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Conserved domains on  [gi|1207122012|ref|XP_021322655|]
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adhesion G protein-coupled receptor B1 isoform X10 [Danio rerio]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
 858-1157 2.91e-160

seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.


The actual alignment was detected with superfamily member cd15990:

Pssm-ID: 475119  Cd Length: 267  Bit Score: 484.88  E-value: 2.91e-160
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  858 MDKTQLPSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 937
Cdd:cd15990      1 MEKALLPSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  938 FFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAA 1017
Cdd:cd15990     81 FFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAA 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1018 AVVLVNMVIGILVFNKLVSKDGITDMKLKERAGqmtvplynmtlkcakcgvisspdvsttatsnamASLWSSCVVLPLLA 1097
Cdd:cd15990    161 AVVLVNMVIGILVFNKLVSKDGITDKKLKERAG---------------------------------ASLWSSCVVLPLLA 207

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1098 LTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVKCRVVDRQEDGN 1157
Cdd:cd15990    208 LTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVVDRQEEGN 267
AGRB_N pfam19188
Adhesion GPCR B N-terminal region; This region is found at the N-terminus of various adhesion ...
 37-207 1.26e-82

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: 268.58  E-value: 1.26e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012   37 DSCSTLVQSRFFGFFLSSSAFPSMP--CTWTLQNPDPRRYTIFIKVTKPTRDCIARQHRTFQFDSFLET-TRTFLGMESF 113
Cdd:pfam19188    1 DPCSTLVQGVLYGSFSLRDLFPTNAsgCSWTLENPDPTKYTLYLKFTKPTQSCLPFSPRLLQFDHYLENtTRTYLGRESF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  114 DEVVKLCDASTHVAFLEAGKQFLQIRKGLPRAGA---GSRNGDGEFKVEYLVVGKRNPSMAACQMLCQWLEDCLTYSSST 190
Cdd:pfam19188   81 DEVVELCDASSPFSFLEFDKNFVQLCLLAEPRGDpesVVPGPSGDFKVEVLVINNENPSQFTCGVLCRWLEECLSASTSS 160

                          170
                   ....*....|....*..
gi 1207122012  191 RPCGIMQTPCQCWDQPP 207
Cdd:pfam19188  161 RPCGIMQTPCICPGTVP 177
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
 583-781 5.00e-55

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: 190.56  E-value: 5.00e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  583 GVSEVMTKLRVTSSDGTSYSGDLLAIIDVLKNMTEIFRRSYYSPSNADMRNFVQSVSNLLMEENRDRWEEAQLLGPNVKE 662
Cdd:pfam16489    1 GAKELARELRNATRHGPLYGGDVLTAVELLSQLFDLLATQDATLSNAFLENFVQTVSNLLDPENRESWEDLQQTERGTAA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  663 --LFRLVEDFVDVISLRMKDFQDTYEVTDNLVLSIHKRPV---AGNADITFPMKGWRGmvdwarSSEDKVRVAKNILLtg 737
Cdd:pfam16489   81 tkLLRTLEEYALLLAQNMKYLTPFTIVTPNIVLSVDRLDThnfKGARFPRFPMKGERP------KDEDSVKLPPKAFK-- 152

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207122012  738 kpEEDDASAFVTGIVLYRNLGSILSLQRN-----------STVLNSKVISVTIKP 781
Cdd:pfam16489  153 --PPDSNGTVVVVFILYRNLGSLLPPSSRydpdrrslrlpRRVVNSPVVSASVHS 205
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 337-387 1.42e-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: 74.93  E-value: 1.42e-16
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207122012   337 WGEWTPWSLCSSTCGRGYRERNRSCK--PPQFGGNPCDGPEKQTKFCNIAVCP 387
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCspPPQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 447-497 3.37e-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: 68.38  E-value: 3.37e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207122012   447 WQLWSTWSGCTKTCGGGSQQRQRLCYGP--FFGGEACPGDREEVRRCNEKRCP 497
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 392-442 6.62e-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: 67.23  E-value: 6.62e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207122012   392 WNEWSGWSSCSSTCSNGTMQRIRECNGP--SYGGLECQGEWHETRDCFLRECP 442
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 242-291 2.38e-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: 62.99  E-value: 2.38e-12
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1207122012   242 WSGWGNWAECSSECGGGVQKRTRNCQSPPDEA--YLCEGVLEEGRPCNAQPC 291
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNggGPCTGEDVETRACNEQPC 52
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 805-849 1.72e-11

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: 60.40  E-value: 1.72e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1207122012  805 TCISWDENDSSSllGSWSARGCRAVPVDSSTTKCLCDRLSTFAIL 849
Cdd:pfam01825    2 QCVFWDFTNSTT--GRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
HRM super family cl02422
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 499-565 5.61e-08

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.


The actual alignment was detected with superfamily member smart00008:

Pssm-ID: 413313  Cd Length: 70  Bit Score: 50.98  E-value: 5.61e-08
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207122012   499 PHEICDEENFSNVVWKKTPAGDTAAVRCPPNAVGL-----ILRRCSLDnegiAYWEN--PTYMKCVSNDYRSIQ 565
Cdd:smart00008    1 TDLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFsyktgASRNCTEN----GGWSPpfPNYSNCTSNDYEELK 70
 
Name Accession Description Interval E-value
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
 858-1157 2.91e-160

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: 484.88  E-value: 2.91e-160
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  858 MDKTQLPSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 937
Cdd:cd15990      1 MEKALLPSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  938 FFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAA 1017
Cdd:cd15990     81 FFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAA 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1018 AVVLVNMVIGILVFNKLVSKDGITDMKLKERAGqmtvplynmtlkcakcgvisspdvsttatsnamASLWSSCVVLPLLA 1097
Cdd:cd15990    161 AVVLVNMVIGILVFNKLVSKDGITDKKLKERAG---------------------------------ASLWSSCVVLPLLA 207

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1098 LTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVKCRVVDRQEDGN 1157
Cdd:cd15990    208 LTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVVDRQEEGN 267
AGRB_N pfam19188
Adhesion GPCR B N-terminal region; This region is found at the N-terminus of various adhesion ...
 37-207 1.26e-82

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: 268.58  E-value: 1.26e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012   37 DSCSTLVQSRFFGFFLSSSAFPSMP--CTWTLQNPDPRRYTIFIKVTKPTRDCIARQHRTFQFDSFLET-TRTFLGMESF 113
Cdd:pfam19188    1 DPCSTLVQGVLYGSFSLRDLFPTNAsgCSWTLENPDPTKYTLYLKFTKPTQSCLPFSPRLLQFDHYLENtTRTYLGRESF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  114 DEVVKLCDASTHVAFLEAGKQFLQIRKGLPRAGA---GSRNGDGEFKVEYLVVGKRNPSMAACQMLCQWLEDCLTYSSST 190
Cdd:pfam19188   81 DEVVELCDASSPFSFLEFDKNFVQLCLLAEPRGDpesVVPGPSGDFKVEVLVINNENPSQFTCGVLCRWLEECLSASTSS 160

                          170
                   ....*....|....*..
gi 1207122012  191 RPCGIMQTPCQCWDQPP 207
Cdd:pfam19188  161 RPCGIMQTPCICPGTVP 177
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 863-1130 1.28e-64

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


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 219.84  E-value: 1.28e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  863 LPSVTLIVGCGVSSLTLLLLIIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNK--------VVCTLVAAF 934
Cdd:pfam00002    3 SLKVIYTVGYSLSLVALLLAIAIFLLF-RKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKqdldhcswVGCKVVAVF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  935 LHFFFLSSFCWVLTEAWQSYMA-VTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTkAKGYGTVNYCWLSLEGGLLYAFV 1013
Cdd:pfam00002   82 LHYFFLANFFWMLVEGLYLYTLlVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVD-PKGYGEDDGCWLSNENGLWWIIR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1014 GPAAAVVLVNMVIGILVFNKLVSKDGITDMKLKERAgqmtvplynmtlkcakcgvisspdvsttatsNAMASLWSSCVVL 1093
Cdd:pfam00002  161 GPILLIILVNFIIFINIVRILVQKLRETNMGKSDLK-------------------------------QYRRLAKSTLLLL 209

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1207122012 1094 PLLALTWMSAVLAITDRR--SALFQILFAVFDSLEGFVI 1130
Cdd:pfam00002  210 PLLGITWVFGLFAFNPENtlRVVFLYLFLILNSFQGFFV 248
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
 583-781 5.00e-55

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: 190.56  E-value: 5.00e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  583 GVSEVMTKLRVTSSDGTSYSGDLLAIIDVLKNMTEIFRRSYYSPSNADMRNFVQSVSNLLMEENRDRWEEAQLLGPNVKE 662
Cdd:pfam16489    1 GAKELARELRNATRHGPLYGGDVLTAVELLSQLFDLLATQDATLSNAFLENFVQTVSNLLDPENRESWEDLQQTERGTAA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  663 --LFRLVEDFVDVISLRMKDFQDTYEVTDNLVLSIHKRPV---AGNADITFPMKGWRGmvdwarSSEDKVRVAKNILLtg 737
Cdd:pfam16489   81 tkLLRTLEEYALLLAQNMKYLTPFTIVTPNIVLSVDRLDThnfKGARFPRFPMKGERP------KDEDSVKLPPKAFK-- 152

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207122012  738 kpEEDDASAFVTGIVLYRNLGSILSLQRN-----------STVLNSKVISVTIKP 781
Cdd:pfam16489  153 --PPDSNGTVVVVFILYRNLGSLLPPSSRydpdrrslrlpRRVVNSPVVSASVHS 205
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 337-387 1.42e-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: 74.93  E-value: 1.42e-16
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207122012   337 WGEWTPWSLCSSTCGRGYRERNRSCK--PPQFGGNPCDGPEKQTKFCNIAVCP 387
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCspPPQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 447-497 3.37e-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: 68.38  E-value: 3.37e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207122012   447 WQLWSTWSGCTKTCGGGSQQRQRLCYGP--FFGGEACPGDREEVRRCNEKRCP 497
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 392-442 6.62e-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: 67.23  E-value: 6.62e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207122012   392 WNEWSGWSSCSSTCSNGTMQRIRECNGP--SYGGLECQGEWHETRDCFLRECP 442
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
TSP_1 pfam00090
Thrombospondin type 1 domain;
448-496 3.98e-13

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 65.13  E-value: 3.98e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1207122012  448 QLWSTWSGCTKTCGGGSQQRQRLCYGPFFGGEACPGDREEVRRCNEKRC 496
Cdd:pfam00090    1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 242-291 2.38e-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: 62.99  E-value: 2.38e-12
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1207122012   242 WSGWGNWAECSSECGGGVQKRTRNCQSPPDEA--YLCEGVLEEGRPCNAQPC 291
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNggGPCTGEDVETRACNEQPC 52
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 805-849 1.72e-11

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: 60.40  E-value: 1.72e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1207122012  805 TCISWDENDSSSllGSWSARGCRAVPVDSSTTKCLCDRLSTFAIL 849
Cdd:pfam01825    2 QCVFWDFTNSTT--GRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
TSP_1 pfam00090
Thrombospondin type 1 domain;
338-386 2.14e-11

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 60.12  E-value: 2.14e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1207122012  338 GEWTPWSLCSSTCGRGYRERNRSCKPPQFGGNPCDGPEKQTKFCNIAVC 386
Cdd:pfam00090    1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
TSP_1 pfam00090
Thrombospondin type 1 domain;
243-291 2.13e-10

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 57.43  E-value: 2.13e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1207122012  243 SGWGNWAECSSECGGGVQKRTRNCQSPPDEAYLCEGVLEEGRPCNAQPC 291
Cdd:pfam00090    1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
TSP_1 pfam00090
Thrombospondin type 1 domain;
394-441 7.60e-10

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 55.89  E-value: 7.60e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1207122012  394 EWSGWSSCSSTCSNGTMQRIRECNGPSYGGLECQGEWHETRDCFLREC 441
Cdd:pfam00090    2 PWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 802-850 1.67e-09

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: 54.70  E-value: 1.67e-09
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*....
gi 1207122012   802 TNQTCISWDENDsssllGSWSARGCRAVPVDSSTTKCLCDRLSTFAILA 850
Cdd:smart00303    1 FNPICVFWDESS-----GEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
HormR smart00008
Domain present in hormone receptors;
499-565 5.61e-08

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 50.98  E-value: 5.61e-08
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207122012   499 PHEICDEENFSNVVWKKTPAGDTAAVRCPPNAVGL-----ILRRCSLDnegiAYWEN--PTYMKCVSNDYRSIQ 565
Cdd:smart00008    1 TDLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFsyktgASRNCTEN----GGWSPpfPNYSNCTSNDYEELK 70
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 500-559 3.48e-05

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: 43.13  E-value: 3.48e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207122012  500 HEICDEENFSNVVWKKTPAGDTAAVRCPP-----NAVGLILRRCSLDNEgiayWENP---TYMKCVSN 559
Cdd:pfam02793    1 GLGCPRTWDGILCWPRTPAGETVEVPCPDyfsgfDPRGNASRNCTEDGT----WSEHppsNYSNCTSN 64
PTZ00087 PTZ00087
thrombosponding-related protein; Provisional
 242-291 3.25e-04

thrombosponding-related protein; Provisional


Pssm-ID: 185438  Cd Length: 340  Bit Score: 44.55  E-value: 3.25e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207122012  242 WSGWGNWAECSSECG--GGVQKRTRNCQSPPDEAYlcEGVLEEGRPCNA--QPC 291
Cdd:PTZ00087   233 YTEWGEWSNCSMECDhpDNVQIRERKCAHPSGDCF--KGDLKETRPCQVplPPC 284
 
Name Accession Description Interval E-value
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
 858-1157 2.91e-160

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: 484.88  E-value: 2.91e-160
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  858 MDKTQLPSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 937
Cdd:cd15990      1 MEKALLPSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  938 FFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAA 1017
Cdd:cd15990     81 FFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAA 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1018 AVVLVNMVIGILVFNKLVSKDGITDMKLKERAGqmtvplynmtlkcakcgvisspdvsttatsnamASLWSSCVVLPLLA 1097
Cdd:cd15990    161 AVVLVNMVIGILVFNKLVSKDGITDKKLKERAG---------------------------------ASLWSSCVVLPLLA 207

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1098 LTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVKCRVVDRQEDGN 1157
Cdd:cd15990    208 LTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVVDRQEEGN 267
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
 863-1151 1.60e-148

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: 453.25  E-value: 1.60e-148
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  863 LPSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSS 942
Cdd:cd15251      3 SPSVTLIVGCGVSCLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNILILVGQTQTLNKGVCTMTAAFLHFFFLSS 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  943 FCWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLV 1022
Cdd:cd15251     83 FCWVLTEAWQSYMAVTGRMRTRLIRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAFVGPAAAVVLV 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1023 NMVIGILVFNKLVSKDGITDmklkeragqmtvplynmtlkcakcgvisspdvsttatsNAMASLWSSCVVLPLLALTWMS 1102
Cdd:cd15251    163 NMVIGILVFNKLVSRDGISD--------------------------------------NAMASLWSSCVVLPLLALTWMS 204

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207122012 1103 AVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVKCRVVD 1151
Cdd:cd15251    205 AVLAMTDRRSVLFQILFAVFDSLQGFVIVMVHCILRREVQDAVKCRMGV 253
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
 861-1149 2.14e-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: 449.02  E-value: 2.14e-146
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  861 TQLPSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFL 940
Cdd:cd15988      1 TGSPSVPLMIGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  941 SSFCWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVV 1020
Cdd:cd15988     81 SSFCWVLTEAWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTASYCWLSLEGGLLYAFVGPAAVIV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1021 LVNMVIGILVFNKLVSKDGITDMKLKERAGQMTVPLYNMTLKCAKCGVISSPDVSTTATSNAMASLWSSCVVLPLLALTW 1100
Cdd:cd15988    161 LVNMLIGIIVFNKLMSRDGISDKSKKQRAGSEAEPCSSLLLKCSKCGVVSSAAMSSATASSAMASLWSSCVVLPLLALTW 240

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207122012 1101 MSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVKCRV 1149
Cdd:cd15988    241 MSAVLAMTDRRSILFQVLFAVFNSVQGFVIITVHCFLRREVQDVVKCQM 289
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
 864-1149 1.00e-138

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: 428.72  E-value: 1.00e-138
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  864 PSVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSF 943
Cdd:cd15989      6 PSVTLIVGCGLSCLALITLAVVYAALWRYIRSERSIILINFCLSIISSNILILVGQTQTHNKGICTMTTAFLHFFFLASF 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  944 CWVLTEAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVN 1023
Cdd:cd15989     86 CWVLTEAWQSYMAVTGKIRTRLIRKRFLCLGWGLPALVVAISMGFTKAKGYGTPHYCWLSLEGGLLYAFVGPAAAVVLVN 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1024 MVIGILVFNKLVSKDGITDMKLKERAGQMTVPLYNMTLKCAKCGVISSPDVSTTATSNAMASLWSSCVVLPLLALTWMSA 1103
Cdd:cd15989    166 MVIGILVFNKLVSRDGILDKKLKHRAGQMSEPHSGLTLKCAKCGVVSTTALSATTASNAMASLWSSCVVLPLLALTWMSA 245

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1207122012 1104 VLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVKCRV 1149
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 ...
 37-207 1.26e-82

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: 268.58  E-value: 1.26e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012   37 DSCSTLVQSRFFGFFLSSSAFPSMP--CTWTLQNPDPRRYTIFIKVTKPTRDCIARQHRTFQFDSFLET-TRTFLGMESF 113
Cdd:pfam19188    1 DPCSTLVQGVLYGSFSLRDLFPTNAsgCSWTLENPDPTKYTLYLKFTKPTQSCLPFSPRLLQFDHYLENtTRTYLGRESF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  114 DEVVKLCDASTHVAFLEAGKQFLQIRKGLPRAGA---GSRNGDGEFKVEYLVVGKRNPSMAACQMLCQWLEDCLTYSSST 190
Cdd:pfam19188   81 DEVVELCDASSPFSFLEFDKNFVQLCLLAEPRGDpesVVPGPSGDFKVEVLVINNENPSQFTCGVLCRWLEECLSASTSS 160

                          170
                   ....*....|....*..
gi 1207122012  191 RPCGIMQTPCQCWDQPP 207
Cdd:pfam19188  161 RPCGIMQTPCICPGTVP 177
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 863-1130 1.28e-64

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


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 219.84  E-value: 1.28e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  863 LPSVTLIVGCGVSSLTLLLLIIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNK--------VVCTLVAAF 934
Cdd:pfam00002    3 SLKVIYTVGYSLSLVALLLAIAIFLLF-RKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKqdldhcswVGCKVVAVF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  935 LHFFFLSSFCWVLTEAWQSYMA-VTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTkAKGYGTVNYCWLSLEGGLLYAFV 1013
Cdd:pfam00002   82 LHYFFLANFFWMLVEGLYLYTLlVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVD-PKGYGEDDGCWLSNENGLWWIIR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1014 GPAAAVVLVNMVIGILVFNKLVSKDGITDMKLKERAgqmtvplynmtlkcakcgvisspdvsttatsNAMASLWSSCVVL 1093
Cdd:pfam00002  161 GPILLIILVNFIIFINIVRILVQKLRETNMGKSDLK-------------------------------QYRRLAKSTLLLL 209

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1207122012 1094 PLLALTWMSAVLAITDRR--SALFQILFAVFDSLEGFVI 1130
Cdd:pfam00002  210 PLLGITWVFGLFAFNPENtlRVVFLYLFLILNSFQGFFV 248
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
 865-1145 1.27e-63

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: 217.06  E-value: 1.27e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  865 SVTLIVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFC 944
Cdd:cd15040      5 SIITYIGCGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFLFGINSTDNPVLCTAVAALLHYFLLASFM 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  945 WVLTEAWQSYMAVTG--RLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLV 1022
Cdd:cd15040     85 WMLVEALLLYLRLVKvfGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYCWLSNGNGLYYAFLGPVLLIILV 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1023 NMVIGILVFNKLVSKDGITDMKLKeragqmtvplynmtlkcakcgvisspdvsttatSNAMASLWSSCVVLPLLALTWMS 1102
Cdd:cd15040    165 NLVIFVLVLRKLLRLSAKRNKKKR---------------------------------KKTKAQLRAAVSLFFLLGLTWIF 211

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1207122012 1103 AVLAITDRRSAlFQILFAVFDSLEGFVIVMVHCILRREVQEAV 1145
Cdd:cd15040    212 GILAIFGARVV-FQYLFAIFNSLQGFFIFIFHCLRNKEVRKAW 253
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
 583-781 5.00e-55

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: 190.56  E-value: 5.00e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  583 GVSEVMTKLRVTSSDGTSYSGDLLAIIDVLKNMTEIFRRSYYSPSNADMRNFVQSVSNLLMEENRDRWEEAQLLGPNVKE 662
Cdd:pfam16489    1 GAKELARELRNATRHGPLYGGDVLTAVELLSQLFDLLATQDATLSNAFLENFVQTVSNLLDPENRESWEDLQQTERGTAA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  663 --LFRLVEDFVDVISLRMKDFQDTYEVTDNLVLSIHKRPV---AGNADITFPMKGWRGmvdwarSSEDKVRVAKNILLtg 737
Cdd:pfam16489   81 tkLLRTLEEYALLLAQNMKYLTPFTIVTPNIVLSVDRLDThnfKGARFPRFPMKGERP------KDEDSVKLPPKAFK-- 152

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207122012  738 kpEEDDASAFVTGIVLYRNLGSILSLQRN-----------STVLNSKVISVTIKP 781
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 ...
 869-1144 2.30e-46

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: 167.50  E-value: 2.30e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  869 IVGCGVSSLTLLLLIIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLT 948
Cdd:cd15933      9 YIGCGISIACLALTLIIFLVL-RVLSSDRFQIHKNLCVALLLAQILLLAGEWAEGNKVACKVVAILLHFFFMAAFSWMLV 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  949 EAWQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGI 1028
Cdd:cd15933     88 EGLHLYLMIVKVFNYKSKMRYYYFIGWGLPAIIVAISLAI-LFDDYGSPNVCWLSLDDGLIWAFVGPVIFIITVNTVILI 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1029 LVfnklvskdgitdmkLKERAGQMTVPLYNMTLKCAkcgVISSpdvsttaTSNAMAslwsscVVLPLLALTWMSAVLAIT 1108
Cdd:cd15933    167 LV--------------VKITVSLSTNDAKKSQGTLA---QIKS-------TAKASV------VLLPILGLTWLFGVLVVN 216

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207122012 1109 DrRSALFQILFAVFDSLEGFVIVMVHCILRREVQEA 1144
Cdd:cd15933    217 S-QTIVFQYIFVILNSLQGLMIFLFHCVLNSEVRSA 251
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
 869-1145 1.79e-41

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: 153.52  E-value: 1.79e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  869 IVGCGVSSLTLLLLIIIYVSVWRYiRSERSVILINFCLSIISSNALILIGQTQTRNK--VVCTLVAAFLHFFFLSSFCWV 946
Cdd:cd13952      9 YIGCSLSLVGLLLTIITYLLFPKL-RNLRGKILINLCLSLLLAQLLFLIGQLLTSSDrpVLCKALAILLHYFLLASFFWM 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  947 LTEAWQSYMAVTGRLRNRiIRKRFL---CLGWGLPALVVAISVGFTKA----KGYGTVNYCWLSLEGGLLYAFVGPAAAV 1019
Cdd:cd13952     88 LVEAFDLYRTFVKVFGSS-ERRRFLkysLYGWGLPLLIVIITAIVDFSlygpSPGYGGEYCWLSNGNALLWAFYGPVLLI 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1020 VLVNMVIGILVFNKLVSKDGITDMKLKeragqmtvplynmtlkcakcgvisspdvsttaTSNAMASLWSSCVVLPLLALT 1099
Cdd:cd13952    167 LLVNLVFFILTVRILLRKLRETPKQSE--------------------------------RKSDRKQLRAYLKLFPLMGLT 214

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1207122012 1100 WMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAV 1145
Cdd:cd13952    215 WIFGILAPFVGGSLVFWYLFDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 891-1143 5.36e-33

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: 129.11  E-value: 5.36e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRF 970
Cdd:cd15438     30 RSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNNQVACAVVAGLLHYFFLAAFCWMSLEGVELYLMVVQVFNTQSLKKRY 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  971 LCL-GWGLPALVVAISVGfTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSK--DGITDMKLKE 1047
Cdd:cd15438    110 LLLiGYGVPLVIVAISAA-VNSKGYGTQRHCWLSLERGFLWSFLGPVCLIILVNAIIFVITVWKLAEKfsSINPDMEKLR 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1048 RAGQMTVplynmtlkcakcgvisspdvsttatsNAMASLWsscvvlpLLALTWMSAVLAITDrRSALFQILFAVFDSLEG 1127
Cdd:cd15438    189 KIRALTI--------------------------TAIAQLC-------ILGCTWIFGFFQFSD-STLVMSYLFTILNSLQG 234

                          250
                   ....*....|....*.
gi 1207122012 1128 FVIVMVHCILRREVQE 1143
Cdd:cd15438    235 LFIFLLHCLLSKQVRE 250
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
 888-1146 9.66e-32

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: 125.44  E-value: 9.66e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  888 SVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSY-MAVTGRLRNRII 966
Cdd:cd15441     27 SCLRGLQSNSNSIHKNLVACLLLAELLFLLGINQTENLFPCKLIAILLHYFYLSAFSWLLVESLHLYrMLTEPRDINHGH 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  967 RKRFLCLGWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKdgitdmklK 1046
Cdd:cd15441    107 MRFYYLLGYGIPAIIVGLSVGL-RPDGYGNPDFCWLSVNETLIWSFAGPIAFVIVITLIIFILALRASCTL--------K 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1047 ERAGQMTvplynmtlkcakcgvisspdvsttatsNAMASLWSSCVVLPLLALTWMSAVLAITDrRSALFQILFAVFDSLE 1126
Cdd:cd15441    178 RHVLEKA---------------------------SVRTDLRSSFLLLPLLGATWVFGLLAVNE-DSELLHYLFAGLNFLQ 229

                          250       260
                   ....*....|....*....|
gi 1207122012 1127 GFVIVMVHCILRREVQEAVK 1146
Cdd:cd15441    230 GLFIFLFYCIFNKKVRRELK 249
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
 891-1146 1.81e-31

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: 124.76  E-value: 1.81e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVtgrlRN------- 963
Cdd:cd15439     30 RSIRNTSTSLHLQLSLCLFLADLLFLVGIDRTDNKVLCSIIAGFLHYLFLACFAWMFLEAVHLFLTV----RNlkvvnyf 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  964 --RIIRKRFLCL-GWGLPALVVAISVGfTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVF----NKLVS 1036
Cdd:cd15439    106 ssHRFKKRFMYPvGYGLPAVIVAISAA-VNPQGYGTPKHCWLSMEKGFIWSFLGPVCVIIVINLVLFCLTLwilrEKLSS 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1037 KDG-ITDMKlKERAgqmtvplynMTLKcakcgvisspdvsttatsnAMASLWsscvvlpLLALTWMSAVLAITDRRSALf 1115
Cdd:cd15439    185 LNAeVSTLK-NTRL---------LTFK-------------------AIAQLF-------ILGCTWILGLFQVGPVATVM- 227

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207122012 1116 QILFAVFDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15439    228 AYLFTITNSLQGVFIFLVHCLLNRQVREEYR 258
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
 890-1143 2.31e-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: 121.46  E-value: 2.31e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  890 WRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNR-IIRK 968
Cdd:cd15252     29 FRGLQSDRTTIHKNLCISLFLAELVFLIGINTTTNKIFCSVIAGLLHYFFLAAFAWMFIEGIQLYLMLVEVFENEgSRHK 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  969 RFLCLGWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIgilvfnklvskdgitdmklker 1048
Cdd:cd15252    109 NFYIFGYGSPAVIVGVSAAL-GYRYYGTTKVCWLSTENYFIWSFIGPATLIILLNLIF---------------------- 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1049 agqMTVPLYNMTLKCAkcgvISSPDVSTTAtsNAMASLWSSCVVLPLLALTWMSAVLAItDRRSALFQILFAVFDSLEGF 1128
Cdd:cd15252    166 ---LGVAIYKMFRHTA----GLKPEVSCLE--NIRSWARGAIALLFLLGLTWIFGVLHI-NHASVVMAYLFTVSNSLQGM 235

                          250
                   ....*....|....*
gi 1207122012 1129 VIVMVHCILRREVQE 1143
Cdd:cd15252    236 FIFLFHCVLSRKVRK 250
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
 870-1142 1.67e-29

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: 118.90  E-value: 1.67e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  870 VGCGVSSLTLLLLIIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTE 949
Cdd:cd15440     10 IGCIISIVCLLLAFITFTCF-RNLQCDRNTIHKNLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFLAAFSWMLLE 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  950 AWQSYM---AVTGRLRNRIirKRFLCLGWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNmvi 1026
Cdd:cd15440     89 GFQLYVmlvEVFEPEKSRI--KWYYLFGYGLPALIVAVSAGV-DPTGYGTEDHCWLSTENGFIWSFVGPVIVVLLAN--- 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1027 giLVFnklvskdgitdmklkeragqMTVPLYNMtlkcakCGVISSPDVSTTATSNAMASLW--SSCVVLPLLALTWMSAV 1104
Cdd:cd15440    163 --LVF--------------------LGMAIYVM------CRHSSRSASKKDASKLKNIRGWlkGSIVLVVLLGLTWTFGL 214

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1207122012 1105 LAItDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQ 1142
Cdd:cd15440    215 LFI-NQESIVMAYIFTILNSLQGLFIFIFHCVLNEKVR 251
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
 860-1146 4.62e-27

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


Pssm-ID: 320384 [Multi-domain]  Cd Length: 260  Bit Score: 111.94  E-value: 4.62e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  860 KTQLPSVTLIvGCGVSSLTLLLLIIIY--VSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF 937
Cdd:cd15256      1 QVALSSITYV-GCSLSIFCLAITLVTFavLSSVSTIRNQRYHIHANLSFAVLVAQILLLISFRFEPGTLPCKIMAILLHF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  938 FFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRFLC-LGWGLPALVVAISVGFTkAKGYGTVNYCWLSLEGGLLYAFVGPA 1016
Cdd:cd15256     80 FFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYgIGWGSPLLICIISLTSA-LDSYGESDNCWLSLENGAIWAFVAPA 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1017 AAVVLVNmvIGILV-FNKLVSKDGITDMKLKERAGQMTVplynmtlkcakcgvisspdvsttaTSNAMAslwsscVVLPL 1095
Cdd:cd15256    159 LFVIVVN--IGILIaVTRVISRISADNYKVHGDANAFKL------------------------TAKAVA------VLLPI 206

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207122012 1096 LALTWMSAVLAItDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15256    207 LGSSWVFGVLAV-NTHALVFQYMFAIFNSLQGFFIFLFHCLLNSEVRAAFK 256
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
 891-1146 1.03e-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: 111.07  E-value: 1.03e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAV-----TGRLRNRI 965
Cdd:cd15931     30 RWIPKINTTAHLHLCLCLSMSHTLFLAGIEYVENELACTVMAGLLHYLFLASFVWMLLEALQLHLLVrrltkVQVIQRDG 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  966 IRKRFLCL-GWGLPALVVAISvGFTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILvfnklvskdgiTDMK 1044
Cdd:cd15931    110 LPRPLLCLiGYGVPFLIVGVS-ALVYSDGYGEAKMCWLSQERGFNWSFLGPVIAIIGINWILFCA-----------TLWC 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1045 LKERAGQMtvplynmtlkcakcgvisSPDVSTTATSNAMasLWSSCVVLPLLALTWMSAvLAITDRRSALFQILFAVFDS 1124
Cdd:cd15931    178 LRQTLSNM------------------NSDISQLKDTRLL--TFKAVAQLFILGCTWVLG-LFQTNPVALVFQYLFTILNS 236

                          250       260
                   ....*....|....*....|..
gi 1207122012 1125 LEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15931    237 LQGAFLFLVHCLLNKEVREEYI 258
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
 887-1146 6.86e-26

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: 108.40  E-value: 6.86e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  887 VSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTgRLRN-RI 965
Cdd:cd15991     26 LVLIRTLRSNLHSIHKNLVAALFFSELIFLIGINQTENPFVCTVVAILLHYFYMSTFAWMFVEGLHIYRMLT-EVRNiNT 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  966 IRKRFL-CLGWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVfnklvskdgitdMK 1044
Cdd:cd15991    105 GHMRFYyVVGWGIPAIITGLAVGL-DPQGYGNPDFCWLSVQDTLIWSFAGPIGIVVIINTVIFVLA------------AK 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1045 LKERAGQMTVplynmtlkcAKCGVISspdvsttatsnamaSLWSSCVVLPLLALTWMSAVLAI-TDRRSalFQILFAVFD 1123
Cdd:cd15991    172 ASCGRRQRYF---------EKSGVIS--------------MLRTAFLLLLLISATWLLGLMAVnSDTLS--FHYLFAIFS 226

                          250       260
                   ....*....|....*....|...
gi 1207122012 1124 SLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15991    227 CLQGIFIFFFHCIFNKEVRKHLK 249
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
 890-1143 1.05e-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: 104.96  E-value: 1.05e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  890 WRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNR-IIRK 968
Cdd:cd15437     29 FSEIQSTRTTIHKNLCCSLFLAELIFLIGINMNANKLFCSIIAGLLHYFFLAAFAWMCIEGIHLYLIVVGVIYNKgFLHK 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  969 RFLCLGWGLPALVVAIS--VGFtkaKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVN-MVIGILVFNKLVSkdgiTDMKL 1045
Cdd:cd15437    109 NFYIFGYGSPAVVVGISaaLGY---KYYGTTKVCWLSTENNFIWSFIGPACLIILVNlLAFGVIIYKVFRH----TAMLK 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1046 KEragqmtVPLYNMTLKCAKcgvisspdvsttatsNAMASLWsscvvlpLLALTWMSAVLAITdRRSALFQILFAVFDSL 1125
Cdd:cd15437    182 PE------VSCYENIRSCAR---------------GALALLF-------LLGATWIFGVLHVV-YGSVVTAYLFTISNAF 232

                          250
                   ....*....|....*...
gi 1207122012 1126 EGFVIVMVHCILRREVQE 1143
Cdd:cd15437    233 QGMFIFIFLCVLSRKIQE 250
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
 891-1147 1.54e-23

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: 101.92  E-value: 1.54e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRF 970
Cdd:cd16007     30 RGLQTDRNTIHKNLCINLFLAELLFLIGIDKTQYQIACPIFAGLLHFFFLAAFSWLCLEGVQLYLMLVEVFESEYSRKKY 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  971 LCL-GWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKDGItdmkLKERA 1049
Cdd:cd16007    110 YYLcGYCFPALVVGISAAI-DYRSYGTEKACWLRVDNYFIWSFIGPVSFVIVVNLVFLMVTLHKMIRSSSV----LKPDS 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1050 GQMTvplynmTLKCAKCGVISspdvsttatsnamaslwsscvVLPLLALTWMSAVLAItDRRSALFQILFAVFDSLEGFV 1129
Cdd:cd16007    185 SRLD------NIKSWALGAIT---------------------LLFLLGLTWAFGLLFI-NKESVVMAYLFTTFNAFQGMF 236

                          250
                   ....*....|....*....
gi 1207122012 1130 IVMVHCILRREV-QEAVKC 1147
Cdd:cd16007    237 IFIFHCALQKKVhKEYSKC 255
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
 890-1147 6.82e-23

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: 100.02  E-value: 6.82e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  890 WRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKR 969
Cdd:cd16005     29 FRGLQSDRNTIHKNLCISLFVAELLFLIGINRTDQPIACAVFAALLHFFFLAAFTWMFLEGVQLYIMLVEVFESEHSRRK 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  970 -FLCLGWGLPALVVAISVGfTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIgilvfnklvskdgitdmklker 1048
Cdd:cd16005    109 yFYLVGYGMPALIVAVSAA-VDYRSYGTDKVCWLRLDTYFIWSFIGPATLIIMLNVIF---------------------- 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1049 agqMTVPLYNMTLKCAkcgvISSPDvsTTATSNAMASLWSSCVVLPLLALTWMSAVLAITDrRSALFQILFAVFDSLEGF 1128
Cdd:cd16005    166 ---LGIALYKMFHHTA----ILKPE--SGCLDNIKSWVIGAIALLCLLGLTWAFGLMYINE-STVIMAYLFTIFNSLQGM 235

                          250       260
                   ....*....|....*....|
gi 1207122012 1129 VIVMVHCILRREV-QEAVKC 1147
Cdd:cd16005    236 FIFIFHCVLQKKVrKEYGKC 255
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 891-1147 1.17e-22

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: 99.10  E-value: 1.17e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKRF 970
Cdd:cd15436     30 RGLQTDRNTIHKNLCINLFIAELLFLIGINRTQYTIACPIFAGLLHFFFLAAFCWLCLEGVQLYLLLVEVFESEYSRRKY 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  971 LCL-GWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKDGItdmkLKERA 1049
Cdd:cd15436    110 FYLcGYSFPALVVAVSAAI-DYRSYGTEKACWLRVDNYFIWSFIGPVTFVITLNLVFLVITLHKMVSHSDL----LKPDS 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1050 GQMtvplynmtlkcakcgvisspdvsttatSNAMASLWSSCVVLPLLALTWMSAVLAItDRRSALFQILFAVFDSLEGFV 1129
Cdd:cd15436    185 SRL---------------------------DNIKSWALGAIALLFLLGLTWSFGLMFI-NEESVVMAYLFTIFNAFQGVF 236

                          250
                   ....*....|....*....
gi 1207122012 1130 IVMVHCILRREVQ-EAVKC 1147
Cdd:cd15436    237 IFIFHCALQKKVRkEYSKC 255
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
 890-1147 1.27e-22

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: 99.22  E-value: 1.27e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  890 WRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNRIIRKR 969
Cdd:cd16006     29 FRGLQSDRNTIHKNLCINLFIAEFIFLIGIDKTEYKIACPIFAGLLHFFFLAAFAWMCLEGVQLYLMLVEVFESEYSRKK 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  970 FLCL-GWGLPALVVAISVGfTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSkdgitdmklker 1048
Cdd:cd16006    109 YYYVaGYLFPATVVGVSAA-IDYKSYGTEKACWLRVDNYFIWSFIGPVTFIILLNLIFLVITLCKMVK------------ 175

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1049 agqmtvplYNMTLKcakcgvissPDVSTtaTSNAMASLWSSCVVLPLLALTWMSAVLAITDrRSALFQILFAVFDSLEGF 1128
Cdd:cd16006    176 --------HSNTLK---------PDSSR--LENIKSWVLGAFALLCLLGLTWSFGLLFINE-ETIVMAYLFTIFNAFQGM 235

                          250       260
                   ....*....|....*....|
gi 1207122012 1129 VIVMVHCILRREV-QEAVKC 1147
Cdd:cd16006    236 FIFIFHCALQKKVrKEYSKC 255
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
 891-1146 1.42e-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: 96.06  E-value: 1.42e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSY-MAVTGRLRNRIIRKR 969
Cdd:cd15993     30 RGLKSNTRGIHSNIAAALFLSELLFLLGINRTENQFLCTVVAILLHYFFLSTFAWLFVQGLHIYrMQTEARNVNFGAMRF 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  970 FLCLGWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVfnklvskdgitdmklkera 1049
Cdd:cd15993    110 YYAIGWGVPAIITGLAVGL-DPEGYGNPDFCWISIHDKLVWSFAGPIVVVIVMNGVMFLLV------------------- 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1050 gqmtvplynMTLKCakcgvisSPDVSTTATSNAMASLWSSCVVLPLLALTWMSAVLAITDRRSAlFQILFAVFDSLEGFV 1129
Cdd:cd15993    170 ---------ARMSC-------SPGQKETKKTSVLMTLRSSFLLLLLISATWLFGLLAVNNSVLA-FHYLHAILCCLQGLA 232

                          250
                   ....*....|....*..
gi 1207122012 1130 IVMVHCILRREVQEAVK 1146
Cdd:cd15993    233 VLLLFCVLNEEVQEAWK 249
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
 886-1146 1.91e-20

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: 92.58  E-value: 1.91e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  886 YVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTG-RLRNR 964
Cdd:cd15992     25 FLLCLRALRSNKTSIRKNGATALFLSELVFILGINQADNPFACTVIAILLHFFYLCTFSWLFLEGLHIYRMLSEvRDINY 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  965 IIRKRFLCLGWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVlvnmvigilvfnklvskdgitdmk 1044
Cdd:cd15992    105 GPMRFYYLIGWGVPAFITGLAVGL-DPEGYGNPDFCWLSIYDTLIWSFAGPVAFAV------------------------ 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1045 lkeragQMTVPLYNMTLKcAKCgviSSPDVSTTATSNAMASLWSSCVVLPLLALTWMSAVLAItDRRSALFQILFAVFDS 1124
Cdd:cd15992    160 ------SMNVFLYILSSR-ASC---SAQQQSFEKKKGPVSGLRTAFTVLLLVSVTCLLALLSV-NSDVILFHYLFAGFNC 228

                          250       260
                   ....*....|....*....|..
gi 1207122012 1125 LEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15992    229 LQGPFIFLSHVVLLKEVRKALK 250
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
 870-1146 1.87e-19

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: 89.91  E-value: 1.87e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  870 VGCGVSSLTLLLLIIIYVSVwRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTE 949
Cdd:cd15255     10 IGCGVSLCALIVTFILFLAV-GVPKSERTTVHKNLIFALAAAEFLLMFSEWAKGNQVACWAVTALLHLFFLAAFSWMLVE 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  950 A---WQSYMAVTGRLRNRIirKRFLCLGWGLPALVVAISVGFTKAKgYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVI 1026
Cdd:cd15255     89 GlllWSKVVAVNMSEDRRM--KFYYVTGWGLPVVIVAVTLATSFNK-YVADQHCWLNVQTDIIWAFVGPVLFVLTVNTFV 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1027 GILVFNKLVSKdgitdmklKERAGQMTVPlynmtlkcakcgvisSPDVSTTATSNAMASLWSSCVVLPLLALTWMSAVLA 1106
Cdd:cd15255    166 LFRVVMVTVSS--------ARRRAKMLTP---------------SSDLEKQIGIQIWATAKPVLVLLPVLGLTWLCGVLV 222

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1207122012 1107 itdRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15255    223 ---HLSDVWAYVFITLNSFQGLYIFLVYAIYNSEVRNAIQ 259
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
 864-1146 3.14e-19

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: 89.29  E-value: 3.14e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  864 PSVTLI--VGCGVSSLTLLLLIIIYVSVWRYI-RSE----RSVILINFCLSIISSNALILIG---QTQTRNKVVCTLVAA 933
Cdd:cd15932      2 PALDYItyVGLGISILSLVLCLIIEALVWKSVtKNKtsymRHVCLVNIALSLLIADIWFIIGaaiSTPPNPSPACTAATF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  934 FLHFFFLSSFCWVLTEA---WQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTV-NYCWLSL-EGGL 1008
Cdd:cd15932     82 FIHFFYLALFFWMLTLGlllFYRLVLVFHDMSKSTMMAIAFSLGYGCPLIIAIITVAATAPQGGYTRkGVCWLNWdKTKA 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1009 LYAFVGPAAAVVLVNMVIGILVFNKLVSKdGITD-MKLKERagqmtvplynmtlkcakcgvisspdvsttatsNAMASLW 1087
Cdd:cd15932    162 LLAFVIPALAIVVVNFIILIVVIFKLLRP-SVGErPSKDEK--------------------------------NALVQIG 208

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1088 SSCVVL-PLLALTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15932    209 KSVAILtPLLGLTWGFGLGTMIDPKSLAFHIIFAILNSFQGFFILVFGTLLDSKVREALL 268
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
 863-1149 1.49e-17

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: 84.43  E-value: 1.49e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  863 LPSVTLI--VGCGVSSLTLLLLIIIYVSVWR-YIRSE----RSVILINFCLSIISSNALILIGQ--TQTRNKVVCTLVAA 933
Cdd:cd15253      1 SFWLDFLsqVGLGASILALLLCLGIYRLVWRsVVRNKisyfRHMTLVNIAFSLLLADTCFLGATflSAGHESPLCLAAAF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  934 FLHFFFLSSFCWVLTEA---WQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVG-FTKAKGYGTVNYCWLSLEGGLL 1009
Cdd:cd15253     81 LCHFFYLATFFWMLVQAlmlFHQLLFVFHQLAKRSVLPLMVTLGYLCPLLIAAATVAyYYPKRQYLHEGACWLNGESGAI 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1010 YAFVGPAAAVVLVNMVIGILVFNKLvskdgitdmklkeragqmtvplynmtlkcakcgviSSPDVSTTATSN---AMASL 1086
Cdd:cd15253    161 YAFSIPVLAIVLVNLLVLFVVLMKL-----------------------------------MRPSVSEGPPPEerkALLSI 205

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207122012 1087 WSSCVVL-PLLALTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVKCRV 1149
Cdd:cd15253    206 FKALLVLtPVFGLTWGLGVATLTGESSQVSHYGFAILNAFQGVFILLFGCLMDKKVREALLKRL 269
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
 867-1143 8.18e-17

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


Pssm-ID: 320386 [Multi-domain]  Cd Length: 267  Bit Score: 82.08  E-value: 8.18e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  867 TLI--VGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILI--GQTQTRNKVVCTLVAAFLHFFFLSS 942
Cdd:cd15258      5 TFIsyVGCGISAIFLAITILTYIAFRKLRRDYPSKIHMNLCAALLLLNLAFLLssWIASFGSDGLCIAVAVALHYFLLAC 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  943 FCWVLTEAWQSYMAVtGRLRNRIIRKRFL---CLGWGLPALVVAIsVGFTKAKGYGTVNY-----------CWLSLEGGL 1008
Cdd:cd15258     85 LTWMGLEAFHLYLLL-VKVFNTYIRRYILklcLVGWGLPALLVTL-VLSVRSDNYGPITIpngegfqndsfCWIRDPVVF 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1009 LYAFVGPAAAVVLVNMVIGILVFNKLVSKDGITDMKLKERAGQMTVPLYNMTLkcakcgvisspdvsttatsnamaslws 1088
Cdd:cd15258    163 YITVVGYFGLTFLFNMVMLATVLVQICRLREKAQATPRKRALHDLLTLLGLTF--------------------------- 215

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207122012 1089 scvvlpLLALTWMSAVLAItdrrsALFQI----LFAVFDSLEGFVIVMVHCILRREVQE 1143
Cdd:cd15258    216 ------LLGLTWGLAFFAW-----GPFNLpflyLFAIFNSLQGFFIFIWYCSMKENVRK 263
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
 867-1149 1.29e-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: 81.63  E-value: 1.29e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  867 TLI--VGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQ--TQTRNKVVCTLVAAFLHFFFLSS 942
Cdd:cd15997      5 TLItyLGCGISSIFLGITLVTYLAFEKLRRDYPSKILINLCTALLMLNLVFLLNSwlSSFNNYGLCITVAAFLHYFLLAS 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  943 FCWVLTEAWQSYMAVTgRLRNRIIRK---RFLCLGWGLPALVVAISVGFTKaKGYGTV----------NYCWLSLEGGLL 1009
Cdd:cd15997     85 FTWMGLEAVHMYFALV-KVFNIYIPNyilKFCIAGWGIPAVVVALVLAINK-DFYGNElssdslhpstPFCWIQDDVVFY 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1010 YAFVGPAAAVVLVNMVIGILVFNKlvskdgITDMKLK-ERAGQMTVPLYNMtlkcakcgvisspdvsttatsNAMASLws 1088
Cdd:cd15997    163 ISVVAYFCLIFLCNISMFITVLIQ------IRSMKAKkPSRNWKQGFLHDL---------------------KSVASL-- 213

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207122012 1089 scvvLPLLALTWMSAVLAITDRRsALFQILFAVFDSLEGFVIVMVHCILRREVQEavKCRV 1149
Cdd:cd15997    214 ----TFLLGLTWGFAFFAWGPVR-IFFLYLFSICNTLQGFFIFVFHCLMKENVRK--QWRI 267
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 337-387 1.42e-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: 74.93  E-value: 1.42e-16
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207122012   337 WGEWTPWSLCSSTCGRGYRERNRSCK--PPQFGGNPCDGPEKQTKFCNIAVCP 387
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCspPPQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 447-497 3.37e-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: 68.38  E-value: 3.37e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207122012   447 WQLWSTWSGCTKTCGGGSQQRQRLCYGP--FFGGEACPGDREEVRRCNEKRCP 497
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 392-442 6.62e-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: 67.23  E-value: 6.62e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207122012   392 WNEWSGWSSCSSTCSNGTMQRIRECNGP--SYGGLECQGEWHETRDCFLRECP 442
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPppQNGGGPCTGEDVETRACNEQPCP 53
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
 886-1144 8.61e-14

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: 73.18  E-value: 8.61e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  886 YVSVWRYIRSERSV--ILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWV----------LTEAWQS 953
Cdd:cd15259     26 YIVFHRLIRISRKGrhMLVNLCLHLLLTCVVFVGGINRTANQLVCQAVGILLHYSTLCTLLWVgvtarnmykqVTKTAKP 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  954 YMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGfTKAKGYGTVNYCWLSLEGGLLyAFVGPAAAVVLVNMVIGIlvfnk 1033
Cdd:cd15259    106 PQDEDQPPRPPKPMLRFYLIGWGIPLIICGITAA-VNLDNYSTYDYCWLAWDPSLG-AFYGPAALIVLVNCIYFL----- 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1034 lvskdgitdmklkeragqmtvplynmtlkCAKCGVisspdvsTTATSNAMASLWSSCVVLPLLALTWMSAVLAITDRR-- 1111
Cdd:cd15259    179 -----------------------------RIYCQL-------KGAPVSFQSQLRGAVITLFLYVAMWACGALAVSQRYfl 222

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1207122012 1112 SALFQILFAVFDSLEGFVIVMVHCILRREVQEA 1144
Cdd:cd15259    223 DLVFSCLYGATCSSLGLFVLIHHCLSREDVRQS 255
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
 870-1143 1.13e-13

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: 73.00  E-value: 1.13e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  870 VGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILI-GQTQTRN-KVVCTLVAAFLHFFFLSSFCWVL 947
Cdd:cd15996     10 IGCGISAIFSAATLLTYIAFEKLRRDYPSKILMNLSTALLFLNLVFLLdGWIASFEiDELCITVAVLLHFFLLATFTWMG 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  948 TEAWQSYMAVTgRLRNRIIRK---RFLCLGWGLPALVVAISVGFTK-----------AKGYGTVNYCWLSLEGGLLYAFV 1013
Cdd:cd15996     90 LEAIHMYIALV-KVFNTYIRRyilKFCIIGWGLPALIVSIVLASTNdnygygyygkdKDGQGGDEFCWIKNPVVFYVTCA 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1014 GPAAAVVLVNMVIGILVFNKLVSKDGitdmklkERAgqmtvplyNMTLKcakcgvisspdvsttatSNAMASLWSSCVVL 1093
Cdd:cd15996    169 AYFGIMFLMNVAMFIVVMVQICGRNG-------KRS--------NRTLR-----------------EEILRNLRSVVSLT 216

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1094 PLLALTWMSAVLAITDRRSAlFQILFAVFDSLEGFVIVMVHCILRREVQE 1143
Cdd:cd15996    217 FLLGMTWGFAFFAWGPVNLA-FMYLFTIFNSLQGLFIFVFHCALKENVQK 265
TSP_1 pfam00090
Thrombospondin type 1 domain;
448-496 3.98e-13

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 65.13  E-value: 3.98e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1207122012  448 QLWSTWSGCTKTCGGGSQQRQRLCYGPFFGGEACPGDREEVRRCNEKRC 496
Cdd:pfam00090    1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
 889-1144 4.13e-13

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: 71.37  E-value: 4.13e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  889 VWRYIRSERS-----VILINFCLSIISSNA-LILIGQTQTRNKVVC-TLVAAFLHFFFLSSFC---WVLTEAWQSYMAVT 958
Cdd:cd15254     29 VWKSVTKNRTsymrhVCILNIAVSLLIADIwFIVVAAIQDQNYAVNgNVCVAATFFIHFFYLCvffWMLALGLMLFYRLV 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  959 GRLRN--RIIRKRF-LCLGWGLPALVVAISVGFTKAK-GYGTVNYCWLSLEGG-LLYAFVGPAAAVVLVNMVIGILVFNK 1033
Cdd:cd15254    109 FILHDtsKTIQKAVaFCLGYGCPLIISVITIAVTLPRdSYTRKKVCWLNWEDSkALLAFVIPALIIVAVNSIITVVVIVK 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1034 lvskdgitdmklkeragqmtvplynmtlkcakcgvISSPDVSTTATSNAMASLW----SSCVVLPLLALTWMSAVLAITD 1109
Cdd:cd15254    189 -----------------------------------ILRPSIGEKPSKQERSSLFqiikSIGVLTPLLGLTWGFGLATVIK 233

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207122012 1110 RRSALFQILFAVFDSLEGFVIVMVHCILRREVQEA 1144
Cdd:cd15254    234 GSSIVFHILFTLLNAFQGLFILVFGTLWDKKVQEA 268
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 242-291 2.38e-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: 62.99  E-value: 2.38e-12
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1207122012   242 WSGWGNWAECSSECGGGVQKRTRNCQSPPDEA--YLCEGVLEEGRPCNAQPC 291
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNggGPCTGEDVETRACNEQPC 52
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
 870-1143 2.96e-12

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: 68.70  E-value: 2.96e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  870 VGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVV---CTLVAAFLHFFFLSSFCWV 946
Cdd:cd15444     10 IGCGLSAIFLSVTLVTYIAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKDIvglCISVAVFLHYFLLVSFTWM 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  947 LTEAWQSYMAVTgRLRNRIIRK---RFLCLGWGLPALVVAISVGFTKaKGYGTVNY-----------CWLSLEGGLLYAF 1012
Cdd:cd15444     90 GLEAFHMYLALV-KVFNTYIRKyilKFCIVGWGVPAVVVAIVLAVSK-DNYGLGSYgkspngstddfCWINNNIVFYITV 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1013 VGPAAAVVLVNMVIGILVFNKLVSkdgitdMKLKERAGqmtvplynmtlkcakcgvisspdvstTATSNAMASLWSSCVV 1092
Cdd:cd15444    168 VGYFCVIFLLNISMFIVVLVQLCR------IKKQKQLG--------------------------AQRKTSLQDLRSVAGI 215

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207122012 1093 LPLLALTWMSAVLAITDrRSALFQILFAVFDSLEGFVIVMVHCILRREVQE 1143
Cdd:cd15444    216 TFLLGITWGFAFFAWGP-VNLAFMYLFAIFNTLQGFFIFIFYCVAKENVRK 265
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
 891-1148 5.55e-12

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


Pssm-ID: 320561 [Multi-domain]  Cd Length: 265  Bit Score: 68.04  E-value: 5.55e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNA------LILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAV-----TG 959
Cdd:cd15445     30 RSIRCLRNIIHWNLITAFILRNAtwfvvqLTMSPEVHQSNVVWCRLVTAAYNYFHVTNFFWMFGEGCYLHTAIvltysTD 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  960 RLRNRIirkrFLCLGWGLP-ALVVAISVGftkaKGYGTVNYCWLSLEGGLL--YAFVGPAAAVVLVNMvigILVFNKlvs 1036
Cdd:cd15445    110 KLRKWM----FICIGWCIPfPIIVAWAIG----KLYYDNEKCWFGKRAGVYtdYIYQGPMILVLLINF---IFLFNI--- 175

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1037 kdgITDMKLKERAGqmtvplynmtlkcakcgvisspdvSTTATSNAMASLWSSCVVLPLLALTWMSA-VLAITDRRSALF 1115
Cdd:cd15445    176 ---VRILMTKLRAS------------------------TTSETIQYRKAVKATLVLLPLLGITYMLFfVNPGEDEISRIV 228

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1207122012 1116 QILFAVF-DSLEGFVIVMVHCILRREVQEAVKCR 1148
Cdd:cd15445    229 FIYFNSFlESFQGFFVSVFYCFLNSEVRSAVRKR 262
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
 870-1146 6.05e-12

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


Pssm-ID: 320660 [Multi-domain]  Cd Length: 267  Bit Score: 67.94  E-value: 6.05e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  870 VGCGVSSLTLLLLIIIYVSVW-RYIRSE----RSVILINFCLSIISSNALILIG---QTQTRNKVVCTLVAAFLHFFFLS 941
Cdd:cd15994     10 IGLGLSIFSLALCLTIEAVVWsHVTKTEitymRHVCIVNIATSLLIADVWFILAsivHNTALNYPLCVAATFFLHFFYLS 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  942 SFCWVLTEAW---QSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTK-AKGYGTVNYCWLSL-EGGLLYAFVGPA 1016
Cdd:cd15994     90 LFFWMLTKALlilYGILLVFFKITKSVFIATAFSIGYGCPLVIAVLTVAITEpKKGYLRPEACWLNWdETKALLAFIIPA 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1017 AAVVLVNMVIGILVFNKlVSKDGITDMKLKERAGQMTVplynmtlkcakcgvisSPDVSttatsnamaslwsscVVLPLL 1096
Cdd:cd15994    170 LSIVVVNLIVVGVVVVK-TQRSSIGESCKQDVSNIIRI----------------SKNVA---------------ILTPLL 217

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1097 ALTWMSAVLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15994    218 GLTWGFGLATIIDSRSLPFHIIFALLNAFQGFFILLFGTILDRKIRIALY 267
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 805-849 1.72e-11

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: 60.40  E-value: 1.72e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1207122012  805 TCISWDENDSSSllGSWSARGCRAVPVDSSTTKCLCDRLSTFAIL 849
Cdd:pfam01825    2 QCVFWDFTNSTT--GRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
TSP_1 pfam00090
Thrombospondin type 1 domain;
338-386 2.14e-11

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 60.12  E-value: 2.14e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1207122012  338 GEWTPWSLCSSTCGRGYRERNRSCKPPQFGGNPCDGPEKQTKFCNIAVC 386
Cdd:pfam00090    1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
 450-496 2.06e-10

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: 57.29  E-value: 2.06e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1207122012  450 WSTWSGCTKTCGGGSQQRQR-LCYGPFFGGEACPgDREEVRRCNEKRC 496
Cdd:pfam19028    6 WSEWSECSVTCGGGVQTRTRtVIVEPQNGGRPCP-ELLERRPCNLPPC 52
TSP_1 pfam00090
Thrombospondin type 1 domain;
243-291 2.13e-10

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 57.43  E-value: 2.13e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1207122012  243 SGWGNWAECSSECGGGVQKRTRNCQSPPDEAYLCEGVLEEGRPCNAQPC 291
Cdd:pfam00090    1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
 338-386 4.68e-10

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: 56.52  E-value: 4.68e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207122012  338 GEWTPWSLCSSTCGRGYRERNRSCK-PPQFGGNPCdGPEKQTKFCNIAVC 386
Cdd:pfam19028    4 SEWSEWSECSVTCGGGVQTRTRTVIvEPQNGGRPC-PELLERRPCNLPPC 52
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
 889-1137 5.25e-10

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: 62.58  E-value: 5.25e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  889 VWRYIRSER-SVILINFCLSIISSNALILIGQTQTRNKV-------------------------VCTLVAAFLHFFFLSS 942
Cdd:cd15257     28 HTRKLRKSSvTWVLLNLCSSLLLFNIIFTSGVENTNNDYeistvpdretntvllseeyvepdtdVCTAVAALLHYFLLVT 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  943 FCWVLTEAWQSYMAVTGRLRN--RIIRKRFLCLGWGLPALVVAISVGFTKA---------KGYGTVNYCWL-------SL 1004
Cdd:cd15257    108 FMWNAVYSAQLYLLLIRMMKPlpEMFILQASAIGWGIPAVVVAITLGATYRfptslpvftRTYRQEEFCWLaaldknfDI 187

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1005 EGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKdgitDMKLKeragqmtvplynmtlkcakcgvisspdvsTTATSNAMA 1084
Cdd:cd15257    188 KKPLLWGFLLPVGLILITNVILFIMTSQKVLKK----NNKKL-----------------------------TTKKRSYMK 234

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207122012 1085 SLWSSCVVLPLLALTWMSA--VLAITDRRSALFQILFAVFDSLEGFVIvmvhCIL 1137
Cdd:cd15257    235 KIYITVSVAVVFGITWILGylMLVNNDLSKLVFSYIFCITNTTQGVQI----FIL 285
TSP_1 pfam00090
Thrombospondin type 1 domain;
394-441 7.60e-10

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 55.89  E-value: 7.60e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1207122012  394 EWSGWSSCSSTCSNGTMQRIRECNGPSYGGLECQGEWHETRDCFLREC 441
Cdd:pfam00090    2 PWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
 891-1149 1.54e-09

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: 60.51  E-value: 1.54e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILIGQ------TQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAV-----TG 959
Cdd:cd15264     30 RSLRCLRNNIHCNLIVTFILRNVTWFIMQntlteiHHQSNQWVCRLIVTVYNYFQVTNFFWMFVEGLYLHTMIvwaysAD 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  960 RLRNRIirkrFLCLGWGLPA-LVVAISVGftkaKGYGTVNYCWLSLEGGLLYAFV--GPAAAVVLVNMVIgilVFNKLVs 1036
Cdd:cd15264    110 KIRFWY----YIVIGWCIPCpFVLAWAIV----KLLYENEHCWLPKSENSYYDYIyqGPILLVLLINFIF---LFNIVW- 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1037 kdgITDMKLKeragqmtvplynmtlkcakcgviSSPDVSTTATSNAM-ASLwsscVVLPLLALTWMSAVLAITDrrSALF 1115
Cdd:cd15264    178 ---VLITKLR-----------------------ASNTLETIQYRKAVkATL----VLLPLLGITYMLFFINPGD--DKTS 225

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1207122012 1116 QILFAVFD----SLEGFVIVMVHCILRREVQEAVKCRV 1149
Cdd:cd15264    226 RLVFIYFNtflqSFQGLFVAVFYCFLNGEVRSAIRKKF 263
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 802-850 1.67e-09

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: 54.70  E-value: 1.67e-09
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*....
gi 1207122012   802 TNQTCISWDENDsssllGSWSARGCRAVPVDSSTTKCLCDRLSTFAILA 850
Cdd:smart00303    1 FNPICVFWDESS-----GEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
 900-1144 2.03e-09

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: 60.65  E-value: 2.03e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  900 ILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRN-----------RIIRk 968
Cdd:cd15999     42 MLVNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYSTLATVLWVGVTARNIYKQVTRKAKRcqdpdepppppRPML- 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  969 RFLCLGWGLPALVVAISVGfTKAKGYGT---VNYCWLSLEGGlLYAFVGPAAAVVLVNMVIGILVFNKLvSKDGITDMKL 1045
Cdd:cd15999    121 RFYLIGGGIPIIVCGITAA-ANIKNYGSrpnAPYCWMAWEPS-LGAFYGPAGFIIFVNCMYFLSIFIQL-KRHPERKYEL 197

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1046 KERAGQMT---------VPLYNMTLKCAKCGVisspdVSTTATSNA---MASLWSSCVVLPLLALTWMSAVLAITDR--R 1111
Cdd:cd15999    198 KEPTEEQQrlaasehgeLNHQDSGSSSASCSL-----VSTSALENEhsfQAQLLGASLALFLYVALWIFGALAVSLYypM 272

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1207122012 1112 SALFQILFAVFD-SLEGFVIVMvHCILRREVQEA 1144
Cdd:cd15999    273 DLVFSCLFGATClSLGAFLVVH-HCVNREDVRRA 305
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
 900-1034 7.29e-09

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: 58.39  E-value: 7.29e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  900 ILINFCLSIISSNALILIGQTQT-RNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNRI---IRKRFL---C 972
Cdd:cd15039     39 CLMCLVLSLFVAYLLLLIGQLLSsGDSTLCVALGILLHFFFLAAFFWLNVMSFDIWRTFRGKRSSSSrskERKRFLrysL 118

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207122012  973 LGWGLPALVVAISVGFTKAK-------GYGTvNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKL 1034
Cdd:cd15039    119 YAWGVPLLLVAVTIIVDFSPntdslrpGYGE-GSCWISNPWALLLYFYGPVALLLLFNIILFILTAIRI 186
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
 891-1146 1.78e-08

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: 57.62  E-value: 1.78e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILI---------------GQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWqsYm 955
Cdd:cd15041     30 RSLRCTRIRLHINLFLSFILRAVFWIIwdllvvydrltssgvETVLMQNPVGCKLLSVLKRYFKSANYFWMLCEGL--Y- 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  956 avtgrLRNRIIR---------KRFLCLGWGLPALVVAIsvgFTKAKGYGTVNYCWLSL-EGGLLYAFVGPAAAVVLVNMV 1025
Cdd:cd15041    107 -----LHRLIVVaffsepsslKLYYAIGWGLPLVIVVI---WAIVRALLSNESCWISYnNGHYEWILYGPNLLALLVNLF 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1026 IGILVFNKLVSKdgitdmklkeragqmtvplynmtLKCAkcgvisspdvSTTATSNAMASLWSSCVVLPLLALTWMSAVL 1105
Cdd:cd15041    179 FLINILRILLTK-----------------------LRSH----------PNAEPSNYRKAVKATLILIPLFGIQYLLTIY 225

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1207122012 1106 --AITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15041    226 rpPDGSEGELVYEYFNAILNSSQGFFVAVIYCFLNGEVQSELK 268
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
 891-1148 2.16e-08

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: 57.28  E-value: 2.16e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILIGQ-----TQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNRI 965
Cdd:cd15446     30 RSIRCLRNIIHWNLITTFILRNVMWFLLQmidhnIHESNEVWCRCITTIYNYFVVTNFFWMFVEGCYLHTAIVMTYSTDK 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  966 IRK-RFLCLGWGLPA-LVVAISVGftkaKGYGTVNYCWLSLEGGLL--YAFVGPAAAVVLVNMVigiLVFNKlvskdgIT 1041
Cdd:cd15446    110 LRKwVFLFIGWCIPCpIIVAWAIG----KLYYENEQCWFGKEPGKYidYIYQGPVILVLLINFV---FLFNI------VR 176

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1042 DMKLKERAGqmtvplynmtlkcakcgvisspdvSTTATSNAMASLWSSCVVLPLLALTWMsaVLAITDRRSALFQILFAV 1121
Cdd:cd15446    177 ILMTKLRAS------------------------TTSETIQYRKAVKATLVLLPLLGITYM--LFFVNPGEDDISQIVFIY 230

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207122012 1122 FD----SLEGFVIVMVHCILRREVQEAVKCR 1148
Cdd:cd15446    231 FNsflqSFQGFFVSVFYCFLNGEVRSAARKR 261
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
 394-441 2.52e-08

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: 51.51  E-value: 2.52e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1207122012  394 EWSGWSSCSSTCSNGTMQRIRECNG-PSYGGLECqGEWHETRDCFLREC 441
Cdd:pfam19028    5 EWSEWSECSVTCGGGVQTRTRTVIVePQNGGRPC-PELLERRPCNLPPC 52
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
 243-291 5.30e-08

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: 50.74  E-value: 5.30e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207122012  243 SGWGNWAECSSECGGGVQKRTRN-CQSPPDEAYLCeGVLEEGRPCNAQPC 291
Cdd:pfam19028    4 SEWSEWSECSVTCGGGVQTRTRTvIVEPQNGGRPC-PELLERRPCNLPPC 52
HormR smart00008
Domain present in hormone receptors;
499-565 5.61e-08

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 50.98  E-value: 5.61e-08
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207122012   499 PHEICDEENFSNVVWKKTPAGDTAAVRCPPNAVGL-----ILRRCSLDnegiAYWEN--PTYMKCVSNDYRSIQ 565
Cdd:smart00008    1 TDLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFsyktgASRNCTEN----GGWSPpfPNYSNCTSNDYEELK 70
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
 945-1149 7.52e-07

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: 52.43  E-value: 7.52e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  945 WVLTEA--WQSYMAVTGRLRnriiRKRFLC---LGWGLPALVVAIsvgFTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAV 1019
Cdd:cd15271     94 WLLVEGmyLQTLLLLTFTSD----RKYFWWyilIGWGAPSVTVTV---WVLTRLQYDNRGCWDDLESRIWWIIKTPILLS 166

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1020 VLVNMVIGILVFNKLVSKdgitdmklkeragqmtvplynmtlkcakcgvISSPDVSTTATSNAMASLWSSCVVLPLLALT 1099
Cdd:cd15271    167 VFVNFLIFINVIRILVQK-------------------------------LKSPDVGGNDTSHYMRLAKSTLLLIPLFGVH 215

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207122012 1100 WMsaVLAITDRRSALFQILF--AVFDSLEGFVIVMVHCILRREVQEAVKCRV 1149
Cdd:cd15271    216 YV--VFAFFPEHVGVEARLYfeLVLGSFQGFIVALLYCFLNGEVQAEIKKRL 265
TSP1_ADAMTS pfam19030
Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found ...
 246-291 7.92e-06

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: 44.75  E-value: 7.92e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207122012  246 GNWAECSSECGGGVQKRTRNCQSPPDEA----YLCEGVL--EEGRPCNAQPC 291
Cdd:pfam19030    4 GPWGECSVTCGGGVQTRLVQCVQKGGGSivpdSECSAQKkpPETQSCNLKPC 55
TSP1_ADAMTS pfam19030
Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found ...
 453-496 9.08e-06

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: 44.37  E-value: 9.08e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207122012  453 WSGCTKTCGGGSQQRQRLCYGPF----FGGEACPGDR--EEVRRCNEKRC 496
Cdd:pfam19030    6 WGECSVTCGGGVQTRLVQCVQKGggsiVPDSECSAQKkpPETQSCNLKPC 55
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 500-559 3.48e-05

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: 43.13  E-value: 3.48e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207122012  500 HEICDEENFSNVVWKKTPAGDTAAVRCPP-----NAVGLILRRCSLDNEgiayWENP---TYMKCVSN 559
Cdd:pfam02793    1 GLGCPRTWDGILCWPRTPAGETVEVPCPDyfsgfDPRGNASRNCTEDGT----WSEHppsNYSNCTSN 64
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
 900-1141 3.67e-05

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: 47.25  E-value: 3.67e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  900 ILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRN----------RIIRKR 969
Cdd:cd16000     42 MLLNFCFHTALTFAVFAGGINRTKYPIICQAVGIVLHYSTLSTMLWIGVTARNIYKQVTKKPHLcqdtdqppypKQPLLR 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  970 FLCLGWGLPALVVAISVGfTKAKGYGT----VNYCWLSLEGGlLYAFVGPAAAVVLVNMVIGILVFNKLvskdgitdmkl 1045
Cdd:cd16000    122 FYLVSGGVPFIICGITAA-TNINNYGTededTPYCWMAWEPS-LGAFYGPVAFIVLVTCIYFLCTYVQL----------- 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1046 kERAGQMTVPLYNmtlkcakcgvisspdvsttaTSNAMASLWSSCVVLPLLALTWMSAVLAITDRR--SALFQILFAVFD 1123
Cdd:cd16000    189 -RRHPERKYELKN--------------------EHSFKAQLRAAAFTLFLFTATWAFGALAVSQGHflDMIFSCLYGAFC 247

                          250
                   ....*....|....*...
gi 1207122012 1124 SLEGFVIVMVHCILRREV 1141
Cdd:cd16000    248 VTLGLFILIHHCAKRDDV 265
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
 944-1148 8.75e-05

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


Pssm-ID: 320395 [Multi-domain]  Cd Length: 281  Bit Score: 46.35  E-value: 8.75e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  944 CWVLTEAWQSY-MAVTGRLRNRIIRKRFLCLGWGLPALVVaisVGFTKAKGYGTVNYCW-LSLEGGLLYAFVGPAAAVVL 1021
Cdd:cd15267    104 CWLLVEGIYLHnLLVLAVFPERSYFSLYLCIGWGAPALFV---VPWVVVKCLYENVQCWtSNDNMGFWWILRFPVFLAIL 180

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1022 VNMVIGILVFNKLVSkdgitdmklKERAGQMTVPLYNMTLkcAKcgvisspdvsttatsnamaslwSSCVVLPLLALTWM 1101
Cdd:cd15267    181 INFFIFVRIIQILVS---------KLRARQMHYTDYKFRL--AK----------------------STLTLIPLLGIHEV 227

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207122012 1102 sAVLAITD-------RRSALFQILFavFDSLEGFVIVMVHCILRREVQEAVKCR 1148
Cdd:cd15267    228 -VFAFVTDehaqgtlRSAKLFFDLF--LSSFQGLLVAVLYCFLNKEVQSELRRR 278
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
 945-1148 1.41e-04

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: 45.50  E-value: 1.41e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  945 WVLTEAWQSYMAVTGRLRNRiiRKR---FLCLGWGLPALVVaisVGFTKAKGYGTVNYCW-LSLEGGLLYAFVGPAAAVV 1020
Cdd:cd15275     94 WLLVEGLYLHSLLSISFFSE--RKHlwwYIALGWGSPLIFI---ISWAIARYLHENEGCWdTRRNAWIWWIIRGPVILSI 168

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1021 LVNMVIGILVFNKLVSKDGITDMKLKEragqmtvplYNMTLKCAKcgvisspdvsttatsnamaslwSSCVVLPLLALTW 1100
Cdd:cd15275    169 FVNFILFLNILRILMRKLRAPDMRGNE---------FSQYKRLAK----------------------STLLLIPLFGLHY 217

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207122012 1101 MSAVLAITDRRSALFQI-LFA--VFDSLEGFVIVMVHCILRREVQEAVKCR 1148
Cdd:cd15275    218 ILFAFFPEDVSSGTMEIwLFFelALGSFQGFVVAVLYCFLNGEVQLEIQRK 268
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
 941-1146 2.50e-04

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: 44.67  E-value: 2.50e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  941 SSFCWVLTEAWQSYMAVTGRLRNRIIRKR-FLCLGWGLPALVVAIsvgFTKAKGYGTVNYCWLSLEGGLL---------- 1009
Cdd:cd15263     84 TNFFWMFVEGLYLYMLVVETFSGENIKLRvYAFIGWGIPAVVIVI---WAIVKALAPTAPNTALDPNGLLkhcpwmaehi 160

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1010 --YAFVGPAAAVVLVNMVIGILVFNKLvskdgITdmKLKeragqmtvplynmtlkcakcgviSSPDVSTTATSNAMASLw 1087
Cdd:cd15263    161 vdWIFQGPAILVLAVNLVFLVRIMWVL-----IT--KLR-----------------------SANTVETQQYRKAAKAL- 209

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1088 ssCVVLPLLALTWMSAVLAITDRRSA-LFQILFAVFDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15263    210 --LVLIPLLGITYILVIAGPTEGIAAnIFEYVRAVLLSTQGFTVALFYCFLNTEVRNTLR 267
PTZ00087 PTZ00087
thrombosponding-related protein; Provisional
 242-291 3.25e-04

thrombosponding-related protein; Provisional


Pssm-ID: 185438  Cd Length: 340  Bit Score: 44.55  E-value: 3.25e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207122012  242 WSGWGNWAECSSECG--GGVQKRTRNCQSPPDEAYlcEGVLEEGRPCNA--QPC 291
Cdd:PTZ00087   233 YTEWGEWSNCSMECDhpDNVQIRERKCAHPSGDCF--KGDLKETRPCQVplPPC 284
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
 869-1142 3.88e-04

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: 43.98  E-value: 3.88e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  869 IVGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKV--VCTLVAAFLHFFFLSSFCWV 946
Cdd:cd15443      9 IVGCSISAAASLLTILLHFFSRKQPKDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQStwLCRAAAALLHYSLLCCLTWM 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  947 LTEAWQSYMaVTGRLRNRIIRKRF--LC-LGWGLPALVVAISVGFTKA----------KGYGTVNYCWLSLEGGLLYAFV 1013
Cdd:cd15443     89 AIEGFHLYL-LLVKVYNIYIRRYVlkLCvLGWGLPALIVLLVLIFKREaygphtiptgTGYQNASMCWITSSKVHYVLVL 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1014 GPAAAVVLVNMVIGILVFNKLvskdgitdMKLKERAGQMtvplynmtlkcakcgvisspdvSTTATSNAMASLWSSCvvl 1093
Cdd:cd15443    168 GYAGLTSLFNLVVLAWVVRML--------RRLRSRKQEL----------------------GERARRDWVTVLGLTC--- 214

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1094 pLLALTWMSAVLAITDrrSALFQI-LFAVFDSLEGFVIVMVHCILRREVQ 1142
Cdd:cd15443    215 -LLGTTWALAFFSFGV--FLIPQLfLFTIINSLYGFFICLWYCTQRRRSD 261
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
 901-1146 6.50e-04

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: 43.61  E-value: 6.50e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  901 LINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEA-WQSYMAVTGRLRNRIIRKRFLCLGWGLPA 979
Cdd:cd15274     48 ILNSIIIIIHLVAVVPNGELVARNPVSCKILHFIHQYMMGCNYFWMLCEGiYLHTLIVVAVFAEKQRLMWYYLLGWGFPL 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  980 LVVAISVgFTKAKGYGtvNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKdgitdMKLKERAGQmtvplyNM 1059
Cdd:cd15274    128 IPTTIHA-ITRAVYYN--DNCWLSSETHLLYIIHGPIMAALVVNFFFLLNIVRVLVTK-----LRETHEAES------HM 193

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1060 TLKCAKcgvisspdvsttatsnamASLwsscVVLPLLALTWMsaVLAITDRRSALFQILFAVFDSL---EGFVIVMVHCI 1136
Cdd:cd15274    194 YLKAVK------------------ATL----ILVPLLGIQFV--LFPWRPSGKILGKIYDYVMHSLihfQGFFVATIFCF 249

                          250
                   ....*....|
gi 1207122012 1137 LRREVQEAVK 1146
Cdd:cd15274    250 CNGEVQATLK 259
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
 928-1148 7.16e-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: 7.16e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  928 CTLVAAFLHFFFLSSFCWVLTEAWQSY-MAVTGRLRNRIIRKRFLCLGWGLPALVVaisVGFTKAKGYGTVNYCWLSLEG 1006
Cdd:cd15266     87 CRVAQVFMHYFVGANYFWLLVEGLYLHtLLVTAVLSERRLLKKYMLIGWGTPVLFV---VPWGVAKILLENTGCWGRNEN 163

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1007 -GLLYAFVGPAAAVVLVNMVIGILVFNKLVSkdgitdmKLKerAGQMTVPLYNMTLkcakcgvisspdvsttatsnAMAS 1085
Cdd:cd15266    164 mGIWWIIRGPILLCITVNFYIFLKILKLLLS-------KLK--AQQMRFTDYKYRL--------------------ARST 214

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207122012 1086 LwsscVVLPLLALTWMsAVLAITDRRSALFQILFAVF-----DSLEGFVIVMVHCILRREVQEAVKCR 1148
Cdd:cd15266    215 L----VLIPLLGIHEV-VFSFITDEQVEGFSRHIRLFiqltlSSFQGFLVAVLYCFANGEVKAELKKR 277
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
 973-1146 7.21e-04

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


Pssm-ID: 320649 [Multi-domain]  Cd Length: 285  Bit Score: 43.37  E-value: 7.21e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  973 LGWGLPALVVAIsvgFTKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKDGITDMKLKERAGQm 1052
Cdd:cd15983    136 IGWGLPAVFVSV---WASVRVSLADTQCWDLSAGNLKWIYQVPILAAILVNFFLFLNIVRVLASKLWETNTGKLDPRQQ- 211

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1053 tvplYNMTLKcakcgvisspdvsttatsnamaslwSSCVVLPLLALTWMS-AVLAITDRRSALFQILF---AVFDSLEGF 1128
Cdd:cd15983    212 ----YRKLLK-------------------------STLVLMPLFGVHYVLfMAMPYTDVTGLLWQIQMhyeMLFNSSQGF 262

                          170
                   ....*....|....*...
gi 1207122012 1129 VIVMVHCILRREVQEAVK 1146
Cdd:cd15983    263 FVAFIYCFCNGEVQAEIK 280
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
 945-1148 1.03e-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: 42.99  E-value: 1.03e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  945 WVLTEAWQSYMAVTGR-LRNRIIRKRFLCLGWGLPALVVaisVGFTKAKGYGTVNYCWlSLEGGLLYAFV--GPAAAVVL 1021
Cdd:cd15985    104 WFFVEAVYLYKLLIGAvFSEKNYYLLYLYLGWGTPVLFV---VPWMLAKYLKENKECW-ALNENMAYWWIirIPILLASL 179

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1022 VNMVIGILVFNKLVSKdgitdmklkERAGQMTVPLYNMTLkcakcgvisspdvsttatsnAMASLwsscVVLPLLALTWM 1101
Cdd:cd15985    180 INLLIFMRILKVILSK---------LRANQKGYADYKLRL--------------------AKATL----TLIPLFGIHEV 226

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207122012 1102 SAVLAITDRRSALF---QILFAVF-DSLEGFVIVMVHCILRREVQEAVKCR 1148
Cdd:cd15985    227 VFIFATDEQTTGILryiKVFFTLFlNSFQGFLVAVLYCFANKEVKSELLKK 277
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
 945-1146 1.07e-03

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: 42.80  E-value: 1.07e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  945 WVLTEAWQSYMAVTGRLRNRiiRKRF---LCLGWGLPALVVAIsvgFTKAKGYGTVNYCW-LSLEGGLLYAFVGPAAAVV 1020
Cdd:cd15930     94 WLLVEGLYLHTLLVISFFSE--RRYFwwyVLIGWGAPTVFVTV---WIVARLYFEDTGCWdINDESPYWWIIKGPILISI 168

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1021 LVNMVIGILVFNKLVSKdgitdmklkeragqmtvplynmtlkcakcgvISSPDVSTTATSNAMASLWSSCVVLPLLALTW 1100
Cdd:cd15930    169 LVNFVLFINIIRILLQK-------------------------------LRSPDIGGNESSQYKRLARSTLLLIPLFGIHY 217

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207122012 1101 MsaVLAIT-DRRSALFQILFA-VFDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15930    218 I--VFAFFpENISLGIRLYFElCLGSFQGFVVAVLYCFLNGEVQAEIK 263
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
 891-1148 1.25e-03

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: 42.64  E-value: 1.25e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  891 RYIRSERSVILINFCLSIISSNALILI--------GQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMA-VTGRL 961
Cdd:cd15260     30 RSLRCTRITIHMNLFISFALNNLLWIVwyklvvdnPEVLLENPIWCQALHVLLQYFMVCNYFWMFCEGLYLHTVlVVAFI 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  962 RNRIIRKRFLCLGWGLPALVVAISVGFTKAKGYGTvNYCWLSlEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKdgit 1041
Cdd:cd15260    110 SEKSLMRWFIAIGWGVPLVITAIYAGVRASLPDDT-ERCWME-ESSYQWILIVPVVLSLLINLIFLINIVRVLLTK---- 183

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1042 dmklkeragqmtvplynmtLKCakcgVISSPDVSTTATsNAMASLwsscVVLPLLALTWmsavLAITDRRSA------LF 1115
Cdd:cd15260    184 -------------------LRA----TSPNPAPAGLRK-AVRATL----ILIPLLGLQF----LLIPFRPEPgapletIY 231

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1207122012 1116 QILFAVFDSLEGFVIVMVHCILRREVQEAVKCR 1148
Cdd:cd15260    232 QYVSALLTSLQGLCVAVLFCFCNGEVIAAIKRK 264
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
 970-1146 1.54e-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: 42.24  E-value: 1.54e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  970 FLCLGWGLPALVVAI--SVGFTKAKgygtvNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSkdgitdmKLKE 1047
Cdd:cd15984    138 FTLFGWGLPAVFVTIwaSVRATLAD-----TGCWDLSAGNLKWIIQVPILAAIVVNFILFINIVRVLAT-------KLRE 205

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1048 -RAGQM-TVPLYNMTLKcakcgvisspdvsttatsnamaslwSSCVVLPLLALTWMS-AVLAITDRRSALFQILF---AV 1121
Cdd:cd15984    206 tNAGRCdTRQQYRKLLK-------------------------STLVLMPLFGVHYIVfMAMPYTEVSGILWQVQMhyeML 260

                          170       180
                   ....*....|....*....|....*
gi 1207122012 1122 FDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15984    261 FNSFQGFFVAIIYCFCNGEVQAEIK 285
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
 870-1137 1.79e-03

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: 42.09  E-value: 1.79e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  870 VGCGVSSLTLLLLIIIYVSV---WRYIRSERSV-ILINFCLSIISSNA--LILIGQTQTRNKVVCTLVAAFLHFFFLSSF 943
Cdd:cd15442     10 AGCGVSMVFLIFTIILYFFLrftYQKFKSEDAPkIHVNLSSSLLLLNLafLLNSGVSSRAHPGLCKALGGVTHYFLLCCF 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  944 CWVLTEAWQSYMAVTgRLRNRIIRKRF--LCL-GWGLPALVVAISvgfTKAKGYG-----------TVNYCWLSlEGGLL 1009
Cdd:cd15442     90 TWMAIEAFHLYLLAI-KVFNTYIHHYFakLCLvGWGFPALVVTIT---GSINSYGaytimdmanrtTLHLCWIN-SKHLT 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1010 YAFV---GPAAAVVLVNMVIGILVFNKLVSKDGITDMKLKeragqmtvplynmtlkcakcgvisspdvsTTATSNAMASL 1086
Cdd:cd15442    165 VHYItvcGYFGLTFLFNTVVLGLVAWKIFHLQSATAGKEK-----------------------------CQAWKGGLTVL 215

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207122012 1087 WSSCvvlpLLALTWMSAVLA-ITDRRSALFqiLFAVFDSLEGFVIVMVHCIL 1137
Cdd:cd15442    216 GLSC----LLGVTWGLAFFTyGSMSVPTVY--IFALLNSLQGLFIFIWFVIL 261
TSP1_ADAMTS pfam19030
Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found ...
 341-386 2.78e-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: 37.43  E-value: 2.78e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207122012  341 TPWSLCSSTCGRGYRERNRSCKPP----QFGGNPCDGPEK--QTKFCNIAVC 386
Cdd:pfam19030    4 GPWGECSVTCGGGVQTRLVQCVQKgggsIVPDSECSAQKKppETQSCNLKPC 55
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
 970-1146 4.84e-03

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


Pssm-ID: 320652 [Multi-domain]  Cd Length: 269  Bit Score: 40.56  E-value: 4.84e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  970 FLCLGWGLPALVVAIsvgFTKAKGYGTVNYCWLSLEGGLLYAFVG-PAAAVVLVNMVIGILVFNKLVSKdgitdmklker 1048
Cdd:cd15986    121 YLLIGWGIPTVFIIA---WIVARIYLEDTGCWDTNDHSVPWWVIRiPIIISIILNFILFISIIRILLQK----------- 186

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1049 agqmtvplynmtlkcakcgvISSPDVSTTATSNAMASLWSSCVVLPLLALTWMSAVLaITDRRSALFQILFAV-FDSLEG 1127
Cdd:cd15986    187 --------------------LRSPDVGGNDQSQYKRLAKSTLLLIPLFGVHYIVFVY-FPDSSSSNYQIFFELcLGSFQG 245

                          170
                   ....*....|....*....
gi 1207122012 1128 FVIVMVHCILRREVQEAVK 1146
Cdd:cd15986    246 LVVAILYCFLNSEVQGELK 264
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
 944-1142 6.14e-03

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


Pssm-ID: 341353 [Multi-domain]  Cd Length: 279  Bit Score: 40.50  E-value: 6.14e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  944 CWVLTEAWQSY--MAVTGRLRNRIIRkRFLCLGWGLPALVVaISVGFTKAKGYGTVnyCWLSLEG-GLLYAFVGPAAAVV 1020
Cdd:cd15929    102 YWLLVEGLYLHtlLVLAVFSERSIFR-LYLLLGWGAPVLFV-VPWGIVKYLYENTG--CWTRNDNmAYWWIIRLPILLAI 177

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1021 LVNMVIGILVFNKLVSkdgitdmklKERAGQMTVPLYNMTLkcAKcgvisspdvsttatsnamaslwSSCVVLPLLALtw 1100
Cdd:cd15929    178 LINFFIFVRILKILVS---------KLRANQMCKTDYKFRL--AK----------------------STLTLIPLLGV-- 222

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1101 MSAVLA-ITD-------RRSALFQILFavFDSLEGFVIVMVHCILRREVQ 1142
Cdd:cd15929    223 HEVVFAfVTDeqargtlRFIKLFFELF--LSSFQGLLVAVLYCFANKEVQ 270
TSP1_CCN pfam19035
CCN3 Nov like TSP1 domain; This entry represents a sub-type of TSP1 domains found in ...
 341-386 6.27e-03

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: 36.16  E-value: 6.27e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207122012  341 TPWSLCSSTCGRG----YRERNRSCKppqfggnpcdgPEKQTKFCNIAVC 386
Cdd:pfam19035    6 TEWSPCSKTCGMGvstrVSNDNAECK-----------LVTETRLCQLRPC 44
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
 944-1147 6.51e-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: 40.43  E-value: 6.51e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  944 CWVLTEA-WQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTKAKGygTVNYCWLSleggllYAFV-------GP 1015
Cdd:cd15261    104 MWMFIEGlYLHNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWAIVTLIKM--KVNRCWFG------YYLTpyywileGP 175

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1016 AAAVVLVNMVIGILVFNKLVskdgitdMKLKERAGQMTVPLynmtlkcakcgvisspdvsTTATSNAMaslwsscVVLPL 1095
Cdd:cd15261    176 RLAVILINLFFLLNIIRVLV-------SKLRESHSREIEQV-------------------RKAVKAAI-------VLLPL 222

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207122012 1096 LALTWMSAVLAITDRRSAlfqILFAVFD-------SLEGFVIVMVHCILRREVQEAVKC 1147
Cdd:cd15261    223 LGITNILQMIPPPLTSVI---VGFAVWSysthfltSFQGFFVALIYCFLNGEVKNVLKK 278
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
 969-1146 6.72e-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: 6.72e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012  969 RFLCLGWGLPALVVAI--SVGFTKAKgygtvNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKdgitdMKLK 1046
Cdd:cd15265    137 GFTLIGWGFPAVFVIPwaSVRATLAD-----TRCWDLSAGNYKWIYQVPILAAIVVNFILFLNIVRVLATK-----LRET 206

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207122012 1047 ERAGQMTVPLYNMTLKcakcgvisspdvsttatsnamaslwSSCVVLPLLALTWMSAVLAITDRRSALFQI-----LFav 1121
Cdd:cd15265    207 NAGRCDTRQQYRKLAK-------------------------STLVLIPLFGVHYIVFMGMPYTEVGLLWQIrmhyeLF-- 259

                          170       180
                   ....*....|....*....|....*
gi 1207122012 1122 FDSLEGFVIVMVHCILRREVQEAVK 1146
Cdd:cd15265    260 FNSFQGFFVAIIYCFCNGEVQAEIK 284
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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