EVLRLCDSSAPLAFLQASKQFLQMQRQQPPQDgdLGPQGEfPSSSDDFSVEYLVVGNRNPSHAACQMLCRWLDACLAGSR 201
Cdd:pfam19188   82 EVVELCDASSPFSFLEFDKNFVQLCLLAEPRG--DPESVV-PGPSGDFKVEVLVINNENPSQFTCGVLCRWLEECLSAST 158
                          170
                   ....*....|....*..
gi 568991003   202 SSHPCGIMQTPCACLGG 218
Cdd:pfam19188  159 SSRPCGIMQTPCICPGT 175
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
945-1212 1.32e-69

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: 234.10  E-value: 1.32e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   945 VPSVTLIVGCGVSSLTLLMLVIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNK--------VVCTLVAAF 1016
Cdd:pfam00002    3 SLKVIYTVGYSLSLVALLLAIAIFLLF-RKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKqdldhcswVGCKVVAVF 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  1017 LHFFFLSSFCWVLTEAWQSYMA-VTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTkAKGYSTMNYCWLSLEGGLLYAFV 1095
Cdd:pfam00002   82 LHYFFLANFFWMLVEGLYLYTLlVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVD-PKGYGEDDGCWLSNENGLWWIIR 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  1096 GPAAAVVLVNMVIGILVFNKLVSKDGITDKKLKERAgqlpvpplgraltcaecgvlsaaeansdatsNAMASLWSSCVVL 1175
Cdd:pfam00002  161 GPILLIILVNFIIFINIVRILVQKLRETNMGKSDLK-------------------------------QYRRLAKSTLLLL 209
                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 568991003  1176 PLLALTWMSAVLAVTDRR--SALFQILFAVFDSLEGFVI 1212
Cdd:pfam00002  210 PLLGITWVFGLFAFNPENtlRVVFLYLFLILNSFQGFFV 248
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
661-858 2.75e-53

GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and beta-strands that is found in cell-adhesion GPCRs and precedes the GPS motif where the autoproteolysis occurs, family, pfam01825. The full GAIN domain, comprises the GPS and the GAIN, in cell-adhesion GPCRs, and is the functional unit for autoproteolysis. The GPS motif at the end of the GAIN domain is an ancient domain that exists in primitive ancestor organizms, and the full GAIN + GPS is conserved in all cell-adhesion GPCRs and all PKD1-related proteins.


Pssm-ID: 465137  Cd Length: 205  Bit Score: 185.55  E-value: 2.75e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   661 GVSEVIQTLLEISQDGTSYSGDLLSTIDVLRNMTEIFRRAYYSPTPGDVQNFVQIISNLLAEENRDKWEEAQLMGPNAKE 740
Cdd:pfam16489    1 GAKELARELRNATRHGPLYGGDVLTAVELLSQLFDLLATQDATLSNAFLENFVQTVSNLLDPENRESWEDLQQTERGTAA 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   741 --LFRLVEDFVDVIGFRMKDLRDAYQVTDNLVLSIHKLPAS---GATDISFPMKGWRATGdwakvpEDRVTVSKSVFStg 815
Cdd:pfam16489   81 tkLLRTLEEYALLLAQNMKYLTPFTIVTPNIVLSVDRLDTHnfkGARFPRFPMKGERPKD------EDSVKLPPKAFK-- 152
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 568991003   816 lAADDSSVFVVGTVLYRNLGSFLALQRN-----------TTVLNSKVISVTVKP 858
Cdd:pfam16489  153 -PPDSNGTVVVVFILYRNLGSLLPPSSRydpdrrslrlpRRVVNSPVVSASVHS 205
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
412-462 5.17e-16

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 73.39  E-value: 5.17e-16
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 568991003    412 WDEWSPWSLCSSTCGRGFRDRTRTC--RPPQFGGNPCEGPEKQTKFCNIALCP 462
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCcsPPPQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
470-520 2.17e-15

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 71.85  E-value: 2.17e-15
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 568991003    470 WNEWSSWSTCSASCSQGRQQRTRECNGP--SYGGAECQGHWVETRDCFLQQCP 520
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
525-575 1.17e-14

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 69.54  E-value: 1.17e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 568991003    525 WQAWASWGSCSVTCGGGSQRRERVCSGP--FFGGAACQGPQDEYRQCGAQRCP 575
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
879-937 3.76e-12

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: 62.40  E-value: 3.76e-12
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 568991003    879 TNQTCILWDETDGPsssappqlgpWSWRGCRTVPLDALRTRCLCDRLSTFAILAQLSAD 937
Cdd:smart00303    1 FNPICVFWDESSGE----------WSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPPI 49
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
359-407 6.64e-12

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 61.83  E-value: 6.64e-12
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 568991003    359 EWSPWSVCSSTCGEGWQTRTRFCVSSSYS---TQCSGPLREQRLCNNSAvCP 407
Cdd:smart00209    3 EWSEWSPCSVTCGGGVQTRTRSCCSPPPQnggGPCTGEDVETRACNEQP-CP 53
TSP_1 pfam00090
Thrombospondin type 1 domain;
414-461 2.76e-11

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 59.74  E-value: 2.76e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568991003   414 EWSPWSLCSSTCGRGFRDRTRTCRPPQFGGNPCEGPEKQTKFCNIALC 461
Cdd:pfam00090    2 PWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
TSP_1 pfam00090
Thrombospondin type 1 domain;
528-574 4.04e-11

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 59.35  E-value: 4.04e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 568991003   528 WASWGSCSVTCGGGSQRRERVCSGPFFGGAACQGPQDEYRQCGAQRC 574
Cdd:pfam00090    3 WSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
HormR smart00008
Domain present in hormone receptors;
577-643 2.10e-10

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 57.91  E-value: 2.10e-10
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568991003    577 PHEICDEDNFGAVVWKETPAGEVAAVRCPRNATGL-----ILRRCELDEegiaFWEP--PTYIRCVSIDYRNIQ 643
Cdd:smart00008    1 TDLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFsyktgASRNCTENG----GWSPpfPNYSNCTSNDYEELK 70
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
882-931 1.17e-09

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: 55.01  E-value: 1.17e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 568991003   882 TCILWDETDGpsssappQLGPWSWRGCRTVPLDALRTRCLCDRLSTFAIL 931
Cdd:pfam01825    2 QCVFWDFTNS-------TTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
472-519 2.26e-09

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 54.59  E-value: 2.26e-09
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568991003   472 EWSSWSTCSASCSQGRQQRTRECNG-PSYGGAECqGHWVETRDCFLQQC 519
Cdd:pfam19028    5 EWSEWSECSVTCGGGVQTRTRTVIVePQNGGRPC-PELLERRPCNLPPC 52
TSP_1 pfam00090
Thrombospondin type 1 domain;
359-401 6.40e-08

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 50.49  E-value: 6.40e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 568991003   359 EWSPWSVCSSTCGEGWQTRTRFCVS-SSYSTQCSGPLREQRLCN 401
Cdd:pfam00090    2 PWSPWSPCSVTCGKGIQVRQRTCKSpFPGGEPCTGDDIETQACK 45
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
578-637 6.10e-07

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


Pssm-ID: 397086  Cd Length: 64  Bit Score: 48.14  E-value: 6.10e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568991003   578 HEICDEDNFGAVVWKETPAGEVAAVRCPR-----NATGLILRRCelDEEGI-AFWEPPTYIRCVSI 637
Cdd:pfam02793    1 GLGCPRTWDGILCWPRTPAGETVEVPCPDyfsgfDPRGNASRNC--TEDGTwSEHPPSNYSNCTSN 64
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
264-314 7.53e-07

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 47.58  E-value: 7.53e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 568991003    264 WKLWSLWGECTRDCGGGLQTRTRTC-LPTLGVEGGGCEGVLEEGRLCNRKAC 314
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCcSPPPQNGGGPCTGEDVETRACNEQPC 52
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
267-287 4.74e-04

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 39.57  E-value: 4.74e-04
                           10        20
                   ....*....|....*....|.
gi 568991003   267 WSLWGECTRDCGGGLQTRTRT 287
Cdd:pfam19028    6 WSEWSECSVTCGGGVQTRTRT 26
 
Name Accession Description Interval E-value
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
944-1233 2.29e-155

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: 472.89  E-value: 2.29e-155
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  944 TVPSVTLIVGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLS 1023
Cdd:cd15251     2 GSPSVTLIVGCGVSCLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNILILVGQTQTLNKGVCTMTAAFLHFFFLS 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1024 SFCWVLTEAWQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVL 1103
Cdd:cd15251    82 SFCWVLTEAWQSYMAVTGRMRTRLIRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAFVGPAAAVVL 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1104 VNMVIGILVFNKLVSKDGITDkklkeragqlpvpplgraltcaecgvlsaaeansdatsNAMASLWSSCVVLPLLALTWM 1183
Cdd:cd15251   162 VNMVIGILVFNKLVSRDGISD--------------------------------------NAMASLWSSCVVLPLLALTWM 203
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 568991003 1184 SAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVVD 1233
Cdd:cd15251   204 SAVLAMTDRRSVLFQILFAVFDSLQGFVIVMVHCILRREVQDAVKCRMGV 253
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
940-1239 2.91e-151

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: 462.54  E-value: 2.91e-151
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  940 MDKVTVPSVTLIVGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 1019
Cdd:cd15990     1 MEKALLPSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1020 FFLSSFCWVLTEAWQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTKAKGYSTMNYCWLSLEGGLLYAFVGPAA 1099
Cdd:cd15990    81 FFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAA 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1100 AVVLVNMVIGILVFNKLVSKDGITDKKLKERAGqlpvpplgraltcaecgvlsaaeansdatsnamASLWSSCVVLPLLA 1179
Cdd:cd15990   161 AVVLVNMVIGILVFNKLVSKDGITDKKLKERAG---------------------------------ASLWSSCVVLPLLA 207
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1180 LTWMSAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVVDRQEEGN 1239
Cdd:cd15990   208 LTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVVDRQEEGN 267
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
946-1231 2.71e-146

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: 450.18  E-value: 2.71e-146
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  946 PSVTLIVGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSF 1025
Cdd:cd15988     4 PSVPLMIGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFLSSF 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1026 CWVLTEAWQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVN 1105
Cdd:cd15988    84 CWVLTEAWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTASYCWLSLEGGLLYAFVGPAAVIVLVN 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1106 MVIGILVFNKLVSKDGITDKKLKERAGQLPVPPLGRALTCAECGVLSAAEANSDATSNAMASLWSSCVVLPLLALTWMSA 1185
Cdd:cd15988   164 MLIGIIVFNKLMSRDGISDKSKKQRAGSEAEPCSSLLLKCSKCGVVSSAAMSSATASSAMASLWSSCVVLPLLALTWMSA 243
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 568991003 1186 VLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRV 1231
Cdd:cd15988   244 VLAMTDRRSILFQVLFAVFNSVQGFVIITVHCFLRREVQDVVKCQM 289
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
946-1231 6.04e-139

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: 430.26  E-value: 6.04e-139
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  946 PSVTLIVGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSF 1025
Cdd:cd15989     6 PSVTLIVGCGLSCLALITLAVVYAALWRYIRSERSIILINFCLSIISSNILILVGQTQTHNKGICTMTTAFLHFFFLASF 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1026 CWVLTEAWQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVN 1105
Cdd:cd15989    86 CWVLTEAWQSYMAVTGKIRTRLIRKRFLCLGWGLPALVVAISMGFTKAKGYGTPHYCWLSLEGGLLYAFVGPAAAVVLVN 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1106 MVIGILVFNKLVSKDGITDKKLKERAGQLPVPPLGRALTCAECGVLSAAEANSDATSNAMASLWSSCVVLPLLALTWMSA 1185
Cdd:cd15989   166 MVIGILVFNKLVSRDGILDKKLKHRAGQMSEPHSGLTLKCAKCGVVSTTALSATTASNAMASLWSSCVVLPLLALTWMSA 245
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 568991003 1186 VLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRV 1231
Cdd:cd15989   246 VLAMTDKRSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFRCRL 291
AGRB_N pfam19188
Adhesion GPCR B N-terminal region; This region is found at the N-terminus of various adhesion ...
43-218 4.23e-88

Adhesion GPCR B N-terminal region; This region is found at the N-terminus of various adhesion G-protein coupled receptor B proteins. This region contains 10 cysteine residues that probably form disulphide bonds.


Pssm-ID: 465991  Cd Length: 177  Bit Score: 284.37  E-value: 4.23e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003    43 CTTLVQGKFFGYFSAAAVFPANASRCSWTLRNPDPRRYTLYMKVAKAPAPCSgPGRVRTYQFDSFLES-TRTYLGVESFD 121
Cdd:pfam19188    3 CSTLVQGVLYGSFSLRDLFPTNASGCSWTLENPDPTKYTLYLKFTKPTQSCL-PFSPRLLQFDHYLENtTRTYLGRESFD 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   122 EVLRLCDSSAPLAFLQASKQFLQMQRQQPPQDgdLGPQGEfPSSSDDFSVEYLVVGNRNPSHAACQMLCRWLDACLAGSR 201
Cdd:pfam19188   82 EVVELCDASSPFSFLEFDKNFVQLCLLAEPRG--DPESVV-PGPSGDFKVEVLVINNENPSQFTCGVLCRWLEECLSAST 158
                          170
                   ....*....|....*..
gi 568991003   202 SSHPCGIMQTPCACLGG 218
Cdd:pfam19188  159 SSRPCGIMQTPCICPGT 175
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
947-1227 1.18e-69

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: 234.39  E-value: 1.18e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  947 SVTLIVGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFC 1026
Cdd:cd15040     5 SIITYIGCGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFLFGINSTDNPVLCTAVAALLHYFLLASFM 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1027 WVLTEAWQSYMAVTG--RLRSRLVRKRFLCLGWGLPALVVAISVGFTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLV 1104
Cdd:cd15040    85 WMLVEALLLYLRLVKvfGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYCWLSNGNGLYYAFLGPVLLIILV 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1105 NMVIGILVFNKLVSKDGITDKKLKeragqlpvpplgraltcaecgvlsaaeansdatSNAMASLWSSCVVLPLLALTWMS 1184
Cdd:cd15040   165 NLVIFVLVLRKLLRLSAKRNKKKR---------------------------------KKTKAQLRAAVSLFFLLGLTWIF 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 568991003 1185 AVLAVTDRRSAlFQILFAVFDSLEGFVIVMVHCILRREVQDAV 1227
Cdd:cd15040   212 GILAIFGARVV-FQYLFAIFNSLQGFFIFIFHCLRNKEVRKAW 253
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
945-1212 1.32e-69

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: 234.10  E-value: 1.32e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   945 VPSVTLIVGCGVSSLTLLMLVIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNK--------VVCTLVAAF 1016
Cdd:pfam00002    3 SLKVIYTVGYSLSLVALLLAIAIFLLF-RKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKqdldhcswVGCKVVAVF 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  1017 LHFFFLSSFCWVLTEAWQSYMA-VTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTkAKGYSTMNYCWLSLEGGLLYAFV 1095
Cdd:pfam00002   82 LHYFFLANFFWMLVEGLYLYTLlVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVD-PKGYGEDDGCWLSNENGLWWIIR 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  1096 GPAAAVVLVNMVIGILVFNKLVSKDGITDKKLKERAgqlpvpplgraltcaecgvlsaaeansdatsNAMASLWSSCVVL 1175
Cdd:pfam00002  161 GPILLIILVNFIIFINIVRILVQKLRETNMGKSDLK-------------------------------QYRRLAKSTLLLL 209
                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 568991003  1176 PLLALTWMSAVLAVTDRR--SALFQILFAVFDSLEGFVI 1212
Cdd:pfam00002  210 PLLGITWVFGLFAFNPENtlRVVFLYLFLILNSFQGFFV 248
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
661-858 2.75e-53

GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and beta-strands that is found in cell-adhesion GPCRs and precedes the GPS motif where the autoproteolysis occurs, family, pfam01825. The full GAIN domain, comprises the GPS and the GAIN, in cell-adhesion GPCRs, and is the functional unit for autoproteolysis. The GPS motif at the end of the GAIN domain is an ancient domain that exists in primitive ancestor organizms, and the full GAIN + GPS is conserved in all cell-adhesion GPCRs and all PKD1-related proteins.


Pssm-ID: 465137  Cd Length: 205  Bit Score: 185.55  E-value: 2.75e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   661 GVSEVIQTLLEISQDGTSYSGDLLSTIDVLRNMTEIFRRAYYSPTPGDVQNFVQIISNLLAEENRDKWEEAQLMGPNAKE 740
Cdd:pfam16489    1 GAKELARELRNATRHGPLYGGDVLTAVELLSQLFDLLATQDATLSNAFLENFVQTVSNLLDPENRESWEDLQQTERGTAA 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003   741 --LFRLVEDFVDVIGFRMKDLRDAYQVTDNLVLSIHKLPAS---GATDISFPMKGWRATGdwakvpEDRVTVSKSVFStg 815
Cdd:pfam16489   81 tkLLRTLEEYALLLAQNMKYLTPFTIVTPNIVLSVDRLDTHnfkGARFPRFPMKGERPKD------EDSVKLPPKAFK-- 152
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 568991003   816 lAADDSSVFVVGTVLYRNLGSFLALQRN-----------TTVLNSKVISVTVKP 858
Cdd:pfam16489  153 -PPDSNGTVVVVFILYRNLGSLLPPSSRydpdrrslrlpRRVVNSPVVSASVHS 205
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
951-1226 1.15e-49

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: 177.13  E-value: 1.15e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  951 IVGCGVSSLTLLMLVIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLT 1030
Cdd:cd15933     9 YIGCGISIACLALTLIIFLVL-RVLSSDRFQIHKNLCVALLLAQILLLAGEWAEGNKVACKVVAILLHFFFMAAFSWMLV 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1031 EAWQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFtKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGI 1110
Cdd:cd15933    88 EGLHLYLMIVKVFNYKSKMRYYYFIGWGLPAIIVAISLAI-LFDDYGSPNVCWLSLDDGLIWAFVGPVIFIITVNTVILI 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1111 LVFNKLVSKDGITDKKLKERAGQLpvpplgraltcaecgvlsaaeansDATSNAMAslwsscVVLPLLALTWMSAVLAVT 1190
Cdd:cd15933   167 LVVKITVSLSTNDAKKSQGTLAQI------------------------KSTAKASV------VLLPILGLTWLFGVLVVN 216
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 568991003 1191 DRrSALFQILFAVFDSLEGFVIVMVHCILRREVQDA 1226
Cdd:cd15933   217 SQ-TIVFQYIFVILNSLQGLMIFLFHCVLNSEVRSA 251
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
951-1227 4.96e-47

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: 169.70  E-value: 4.96e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  951 IVGCGVSSLTLLMLVIIYVSVWRYiRSERSVILINFCLSIISSNALILIGQTQTRNK--VVCTLVAAFLHFFFLSSFCWV 1028
Cdd:cd13952     9 YIGCSLSLVGLLLTIITYLLFPKL-RNLRGKILINLCLSLLLAQLLFLIGQLLTSSDrpVLCKALAILLHYFLLASFFWM 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1029 LTEAWQSYMAVTGRLRSRlVRKRFL---CLGWGLPALVVAISVGFTKAKGYSTM----NYCWLSLEGGLLYAFVGPAAAV 1101
Cdd:cd13952    88 LVEAFDLYRTFVKVFGSS-ERRRFLkysLYGWGLPLLIVIITAIVDFSLYGPSPgyggEYCWLSNGNALLWAFYGPVLLI 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1102 VLVNMVIGILVFNKLVSKDGITDKKLKeragqlpvpplgraltcaecgvlsaaeansdaTSNAMASLWSSCVVLPLLALT 1181
Cdd:cd13952   167 LLVNLVFFILTVRILLRKLRETPKQSE--------------------------------RKSDRKQLRAYLKLFPLMGLT 214
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 568991003 1182 WMSAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAV 1227
Cdd:cd13952   215 WIFGILAPFVGGSLVFWYLFDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
952-1224 4.50e-36

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: 138.16  E-value: 4.50e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTE 1031
Cdd:cd15440    10 IGCIISIVCLLLAFITFTCF-RNLQCDRNTIHKNLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFLAAFSWMLLE 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1032 AWQSYMA---VTGRLRSRlvRKRFLCLGWGLPALVVAISVGFtKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVNmvi 1108
Cdd:cd15440    89 GFQLYVMlveVFEPEKSR--IKWYYLFGYGLPALIVAVSAGV-DPTGYGTEDHCWLSTENGFIWSFVGPVIVVLLAN--- 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1109 giLVFnklvskdgitdkklkeragqlpvppLGRALtCAECGVLSAAEANSDATSNAMASLW--SSCVVLPLLALTWMSAV 1186
Cdd:cd15440   163 --LVF-------------------------LGMAI-YVMCRHSSRSASKKDASKLKNIRGWlkGSIVLVVLLGLTWTFGL 214
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 568991003 1187 LAVtDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQ 1224
Cdd:cd15440   215 LFI-NQESIVMAYIFTILNSLQGLFIFIFHCVLNEKVR 251
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
948-1225 6.15e-35

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: 134.89  E-value: 6.15e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  948 VTLIVGCGVS-SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFC 1026
Cdd:cd15438     4 LTLITKVGLSvSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNNQVACAVVAGLLHYFFLAAFC 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1027 WVLTEAWQSYMAVTGRLRSRLVRKRFLCL-GWGLPALVVAISVGfTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVN 1105
Cdd:cd15438    84 WMSLEGVELYLMVVQVFNTQSLKKRYLLLiGYGVPLVIVAISAA-VNSKGYGTQRHCWLSLERGFLWSFLGPVCLIILVN 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1106 MVIGILVFNKLVSKDGITD---KKLKERagqlpvpplgRALTCaecgvlsaaeansdatsNAMASLwssCVvlplLALTW 1182
Cdd:cd15438   163 AIIFVITVWKLAEKFSSINpdmEKLRKI----------RALTI-----------------TAIAQL---CI----LGCTW 208
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 568991003 1183 MSAVLAVTDrRSALFQILFAVFDSLEGFVIVMVHCILRREVQD 1225
Cdd:cd15438   209 IFGFFQFSD-STLVMSYLFTILNSLQGLFIFLLHCLLSKQVRE 250
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
948-1223 1.06e-33

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: 131.22  E-value: 1.06e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  948 VTLIVGCGVSsLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCW 1027
Cdd:cd15441     6 IVTYIGIGIS-LVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLLAELLFLLGINQTENLFPCKLIAILLHYFYLSAFSW 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1028 VLTEAWQSYMAVTgrlRSRLVRK---RF-LCLGWGLPALVVAISVGFtKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVL 1103
Cdd:cd15441    85 LLVESLHLYRMLT---EPRDINHghmRFyYLLGYGIPAIIVGLSVGL-RPDGYGNPDFCWLSVNETLIWSFAGPIAFVIV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1104 VNMVIGILVFNKLVSKdgitdKKLKERAGQLpvpplgRALtcaecgvlsaaeansdatsnamasLWSSCVVLPLLALTWM 1183
Cdd:cd15441   161 ITLIIFILALRASCTL-----KRHVLEKASV------RTD------------------------LRSSFLLLPLLGATWV 205
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 568991003 1184 SAVLAVTDrRSALFQILFAVFDSLEGFVIVMVHCILRREV 1223
Cdd:cd15441   206 FGLLAVNE-DSELLHYLFAGLNFLQGLFIFLFYCIFNKKV 244
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
946-1228 5.10e-32

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: 126.69  E-value: 5.10e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  946 PSVTLIVGCGVS-SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSS 1024
Cdd:cd15439     2 LALTVITYVGLIiSLLCLFLAILTFLLCRSIRNTSTSLHLQLSLCLFLADLLFLVGIDRTDNKVLCSIIAGFLHYLFLAC 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1025 FCWVLTEAWQSYMAV-----TGRLRSRLVRKRFLCL-GWGLPALVVAISVGfTKAKGYSTMNYCWLSLEGGLLYAFVGPA 1098
Cdd:cd15439    82 FAWMFLEAVHLFLTVrnlkvVNYFSSHRFKKRFMYPvGYGLPAVIVAISAA-VNPQGYGTPKHCWLSMEKGFIWSFLGPV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1099 AAVVLVNMVIGILVFnklvskdgitdKKLKERAGQLPvpplgraltcAEcgvLSAAEANSDATSNAMASLWsscvvlpLL 1178
Cdd:cd15439   161 CVIIVINLVLFCLTL-----------WILREKLSSLN----------AE---VSTLKNTRLLTFKAIAQLF-------IL 209
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 568991003 1179 ALTWMSAVLAVTDRRSALfQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15439   210 GCTWILGLFQVGPVATVM-AYLFTITNSLQGVFIFLVHCLLNRQVREEYR 258
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
952-1224 1.25e-30

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: 122.23  E-value: 1.25e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCgVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTE 1031
Cdd:cd15252    10 VGI-IISLVCLAICIFTFWFFRGLQSDRTTIHKNLCISLFLAELVFLIGINTTTNKIFCSVIAGLLHYFFLAAFAWMFIE 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1032 AWQSYMAVTGRLRSR-LVRKRFLCLGWGLPALVVAISVGFtKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVNMV-IG 1109
Cdd:cd15252    89 GIQLYLMLVEVFENEgSRHKNFYIFGYGSPAVIVGVSAAL-GYRYYGTTKVCWLSTENYFIWSFIGPATLIILLNLIfLG 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1110 ILVFnklvskdgitdKKLKERAGQLPVpplgraltcaecgvlsaaeanSDATSNAMASLWSSCVVLPLLALTWMSAVLAV 1189
Cdd:cd15252   168 VAIY-----------KMFRHTAGLKPE---------------------VSCLENIRSWARGAIALLFLLGLTWIFGVLHI 215
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 568991003 1190 tDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQ 1224
Cdd:cd15252   216 -NHASVVMAYLFTVSNSLQGMFIFLFHCVLSRKVR 249
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
942-1228 4.71e-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: 118.10  E-value: 4.71e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  942 KVTVPSVTLIvGCGVSSLTLLMLVIIY--VSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 1019
Cdd:cd15256     1 QVALSSITYV-GCSLSIFCLAITLVTFavLSSVSTIRNQRYHIHANLSFAVLVAQILLLISFRFEPGTLPCKIMAILLHF 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1020 FFLSSFCWVLTEAWQSYMAVTGRLRSRLVRKRFLC-LGWGLPALVVAISVGFTkAKGYSTMNYCWLSLEGGLLYAFVGPA 1098
Cdd:cd15256    80 FFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYgIGWGSPLLICIISLTSA-LDSYGESDNCWLSLENGAIWAFVAPA 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1099 AAVVLVNmvIGILV-FNKLVSKDGITDKKLKERAGQLPVpplgraltcaecgvlsaaeansdaTSNAMAslwsscVVLPL 1177
Cdd:cd15256   159 LFVIVVN--IGILIaVTRVISRISADNYKVHGDANAFKL------------------------TAKAVA------VLLPI 206
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568991003 1178 LALTWMSAVLAVtDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15256   207 LGSSWVFGVLAV-NTHALVFQYMFAIFNSLQGFFIFLFHCLLNSEVRAAFK 256
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
958-1228 2.57e-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: 112.63  E-value: 2.57e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  958 SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYM 1037
Cdd:cd15991    15 SLVALLITFILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIGINQTENPFVCTVVAILLHYFYMSTFAWMFVEGLHIYR 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1038 AVTGRLRSRLVRKRFL-CLGWGLPALVVAISVGFtKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNkl 1116
Cdd:cd15991    95 MLTEVRNINTGHMRFYyVVGWGIPAIITGLAVGL-DPQGYGNPDFCWLSVQDTLIWSFAGPIGIVVIINTVIFVLAAK-- 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1117 vskdgitdkklkeragqlpvpplgraltcAECGVLSAAEANSDATSnamaSLWSSCVVLPLLALTWMSAVLAV-TDRRSa 1195
Cdd:cd15991   172 -----------------------------ASCGRRQRYFEKSGVIS----MLRTAFLLLLLISATWLLGLMAVnSDTLS- 217
                         250       260       270
                  ....*....|....*....|....*....|...
gi 568991003 1196 lFQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15991   218 -FHYLFAIFSCLQGIFIFFFHCIFNKEVRKHLK 249
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
946-1228 1.66e-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: 110.68  E-value: 1.66e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  946 PSVTLIVGCGVS-SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSS 1024
Cdd:cd15931     2 PFLEWINRVGVIvSLFCLGLAIFTFLLCRWIPKINTTAHLHLCLCLSMSHTLFLAGIEYVENELACTVMAGLLHYLFLAS 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1025 FCWVLTEAWQSYMAV-----TGRLRSRLVRKRFLCL-GWGLPALVVAISvGFTKAKGYSTMNYCWLSLEGGLLYAFVGPA 1098
Cdd:cd15931    82 FVWMLLEALQLHLLVrrltkVQVIQRDGLPRPLLCLiGYGVPFLIVGVS-ALVYSDGYGEAKMCWLSQERGFNWSFLGPV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1099 AAVVLVNMVIGILVFNKLVSKdgitdkklkeragqlpvpplgraltcaecgvLSAAEANSDATSNAMASLWSSCVVLPLL 1178
Cdd:cd15931   161 IAIIGINWILFCATLWCLRQT-------------------------------LSNMNSDISQLKDTRLLTFKAVAQLFIL 209
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 568991003 1179 ALTWMSAvLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15931   210 GCTWVLG-LFQTNPVALVFQYLFTILNSLQGAFLFLVHCLLNKEVREEYI 258
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
948-1229 1.80e-24

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: 104.49  E-value: 1.80e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  948 VTLIVGCGVS-SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFC 1026
Cdd:cd15436     4 LFVITWVGIViSLVCLLICIFTFCFFRGLQTDRNTIHKNLCINLFIAELLFLIGINRTQYTIACPIFAGLLHFFFLAAFC 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1027 WVLTEAWQSYMAVTGRLRSRLVRKRFLCL-GWGLPALVVAISVGFtKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVN 1105
Cdd:cd15436    84 WLCLEGVQLYLLLVEVFESEYSRRKYFYLcGYSFPALVVAVSAAI-DYRSYGTEKACWLRVDNYFIWSFIGPVTFVITLN 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1106 MVIGILVFNKLVSKDGItdkklkeragqlpVPPLGRALtcaecgvlsaaeansdatSNAMASLWSSCVVLPLLALTWMSA 1185
Cdd:cd15436   163 LVFLVITLHKMVSHSDL-------------LKPDSSRL------------------DNIKSWALGAIALLFLLGLTWSFG 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 568991003 1186 VLAVtDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQ-DAVKC 1229
Cdd:cd15436   212 LMFI-NEESVVMAYLFTIFNAFQGVFIFIFHCALQKKVRkEYSKC 255
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
958-1224 4.04e-24

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: 103.48  E-value: 4.04e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  958 SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYM 1037
Cdd:cd16005    15 SLVCLLICIFTFCFFRGLQSDRNTIHKNLCISLFVAELLFLIGINRTDQPIACAVFAALLHFFFLAAFTWMFLEGVQLYI 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1038 AVTGRLRSRLVRKR-FLCLGWGLPALVVAISVGfTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKL 1116
Cdd:cd16005    95 MLVEVFESEHSRRKyFYLVGYGMPALIVAVSAA-VDYRSYGTDKVCWLRLDTYFIWSFIGPATLIIMLNVIFLGIALYKM 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1117 VSKDGItdkkLKERAGQLPvpplgraltcaecgvlsaaeansdatsNAMASLWSSCVVLPLLALTWMSAVLAVTDrRSAL 1196
Cdd:cd16005   174 FHHTAI----LKPESGCLD---------------------------NIKSWVIGAIALLCLLGLTWAFGLMYINE-STVI 221
                         250       260
                  ....*....|....*....|....*...
gi 568991003 1197 FQILFAVFDSLEGFVIVMVHCILRREVQ 1224
Cdd:cd16005   222 MAYLFTIFNSLQGMFIFIFHCVLQKKVR 249
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
956-1225 4.65e-24

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: 103.42  E-value: 4.65e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  956 VSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQS 1035
Cdd:cd15437    13 IISLICLSMCIFTFWFFSEIQSTRTTIHKNLCCSLFLAELIFLIGINMNANKLFCSIIAGLLHYFFLAAFAWMCIEGIHL 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1036 YMAVTGRLRSR-LVRKRFLCLGWGLPALVVAIS--VGFtkaKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVN-MVIGIL 1111
Cdd:cd15437    93 YLIVVGVIYNKgFLHKNFYIFGYGSPAVVVGISaaLGY---KYYGTTKVCWLSTENNFIWSFIGPACLIILVNlLAFGVI 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1112 VFnklvskdgitdKKLKERAGQLPvpplgrALTCAEcGVLSAAEAnsdatsnAMASLWsscvvlpLLALTWMSAVLAVTd 1191
Cdd:cd15437   170 IY-----------KVFRHTAMLKP------EVSCYE-NIRSCARG-------ALALLF-------LLGATWIFGVLHVV- 216
                         250       260       270
                  ....*....|....*....|....*....|....
gi 568991003 1192 RRSALFQILFAVFDSLEGFVIVMVHCILRREVQD 1225
Cdd:cd15437   217 YGSVVTAYLFTISNAFQGMFIFIFLCVLSRKIQE 250
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
946-1228 4.74e-24

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


Pssm-ID: 320598 [Multi-domain]  Cd Length: 268  Bit Score: 103.55  E-value: 4.74e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  946 PSVTLI--VGCGVSSLTLLMLVIIYVSVWRYI-RSE----RSVILINFCLSIISSNALILIG---QTQTRNKVVCTLVAA 1015
Cdd:cd15932     2 PALDYItyVGLGISILSLVLCLIIEALVWKSVtKNKtsymRHVCLVNIALSLLIADIWFIIGaaiSTPPNPSPACTAATF 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1016 FLHFFFLSSFCWVLTEA---WQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTK-AKGYSTMNYCWLSL-EGGL 1090
Cdd:cd15932    82 FIHFFYLALFFWMLTLGlllFYRLVLVFHDMSKSTMMAIAFSLGYGCPLIIAIITVAATApQGGYTRKGVCWLNWdKTKA 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1091 LYAFVGPAAAVVLVNMVIGILVFNKLVSkdgitdkklkeragqlpvPPLGraltcaecgvlsaaEANSDATSNAMASLWS 1170
Cdd:cd15932   162 LLAFVIPALAIVVVNFIILIVVIFKLLR------------------PSVG--------------ERPSKDEKNALVQIGK 209
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568991003 1171 SCVVL-PLLALTWMSAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15932   210 SVAILtPLLGLTWGFGLGTMIDPKSLAFHIIFAILNSFQGFFILVFGTLLDSKVREALL 268
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
947-1229 8.69e-24

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: 102.69  E-value: 8.69e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  947 SVTLIVGCgVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFC 1026
Cdd:cd16007     5 SVITWVGI-VISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLIGIDKTQYQIACPIFAGLLHFFFLAAFS 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1027 WVLTEAWQSYMAVTGRLRSRLVRKRFLCL-GWGLPALVVAISVGFtKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVN 1105
Cdd:cd16007    84 WLCLEGVQLYLMLVEVFESEYSRKKYYYLcGYCFPALVVGISAAI-DYRSYGTEKACWLRVDNYFIWSFIGPVSFVIVVN 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1106 MVIGILVFNKLVSKDgitdkklkeragqlpvpplgraltcaecgvlSAAEANSDATSNAMASLWSSCVVLPLLALTWMSA 1185
Cdd:cd16007   163 LVFLMVTLHKMIRSS-------------------------------SVLKPDSSRLDNIKSWALGAITLLFLLGLTWAFG 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 568991003 1186 VLAVtDRRSALFQILFAVFDSLEGFVIVMVHCILRREV-QDAVKC 1229
Cdd:cd16007   212 LLFI-NKESVVMAYLFTTFNAFQGMFIFIFHCALQKKVhKEYSKC 255
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
948-1224 6.25e-23

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: 99.99  E-value: 6.25e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  948 VTLIVGCGVS-SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFC 1026
Cdd:cd16006     4 LTVITWVGIViSLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIGIDKTEYKIACPIFAGLLHFFFLAAFA 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1027 WVLTEAWQSYMAVTGRLRSRLVRKRFLCL-GWGLPALVVAISVGfTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVN 1105
Cdd:cd16006    84 WMCLEGVQLYLMLVEVFESEYSRKKYYYVaGYLFPATVVGVSAA-IDYKSYGTEKACWLRVDNYFIWSFIGPVTFIILLN 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1106 MVIGILVFNKLVsKDGITDKKLKERAGQLPVPPLGraltcaecgvlsaaeansdatsnamaslwsSCVVLPLLALTWMSA 1185
Cdd:cd16006   163 LIFLVITLCKMV-KHSNTLKPDSSRLENIKSWVLG------------------------------AFALLCLLGLTWSFG 211
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 568991003 1186 VLAVTDrRSALFQILFAVFDSLEGFVIVMVHCILRREVQ 1224
Cdd:cd16006   212 LLFINE-ETIVMAYLFTIFNAFQGMFIFIFHCALQKKVR 249
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
946-1231 1.22e-22

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: 99.45  E-value: 1.22e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  946 PSVTLI--VGCGVSSLTLLMLVIIYVSVWR-YIRSE----RSVILINFCLSIISSNALILIGQ--TQTRNKVVCTLVAAF 1016
Cdd:cd15253     2 FWLDFLsqVGLGASILALLLCLGIYRLVWRsVVRNKisyfRHMTLVNIAFSLLLADTCFLGATflSAGHESPLCLAAAFL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1017 LHFFFLSSFCWVLTEA---WQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVG-FTKAKGYSTMNYCWLSLEGGLLY 1092
Cdd:cd15253    82 CHFFYLATFFWMLVQAlmlFHQLLFVFHQLAKRSVLPLMVTLGYLCPLLIAAATVAyYYPKRQYLHEGACWLNGESGAIY 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1093 AFVGPAAAVVLVNMVIGILVFNKLVSKdgitdkklkeragqlpvpplgraltcaecgvlSAAEANSDATSNAMASLWSSC 1172
Cdd:cd15253   162 AFSIPVLAIVLVNLLVLFVVLMKLMRP--------------------------------SVSEGPPPEERKALLSIFKAL 209
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1173 VVL-PLLALTWMSAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRV 1231
Cdd:cd15253   210 LVLtPVFGLTWGLGVATLTGESSQVSHYGFAILNAFQGVFILLFGCLMDKKVREALLKRL 269
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
958-1228 2.46e-22

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


Pssm-ID: 320658  Cd Length: 255  Bit Score: 98.35  E-value: 2.46e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  958 SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYM 1037
Cdd:cd15992    15 TLGFLLLTFLFLLCLRALRSNKTSIRKNGATALFLSELVFILGINQADNPFACTVIAILLHFFYLCTFSWLFLEGLHIYR 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1038 AVTGRLRSRLVRKRFLCL-GWGLPALVVAISVGFtKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVfnkl 1116
Cdd:cd15992    95 MLSEVRDINYGPMRFYYLiGWGVPAFITGLAVGL-DPEGYGNPDFCWLSIYDTLIWSFAGPVAFAVSMNVFLYILS---- 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1117 vskdgitdkklkeragqlpvpplgralTCAECgvlSAAEANSDATSNAMASLWSSCVVLPLLALTWMSAVLAVtDRRSAL 1196
Cdd:cd15992   170 ---------------------------SRASC---SAQQQSFEKKKGPVSGLRTAFTVLLLVSVTCLLALLSV-NSDVIL 218
                         250       260       270
                  ....*....|....*....|....*....|..
gi 568991003 1197 FQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15992   219 FHYLFAGFNCLQGPFIFLSHVVLLKEVRKALK 250
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
958-1228 2.05e-21

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: 95.68  E-value: 2.05e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  958 SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSY- 1036
Cdd:cd15993    15 SLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELLFLLGINRTENQFLCTVVAILLHYFFLSTFAWLFVQGLHIYr 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1037 MAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFtKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKL 1116
Cdd:cd15993    95 MQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGL-DPEGYGNPDFCWISIHDKLVWSFAGPIVVVIVMNGVMFLLVARMS 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1117 VSKDGITDKKLkeragqlpvpplgraltcaecgvlsaaeansdatsNAMASLWSSCVVLPLLALTWMSAVLAVTDRRSAl 1196
Cdd:cd15993   174 CSPGQKETKKT-----------------------------------SVLMTLRSSFLLLLLISATWLFGLLAVNNSVLA- 217
                         250       260       270
                  ....*....|....*....|....*....|..
gi 568991003 1197 FQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15993   218 FHYLHAILCCLQGLAVLLLFCVLNEEVQEAWK 249
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
952-1228 2.56e-21

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: 95.30  E-value: 2.56e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTE 1031
Cdd:cd15255    10 IGCGVSLCALIVTFILFLAV-GVPKSERTTVHKNLIFALAAAEFLLMFSEWAKGNQVACWAVTALLHLFFLAAFSWMLVE 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1032 A---WQSYMAVTGRLRSRLvrKRFLCLGWGLPALVVAISVGFTKAKgYSTMNYCWLSLEGGLLYAFVGPAAAVVLVNMVI 1108
Cdd:cd15255    89 GlllWSKVVAVNMSEDRRM--KFYYVTGWGLPVVIVAVTLATSFNK-YVADQHCWLNVQTDIIWAFVGPVLFVLTVNTFV 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1109 GILVFNKLVSKdgitdkkLKERAgqlpvpplgRALTcaecgvlsaaeANSDATSNAMASLWSSC----VVLPLLALTWMS 1184
Cdd:cd15255   166 LFRVVMVTVSS-------ARRRA---------KMLT-----------PSSDLEKQIGIQIWATAkpvlVLLPVLGLTWLC 218
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 568991003 1185 AVLAvtdRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15255   219 GVLV---HLSDVWAYVFITLNSFQGLYIFLVYAIYNSEVRNAIQ 259
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
952-1223 7.85e-18

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: 85.12  E-value: 7.85e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSVWRYIRSERSV--ILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVL 1029
Cdd:cd15259    10 AGAALCLLCLLATIITYIVFHRLIRISRKGrhMLVNLCLHLLLTCVVFVGGINRTANQLVCQAVGILLHYSTLCTLLWVG 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1030 TEAWQSYMAVTGRLRSR-------LVRK---RFLCLGWGLPALVVAISVGfTKAKGYSTMNYCWLSLEGGLLyAFVGPAA 1099
Cdd:cd15259    90 VTARNMYKQVTKTAKPPqdedqppRPPKpmlRFYLIGWGIPLIICGITAA-VNLDNYSTYDYCWLAWDPSLG-AFYGPAA 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1100 AVVLVNMVIGIlvfnklvskdgitdkklkeragqlpvpplgraltCAECGVLSAAEANsdatsnaMASLWSSCVVLPLLA 1179
Cdd:cd15259   168 LIVLVNCIYFL----------------------------------RIYCQLKGAPVSF-------QSQLRGAVITLFLYV 206
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 568991003 1180 LTWMSAVLAVTDRR--SALFQILFAVFDSLEGFVIVMVHCILRREV 1223
Cdd:cd15259   207 AMWACGALAVSQRYflDLVFSCLYGATCSSLGLFVLIHHCLSREDV 252
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
952-1228 2.10e-17

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: 84.12  E-value: 2.10e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSVW-RYIRSE----RSVILINFCLSIISSNALILIG---QTQTRNKVVCTLVAAFLHFFFLS 1023
Cdd:cd15994    10 IGLGLSIFSLALCLTIEAVVWsHVTKTEitymRHVCIVNIATSLLIADVWFILAsivHNTALNYPLCVAATFFLHFFYLS 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1024 SFCWVLTEAW---QSYMAVTGRL-RSRLVRKRFlCLGWGLPALVVAISVGFTK-AKGYSTMNYCWLSL-EGGLLYAFVGP 1097
Cdd:cd15994    90 LFFWMLTKALlilYGILLVFFKItKSVFIATAF-SIGYGCPLVIAVLTVAITEpKKGYLRPEACWLNWdETKALLAFIIP 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1098 AAAVVLVNMVIGILVFNKlvskdgitdkklkeragqlpvppLGRAltcaecgvlSAAEANSDATSNAMASLWSSCVVLPL 1177
Cdd:cd15994   169 ALSIVVVNLIVVGVVVVK-----------------------TQRS---------SIGESCKQDVSNIIRISKNVAILTPL 216
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568991003 1178 LALTWMSAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15994   217 LGLTWGFGLATIIDSRSLPFHIIFALLNAFQGFFILLFGTILDRKIRIALY 267
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
952-1226 5.51e-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: 82.93  E-value: 5.51e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSVWRYIRSERS-----VILINFCLSIISSNA-LILIGQTQTRNKVVC-TLVAAFLHFFFLSS 1024
Cdd:cd15254    10 IGLSISILSLAICIVIESLVWKSVTKNRTsymrhVCILNIAVSLLIADIwFIVVAAIQDQNYAVNgNVCVAATFFIHFFY 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1025 FC---WVLTEAWQSYMAVTGRLR--SRLVRKRF-LCLGWGLPALVVAISVGFTKAK-GYSTMNYCWLSLEGG-LLYAFVG 1096
Cdd:cd15254    90 LCvffWMLALGLMLFYRLVFILHdtSKTIQKAVaFCLGYGCPLIISVITIAVTLPRdSYTRKKVCWLNWEDSkALLAFVI 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1097 PAAAVVLVNMVIGILVFNKlVSKDGITDKKLKERAGQLpvpplgraltcaecgvlsaaeansdatsnaMASLWSSCVVLP 1176
Cdd:cd15254   170 PALIIVAVNSIITVVVIVK-ILRPSIGEKPSKQERSSL------------------------------FQIIKSIGVLTP 218
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 568991003 1177 LLALTWMSAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDA 1226
Cdd:cd15254   219 LLGLTWGFGLATVIKGSSIVFHILFTLLNAFQGLFILVFGTLWDKKVQEA 268
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
949-1231 1.22e-16

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: 82.02  E-value: 1.22e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  949 TLI--VGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQ--TQTRNKVVCTLVAAFLHFFFLSS 1024
Cdd:cd15997     5 TLItyLGCGISSIFLGITLVTYLAFEKLRRDYPSKILINLCTALLMLNLVFLLNSwlSSFNNYGLCITVAAFLHYFLLAS 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1025 FCWVLTEAWQSYMAVTgRLRSRLVRK---RFLCLGWGLPALVVAISVGFTK--------AKGY-STMNYCWLSLEGGLLY 1092
Cdd:cd15997    85 FTWMGLEAVHMYFALV-KVFNIYIPNyilKFCIAGWGIPAVVVALVLAINKdfygnelsSDSLhPSTPFCWIQDDVVFYI 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1093 AFVGPAAAVVLVNMVIGILVFNKLVSkdgITDKKLKERAGQLPVPPLGRAltcaecgvlsaaeansdatsnamASLwssc 1172
Cdd:cd15997   164 SVVAYFCLIFLCNISMFITVLIQIRS---MKAKKPSRNWKQGFLHDLKSV-----------------------ASL---- 213
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568991003 1173 vvLPLLALTWMSAVLAVTDRRsALFQILFAVFDSLEGFVIVMVHCILRREVQDavKCRV 1231
Cdd:cd15997   214 --TFLLGLTWGFAFFAWGPVR-IFFLYLFSICNTLQGFFIFVFHCLMKENVRK--QWRI 267
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
949-1224 1.85e-16

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


Pssm-ID: 320386 [Multi-domain]  Cd Length: 267  Bit Score: 81.31  E-value: 1.85e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  949 TLI--VGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILI--GQTQTRNKVVCTLVAAFLHFFFLSS 1024
Cdd:cd15258     5 TFIsyVGCGISAIFLAITILTYIAFRKLRRDYPSKIHMNLCAALLLLNLAFLLssWIASFGSDGLCIAVAVALHYFLLAC 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1025 FCWVLTEAWQSYMAVtGRLRSRLVRKRFL---CLGWGLPALVVAIS----------VGFTKAKGYSTMNYCWLSLEGGLL 1091
Cdd:cd15258    85 LTWMGLEAFHLYLLL-VKVFNTYIRRYILklcLVGWGLPALLVTLVlsvrsdnygpITIPNGEGFQNDSFCWIRDPVVFY 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1092 YAFVGPAAAVVLVNMVIGILVFNKLVSKDGITDKKLKERAGQLPVPPLGRALtcaecgvlsaaeansdatsnamaslwss 1171
Cdd:cd15258   164 ITVVGYFGLTFLFNMVMLATVLVQICRLREKAQATPRKRALHDLLTLLGLTF---------------------------- 215
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568991003 1172 cvvlpLLALTWMSAVLAVtdrrsALFQI----LFAVFDSLEGFVIVMVHCILRREVQ 1224
Cdd:cd15258   216 -----LLGLTWGLAFFAW-----GPFNLpflyLFAIFNSLQGFFIFIWYCSMKENVR 262
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
412-462 5.17e-16

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 73.39  E-value: 5.17e-16
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 568991003    412 WDEWSPWSLCSSTCGRGFRDRTRTC--RPPQFGGNPCEGPEKQTKFCNIALCP 462
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCcsPPPQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
470-520 2.17e-15

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 71.85  E-value: 2.17e-15
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 568991003    470 WNEWSSWSTCSASCSQGRQQRTRECNGP--SYGGAECQGHWVETRDCFLQQCP 520
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
952-1219 5.52e-15

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: 77.61  E-value: 5.52e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSsLTLLMLVIIYVSVWRYIRSER-SVILINFCLSIISSNALILIGQTQTRNKV---------------------- 1008
Cdd:cd15257    10 IGCVLS-IAGLVITIIFHLHTRKLRKSSvTWVLLNLCSSLLLFNIIFTSGVENTNNDYeistvpdretntvllseeyvep 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1009 ---VCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTgRLRSRLVRKRFL---CLGWGLPALVVAISVGFTKA--------- 1073
Cdd:cd15257    89 dtdVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLI-RMMKPLPEMFILqasAIGWGIPAVVVAITLGATYRfptslpvft 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1074 KGYSTMNYCWL-------SLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKDgITDKKLKERAgqlpvpplgraltca 1146
Cdd:cd15257   168 RTYRQEEFCWLaaldknfDIKKPLLWGFLLPVGLILITNVILFIMTSQKVLKKN-NKKLTTKKRS--------------- 231
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568991003 1147 ecgvlsaaeansdatsnAMASLWSSCVVLPLLALTWMSA--VLAVTDRRSALFQILFAVFDSLEGFVIvmvhCIL 1219
Cdd:cd15257   232 -----------------YMKKIYITVSVAVVFGITWILGylMLVNNDLSKLVFSYIFCITNTTQGVQI----FIL 285
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
525-575 1.17e-14

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 69.54  E-value: 1.17e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 568991003    525 WQAWASWGSCSVTCGGGSQRRERVCSGP--FFGGAACQGPQDEYRQCGAQRCP 575
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
952-1230 9.96e-14

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: 73.05  E-value: 9.96e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSVwRYIRSERSVILINFCLSIISSNA------LILIGQTQTRNKVVCTLVAAFLHFFFLSSF 1025
Cdd:cd15445    10 LGHCISLVALLVAFVLFLRL-RSIRCLRNIIHWNLITAFILRNAtwfvvqLTMSPEVHQSNVVWCRLVTAAYNYFHVTNF 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1026 CWVLTEAWQSYMAV-----TGRLRSRLvrkrFLCLGWGLP-ALVVAISVGftkaKGYSTMNYCWLSLEGGLL--YAFVGP 1097
Cdd:cd15445    89 FWMFGEGCYLHTAIvltysTDKLRKWM----FICIGWCIPfPIIVAWAIG----KLYYDNEKCWFGKRAGVYtdYIYQGP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1098 AAAVVLVNMvigILVFNKLvskdGITDKKLkeragqlpvpplgRALTCAEcgvlsaaeansdaTSNAMASLWSSCVVLPL 1177
Cdd:cd15445   161 MILVLLINF---IFLFNIV----RILMTKL-------------RASTTSE-------------TIQYRKAVKATLVLLPL 207
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568991003 1178 LALTWMSA-VLAVTDRRSALFQILFAVF-DSLEGFVIVMVHCILRREVQDAVKCR 1230
Cdd:cd15445   208 LGITYMLFfVNPGEDEISRIVFIYFNSFlESFQGFFVSVFYCFLNSEVRSAVRKR 262
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
952-1224 2.04e-13

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: 72.55  E-value: 2.04e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVV---CTLVAAFLHFFFLSSFCWV 1028
Cdd:cd15444    10 IGCGLSAIFLSVTLVTYIAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKDIvglCISVAVFLHYFLLVSFTWM 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1029 LTEAWQSYMAVTgRLRSRLVRK---RFLCLGWGLPALVVAISVGFTK------AKGY----STMNYCWLSLEGGLLYAFV 1095
Cdd:cd15444    90 GLEAFHMYLALV-KVFNTYIRKyilKFCIVGWGVPAVVVAIVLAVSKdnyglgSYGKspngSTDDFCWINNNIVFYITVV 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1096 GPAAAVVLVNMVIGILVFNKLVSKdgitdKKLKERAGQlpvpplgraltcaecgvlsaaeansdaTSNAMASLWSSCVVL 1175
Cdd:cd15444   169 GYFCVIFLLNISMFIVVLVQLCRI-----KKQKQLGAQ---------------------------RKTSLQDLRSVAGIT 216
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 568991003 1176 PLLALTWMSAVLAvTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQ 1224
Cdd:cd15444   217 FLLGITWGFAFFA-WGPVNLAFMYLFAIFNTLQGFFIFIFYCVAKENVR 264
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
948-1231 2.72e-13

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: 71.68  E-value: 2.72e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  948 VTLI---VGCGVSSLTLLMLVIIYVsVWRYIRSERSVILINFCLSIISSNALILIGQ------TQTRNKVVCTLVAAFLH 1018
Cdd:cd15264     3 VALIiyyLGFSISLVALAVALIIFL-YFRSLRCLRNNIHCNLIVTFILRNVTWFIMQntlteiHHQSNQWVCRLIVTVYN 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1019 FFFLSSFCWVLTEAWQSYMAVTGRLRSRLVRK-RFLCLGWGLPA-LVVAISVGftkaKGYSTMNYCWLSLEGGLLYAFV- 1095
Cdd:cd15264    82 YFQVTNFFWMFVEGLYLHTMIVWAYSADKIRFwYYIVIGWCIPCpFVLAWAIV----KLLYENEHCWLPKSENSYYDYIy 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1096 -GPAAAVVLVNMVIgilVFNKLVskdgITDKKLKeragqlpvpplgraltcaecgvlsaaEANSDATSNAMASLWSSCVV 1174
Cdd:cd15264   158 qGPILLVLLINFIF---LFNIVW----VLITKLR--------------------------ASNTLETIQYRKAVKATLVL 204
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568991003 1175 LPLLALTWMSAVLAVTDrrSALFQILFAVFD----SLEGFVIVMVHCILRREVQDAVKCRV 1231
Cdd:cd15264   205 LPLLGITYMLFFINPGD--DKTSRLVFIYFNtflqSFQGLFVAVFYCFLNGEVRSAIRKKF 263
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
952-1224 1.25e-12

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: 69.92  E-value: 1.25e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILI-GQTQTRN-KVVCTLVAAFLHFFFLSSFCWVL 1029
Cdd:cd15996    10 IGCGISAIFSAATLLTYIAFEKLRRDYPSKILMNLSTALLFLNLVFLLdGWIASFEiDELCITVAVLLHFFLLATFTWMG 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1030 TEAWQSYMAVTGRLRSRLVRK--RFLCLGWGLPALVVAISVGFTK---AKGYSTMNY--------CWLSLEGGLLYAFVG 1096
Cdd:cd15996    90 LEAIHMYIALVKVFNTYIRRYilKFCIIGWGLPALIVSIVLASTNdnyGYGYYGKDKdgqggdefCWIKNPVVFYVTCAA 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1097 PAAAVVLVNMVIGILVFNKLVSKDGI-TDKKLKEragqlpvpplgraltcaecgvlsaaeansdatsNAMASLWSSCVVL 1175
Cdd:cd15996   170 YFGIMFLMNVAMFIVVMVQICGRNGKrSNRTLRE---------------------------------EILRNLRSVVSLT 216
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 568991003 1176 PLLALTWMSAVLAVTDRRSAlFQILFAVFDSLEGFVIVMVHCILRREVQ 1224
Cdd:cd15996   217 FLLGMTWGFAFFAWGPVNLA-FMYLFTIFNSLQGLFIFVFHCALKENVQ 264
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
879-937 3.76e-12

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: 62.40  E-value: 3.76e-12
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 568991003    879 TNQTCILWDETDGPsssappqlgpWSWRGCRTVPLDALRTRCLCDRLSTFAILAQLSAD 937
Cdd:smart00303    1 FNPICVFWDESSGE----------WSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPPI 49
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
359-407 6.64e-12

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 61.83  E-value: 6.64e-12
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 568991003    359 EWSPWSVCSSTCGEGWQTRTRFCVSSSYS---TQCSGPLREQRLCNNSAvCP 407
Cdd:smart00209    3 EWSEWSPCSVTCGGGVQTRTRSCCSPPPQnggGPCTGEDVETRACNEQP-CP 53
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
945-1228 1.48e-11

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: 66.86  E-value: 1.48e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  945 VPSVTLI-VGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILI---------------GQTQTRNKV 1008
Cdd:cd15041     1 LLVVYYIyLVGYSLSLVALLPAIVIFLYFRSLRCTRIRLHINLFLSFILRAVFWIIwdllvvydrltssgvETVLMQNPV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1009 VCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVT---GRLRSRLvrKRFLCLGWGLPALVVAIsVGFTKAKGYSTMnyCWLS 1085
Cdd:cd15041    81 GCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVvafFSEPSSL--KLYYAIGWGLPLVIVVI-WAIVRALLSNES--CWIS 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1086 L-EGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSkdgitdkKLKeragqlpvpplgraltcaecgvlsaaEANSDATSNA 1164
Cdd:cd15041   156 YnNGHYEWILYGPNLLALLVNLFFLINILRILLT-------KLR--------------------------SHPNAEPSNY 202
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568991003 1165 MASLWSSCVVLPLLALTWMSAVL--AVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15041   203 RKAVKATLILIPLFGIQYLLTIYrpPDGSEGELVYEYFNAILNSSQGFFVAVIYCFLNGEVQSELK 268
TSP_1 pfam00090
Thrombospondin type 1 domain;
414-461 2.76e-11

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 59.74  E-value: 2.76e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568991003   414 EWSPWSLCSSTCGRGFRDRTRTCRPPQFGGNPCEGPEKQTKFCNIALC 461
Cdd:pfam00090    2 PWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
414-461 3.37e-11

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 59.60  E-value: 3.37e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568991003   414 EWSPWSLCSSTCGRGFRDRTRT-CRPPQFGGNPCeGPEKQTKFCNIALC 461
Cdd:pfam19028    5 EWSEWSECSVTCGGGVQTRTRTvIVEPQNGGRPC-PELLERRPCNLPPC 52
TSP_1 pfam00090
Thrombospondin type 1 domain;
528-574 4.04e-11

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 59.35  E-value: 4.04e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 568991003   528 WASWGSCSVTCGGGSQRRERVCSGPFFGGAACQGPQDEYRQCGAQRC 574
Cdd:pfam00090    3 WSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
951-1116 1.20e-10

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


Pssm-ID: 410632 [Multi-domain]  Cd Length: 270  Bit Score: 64.17  E-value: 1.20e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  951 IVGCGVSSLTLLMLVIIYVsvwrYIRSERSV---ILINFCLSIISSNALILIGQTQT-RNKVVCTLVAAFLHFFFLSSFC 1026
Cdd:cd15039     9 LIGLIISLVFLLLTLAVYA----LLPELRNLhgkCLMCLVLSLFVAYLLLLIGQLLSsGDSTLCVALGILLHFFFLAAFF 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1027 WVLTEAWQSYMAVTGRLRSRL---VRKRFL---CLGWGLPALVVAISVGFTKAK-------GYSTmNYCWLSLEGGLLYA 1093
Cdd:cd15039    85 WLNVMSFDIWRTFRGKRSSSSrskERKRFLrysLYAWGVPLLLVAVTIIVDFSPntdslrpGYGE-GSCWISNPWALLLY 163
                         170       180
                  ....*....|....*....|...
gi 568991003 1094 FVGPAAAVVLVNMVIGILVFNKL 1116
Cdd:cd15039   164 FYGPVALLLLFNIILFILTAIRI 186
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
959-1226 1.45e-10

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: 64.50  E-value: 1.45e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  959 LTLLMLVIIYVSVWRYIRSERSV--ILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSY 1036
Cdd:cd15999    17 LCLLTIIVSYIYHHSLVRISRKSwhMLVNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYSTLATVLWVGVTARNIY 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1037 MAVTGRL-------------RSRLvrkRFLCLGWGLPALVVAISVGfTKAKGY-STMN--YCWLSLEGGlLYAFVGPAAA 1100
Cdd:cd15999    97 KQVTRKAkrcqdpdepppppRPML---RFYLIGGGIPIIVCGITAA-ANIKNYgSRPNapYCWMAWEPS-LGAFYGPAGF 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1101 VVLVNMVIGILVFNKLvskdgitdKKLKERAGQL----------------PVPPLGRALTCAECGVLSAAEANSDATSNa 1164
Cdd:cd15999   172 IIFVNCMYFLSIFIQL--------KRHPERKYELkepteeqqrlaasehgELNHQDSGSSSASCSLVSTSALENEHSFQ- 242
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568991003 1165 mASLWSSCVVLPLLALTWMSAVLAVTDR--RSALFQILFAVFD-SLEGFVIVMvHCILRREVQDA 1226
Cdd:cd15999   243 -AQLLGASLALFLYVALWIFGALAVSLYypMDLVFSCLFGATClSLGAFLVVH-HCVNREDVRRA 305
HormR smart00008
Domain present in hormone receptors;
577-643 2.10e-10

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 57.91  E-value: 2.10e-10
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568991003    577 PHEICDEDNFGAVVWKETPAGEVAAVRCPRNATGL-----ILRRCELDEegiaFWEP--PTYIRCVSIDYRNIQ 643
Cdd:smart00008    1 TDLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFsyktgASRNCTENG----GWSPpfPNYSNCTSNDYEELK 70
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
952-1230 7.79e-10

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: 61.51  E-value: 7.79e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQ-----TQTRNKVVCTLVAAFLHFFFLSSFC 1026
Cdd:cd15446    10 LGHCISVGALVVAFLLFLCL-RSIRCLRNIIHWNLITTFILRNVMWFLLQmidhnIHESNEVWCRCITTIYNYFVVTNFF 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1027 WVLTEAWQSYMAVTGRLRSRLVRK-RFLCLGWGLPA-LVVAISVGftkaKGYSTMNYCWLSLEGGLL--YAFVGPAAAVV 1102
Cdd:cd15446    89 WMFVEGCYLHTAIVMTYSTDKLRKwVFLFIGWCIPCpIIVAWAIG----KLYYENEQCWFGKEPGKYidYIYQGPVILVL 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1103 LVNMVIGILVFNKLVSKDgitdkklkeragqlpvpplgRALTCAEcgvlsaaeansdaTSNAMASLWSSCVVLPLLALTW 1182
Cdd:cd15446   165 LINFVFLFNIVRILMTKL--------------------RASTTSE-------------TIQYRKAVKATLVLLPLLGITY 211
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568991003 1183 MsaVLAVTDRRSALFQILFAVFD----SLEGFVIVMVHCILRREVQDAVKCR 1230
Cdd:cd15446   212 M--LFFVNPGEDDISQIVFIYFNsflqSFQGFFVSVFYCFLNGEVRSAARKR 261
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
882-931 1.17e-09

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: 55.01  E-value: 1.17e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 568991003   882 TCILWDETDGpsssappQLGPWSWRGCRTVPLDALRTRCLCDRLSTFAIL 931
Cdd:pfam01825    2 QCVFWDFTNS-------TTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
472-519 2.26e-09

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 54.59  E-value: 2.26e-09
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568991003   472 EWSSWSTCSASCSQGRQQRTRECNG-PSYGGAECqGHWVETRDCFLQQC 519
Cdd:pfam19028    5 EWSEWSECSVTCGGGVQTRTRTVIVePQNGGRPC-PELLERRPCNLPPC 52
TSP_1 pfam00090
Thrombospondin type 1 domain;
472-519 2.63e-08

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 51.65  E-value: 2.63e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568991003   472 EWSSWSTCSASCSQGRQQRTRECNGPSYGGAECQGHWVETRDCFLQQC 519
Cdd:pfam00090    2 PWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
951-1230 4.70e-08

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: 56.13  E-value: 4.70e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  951 IVGCGVSSLTLLMLVIIYVSvWRYIRSERSVILINFCLSIISSNALILI--------GQTQTRNKVVCTLVAAFLHFFFL 1022
Cdd:cd15260     9 IGGYSVSLIALIISLAIFFS-FRSLRCTRITIHMNLFISFALNNLLWIVwyklvvdnPEVLLENPIWCQALHVLLQYFMV 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1023 SSFCWVLTEAW--QSYMAVTGRLRSRLVRKrFLCLGWGLPALVVAISVGFTKAKGYSTmNYCWLSlEGGLLYAFVGPAAA 1100
Cdd:cd15260    88 CNYFWMFCEGLylHTVLVVAFISEKSLMRW-FIAIGWGVPLVITAIYAGVRASLPDDT-ERCWME-ESSYQWILIVPVVL 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1101 VVLVNMVIGILVFNKLVSKdgitdkklkeragqlpvpplgraltcaecgvLSAAEANSDATSNAMAsLWSSCVVLPLLAL 1180
Cdd:cd15260   165 SLLINLIFLINIVRVLLTK-------------------------------LRATSPNPAPAGLRKA-VRATLILIPLLGL 212
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568991003 1181 TWMsaVLAVTDRRSA----LFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCR 1230
Cdd:cd15260   213 QFL--LIPFRPEPGApletIYQYVSALLTSLQGLCVAVLFCFCNGEVIAAIKRK 264
TSP_1 pfam00090
Thrombospondin type 1 domain;
359-401 6.40e-08

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 50.49  E-value: 6.40e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 568991003   359 EWSPWSVCSSTCGEGWQTRTRFCVS-SSYSTQCSGPLREQRLCN 401
Cdd:pfam00090    2 PWSPWSPCSVTCGKGIQVRQRTCKSpFPGGEPCTGDDIETQACK 45
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
527-574 1.28e-07

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 49.59  E-value: 1.28e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568991003   527 AWASWGSCSVTCGGGSQRRER-VCSGPFFGGAACqGPQDEYRQCGAQRC 574
Cdd:pfam19028    5 EWSEWSECSVTCGGGVQTRTRtVIVEPQNGGRPC-PELLERRPCNLPPC 52
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
943-1228 2.53e-07

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: 53.91  E-value: 2.53e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  943 VTVPSVTLIVGCGVSSLTLLMLVIIYVSvWRYIRSERSVILINFCLSIISSNA-----LILIGQTQTRNKVVCTLVAaFL 1017
Cdd:cd15263     1 VEVTTTIYFIGYSLSLVALSLALWIFLY-FKDLRCLRNTIHTNLMFTYILADLtwiltLTLQVSIGEDQKSCIILVV-LL 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1018 HFFFLSSFCWVLTEAWQSYMAVTGRLRSRLVRKR-FLCLGWGLPALVVAIsvgFTKAKGYSTMNYCWLSLEGGLL----- 1091
Cdd:cd15263    79 HYFHLTNFFWMFVEGLYLYMLVVETFSGENIKLRvYAFIGWGIPAVVIVI---WAIVKALAPTAPNTALDPNGLLkhcpw 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1092 -------YAFVGPAAAVVLVNMVIGILVFNKLvskdgITdkKLKeragqlpvpplgraltcaecgvlSAAEANSDATSNA 1164
Cdd:cd15263   156 maehivdWIFQGPAILVLAVNLVFLVRIMWVL-----IT--KLR-----------------------SANTVETQQYRKA 205
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568991003 1165 MASLwssCVVLPLLALTWMSAVLAVTDRRSA-LFQILFAVFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15263   206 AKAL---LVLIPLLGITYILVIAGPTEGIAAnIFEYVRAVLLSTQGFTVALFYCFLNTEVRNTLR 267
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
578-637 6.10e-07

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


Pssm-ID: 397086  Cd Length: 64  Bit Score: 48.14  E-value: 6.10e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568991003   578 HEICDEDNFGAVVWKETPAGEVAAVRCPR-----NATGLILRRCelDEEGI-AFWEPPTYIRCVSI 637
Cdd:pfam02793    1 GLGCPRTWDGILCWPRTPAGETVEVPCPDyfsgfDPRGNASRNC--TEDGTwSEHPPSNYSNCTSN 64
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
956-1223 7.08e-07

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: 52.65  E-value: 7.08e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  956 VSSLTLLMLVIIYVSVWRYIRSERSV--------ILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCW 1027
Cdd:cd16000     8 VYACTAVMLLCLFASIITYIVHHSTIrisrkgwhMLLNFCFHTALTFAVFAGGINRTKYPIICQAVGIVLHYSTLSTMLW 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1028 VLTEAWQSYMAVTGRLRS----------RLVRKRFLCLGWGLPALVVAISVGfTKAKGYSTMN----YCWLSLEGGlLYA 1093
Cdd:cd16000    88 IGVTARNIYKQVTKKPHLcqdtdqppypKQPLLRFYLVSGGVPFIICGITAA-TNINNYGTEDedtpYCWMAWEPS-LGA 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1094 FVGPAAAVVLVNMVIGILVFNKLvskdgitdKKLKERAGQLpvpplgraltcaecgvlsaaeansDATSNAMASLWSSCV 1173
Cdd:cd16000   166 FYGPVAFIVLVTCIYFLCTYVQL--------RRHPERKYEL------------------------KNEHSFKAQLRAAAF 213
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568991003 1174 VLPLLALTWMSAVLAVTDRR--SALFQILFAVFDSLEGFVIVMVHCILRREV 1223
Cdd:cd16000   214 TLFLFTATWAFGALAVSQGHflDMIFSCLYGAFCVTLGLFILIHHCAKRDDV 265
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
264-314 7.53e-07

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 47.58  E-value: 7.53e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 568991003    264 WKLWSLWGECTRDCGGGLQTRTRTC-LPTLGVEGGGCEGVLEEGRLCNRKAC 314
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCcSPPPQNGGGPCTGEDVETRACNEQPC 52
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
359-379 1.32e-06

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 46.89  E-value: 1.32e-06
                           10        20
                   ....*....|....*....|.
gi 568991003   359 EWSPWSVCSSTCGEGWQTRTR 379
Cdd:pfam19028    5 EWSEWSECSVTCGGGVQTRTR 25
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
947-1231 1.44e-06

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: 51.65  E-value: 1.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  947 SVTLIVGCGVS-SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILI-------GQTQ---TRNKVVCTLVAA 1015
Cdd:cd15271     3 TVKLLYTVGYGtSLTSLITAVLIFCTFRKLHCTRNYIHINLFVSFILRALAVFIkdavlfaDESVdhcTMSTVACKAAVT 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1016 FLHFFFLSSFCWVLTEA--WQSYMAVTgrlrsrLVRKR-----FLCLGWGLPALVVAIsvgFTKAKGYSTMNYCWLSLEG 1088
Cdd:cd15271    83 FFQFCVLANFFWLLVEGmyLQTLLLLT------FTSDRkyfwwYILIGWGAPSVTVTV---WVLTRLQYDNRGCWDDLES 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1089 GLLYAFVGPAAAVVLVNMVIGILVFNKLVSKdgitdkklkeragqlpvpplgraltcaecgvLSAAEANSDATSNAMASL 1168
Cdd:cd15271   154 RIWWIIKTPILLSVFVNFLIFINVIRILVQK-------------------------------LKSPDVGGNDTSHYMRLA 202
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568991003 1169 WSSCVVLPLLALTWMsaVLAVTDRRSALFQILF--AVFDSLEGFVIVMVHCILRREVQDAVKCRV 1231
Cdd:cd15271   203 KSTLLLIPLFGVHYV--VFAFFPEHVGVEARLYfeLVLGSFQGFIVALLYCFLNGEVQAEIKKRL 265
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
951-1224 2.74e-06

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: 50.91  E-value: 2.74e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  951 IVGCGVSSLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKV--VCTLVAAFLHFFFLSSFCWV 1028
Cdd:cd15443     9 IVGCSISAAASLLTILLHFFSRKQPKDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQStwLCRAAAALLHYSLLCCLTWM 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1029 LTEAWQSYMaVTGRLRSRLVRKRF--LC-LGWGLPALVVAISVGFTKA----------KGYSTMNYCWLSLEGGLLYAFV 1095
Cdd:cd15443    89 AIEGFHLYL-LLVKVYNIYIRRYVlkLCvLGWGLPALIVLLVLIFKREaygphtiptgTGYQNASMCWITSSKVHYVLVL 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1096 GPAAAVVLVNMVIGILVFnKLVSKDGITDKKLKERAGQLPVPPLGraLTCaecgvlsaaeansdatsnamaslwsscvvl 1175
Cdd:cd15443   168 GYAGLTSLFNLVVLAWVV-RMLRRLRSRKQELGERARRDWVTVLG--LTC------------------------------ 214
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 568991003 1176 pLLALTWMSAVLAVTDrrSALFQI-LFAVFDSLEGFVIVMVHCILRREVQ 1224
Cdd:cd15443   215 -LLGTTWALAFFSFGV--FLIPQLfLFTIINSLYGFFICLWYCTQRRRSD 261
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
951-1119 3.36e-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: 50.55  E-value: 3.36e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  951 IVGCGVSSLTLLMLVIIYVSvWRYIRSERSVILINFCLSIISsNALILI---------GQTQTRNKVVCTLVAAFLHFFF 1021
Cdd:cd15274     9 IVGHSLSIATLLISLGIFFF-FRSLSCQRVTLHKNLFLSYIL-NSIIIIihlvavvpnGELVARNPVSCKILHFIHQYMM 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1022 LSSFCWVLTEA-WQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVgFTKAKGYStmNYCWLSLEGGLLYAFVGPAAA 1100
Cdd:cd15274    87 GCNYFWMLCEGiYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHA-ITRAVYYN--DNCWLSSETHLLYIIHGPIMA 163
                         170
                  ....*....|....*....
gi 568991003 1101 VVLVNMVIGILVFNKLVSK 1119
Cdd:cd15274   164 ALVVNFFFLLNIVRVLVTK 182
TSP1_ADAMTS pfam19030
Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found ...
362-402 1.97e-05

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.


Pssm-ID: 465950 [Multi-domain]  Cd Length: 55  Bit Score: 43.60  E-value: 1.97e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568991003   362 PWSVCSSTCGEGWQTRTRFCVSSSY-----STQCSGPLR--EQRLCNN 402
Cdd:pfam19030    5 PWGECSVTCGGGVQTRLVQCVQKGGgsivpDSECSAQKKppETQSCNL 52
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
952-1230 3.00e-05

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: 47.81  E-value: 3.00e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIyVSVWRYIRSERSVILINFCLSIISSNALILI-----GQTQTRN-----KVVCTLVAAFLHFFF 1021
Cdd:cd15275    10 VGYSVSLVSLAIALAI-LCSFRRLHCTRNYIHMQLFLSFILRAISIFIkdavlFSSEDDNhcdiyTVGCKVAMVFSNYCI 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1022 LSSFCWVLTEAWQSYMAVTGRLRSRlvRKR---FLCLGWGLPALVVaisVGFTKAKGYSTMNYCW-LSLEGGLLYAFVGP 1097
Cdd:cd15275    89 MANYSWLLVEGLYLHSLLSISFFSE--RKHlwwYIALGWGSPLIFI---ISWAIARYLHENEGCWdTRRNAWIWWIIRGP 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1098 AAAVVLVNMVIGILVFNKLVSKdgitdkklkeragqlpvpplgraltcaecgvLSAAEANSDATSNAMASLWSSCVVLPL 1177
Cdd:cd15275   164 VILSIFVNFILFLNILRILMRK-------------------------------LRAPDMRGNEFSQYKRLAKSTLLLIPL 212
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568991003 1178 LALTWMSAVLAVTDRRSALFQI-LFA--VFDSLEGFVIVMVHCILRREVQDAVKCR 1230
Cdd:cd15275   213 FGLHYILFAFFPEDVSSGTMEIwLFFelALGSFQGFVVAVLYCFLNGEVQLEIQRK 268
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
947-1228 5.62e-05

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: 46.66  E-value: 5.62e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  947 SVTLIVGCGVS-SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQT----------QTRNKVVCTLVAA 1015
Cdd:cd15930     3 TVKIIYTVGYSlSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAVFIKDAvlfssedvdhCFVSTVGCKASMV 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1016 FLHFFFLSSFCWVLTEAWQSYMAVTGRLRSRlvRKRF---LCLGWGLPALVVAIsvgFTKAKGYSTMNYCW-LSLEGGLL 1091
Cdd:cd15930    83 FFQYCVMANFFWLLVEGLYLHTLLVISFFSE--RRYFwwyVLIGWGAPTVFVTV---WIVARLYFEDTGCWdINDESPYW 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1092 YAFVGPAAAVVLVNMVIGILVFNKLVSKdgitdkklkeragqlpvpplgraltcaecgvLSAAEANSDATSNAMASLWSS 1171
Cdd:cd15930   158 WIIKGPILISILVNFVLFINIIRILLQK-------------------------------LRSPDIGGNESSQYKRLARST 206
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568991003 1172 CVVLPLLALTWMsaVLAVT-DRRSALFQILFA-VFDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15930   207 LLLIPLFGIHYI--VFAFFpENISLGIRLYFElCLGSFQGFVVAVLYCFLNGEVQAEIK 263
TSP1_ADAMTS pfam19030
Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found ...
525-581 6.86e-05

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.


Pssm-ID: 465950 [Multi-domain]  Cd Length: 55  Bit Score: 42.05  E-value: 6.86e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 568991003   525 WQAwASWGSCSVTCGGGSQRRERVCSGPffGGAACQGPQdeyrQCGAQRCPEPHEIC 581
Cdd:pfam19030    1 WVA-GPWGECSVTCGGGVQTRLVQCVQK--GGGSIVPDS----ECSAQKKPPETQSC 50
TSP1_CCN pfam19035
CCN3 Nov like TSP1 domain; This entry represents a sub-type of TSP1 domains found in ...
361-402 2.38e-04

CCN3 Nov like TSP1 domain; This entry represents a sub-type of TSP1 domains found in matricellular CCN proteins that have an alternative disulphide binding pattern compared to the canonical TSP1 domains.


Pssm-ID: 465952  Cd Length: 44  Bit Score: 40.01  E-value: 2.38e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 568991003   361 SPWSVCSSTCGEGWQTRTrfcvsSSYSTQCSgPLREQRLCNN 402
Cdd:pfam19035    6 TEWSPCSKTCGMGVSTRV-----SNDNAECK-LVTETRLCQL 41
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
952-1219 2.65e-04

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


Pssm-ID: 320558 [Multi-domain]  Cd Length: 277  Bit Score: 44.79  E-value: 2.65e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  952 VGCGVSSLTLLMLVIIYVSV---WRYIRSERSV-ILINFCLSIISSNA--LILIGQTQTRNKVVCTLVAAFLHFFFLSSF 1025
Cdd:cd15442    10 AGCGVSMVFLIFTIILYFFLrftYQKFKSEDAPkIHVNLSSSLLLLNLafLLNSGVSSRAHPGLCKALGGVTHYFLLCCF 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1026 CWVLTEAWQSYMAVTgRLRSRLVRKRF--LCL-GWGLPALVVAISvGFTKAKGY---------STMNYCWLSlEGGLLYA 1093
Cdd:cd15442    90 TWMAIEAFHLYLLAI-KVFNTYIHHYFakLCLvGWGFPALVVTIT-GSINSYGAytimdmanrTTLHLCWIN-SKHLTVH 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1094 FV---GPAAAVVLVNMVIGILVFNKLVSKDGITdkklkeragqlpvpplgraltcaecgvlsAAEANSDATSNAMASLWS 1170
Cdd:cd15442   167 YItvcGYFGLTFLFNTVVLGLVAWKIFHLQSAT-----------------------------AGKEKCQAWKGGLTVLGL 217
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 568991003 1171 SCvvlpLLALTWMSAVLAVTDrRSALFQILFAVFDSLEGFVIVMVHCIL 1219
Cdd:cd15442   218 SC----LLGVTWGLAFFTYGS-MSVPTVYIFALLNSLQGLFIFIWFVIL 261
TSP1_ADAMTS pfam19030
Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found ...
417-461 3.69e-04

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.


Pssm-ID: 465950 [Multi-domain]  Cd Length: 55  Bit Score: 40.13  E-value: 3.69e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 568991003   417 PWSLCSSTCGRGFRDRTRTCRPP----QFGGNPCEGPEK--QTKFCNIALC 461
Cdd:pfam19030    5 PWGECSVTCGGGVQTRLVQCVQKgggsIVPDSECSAQKKppETQSCNLKPC 55
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
956-1226 4.18e-04

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: 44.18  E-value: 4.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  956 VSSLTLLMLVIIYVSVWRYIRSERSV--------ILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCW 1027
Cdd:cd15998     8 VYPCTALLLLCLFSTIITYILNHSSIhvsrkgwhMLLNLCFHIAMTSAVFAGGITLTNYQMVCQAVGITLHYSSLSTLLW 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1028 VLTEAWQSYMAVTGR----------LRSRLVRKRFLCLGWGLPALVVAISVGFTKAKGYSTMNYCWLSLEGGlLYAFVGP 1097
Cdd:cd15998    88 MGVKARVLHKELTWRapppqegdpaLPTPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSPYCWLVWRPS-LGAFYIP 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1098 AAAVVLVNMVIgilvfnklvskdgitdkklkeragqlpvpplgraLTCAecGV-LSAAEANSDATSNAMASLWSSCVVLP 1176
Cdd:cd15998   167 VALILLVTWIY----------------------------------FLCA--GLhLRGPSADGDSVYSPGVQLGALVTTHF 210
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568991003 1177 LLALTWMSAVLAVTDR--RSALFQILFAVFDSLEGFVIVMVHCILRREVQDA 1226
Cdd:cd15998   211 LYLAMWACGALAVSQRwlPRVVCSCLYGVAASALGLFVFTHHCARRRDVRAS 262
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
267-287 4.74e-04

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 39.57  E-value: 4.74e-04
                           10        20
                   ....*....|....*....|.
gi 568991003   267 WSLWGECTRDCGGGLQTRTRT 287
Cdd:pfam19028    6 WSEWSECSVTCGGGVQTRTRT 26
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
945-1228 6.08e-04

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: 43.53  E-value: 6.08e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  945 VPSVTLI--VGCGVSSLTLLMLVIIyVSVWRYIRSERSVILINFCLSIISSNALILIGQ-------------TQTRNKVV 1009
Cdd:cd15272     1 LPSIRLMynIGYGLSLVSLLIAVII-MLYFKKLHCPRNTIHINLFVSFILRAVLSFIKEnllvqgvgfpgdvYYDSNGVI 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1010 ----------CTLVAAFLHFFFLSSFCWVLTEAWQSYMAV---TGRLRSRLvrKRFLCLGWGLPALVVAISVgFTKAKGY 1076
Cdd:cd15272    80 efkdegshweCKLFFTMFNYILGANYMWIFVEGLYLHMLIfvaVFSENSRV--KWYILLGWLSPLLFVLPWV-FVRATLE 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1077 STMnyCW-LSLEGGLLYAFVGPAAAVVLVNMVIGI----LVFNKLvsKDGITDKKLKERAGQLPVpplgraltcaecgvl 1151
Cdd:cd15272   157 DTL--CWnTNTNKGYFWIIRGPIVISIAINFLFFInivrVLFTKL--KASNTQESRPFRYRKLAK--------------- 217
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1152 saaeansdatsnamaslwSSCVVLPLLALTWMSAVlAVTDRRSA-------LFQILFavFDSLEGFVIVMVHCILRREVQ 1224
Cdd:cd15272   218 ------------------STLVLIPLFGVHYMVFV-VLPDSMSSdeaelvwLYFEMF--FNSFQGFIVALLFCFLNGEVQ 276

                  ....
gi 568991003 1225 DAVK 1228
Cdd:cd15272   277 SEIK 280
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
958-1119 8.04e-04

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: 43.20  E-value: 8.04e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  958 SLTLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNK--------------------VVCTLVAAFL 1017
Cdd:cd15266    15 SLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIKDIVLYSTyskrpddetgwisylseessTSCRVAQVFM 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1018 HFFFLSSFCWVLTEAWQSY-MAVTGRLRSRLVRKRFLCLGWGLPALVVaisVGFTKAKGYSTMNYCWLSLEG-GLLYAFV 1095
Cdd:cd15266    95 HYFVGANYFWLLVEGLYLHtLLVTAVLSERRLLKKYMLIGWGTPVLFV---VPWGVAKILLENTGCWGRNENmGIWWIIR 171
                         170       180
                  ....*....|....*....|....
gi 568991003 1096 GPAAAVVLVNMVIGILVFNKLVSK 1119
Cdd:cd15266   172 GPILLCITVNFYIFLKILKLLLSK 195
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
1052-1228 1.42e-03

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: 42.63  E-value: 1.42e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1052 FLCLGWGLPALVVAIsvgFTKAKGYSTMNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSkdgitdkKLKERA 1131
Cdd:cd15984   138 FTLFGWGLPAVFVTI---WASVRATLADTGCWDLSAGNLKWIIQVPILAAIVVNFILFINIVRVLAT-------KLRETN 207
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1132 GqlpvpplGRAltcaecgvlsaaeansDATSNAMASLWSSCVVLPLLALTWMS-AVLAVTDRRSALFQILF---AVFDSL 1207
Cdd:cd15984   208 A-------GRC----------------DTRQQYRKLLKSTLVLMPLFGVHYIVfMAMPYTEVSGILWQVQMhyeMLFNSF 264
                         170       180
                  ....*....|....*....|.
gi 568991003 1208 EGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15984   265 QGFFVAIIYCFCNGEVQAEIK 285
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
951-1229 4.23e-03

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: 41.20  E-value: 4.23e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003  951 IVGCGVSSLTLLMLVIIYvSVWRYIRSERSVILINFCLSIISSNALIL---IGQTQTRNKVVCTLVAAFLHF-------- 1019
Cdd:cd15261     9 IVGLCLSLVSLIISLFIF-SYFRTLRNHRTRIHKNLFLAILLQVIIRLvlyIDQAITRSRGSHTNAATTEGRtinstpil 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1020 ----------FFLSSFCWVLTEA-WQSYMAVTGRLRSRLVRKRFLCLGWGLPALVVAISVGFTKAKgySTMNYCWLSleg 1088
Cdd:cd15261    88 cegfyvlleyAKTVMFMWMFIEGlYLHNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWAIVTLIK--MKVNRCWFG--- 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1089 gllYAFV-------GPAAAVVLVNMVIGILVFNKLVSkdgitdkKLKERAGqlpvpplgraltcaecgvlSAAEANSDAT 1161
Cdd:cd15261   163 ---YYLTpyywileGPRLAVILINLFFLLNIIRVLVS-------KLRESHS-------------------REIEQVRKAV 213
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568991003 1162 SNAMaslwsscVVLPLLALTWMSAVLAVTDRRSAlfqILFAVFD-------SLEGFVIVMVHCILRREVQDAVKC 1229
Cdd:cd15261   214 KAAI-------VLLPLLGITNILQMIPPPLTSVI---VGFAVWSysthfltSFQGFFVALIYCFLNGEVKNVLKK 278
TSP1_ADAMTS pfam19030
Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found ...
270-314 4.63e-03

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.


Pssm-ID: 465950 [Multi-domain]  Cd Length: 55  Bit Score: 36.66  E-value: 4.63e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 568991003   270 WGECTRDCGGGLQTRTRTCLPTLGVEGGGCEGVL-----EEGRLCNRKAC 314
Cdd:pfam19030    6 WGECSVTCGGGVQTRLVQCVQKGGGSIVPDSECSaqkkpPETQSCNLKPC 55
TSP_1 pfam00090
Thrombospondin type 1 domain;
266-288 6.36e-03

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 36.24  E-value: 6.36e-03
                           10        20
                   ....*....|....*....|...
gi 568991003   266 LWSLWGECTRDCGGGLQTRTRTC 288
Cdd:pfam00090    2 PWSPWSPCSVTCGKGIQVRQRTC 24
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
1051-1228 7.41e-03

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: 40.44  E-value: 7.41e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1051 RFLCLGWGLPALVVAI--SVGFTKAKgystmNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKdgitdkkLK 1128
Cdd:cd15265   137 GFTLIGWGFPAVFVIPwaSVRATLAD-----TRCWDLSAGNYKWIYQVPILAAIVVNFILFLNIVRVLATK-------LR 204
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1129 ERAGqlpvpplGRALTCAECGVLsaaeansdatsnamasLWSSCVVLPLLALTWMSAVLAVTDRRSALFQI-----LFav 1203
Cdd:cd15265   205 ETNA-------GRCDTRQQYRKL----------------AKSTLVLIPLFGVHYIVFMGMPYTEVGLLWQIrmhyeLF-- 259
                         170       180
                  ....*....|....*....|....*
gi 568991003 1204 FDSLEGFVIVMVHCILRREVQDAVK 1228
Cdd:cd15265   260 FNSFQGFFVAIIYCFCNGEVQAEIK 284
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
1027-1230 8.35e-03

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: 39.91  E-value: 8.35e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1027 WVLTEAWQSYMAVTGRLRSRLVRKR-FLCLGWGLPALVVaisVGFTKAKGYSTMNYCWlSLEGGLLYAFV--GPAAAVVL 1103
Cdd:cd15985   104 WFFVEAVYLYKLLIGAVFSEKNYYLlYLYLGWGTPVLFV---VPWMLAKYLKENKECW-ALNENMAYWWIirIPILLASL 179
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568991003 1104 VNMVIGILVFNKLVSK-----DGITDKKLKeragqlpvppLGRAltcaecgvlsaaeansdatsnamaslwsSCVVLPLL 1178
Cdd:cd15985   180 INLLIFMRILKVILSKlranqKGYADYKLR----------LAKA----------------------------TLTLIPLF 221
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568991003 1179 ALTWMSAVLAVTDRRSALF---QILFAVF-DSLEGFVIVMVHCILRREVQDAVKCR 1230
Cdd:cd15985   222 GIHEVVFIFATDEQTTGILryiKVFFTLFlNSFQGFLVAVLYCFANKEVKSELLKK 277
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH