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Conserved domains on  [gi|1894698391|ref|XP_035750714|]
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LOW QUALITY PROTEIN: cadherin EGF LAG seven-pass G-type receptor 3, partial [Egretta garzetta]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
 2074-2327 4.17e-153

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: 474.72  E-value: 4.17e-153
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2074 LETLAIVTYSLVSLSLVALLLTFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLS 2153
Cdd:cd15993      1 LETLAIVTYSSVSASLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELLFLLGINRTENQFLCTVVAILLHYFFLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2154 TFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIV 2233
Cdd:cd15993     81 TFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPIVVVIV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2234 MNGVMFLLVAKMSCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVL 2313
Cdd:cd15993    161 MNGVMFLLVARMSCSPGQKETKKTSVLMTLRSSFLLLLLISATWLFGLLAVNNSVLAFHYLHAILCCLQGLAVLLLFCVL 240

                          250
                   ....*....|....
gi 1894698391 2314 NEEVREAWKLACLG 2327
Cdd:cd15993    241 NEEVQEAWKLACLG 254
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
 1743-1988 1.96e-52

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: 184.01  E-value: 1.96e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1743 EAKKLAHRLRAVTDHmDHYFGNDVHITFRLLSRLmafesrqrgFGLTATQDA----HFNENLLRAGSSVLAPENREHWAM 1818
Cdd:pfam16489    1 GAKELARELRNATRH-GPLYGGDVLTAVELLSQL---------FDLLATQDAtlsnAFLENFVQTVSNLLDPENRESWED 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1819 LPHSEHSSA--SLMEQLRDYSGTLASNMKltYLNPVGVVTPNIMLSIDRMENHSHIRRRYPRYHSSLFRgqpaWDPHTHV 1896
Cdd:pfam16489   71 LQQTERGTAatKLLRTLEEYALLLAQNMK--YLTPFTIVTPNIVLSVDRLDTHNFKGARFPRFPMKGER----PKDEDSV 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1897 VLPLSVLSPPkaeaaptavptlaGGEGNytvenssprqalpepepalTVIILIMYRTLGGLLPA--RYQVDRRSVRLPKN 1974
Cdd:pfam16489  145 KLPPKAFKPP-------------DSNGT-------------------VVVVFILYRNLGSLLPPssRYDPDRRSLRLPRR 192

                          250
                   ....*....|....
gi 1894698391 1975 pVMNSPIVSVSVFS 1988
Cdd:pfam16489  193 -VVNSPVVSASVHS 205
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 199-296 1.90e-36

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


:

Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 133.98  E-value: 1.90e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  199 PFQISVLENAPLGHSVIHIQAVDADYGENSRLEYKLTGVSADTPFVVNSATGWITVSGPLDRESVEHYFFGVEARDHGSP 278
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                           90
                   ....*....|....*...
gi 1894698391  279 SLSASASVTITVMDVNDN 296
Cdd:cd11304     81 PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 509-607 3.37e-35

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


:

Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 130.51  E-value: 3.37e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  509 HYQGMISEDAPPFTSVLQISATDRDAHTNGRVQYTFQNGeDGDGDFTIEPTSGIIRTVRRLDRENVPVYELTAYAVDRGI 588
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSG-NEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGG 79

                           90
                   ....*....|....*....
gi 1894698391  589 PPQRTPVHIQVTIQDVNDN 607
Cdd:cd11304     80 PPLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 94-191 2.49e-34

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


:

Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 127.81  E-value: 2.49e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   94 YIVQVREDIRPHTEILRVTATDLDKDNNALVHYNIISGNSRGQFSIDSVTGEIQVVAPLDFEVEREYALRIRAQDAGRPP 173
Cdd:cd11304      2 YEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGPP 81

                           90
                   ....*....|....*...
gi 1894698391  174 LSnNTGMASIQVVDINDH 191
Cdd:cd11304     82 LS-STATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 406-501 2.99e-33

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


:

Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 124.73  E-value: 2.99e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  406 HYSVSINEDRPVGSTVVVISATDDDVGENARITYYLEDNVPQ--FRIDPDSGAITLQAELDYEDQVTYTLAITAKDNGIP 483
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDglFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                           90
                   ....*....|....*...
gi 1894698391  484 QKADTTYVEIMVNDVNDN 501
Cdd:cd11304     81 PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 615-709 1.71e-30

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


:

Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 117.03  E-value: 1.71e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  615 EFEVLVKENSIVGSVVAQITAVDPDEGPNAQIMYQIVEGNIPEIFQMDIFSGELTALIDLDYETKPEYVIVVQAT---SA 691
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATdggGP 80

                           90
                   ....*....|....*...
gi 1894698391  692 PLVSRATVHIKLIDQNDN 709
Cdd:cd11304     81 PLSSTATVTITVLDVNDN 98
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1054-1237 3.93e-30

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.


:

Pssm-ID: 238058 [Multi-domain]  Cd Length: 151  Bit Score: 117.90  E-value: 3.93e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1054 TRSFPPRSFVMFRGLR-QRFHLTLALSFSTVEPSGLLLYNGRLNeRHDFLAVEIIQGQIQLKYSTGESSTVVSPylPGGV 1132
Cdd:cd00110      1 GVSFSGSSYVRLPTLPaPRTRLSISFSFRTTSPNGLLLYAGSQN-GGDFLALELEDGRLVLRYDLGSGSLVLSS--KTPL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1133 SDGQWHTLQLHYYNkpkvsalgvvqgpskdKVAILTVDECDasvalqfgneignyscAAEGVQTSSKKSLDLTGPLLLGG 1212
Cdd:cd00110     78 NDGQWHSVSVERNG----------------RSVTLSVDGER----------------VVESGSPGGSALLNLDGPLYLGG 125

                          170       180
                   ....*....|....*....|....*.
gi 1894698391 1213 VPNLPENFPVTHRD-FVGCMRDLYID 1237
Cdd:cd00110    126 LPEDLKSPGLPVSPgFVGCIRDLKVN 151
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 4-87 6.41e-25

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


:

Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 100.50  E-value: 6.41e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391     4 RATEGDSPPNANIRYRFVNERAAHaVFEIDPRSGLITTSGPVDREKMERYSLVVEANDQGrePGPRSATVKVYITVLDEN 83
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDG-LFSIDPETGEITTTKPLDREEQPEYTLTVEATDGG--GPPLSSTATVTITVLDVN 77


                    ....
gi 1894698391    84 DNTP 87
Cdd:smart00112   78 DNAP 81
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 304-398 2.25e-24

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


:

Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 99.70  E-value: 2.25e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  304 EYFIRLNEDAAVGTSVLSVTAIDRD--VNSAITYQITGGNTRNRFSISTQggMGLITLSLPLDYKQERRYVLTVTASDR- 380
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDsgENGEVTYSIVSGNEDGLFSIDPS--TGEITTAKPLDREEQSSYTLTVTATDGg 78

                           90       100
                   ....*....|....*....|
gi 1894698391  381 --TLRDNCHVHINITDANTH 398
Cdd:cd11304     79 gpPLSSTATVTITVLDVNDN 98
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1303-1456 5.10e-20

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.


:

Pssm-ID: 238058 [Multi-domain]  Cd Length: 151  Bit Score: 89.01  E-value: 5.10e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1303 YFQGNSVLtwDFKTDVKISVPWYLGLAFRTRQPDGVLLQAHAGQYT-TLLCQLAGGLLSFMVSRGSGRSTslLLDQLRLS 1381
Cdd:cd00110      3 SFSGSSYV--RLPTLPAPRTRLSISFSFRTTSPNGLLLYAGSQNGGdFLALELEDGRLVLRYDLGSGSLV--LSSKTPLN 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1382 DGRWHDLQLElrdvRSGRdsryVITLTVDFGLYQDTVVVGNELHGLKVKHLHVGGVLGSGE-----VQNGLRGCIQGVRL 1456
Cdd:cd00110     79 DGQWHSVSVE----RNGR----SVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDLKspglpVSPGFVGCIRDLKV 150
HormR smart00008
Domain present in hormone receptors;
1660-1726 1.58e-16

Domain present in hormone receptors;


:

Pssm-ID: 214468  Cd Length: 70  Bit Score: 76.40  E-value: 1.58e-16
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1894698391  1660 YDGCPKSLKAGVWWPQTKFGFSAAVLCPKGSLGLRGAGAAIRHCDEEKGWLE--PDLFNCTSPAFKELS 1726
Cdd:smart00008    2 DLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFSYKTGASRNCTENGGWSPpfPNYSNCTSNDYEELK 70
EGF_Lam smart00180
Laminin-type epidermal growth factor-like domai;
1611-1656 5.19e-14

Laminin-type epidermal growth factor-like domai;


:

Pssm-ID: 214543  Cd Length: 46  Bit Score: 68.11  E-value: 5.19e-14
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 1894698391  1611 CDCYPVGSTSRSCDKETGRCHCRPGVIGRQCNSCDSPFAEVTPSGC 1656
Cdd:smart00180    1 CDCDPGGSASGTCDPDTGQCECKPNVTGRRCDRCAPGYYGDGPPGC 46
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 2014-2065 5.45e-14

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


:

Pssm-ID: 197639  Cd Length: 49  Bit Score: 68.18  E-value: 5.45e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1894698391  2014 SKPLCVQWNHSnltnpSGFWTARDCELVYRNTTHVHCQCSQFGTFGVLMDSS 2065
Cdd:smart00303    1 FNPICVFWDES-----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVP 47
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 729-810 1.81e-10

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


:

Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 60.02  E-value: 1.81e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  729 NTFPSGVIGKVPAYDPDVSD--RLFYTFERGNELHLLIVNQSSGELRLSRKLDNNRPLVASMLVTVTD-GIHSVTAQCVL 805
Cdd:cd11304      9 NAPPGTVVLTVSATDPDSGEngEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDgGGPPLSSTATV 88


                   ....*
gi 1894698391  806 RVIII 810
Cdd:cd11304     89 TITVL 93
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1263-1293 3.73e-08

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.


:

Pssm-ID: 394967  Cd Length: 31  Bit Score: 51.23  E-value: 3.73e-08
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1894698391 1263 CDSSPCKNGGTCSVSWGTYSCLCPVGFGGKD 1293
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 977-1006 2.80e-07

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.


:

Pssm-ID: 394967  Cd Length: 31  Bit Score: 48.92  E-value: 2.80e-07
                           10        20        30
                   ....*....|....*....|....*....|
gi 1894698391  977 CYSNPCLNGGICTRKEGGYTCVCRQHFSGE 1006
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGK 30
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1484-1516 8.66e-07

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


:

Pssm-ID: 238011  Cd Length: 38  Bit Score: 47.63  E-value: 8.66e-07
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1894698391 1484 CDS-NPCPVNSICKDEWQSYSCVCQPGYYGGDCV 1516
Cdd:cd00054      5 CASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1019-1051 3.48e-06

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


:

Pssm-ID: 238011  Cd Length: 38  Bit Score: 45.71  E-value: 3.48e-06
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1894698391 1019 PGVCRNGGTCTNGaDGGFRCQCPAgGFEMPFCE 1051
Cdd:cd00054      8 GNPCQNGGTCVNT-VGSYRCSCPP-GYTGRNCE 38
 
Name Accession Description Interval E-value
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
 2074-2327 4.17e-153

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: 474.72  E-value: 4.17e-153
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2074 LETLAIVTYSLVSLSLVALLLTFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLS 2153
Cdd:cd15993      1 LETLAIVTYSSVSASLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELLFLLGINRTENQFLCTVVAILLHYFFLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2154 TFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIV 2233
Cdd:cd15993     81 TFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPIVVVIV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2234 MNGVMFLLVAKMSCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVL 2313
Cdd:cd15993    161 MNGVMFLLVARMSCSPGQKETKKTSVLMTLRSSFLLLLLISATWLFGLLAVNNSVLAFHYLHAILCCLQGLAVLLLFCVL 240

                          250
                   ....*....|....
gi 1894698391 2314 NEEVREAWKLACLG 2327
Cdd:cd15993    241 NEEVQEAWKLACLG 254
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 2095-2306 3.34e-59

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: 205.21  E-value: 3.34e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQ--------FLCTVIAILLHCFFLSTFAWLFIQGLHIY 2166
Cdd:pfam00002   22 AIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKqdldhcswVGCKVVAVFLHYFFLANFFWMLVEGLYLY 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2167 RMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMS 2246
Cdd:pfam00002  102 TLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYGEDDGCWLSNENGLWWIIRGPILLIILVNFIIFINIVRIL 181

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1894698391 2247 CS----PGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVN---NSVLAFHYLYTVLCSLQGLAV 2306
Cdd:pfam00002  182 VQklreTNMGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFAFNpenTLRVVFLYLFLILNSFQGFFV 248
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
 1743-1988 1.96e-52

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: 184.01  E-value: 1.96e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1743 EAKKLAHRLRAVTDHmDHYFGNDVHITFRLLSRLmafesrqrgFGLTATQDA----HFNENLLRAGSSVLAPENREHWAM 1818
Cdd:pfam16489    1 GAKELARELRNATRH-GPLYGGDVLTAVELLSQL---------FDLLATQDAtlsnAFLENFVQTVSNLLDPENRESWED 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1819 LPHSEHSSA--SLMEQLRDYSGTLASNMKltYLNPVGVVTPNIMLSIDRMENHSHIRRRYPRYHSSLFRgqpaWDPHTHV 1896
Cdd:pfam16489   71 LQQTERGTAatKLLRTLEEYALLLAQNMK--YLTPFTIVTPNIVLSVDRLDTHNFKGARFPRFPMKGER----PKDEDSV 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1897 VLPLSVLSPPkaeaaptavptlaGGEGNytvenssprqalpepepalTVIILIMYRTLGGLLPA--RYQVDRRSVRLPKN 1974
Cdd:pfam16489  145 KLPPKAFKPP-------------DSNGT-------------------VVVVFILYRNLGSLLPPssRYDPDRRSLRLPRR 192

                          250
                   ....*....|....
gi 1894698391 1975 pVMNSPIVSVSVFS 1988
Cdd:pfam16489  193 -VVNSPVVSASVHS 205
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 199-296 1.90e-36

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 133.98  E-value: 1.90e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  199 PFQISVLENAPLGHSVIHIQAVDADYGENSRLEYKLTGVSADTPFVVNSATGWITVSGPLDRESVEHYFFGVEARDHGSP 278
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                           90
                   ....*....|....*...
gi 1894698391  279 SLSASASVTITVMDVNDN 296
Cdd:cd11304     81 PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 509-607 3.37e-35

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 130.51  E-value: 3.37e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  509 HYQGMISEDAPPFTSVLQISATDRDAHTNGRVQYTFQNGeDGDGDFTIEPTSGIIRTVRRLDRENVPVYELTAYAVDRGI 588
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSG-NEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGG 79

                           90
                   ....*....|....*....
gi 1894698391  589 PPQRTPVHIQVTIQDVNDN 607
Cdd:cd11304     80 PPLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 94-191 2.49e-34

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 127.81  E-value: 2.49e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   94 YIVQVREDIRPHTEILRVTATDLDKDNNALVHYNIISGNSRGQFSIDSVTGEIQVVAPLDFEVEREYALRIRAQDAGRPP 173
Cdd:cd11304      2 YEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGPP 81

                           90
                   ....*....|....*...
gi 1894698391  174 LSnNTGMASIQVVDINDH 191
Cdd:cd11304     82 LS-STATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 406-501 2.99e-33

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 124.73  E-value: 2.99e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  406 HYSVSINEDRPVGSTVVVISATDDDVGENARITYYLEDNVPQ--FRIDPDSGAITLQAELDYEDQVTYTLAITAKDNGIP 483
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDglFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                           90
                   ....*....|....*...
gi 1894698391  484 QKADTTYVEIMVNDVNDN 501
Cdd:cd11304     81 PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 615-709 1.71e-30

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 117.03  E-value: 1.71e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  615 EFEVLVKENSIVGSVVAQITAVDPDEGPNAQIMYQIVEGNIPEIFQMDIFSGELTALIDLDYETKPEYVIVVQAT---SA 691
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATdggGP 80

                           90
                   ....*....|....*...
gi 1894698391  692 PLVSRATVHIKLIDQNDN 709
Cdd:cd11304     81 PLSSTATVTITVLDVNDN 98
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1054-1237 3.93e-30

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.


Pssm-ID: 238058 [Multi-domain]  Cd Length: 151  Bit Score: 117.90  E-value: 3.93e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1054 TRSFPPRSFVMFRGLR-QRFHLTLALSFSTVEPSGLLLYNGRLNeRHDFLAVEIIQGQIQLKYSTGESSTVVSPylPGGV 1132
Cdd:cd00110      1 GVSFSGSSYVRLPTLPaPRTRLSISFSFRTTSPNGLLLYAGSQN-GGDFLALELEDGRLVLRYDLGSGSLVLSS--KTPL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1133 SDGQWHTLQLHYYNkpkvsalgvvqgpskdKVAILTVDECDasvalqfgneignyscAAEGVQTSSKKSLDLTGPLLLGG 1212
Cdd:cd00110     78 NDGQWHSVSVERNG----------------RSVTLSVDGER----------------VVESGSPGGSALLNLDGPLYLGG 125

                          170       180
                   ....*....|....*....|....*.
gi 1894698391 1213 VPNLPENFPVTHRD-FVGCMRDLYID 1237
Cdd:cd00110    126 LPEDLKSPGLPVSPgFVGCIRDLKVN 151
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 218-298 2.99e-28

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 110.13  E-value: 2.99e-28
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   218 QAVDADYGENSRLEYKLTGVSADTPFVVNSATGWITVSGPLDRESVEHYFFGVEARDHGSPSLSASASVTITVMDVNDNR 297
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDNA 80


                    .
gi 1894698391   298 P 298
Cdd:smart00112   81 P 81
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 528-609 4.64e-27

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 106.66  E-value: 4.64e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   528 SATDRDAHTNGRVQYTFqNGEDGDGDFTIEPTSGIIRTVRRLDRENVPVYELTAYAVDRGIPPQRTPVHIQVTIQDVNDN 607
Cdd:smart00112    1 SATDADSGENGKVTYSI-LSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDN 79


                    ..
gi 1894698391   608 AP 609
Cdd:smart00112   80 AP 81
Cadherin pfam00028
Cadherin domain;
94-185 2.53e-26

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 104.69  E-value: 2.53e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   94 YIVQVREDIRPHTEILRVTATDLDKDNNALVHYNIISGNSRGQFSIDSVTGEIQVVAPLDFEVEREYALRIRAQDAGRPP 173
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|..
gi 1894698391  174 LSnNTGMASIQV 185
Cdd:pfam00028   81 LS-STATVTITV 91
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 112-193 3.18e-26

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 104.35  E-value: 3.18e-26
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   112 TATDLDKDNNALVHYNIISGNSRGQFSIDSVTGEIQVVAPLDFEVEREYALRIRAQDAGRPPLSnNTGMASIQVVDINDH 191
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLS-STATVTITVLDVNDN 79


                    ..
gi 1894698391   192 AP 193
Cdd:smart00112   80 AP 81
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 425-503 4.42e-26

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 103.97  E-value: 4.42e-26
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   425 SATDDDVGENARITYYLEDNVPQ--FRIDPDSGAITLQAELDYEDQVTYTLAITAKDNGIPQKADTTYVEIMVNDVNDNA 502
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDglFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDNA 80


                    .
gi 1894698391   503 P 503
Cdd:smart00112   81 P 81
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 4-87 6.41e-25

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 100.50  E-value: 6.41e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391     4 RATEGDSPPNANIRYRFVNERAAHaVFEIDPRSGLITTSGPVDREKMERYSLVVEANDQGrePGPRSATVKVYITVLDEN 83
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDG-LFSIDPETGEITTTKPLDREEQPEYTLTVEATDGG--GPPLSSTATVTITVLDVN 77


                    ....
gi 1894698391    84 DNTP 87
Cdd:smart00112   78 DNAP 81
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 4-85 1.44e-24

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 100.08  E-value: 1.44e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391    4 RATEGDSPPNANIRYRFVNERAAHaVFEIDPRSGLITTSGPVDREKMERYSLVVEANDQGrePGPRSATVKVYITVLDEN 83
Cdd:cd11304     20 SATDPDSGENGEVTYSIVSGNEDG-LFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGG--GPPLSSTATVTITVLDVN 96


                   ..
gi 1894698391   84 DN 85
Cdd:cd11304     97 DN 98
Cadherin pfam00028
Cadherin domain;
200-290 1.53e-24

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 99.68  E-value: 1.53e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  200 FQISVLENAPLGHSVIHIQAVDADYGENSRLEYKLTGVSADTPFVVNSATGWITVSGPLDRESVEHYFFGVEARDHGSPS 279
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|.
gi 1894698391  280 LSASASVTITV 290
Cdd:pfam00028   81 LSSTATVTITV 91
Cadherin pfam00028
Cadherin domain;
510-602 1.82e-24

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 99.68  E-value: 1.82e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  510 YQGMISEDAPPFTSVLQISATDRDAHTNGRVQYTFQNGEDGdGDFTIEPTSGIIRTVRRLDRENVPVYELTAYAVDRGIP 589
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPG-GNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGP 79

                           90
                   ....*....|...
gi 1894698391  590 PQRTPVHIQVTIQ 602
Cdd:pfam00028   80 PLSSTATVTITVL 92
LamG smart00282
Laminin G domain;
1075-1239 2.05e-24

Laminin G domain;


Pssm-ID: 214598 [Multi-domain]  Cd Length: 132  Bit Score: 100.88  E-value: 2.05e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  1075 TLALSFSTVEPSGLLLYNGRLNeRHDFLAVEIIQGQIQLKYSTGESSTVVSpYLPGGVSDGQWHTLQLHYYNkpkvsalg 1154
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKG-GGDYLALELRDGRLVLRYDLGSGPARLT-SDPTPLNDGQWHRVAVERNG-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  1155 vvqgpskdKVAILTVDECDasvalqfgneignyscAAEGVQTSSKKSLDLTGPLLLGGVPNLPENFPVTHRD-FVGCMRD 1233
Cdd:smart00282   71 --------RSVTLSVDGGN----------------RVSGESPGGLTILNLDGPLYLGGLPEDLKLPPLPVTPgFRGCIRN 126


                    ....*.
gi 1894698391  1234 LYIDSK 1239
Cdd:smart00282  127 LKVNGK 132
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 304-398 2.25e-24

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 99.70  E-value: 2.25e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  304 EYFIRLNEDAAVGTSVLSVTAIDRD--VNSAITYQITGGNTRNRFSISTQggMGLITLSLPLDYKQERRYVLTVTASDR- 380
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDsgENGEVTYSIVSGNEDGLFSIDPS--TGEITTAKPLDREEQSSYTLTVTATDGg 78

                           90       100
                   ....*....|....*....|
gi 1894698391  381 --TLRDNCHVHINITDANTH 398
Cdd:cd11304     79 gpPLSSTATVTITVLDVNDN 98
Laminin_G_2 pfam02210
Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G ...
 1080-1239 7.44e-24

Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G subfamily.


Pssm-ID: 460494 [Multi-domain]  Cd Length: 126  Bit Score: 99.03  E-value: 7.44e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1080 FSTVEPSGLLLYNGrlNERHDFLAVEIIQGQIQLKYSTGESSTVVSpYLPGGVSDGQWHTLQLHYynkpkvsalgvvqgp 1159
Cdd:pfam02210    1 FRTRQPNGLLLYAG--GGGSDFLALELVNGRLVLRYDLGSGPESLL-SSGKNLNDGQWHSVRVER--------------- 62

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1160 sKDKVAILTVDECDASVALQFGNEIGnyscaaegvqtsskksLDLTGPLLLGGVPN-LPENFPVTHRDFVGCMRDLYIDS 1238
Cdd:pfam02210   63 -NGNTLTLSVDGQTVVSSLPPGESLL----------------LNLNGPLYLGGLPPlLLLPALPVRAGFVGCIRDVRVNG 125


                   .
gi 1894698391 1239 K 1239
Cdd:pfam02210  126 E 126
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 634-711 2.93e-23

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 95.88  E-value: 2.93e-23
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   634 TAVDPDEGPNAQIMYQIVEGNIPEIFQMDIFSGELTALIDLDYETKPEYVIVVQAT---SAPLVSRATVHIKLIDQNDNS 710
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATdggGPPLSSTATVTITVLDVNDNA 80


                    .
gi 1894698391   711 P 711
Cdd:smart00112   81 P 81
Cadherin pfam00028
Cadherin domain;
407-495 2.05e-22

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 93.90  E-value: 2.05e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  407 YSVSINEDRPVGSTVVVISATDDDVGENARITYY-LEDNVPQ-FRIDPDSGAITLQAELDYEDQVTYTLAITAKDNGIPQ 484
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSiLGGGPGGnFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|.
gi 1894698391  485 KADTTYVEIMV 495
Cdd:pfam00028   81 LSSTATVTITV 91
Cadherin pfam00028
Cadherin domain;
616-704 3.42e-21

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 90.44  E-value: 3.42e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  616 FEVLVKENSIVGSVVAQITAVDPDEGPNAQIMYQIVEGNIPEIFQMDIFSGELTALIDLDYETKPEYVIVVQATSA---P 692
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSggpP 80

                           90
                   ....*....|..
gi 1894698391  693 LVSRATVHIKLI 704
Cdd:pfam00028   81 LSSTATVTITVL 92
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1303-1456 5.10e-20

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.


Pssm-ID: 238058 [Multi-domain]  Cd Length: 151  Bit Score: 89.01  E-value: 5.10e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1303 YFQGNSVLtwDFKTDVKISVPWYLGLAFRTRQPDGVLLQAHAGQYT-TLLCQLAGGLLSFMVSRGSGRSTslLLDQLRLS 1381
Cdd:cd00110      3 SFSGSSYV--RLPTLPAPRTRLSISFSFRTTSPNGLLLYAGSQNGGdFLALELEDGRLVLRYDLGSGSLV--LSSKTPLN 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1382 DGRWHDLQLElrdvRSGRdsryVITLTVDFGLYQDTVVVGNELHGLKVKHLHVGGVLGSGE-----VQNGLRGCIQGVRL 1456
Cdd:cd00110     79 DGQWHSVSVE----RNGR----SVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDLKspglpVSPGFVGCIRDLKV 150
Laminin_G_2 pfam02210
Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G ...
 1330-1458 6.72e-20

Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G subfamily.


Pssm-ID: 460494 [Multi-domain]  Cd Length: 126  Bit Score: 87.86  E-value: 6.72e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1330 FRTRQPDGVLLQAHAGQYTTLLCQLAGGLLSFMVSRGSGRSTSLLLDQlRLSDGRWHDLQLElrdvRSGRDsryvITLTV 1409
Cdd:pfam02210    1 FRTRQPNGLLLYAGGGGSDFLALELVNGRLVLRYDLGSGPESLLSSGK-NLNDGQWHSVRVE----RNGNT----LTLSV 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1894698391 1410 DFGLYQDTVVVGNELHGLKVKHLHVGGVLGSG-----EVQNGLRGCIQGVRLGD 1458
Cdd:pfam02210   72 DGQTVVSSLPPGESLLLNLNGPLYLGGLPPLLllpalPVRAGFVGCIRDVRVNG 125
Cadherin pfam00028
Cadherin domain;
305-393 6.82e-18

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 80.81  E-value: 6.82e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  305 YFIRLNEDAAVGTSVLSVTAIDRD--VNSAITYQITGGNTRNRFSISTQGgmGLITLSLPLDYKQERRYVLTVTASDR-- 380
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDlgPNGRIFYSILGGGPGGNFRIDPDT--GDISTTKPLDRESIGEYELTVEATDSgg 78

                           90
                   ....*....|....
gi 1894698391  381 -TLRDNCHVHINIT 393
Cdd:pfam00028   79 pPLSSTATVTITVL 92
LamG smart00282
Laminin G domain;
1325-1456 8.36e-18

Laminin G domain;


Pssm-ID: 214598 [Multi-domain]  Cd Length: 132  Bit Score: 82.00  E-value: 8.36e-18
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  1325 YLGLAFRTRQPDGVLLQAHAGQYT-TLLCQLAGGLLSFMVSRGSGRsTSLLLDQLRLSDGRWHDLQLElrdvRSGRdsry 1403
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGdYLALELRDGRLVLRYDLGSGP-ARLTSDPTPLNDGQWHRVAVE----RNGR---- 71

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 1894698391  1404 VITLTVDFGLYQDTVVVGNELhGLKVK-HLHVGGVLGSGE-----VQNGLRGCIQGVRL 1456
Cdd:smart00282   72 SVTLSVDGGNRVSGESPGGLT-ILNLDgPLYLGGLPEDLKlpplpVTPGFRGCIRNLKV 129
HormR smart00008
Domain present in hormone receptors;
1660-1726 1.58e-16

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 76.40  E-value: 1.58e-16
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1894698391  1660 YDGCPKSLKAGVWWPQTKFGFSAAVLCPKGSLGLRGAGAAIRHCDEEKGWLE--PDLFNCTSPAFKELS 1726
Cdd:smart00008    2 DLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFSYKTGASRNCTENGGWSPpfPNYSNCTSNDYEELK 70
Cadherin pfam00028
Cadherin domain;
4-80 1.64e-16

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 76.96  E-value: 1.64e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1894698391    4 RATEGDSPPNANIRYRFVNERAAHaVFEIDPRSGLITTSGPVDREKMERYSLVVEANDQGrePGPRSATVKVYITVL 80
Cdd:pfam00028   19 TATDPDLGPNGRIFYSILGGGPGG-NFRIDPDTGDISTTKPLDRESIGEYELTVEATDSG--GPPLSSTATVTITVL 92
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 323-400 1.81e-16

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 76.23  E-value: 1.81e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   323 TAIDRD--VNSAITYQITGGNTRNRFSISTQGGMglITLSLPLDYKQERRYVLTVTASDR---TLRDNCHVHINITDANT 397
Cdd:smart00112    1 SATDADsgENGKVTYSILSGNDDGLFSIDPETGE--ITTTKPLDREEQPEYTLTVEATDGggpPLSSTATVTITVLDVND 78


                    ...
gi 1894698391   398 HRP 400
Cdd:smart00112   79 NAP 81
EGF_Lam smart00180
Laminin-type epidermal growth factor-like domai;
1611-1656 5.19e-14

Laminin-type epidermal growth factor-like domai;


Pssm-ID: 214543  Cd Length: 46  Bit Score: 68.11  E-value: 5.19e-14
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 1894698391  1611 CDCYPVGSTSRSCDKETGRCHCRPGVIGRQCNSCDSPFAEVTPSGC 1656
Cdd:smart00180    1 CDCDPGGSASGTCDPDTGQCECKPNVTGRRCDRCAPGYYGDGPPGC 46
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 2014-2065 5.45e-14

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


Pssm-ID: 197639  Cd Length: 49  Bit Score: 68.18  E-value: 5.45e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1894698391  2014 SKPLCVQWNHSnltnpSGFWTARDCELVYRNTTHVHCQCSQFGTFGVLMDSS 2065
Cdd:smart00303    1 FNPICVFWDES-----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVP 47
EGF_Lam cd00055
Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous ...
 1610-1648 4.28e-13

Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in tandem arrays; the domain contains 4 disulfide bonds (loops a-d) the first three resemble epidermal growth factor (EGF); the number of copies of this domain in the different forms of laminins is highly variable ranging from 3 up to 22 copies


Pssm-ID: 238012  Cd Length: 50  Bit Score: 65.84  E-value: 4.28e-13
                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1894698391 1610 PCDCYPVGSTSRSCDKETGRCHCRPGVIGRQCNSCDSPF 1648
Cdd:cd00055      1 PCDCNGHGSLSGQCDPGTGQCECKPNTTGRRCDRCAPGY 39
Laminin_EGF pfam00053
Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.
 1611-1644 1.90e-12

Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.


Pssm-ID: 395007  Cd Length: 49  Bit Score: 63.91  E-value: 1.90e-12
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1894698391 1611 CDCYPVGSTSRSCDKETGRCHCRPGVIGRQCNSC 1644
Cdd:pfam00053    1 CDCNPHGSLSDTCDPETGQCLCKPGVTGRHCDRC 34
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 729-810 1.81e-10

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 60.02  E-value: 1.81e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  729 NTFPSGVIGKVPAYDPDVSD--RLFYTFERGNELHLLIVNQSSGELRLSRKLDNNRPLVASMLVTVTD-GIHSVTAQCVL 805
Cdd:cd11304      9 NAPPGTVVLTVSATDPDSGEngEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDgGGPPLSSTATV 88


                   ....*
gi 1894698391  806 RVIII 810
Cdd:cd11304     89 TITVL 93
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 1660-1720 5.50e-10

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: 57.38  E-value: 5.50e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1894698391 1660 YDGCPKSLKAGVWWPQTKFGFSAAVLCPKGSLGLRGAGAAIRHCDEEKGWLEP---DLFNCTSP 1720
Cdd:pfam02793    1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDPRGNASRNCTEDGTWSEHppsNYSNCTSN 64
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 2016-2061 1.40e-08

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: 52.69  E-value: 1.40e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1894698391 2016 PLCVQWNHSNltNPSGFWTARDCELVYRNTTHVHCQCSQFGTFGVL 2061
Cdd:pfam01825    1 PQCVFWDFTN--STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1263-1293 3.73e-08

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.


Pssm-ID: 394967  Cd Length: 31  Bit Score: 51.23  E-value: 3.73e-08
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1894698391 1263 CDSSPCKNGGTCSVSWGTYSCLCPVGFGGKD 1293
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 977-1006 2.80e-07

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.


Pssm-ID: 394967  Cd Length: 31  Bit Score: 48.92  E-value: 2.80e-07
                           10        20        30
                   ....*....|....*....|....*....|
gi 1894698391  977 CYSNPCLNGGICTRKEGGYTCVCRQHFSGE 1006
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGK 30
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1263-1294 3.25e-07

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 48.79  E-value: 3.25e-07
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1894698391 1263 CDS-SPCKNGGTCSVSWGTYSCLCPVGFGGKDC 1294
Cdd:cd00054      5 CASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1484-1516 8.66e-07

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 47.63  E-value: 8.66e-07
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1894698391 1484 CDS-NPCPVNSICKDEWQSYSCVCQPGYYGGDCV 1516
Cdd:cd00054      5 CASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1019-1051 3.48e-06

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 45.71  E-value: 3.48e-06
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1894698391 1019 PGVCRNGGTCTNGaDGGFRCQCPAgGFEMPFCE 1051
Cdd:cd00054      8 GNPCQNGGTCVNT-VGSYRCSCPP-GYTGRNCE 38
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 974-1005 5.47e-06

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 45.32  E-value: 5.47e-06
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1894698391  974 INLCYS-NPCLNGGICTRKEGGYTCVCRQHFSG 1005
Cdd:cd00054      2 IDECASgNPCQNGGTCVNTVGSYRCSCPPGYTG 34
EGF_CA smart00179
Calcium-binding EGF-like domain;
1019-1051 1.56e-05

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 44.16  E-value: 1.56e-05
                            10        20        30
                    ....*....|....*....|....*....|...
gi 1894698391  1019 PGVCRNGGTCTNGaDGGFRCQCPAGGFEMPFCE 1051
Cdd:smart00179    8 GNPCQNGGTCVNT-VGSYRCECPPGYTDGRNCE 39
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1484-1512 1.53e-04

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.


Pssm-ID: 394967  Cd Length: 31  Bit Score: 41.21  E-value: 1.53e-04
                           10        20
                   ....*....|....*....|....*....
gi 1894698391 1484 CDSNPCPVNSICKDEWQSYSCVCQPGYYG 1512
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTG 29
EGF_CA smart00179
Calcium-binding EGF-like domain;
1263-1294 1.80e-04

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 41.08  E-value: 1.80e-04
                            10        20        30
                    ....*....|....*....|....*....|....
gi 1894698391  1263 CDS-SPCKNGGTCSVSWGTYSCLCPVGF-GGKDC 1294
Cdd:smart00179    5 CASgNPCQNGGTCVNTVGSYRCECPPGYtDGRNC 38
EGF_CA smart00179
Calcium-binding EGF-like domain;
973-1000 2.82e-04

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 40.31  E-value: 2.82e-04
                            10        20
                    ....*....|....*....|....*....
gi 1894698391   973 EINLCYS-NPCLNGGICTRKEGGYTCVCR 1000
Cdd:smart00179    1 DIDECASgNPCQNGGTCVNTVGSYRCECP 29
hEGF pfam12661
Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six ...
 1022-1043 4.38e-04

Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six conserved residues disulfide-bonded into the characteriztic 'ababcc' pattern. They are involved in growth and proliferation of cells, in proteins of the Notch/Delta pathway, neurogulin and selectins. hEGFs are also found in mosaic proteins with four-disulfide laminin EGFs such as aggrecan and perlecan. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal Cys residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In hEGFs the C-terminal thiol resides in the beta-turn, resulting in shorter loop-lengths between the Cys residues of disulfide 'c', typically C[8-9]XC. These shorter loop-lengths are also typical of the four-disulfide EGF domains, laminin ad integrin. Tandem hEGF domains have six linking residues between terminal cysteines of adjacent domains. hEGF domains may or may not bind calcium in the linker region. hEGF domains with the consensus motif CXD4X[F,Y]XCXC are hydroxylated exclusively in the Asp residue.


Pssm-ID: 463660  Cd Length: 22  Bit Score: 39.62  E-value: 4.38e-04
                           10        20
                   ....*....|....*....|..
gi 1894698391 1022 CRNGGTCTNGaDGGFRCQCPAG 1043
Cdd:pfam12661    1 CQNGGTCVDG-VNGYKCQCPPG 21
EGF_CA smart00179
Calcium-binding EGF-like domain;
1484-1516 1.12e-03

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 38.77  E-value: 1.12e-03
                            10        20        30
                    ....*....|....*....|....*....|....*
gi 1894698391  1484 CDS-NPCPVNSICKDEWQSYSCVCQPGYY-GGDCV 1516
Cdd:smart00179    5 CASgNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39
 
Name Accession Description Interval E-value
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
 2074-2327 4.17e-153

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: 474.72  E-value: 4.17e-153
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2074 LETLAIVTYSLVSLSLVALLLTFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLS 2153
Cdd:cd15993      1 LETLAIVTYSSVSASLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELLFLLGINRTENQFLCTVVAILLHYFFLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2154 TFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIV 2233
Cdd:cd15993     81 TFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPIVVVIV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2234 MNGVMFLLVAKMSCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVL 2313
Cdd:cd15993    161 MNGVMFLLVARMSCSPGQKETKKTSVLMTLRSSFLLLLLISATWLFGLLAVNNSVLAFHYLHAILCCLQGLAVLLLFCVL 240

                          250
                   ....*....|....
gi 1894698391 2314 NEEVREAWKLACLG 2327
Cdd:cd15993    241 NEEVQEAWKLACLG 254
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
 2076-2327 2.94e-109

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: 348.86  E-value: 2.94e-109
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2076 TLAIVTYSLVSLSLVALLLTFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTF 2155
Cdd:cd15441      3 LLKIVTYIGIGISLVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLLAELLFLLGINQTENLFPCKLIAILLHYFYLSAF 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2156 AWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMN 2235
Cdd:cd15441     83 SWLLVESLHLYRMLTEPRDINHGHMRFYYLLGYGIPAIIVGLSVGLRPDGYGNPDFCWLSVNETLIWSFAGPIAFVIVIT 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2236 GVMFLLVAKMSCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNE 2315
Cdd:cd15441    163 LIIFILALRASCTLKRHVLEKASVRTDLRSSFLLLPLLGATWVFGLLAVNEDSELLHYLFAGLNFLQGLFIFLFYCIFNK 242

                          250
                   ....*....|..
gi 1894698391 2316 EVREAWKLACLG 2327
Cdd:cd15441    243 KVRRELKNALLR 254
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
 2077-2322 4.83e-99

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: 319.87  E-value: 4.83e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2077 LAIVTYSLVSLSLVALLLTFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFA 2156
Cdd:cd15991      4 LKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIGINQTENPFVCTVVAILLHYFYMSTFA 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2157 WLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNG 2236
Cdd:cd15991     84 WMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWGIPAIITGLAVGLDPQGYGNPDFCWLSVQDTLIWSFAGPIGIVVIINT 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2237 VMFLLVAKMSCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEE 2316
Cdd:cd15991    164 VIFVLAAKASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLGLMAVNSDTLSFHYLFAIFSCLQGIFIFFFHCIFNKE 243


                   ....*.
gi 1894698391 2317 VREAWK 2322
Cdd:cd15991    244 VRKHLK 249
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
 2077-2325 1.01e-88

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: 290.18  E-value: 1.01e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2077 LAIVTYSLVSLSLVALLLTFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFA 2156
Cdd:cd15992      4 LKTLTWSSVGVTLGFLLLTFLFLLCLRALRSNKTSIRKNGATALFLSELVFILGINQADNPFACTVIAILLHFFYLCTFS 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2157 WLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNG 2236
Cdd:cd15992     84 WLFLEGLHIYRMLSEVRDINYGPMRFYYLIGWGVPAFITGLAVGLDPEGYGNPDFCWLSIYDTLIWSFAGPVAFAVSMNV 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2237 VMFLLVAKMSCSPGQKETKKKSVLMT-LRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNE 2315
Cdd:cd15992    164 FLYILSSRASCSAQQQSFEKKKGPVSgLRTAFTVLLLVSVTCLLALLSVNSDVILFHYLFAGFNCLQGPFIFLSHVVLLK 243

                          250
                   ....*....|
gi 1894698391 2316 EVREAWKLAC 2325
Cdd:cd15992    244 EVRKALKTLC 253
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
 2095-2321 4.11e-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: 216.67  E-value: 4.11e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLTCLKGLKSNTrsIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTE-AR 2173
Cdd:cd15040     25 TYILFRKLRKRKPTK--ILLNLCLALLLANLLFLFGINSTDNPVLCTAVAALLHYFLLASFMWMLVEALLLYLRLVKvFG 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2174 NVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGN-PDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMSCSPGQK 2252
Cdd:cd15040    103 TYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNsSGYCWLSNGNGLYYAFLGPVLLIILVNLVIFVLVLRKLLRLSAK 182

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1894698391 2253 ETK--KKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAW 2321
Cdd:cd15040    183 RNKkkRKKTKAQLRAAVSLFFLLGLTWIFGILAIFGARVVFQYLFAIFNSLQGFFIFIFHCLRNKEVRKAW 253
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
 2095-2322 6.37e-63

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: 216.36  E-value: 6.37e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARN 2174
Cdd:cd15440     22 AFITFTCFRNLQCDRNTIHKNLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFLAAFSWMLLEGFQLYVMLVEVFE 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2175 VNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNgVMFLLVA-KMSC-----S 2248
Cdd:cd15440    102 PEKSRIKWYYLFGYGLPALIVAVSAGVDPTGYGTEDHCWLSTENGFIWSFVGPVIVVLLAN-LVFLGMAiYVMCrhssrS 180

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1894698391 2249 PGQKE-TKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15440    181 ASKKDaSKLKNIRGWLKGSIVLVVLLGLTWTFGLLFINQESIVMAYIFTILNSLQGLFIFIFHCVLNEKVRKELR 255
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
 2077-2321 1.31e-61

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: 212.19  E-value: 1.31e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2077 LAIVTYSLVSLSLVALLLTFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFA 2156
Cdd:cd15933      4 LSIISYIGCGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQILLLAGEWAEGNKVACKVVAILLHFFFMAAFS 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2157 WLFIQGLHIYRMQTEARNVNFGaMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNG 2236
Cdd:cd15933     84 WMLVEGLHLYLMIVKVFNYKSK-MRYYYFIGWGLPAIIVAISLAILFDDYGSPNVCWLSLDDGLIWAFVGPVIFIITVNT 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2237 VMFLLVAKMSCS----PGQKETKKKSVL-MTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFC 2311
Cdd:cd15933    163 VILILVVKITVSlstnDAKKSQGTLAQIkSTAKASVVLLPILGLTWLFGVLVVNSQTIVFQYIFVILNSLQGLMIFLFHC 242

                          250
                   ....*....|
gi 1894698391 2312 VLNEEVREAW 2321
Cdd:cd15933    243 VLNSEVRSAF 252
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 2095-2306 3.34e-59

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: 205.21  E-value: 3.34e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQ--------FLCTVIAILLHCFFLSTFAWLFIQGLHIY 2166
Cdd:pfam00002   22 AIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKqdldhcswVGCKVVAVFLHYFFLANFFWMLVEGLYLY 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2167 RMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMS 2246
Cdd:pfam00002  102 TLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYGEDDGCWLSNENGLWWIIRGPILLIILVNFIIFINIVRIL 181

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1894698391 2247 CS----PGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVN---NSVLAFHYLYTVLCSLQGLAV 2306
Cdd:pfam00002  182 VQklreTNMGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFAFNpenTLRVVFLYLFLILNSFQGFFV 248
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
 1743-1988 1.96e-52

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: 184.01  E-value: 1.96e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1743 EAKKLAHRLRAVTDHmDHYFGNDVHITFRLLSRLmafesrqrgFGLTATQDA----HFNENLLRAGSSVLAPENREHWAM 1818
Cdd:pfam16489    1 GAKELARELRNATRH-GPLYGGDVLTAVELLSQL---------FDLLATQDAtlsnAFLENFVQTVSNLLDPENRESWED 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1819 LPHSEHSSA--SLMEQLRDYSGTLASNMKltYLNPVGVVTPNIMLSIDRMENHSHIRRRYPRYHSSLFRgqpaWDPHTHV 1896
Cdd:pfam16489   71 LQQTERGTAatKLLRTLEEYALLLAQNMK--YLTPFTIVTPNIVLSVDRLDTHNFKGARFPRFPMKGER----PKDEDSV 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1897 VLPLSVLSPPkaeaaptavptlaGGEGNytvenssprqalpepepalTVIILIMYRTLGGLLPA--RYQVDRRSVRLPKN 1974
Cdd:pfam16489  145 KLPPKAFKPP-------------DSNGT-------------------VVVVFILYRNLGSLLPPssRYDPDRRSLRLPRR 192

                          250
                   ....*....|....
gi 1894698391 1975 pVMNSPIVSVSVFS 1988
Cdd:pfam16489  193 -VVNSPVVSASVHS 205
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
 2095-2321 2.42e-50

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: 180.10  E-value: 2.42e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQ--FLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEA 2172
Cdd:cd13952     22 TIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIGQLLTSSDrpVLCKALAILLHYFLLASFFWMLVEAFDLYRTFVKV 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2173 RNVNFGA-MRFYYAIGWGVPAIITGLAVGLDPEGYGNP-----DFCWISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMS 2246
Cdd:cd13952    102 FGSSERRrFLKYSLYGWGLPLLIVIITAIVDFSLYGPSpgyggEYCWLSNGNALLWAFYGPVLLILLVNLVFFILTVRIL 181

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1894698391 2247 CSPGQ---KETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSV-LAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAW 2321
Cdd:cd13952    182 LRKLRetpKQSERKSDRKQLRAYLKLFPLMGLTWIFGILAPFVGGsLVFWYLFDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
 2095-2321 2.73e-48

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: 174.23  E-value: 2.73e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLtclKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARN 2174
Cdd:cd15252     25 TFWFF---RGLQSDRTTIHKNLCISLFLAELVFLIGINTTTNKIFCSVIAGLLHYFFLAAFAWMFIEGIQLYLMLVEVFE 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2175 VNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMSCSPGQKET 2254
Cdd:cd15252    102 NEGSRHKNFYIFGYGSPAVIVGVSAALGYRYYGTTKVCWLSTENYFIWSFIGPATLIILLNLIFLGVAIYKMFRHTAGLK 181

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1894698391 2255 KKKSVLMTLRS----SFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAW 2321
Cdd:cd15252    182 PEVSCLENIRSwargAIALLFLLGLTWIFGVLHINHASVVMAYLFTVSNSLQGMFIFLFHCVLSRKVRKEY 252
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
 2096-2322 3.98e-47

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: 170.99  E-value: 3.98e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2096 FSFLTClKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMqteARNV 2175
Cdd:cd15439     24 LTFLLC-RSIRNTSTSLHLQLSLCLFLADLLFLVGIDRTDNKVLCSIIAGFLHYLFLACFAWMFLEAVHLFLT---VRNL 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2176 N----FGA----MRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLV----- 2242
Cdd:cd15439    100 KvvnyFSShrfkKRFMYPVGYGLPAVIVAISAAVNPQGYGTPKHCWLSMEKGFIWSFLGPVCVIIVINLVLFCLTlwilr 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2243 AKMSCSPGQKETKKKSVLMTLRsSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15439    180 EKLSSLNAEVSTLKNTRLLTFK-AIAQLFILGCTWILGLFQVGPVATVMAYLFTITNSLQGVFIFLVHCLLNRQVREEYR 258
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 2095-2326 3.88e-46

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: 168.02  E-value: 3.88e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLTCLKGLKSntrSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARN 2174
Cdd:cd15438     25 TFLFCRSIRGTRN---TIHLHLCLSLFLAHLIFLLGINNTNNQVACAVVAGLLHYFFLAAFCWMSLEGVELYLMVVQVFN 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2175 VNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGVMFL-----LVAKMS-CS 2248
Cdd:cd15438    102 TQSLKKRYLLLIGYGVPLVIVAISAAVNSKGYGTQRHCWLSLERGFLWSFLGPVCLIILVNAIIFVitvwkLAEKFSsIN 181

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1894698391 2249 PGQKETKKKSVLMTlrSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAW-KLACL 2326
Cdd:cd15438    182 PDMEKLRKIRALTI--TAIAQLCILGCTWIFGFFQFSDSTLVMSYLFTILNSLQGLFIFLLHCLLSKQVREEYsRWLCA 258
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
 2095-2322 4.94e-43

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: 158.93  E-value: 4.94e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARN 2174
Cdd:cd15256     25 TFAVLSSVSTIRNQRYHIHANLSFAVLVAQILLLISFRFEPGTLPCKIMAILLHFFFLSAFAWMLVEGLHLYSMVIKVFG 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2175 VNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMN-GVMFL---LVAKMSCSPG 2250
Cdd:cd15256    105 SEESKHFYYYGIGWGSPLLICIISLTSALDSYGESDNCWLSLENGAIWAFVAPALFVIVVNiGILIAvtrVISRISADNY 184

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1894698391 2251 QKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15256    185 KVHGDANAFKLTAKAVAVLLPILGSSWVFGVLAVNTHALVFQYMFAIFNSLQGFFIFLFHCLLNSEVRAAFK 256
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
 2095-2326 1.26e-42

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: 157.78  E-value: 1.26e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLtclKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARN 2174
Cdd:cd16007     25 TFCFL---RGLQTDRNTIHKNLCINLFLAELLFLIGIDKTQYQIACPIFAGLLHFFFLAAFSWLCLEGVQLYLMLVEVFE 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2175 VNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNgVMFLLVA--KMSCSPGQK 2252
Cdd:cd16007    102 SEYSRKKYYYLCGYCFPALVVGISAAIDYRSYGTEKACWLRVDNYFIWSFIGPVSFVIVVN-LVFLMVTlhKMIRSSSVL 180

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1894698391 2253 EtKKKSVLMTLRS----SFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWKlACL 2326
Cdd:cd16007    181 K-PDSSRLDNIKSwalgAITLLFLLGLTWAFGLLFINKESVVMAYLFTTFNAFQGMFIFIFHCALQKKVHKEYS-KCL 256
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
 2095-2321 8.24e-42

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: 155.46  E-value: 8.24e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLtclKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARN 2174
Cdd:cd16006     25 TFCFF---RGLQSDRNTIHKNLCINLFIAEFIFLIGIDKTEYKIACPIFAGLLHFFFLAAFAWMCLEGVQLYLMLVEVFE 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2175 VNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGVMFLL----VAKMSCSPG 2250
Cdd:cd16006    102 SEYSRKKYYYVAGYLFPATVVGVSAAIDYKSYGTEKACWLRVDNYFIWSFIGPVTFIILLNLIFLVItlckMVKHSNTLK 181

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1894698391 2251 QKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAW 2321
Cdd:cd16006    182 PDSSRLENIKSWVLGAFALLCLLGLTWSFGLLFINEETIVMAYLFTIFNAFQGMFIFIFHCALQKKVRKEY 252
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 2099-2321 1.94e-41

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: 154.57  E-value: 1.94e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2099 LTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFG 2178
Cdd:cd15436     26 FCFFRGLQTDRNTIHKNLCINLFIAELLFLIGINRTQYTIACPIFAGLLHFFFLAAFCWLCLEGVQLYLLLVEVFESEYS 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2179 AMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNgVMFLLVA--KMSCSPGQKEtKK 2256
Cdd:cd15436    106 RRKYFYLCGYSFPALVVAVSAAIDYRSYGTEKACWLRVDNYFIWSFIGPVTFVITLN-LVFLVITlhKMVSHSDLLK-PD 183

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1894698391 2257 KSVLMTLRS----SFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAW 2321
Cdd:cd15436    184 SSRLDNIKSwalgAIALLFLLGLTWSFGLMFINEESVVMAYLFTIFNAFQGVFIFIFHCALQKKVRKEY 252
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
 2095-2321 8.19e-41

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: 152.79  E-value: 8.19e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLtclKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARN 2174
Cdd:cd16005     25 TFCFF---RGLQSDRNTIHKNLCISLFVAELLFLIGINRTDQPIACAVFAALLHFFFLAAFTWMFLEGVQLYIMLVEVFE 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2175 VNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGV--------MFLLVAKMS 2246
Cdd:cd16005    102 SEHSRRKYFYLVGYGMPALIVAVSAAVDYRSYGTDKVCWLRLDTYFIWSFIGPATLIIMLNVIflgialykMFHHTAILK 181

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1894698391 2247 CSPGQKETKKKSVLmtlrSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAW 2321
Cdd:cd16005    182 PESGCLDNIKSWVI----GAIALLCLLGLTWAFGLMYINESTVIMAYLFTIFNSLQGMFIFIFHCVLQKKVRKEY 252
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
 2096-2322 6.37e-40

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: 150.36  E-value: 6.37e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2096 FSFLTCLKGLKSNTrSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNV 2175
Cdd:cd15931     24 FTFLLCRWIPKINT-TAHLHLCLCLSMSHTLFLAGIEYVENELACTVMAGLLHYLFLASFVWMLLEALQLHLLVRRLTKV 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2176 NFGA-----MRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGVMF-----LLVAKM 2245
Cdd:cd15931    103 QVIQrdglpRPLLCLIGYGVPFLIVGVSALVYSDGYGEAKMCWLSQERGFNWSFLGPVIAIIGINWILFcatlwCLRQTL 182

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1894698391 2246 SCSPGQKETKKKSVLMTLRsSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15931    183 SNMNSDISQLKDTRLLTFK-AVAQLFILGCTWVLGLFQTNPVALVFQYLFTILNSLQGAFLFLVHCLLNKEVREEYI 258
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 199-296 1.90e-36

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 133.98  E-value: 1.90e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  199 PFQISVLENAPLGHSVIHIQAVDADYGENSRLEYKLTGVSADTPFVVNSATGWITVSGPLDRESVEHYFFGVEARDHGSP 278
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                           90
                   ....*....|....*...
gi 1894698391  279 SLSASASVTITVMDVNDN 296
Cdd:cd11304     81 PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 509-607 3.37e-35

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 130.51  E-value: 3.37e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  509 HYQGMISEDAPPFTSVLQISATDRDAHTNGRVQYTFQNGeDGDGDFTIEPTSGIIRTVRRLDRENVPVYELTAYAVDRGI 588
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSG-NEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGG 79

                           90
                   ....*....|....*....
gi 1894698391  589 PPQRTPVHIQVTIQDVNDN 607
Cdd:cd11304     80 PPLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 94-191 2.49e-34

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 127.81  E-value: 2.49e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   94 YIVQVREDIRPHTEILRVTATDLDKDNNALVHYNIISGNSRGQFSIDSVTGEIQVVAPLDFEVEREYALRIRAQDAGRPP 173
Cdd:cd11304      2 YEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGPP 81

                           90
                   ....*....|....*...
gi 1894698391  174 LSnNTGMASIQVVDINDH 191
Cdd:cd11304     82 LS-STATVTITVLDVNDN 98
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
 2095-2321 2.69e-34

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: 133.85  E-value: 2.69e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2095 TFSFLTclkGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEA-R 2173
Cdd:cd15437     25 TFWFFS---EIQSTRTTIHKNLCCSLFLAELIFLIGINMNANKLFCSIIAGLLHYFFLAAFAWMCIEGIHLYLIVVGViY 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2174 NVNFgAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMN----GVMFLLVAKMSCSP 2249
Cdd:cd15437    102 NKGF-LHKNFYIFGYGSPAVVVGISAALGYKYYGTTKVCWLSTENNFIWSFIGPACLIILVNllafGVIIYKVFRHTAML 180

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1894698391 2250 GQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAW 2321
Cdd:cd15437    181 KPEVSCYENIRSCARGALALLFLLGATWIFGVLHVVYGSVVTAYLFTISNAFQGMFIFIFLCVLSRKIQEEY 252
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 406-501 2.99e-33

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 124.73  E-value: 2.99e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  406 HYSVSINEDRPVGSTVVVISATDDDVGENARITYYLEDNVPQ--FRIDPDSGAITLQAELDYEDQVTYTLAITAKDNGIP 483
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDglFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                           90
                   ....*....|....*...
gi 1894698391  484 QKADTTYVEIMVNDVNDN 501
Cdd:cd11304     81 PLSSTATVTITVLDVNDN 98
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
 2096-2325 2.26e-32

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: 128.26  E-value: 2.26e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2096 FSFLTCLKGLKSNTRSIHS--NISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEA- 2172
Cdd:cd15259     24 ITYIVFHRLIRISRKGRHMlvNLCLHLLLTCVVFVGGINRTANQLVCQAVGILLHYSTLCTLLWVGVTARNMYKQVTKTa 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2173 --------RNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWisihdkLVWS-----FAGPITVVIVMNGVMF 2239
Cdd:cd15259    104 kppqdedqPPRPPKPMLRFYLIGWGIPLIICGITAAVNLDNYSTYDYCW------LAWDpslgaFYGPAALIVLVNCIYF 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2240 LlvakmsCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSV---LAFHYLYTVLCSLQGLAVLVLFCVLNEE 2316
Cdd:cd15259    178 L------RIYCQLKGAPVSFQSQLRGAVITLFLYVAMWACGALAVSQRYfldLVFSCLYGATCSSLGLFVLIHHCLSRED 251


                   ....*....
gi 1894698391 2317 VREAWKLAC 2325
Cdd:cd15259    252 VRQSWRQCC 260
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
 2136-2320 2.52e-31

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: 125.35  E-value: 2.52e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2136 NQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRmQTEARNVNFG-AMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWI 2214
Cdd:cd15255     63 NQVACWAVTALLHLFFLAAFSWMLVEGLLLWS-KVVAVNMSEDrRMKFYYVTGWGLPVVIVAVTLATSFNKYVADQHCWL 141

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2215 SIHDKLVWSFAGPITVVIVMNGVMFLLV-----------AKM-SCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLL 2282
Cdd:cd15255    142 NVQTDIIWAFVGPVLFVLTVNTFVLFRVvmvtvssarrrAKMlTPSSDLEKQIGIQIWATAKPVLVLLPVLGLTWLCGVL 221

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1894698391 2283 AVNNSVLAfhYLYTVLCSLQGLAVLVLFCVLNEEVREA 2320
Cdd:cd15255    222 VHLSDVWA--YVFITLNSFQGLYIFLVYAIYNSEVRNA 257
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 615-709 1.71e-30

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 117.03  E-value: 1.71e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  615 EFEVLVKENSIVGSVVAQITAVDPDEGPNAQIMYQIVEGNIPEIFQMDIFSGELTALIDLDYETKPEYVIVVQAT---SA 691
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATdggGP 80

                           90
                   ....*....|....*...
gi 1894698391  692 PLVSRATVHIKLIDQNDN 709
Cdd:cd11304     81 PLSSTATVTITVLDVNDN 98
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1054-1237 3.93e-30

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.


Pssm-ID: 238058 [Multi-domain]  Cd Length: 151  Bit Score: 117.90  E-value: 3.93e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1054 TRSFPPRSFVMFRGLR-QRFHLTLALSFSTVEPSGLLLYNGRLNeRHDFLAVEIIQGQIQLKYSTGESSTVVSPylPGGV 1132
Cdd:cd00110      1 GVSFSGSSYVRLPTLPaPRTRLSISFSFRTTSPNGLLLYAGSQN-GGDFLALELEDGRLVLRYDLGSGSLVLSS--KTPL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1133 SDGQWHTLQLHYYNkpkvsalgvvqgpskdKVAILTVDECDasvalqfgneignyscAAEGVQTSSKKSLDLTGPLLLGG 1212
Cdd:cd00110     78 NDGQWHSVSVERNG----------------RSVTLSVDGER----------------VVESGSPGGSALLNLDGPLYLGG 125

                          170       180
                   ....*....|....*....|....*.
gi 1894698391 1213 VPNLPENFPVTHRD-FVGCMRDLYID 1237
Cdd:cd00110    126 LPEDLKSPGLPVSPgFVGCIRDLKVN 151
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
 2136-2322 1.04e-28

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: 118.10  E-value: 1.04e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2136 NQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRM-----QTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLD---PEGYG 2207
Cdd:cd15039     64 DSTLCVALGILLHFFFLAAFFWLNVMSFDIWRTfrgkrSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDfspNTDSL 143

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2208 NPDF----CWISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMSCSpGQKETKK-KSVLMTLRSSFVLLLVIST----TWL 2278
Cdd:cd15039    144 RPGYgegsCWISNPWALLLYFYGPVALLLLFNIILFILTAIRIRK-VKKETAKvQSRLRSDKQRFRLYLKLFVimgvTWI 222

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1894698391 2279 FGLLA--VNNSVLAFhYLYTVLCSLQGLAVLVLFcVLNEEVREAWK 2322
Cdd:cd15039    223 LEIISwfVGGSSVLW-YIFDILNGLQGVFIFLIF-VCKRRVLRLLK 266
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
 2130-2322 1.20e-28

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: 117.36  E-value: 1.20e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2130 GINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFyYAIGWGVPAIITGLAVGLD-PEGYGN 2208
Cdd:cd15251     58 GQTQTLNKGVCTMTAAFLHFFFLSSFCWVLTEAWQSYMAVTGRMRTRLIRKRF-LCLGWGLPALVVAVSVGFTrTKGYGT 136

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2209 PDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMSCSpgqKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNN-- 2286
Cdd:cd15251    137 SSYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVS---RDGISDNAMASLWSSCVVLPLLALTWMSAVLAMTDrr 213

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1894698391 2287 SVLaFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15251    214 SVL-FQILFAVFDSLQGFVIVMVHCILRREVQDAVK 248
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 218-298 2.99e-28

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 110.13  E-value: 2.99e-28
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   218 QAVDADYGENSRLEYKLTGVSADTPFVVNSATGWITVSGPLDRESVEHYFFGVEARDHGSPSLSASASVTITVMDVNDNR 297
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDNA 80


                    .
gi 1894698391   298 P 298
Cdd:smart00112   81 P 81
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
 2098-2329 8.10e-28

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: 115.47  E-value: 8.10e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2098 FLTCLKGLKSNTRSIHSNISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYrMQTEARNVNF 2177
Cdd:cd15990     29 YVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSY-MAVTGRLRNR 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2178 GAMRFYYAIGWGVPAIITGLAVGL-DPEGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLV-AKMSCSPGQKETK 2255
Cdd:cd15990    108 IIRKRFLCLGWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVfNKLVSKDGITDKK 187

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1894698391 2256 -KKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLA-FHYLYTVLCSLQGLAVLVLFCVLNEEVREAWKLACLGKK 2329
Cdd:cd15990    188 lKERAGASLWSSCVVLPLLALTWMSAVLAITDRRSAlFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVVDRQ 263
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
 2139-2322 4.35e-27

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: 113.44  E-value: 4.35e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2139 LCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVnfgAMRFYY----AIGWGVPAIITGLAV------------GLD 2202
Cdd:cd15996     69 LCITVAVLLHFFLLATFTWMGLEAIHMYIALVKVFNT---YIRRYIlkfcIIGWGLPALIVSIVLastndnygygyyGKD 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2203 PEGYGNPDFCWISihDKLVW--SFAGPITVVIVMNGVMFLLVAKMSCSPGQKETK---KKSVLMTLRSSFVLLLVISTTW 2277
Cdd:cd15996    146 KDGQGGDEFCWIK--NPVVFyvTCAAYFGIMFLMNVAMFIVVMVQICGRNGKRSNrtlREEILRNLRSVVSLTFLLGMTW 223

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1894698391 2278 LFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15996    224 GFAFFAWGPVNLAFMYLFTIFNSLQGLFIFVFHCALKENVQKQWR 268
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 528-609 4.64e-27

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 106.66  E-value: 4.64e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   528 SATDRDAHTNGRVQYTFqNGEDGDGDFTIEPTSGIIRTVRRLDRENVPVYELTAYAVDRGIPPQRTPVHIQVTIQDVNDN 607
Cdd:smart00112    1 SATDADSGENGKVTYSI-LSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDN 79


                    ..
gi 1894698391   608 AP 609
Cdd:smart00112   80 AP 81
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
 2135-2323 1.81e-26

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: 111.29  E-value: 1.81e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2135 ENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNfgaMRFYY----AIGWGVPAIITGLAVGLDPEGYGN-- 2208
Cdd:cd15997     65 NNYGLCITVAAFLHYFLLASFTWMGLEAVHMYFALVKVFNIY---IPNYIlkfcIAGWGIPAVVVALVLAINKDFYGNel 141

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2209 --------PDFCWIsiHDKLVW--SFAGPITVVIVMNGVMFLLV----AKMSCSpGQKETKKKSVLMTLRSSFVLLLVIS 2274
Cdd:cd15997    142 ssdslhpsTPFCWI--QDDVVFyiSVVAYFCLIFLCNISMFITVliqiRSMKAK-KPSRNWKQGFLHDLKSVASLTFLLG 218

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1894698391 2275 TTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWKL 2323
Cdd:cd15997    219 LTWGFAFFAWGPVRIFFLYLFSICNTLQGFFIFVFHCLMKENVRKQWRI 267
Cadherin pfam00028
Cadherin domain;
94-185 2.53e-26

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 104.69  E-value: 2.53e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   94 YIVQVREDIRPHTEILRVTATDLDKDNNALVHYNIISGNSRGQFSIDSVTGEIQVVAPLDFEVEREYALRIRAQDAGRPP 173
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|..
gi 1894698391  174 LSnNTGMASIQV 185
Cdd:pfam00028   81 LS-STATVTITV 91
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 112-193 3.18e-26

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 104.35  E-value: 3.18e-26
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   112 TATDLDKDNNALVHYNIISGNSRGQFSIDSVTGEIQVVAPLDFEVEREYALRIRAQDAGRPPLSnNTGMASIQVVDINDH 191
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLS-STATVTITVLDVNDN 79


                    ..
gi 1894698391   192 AP 193
Cdd:smart00112   80 AP 81
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 425-503 4.42e-26

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 103.97  E-value: 4.42e-26
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   425 SATDDDVGENARITYYLEDNVPQ--FRIDPDSGAITLQAELDYEDQVTYTLAITAKDNGIPQKADTTYVEIMVNDVNDNA 502
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDglFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDNA 80


                    .
gi 1894698391   503 P 503
Cdd:smart00112   81 P 81
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
 2139-2322 2.08e-25

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: 108.27  E-value: 2.08e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2139 LCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYY-AIGWGVPAIITGLAVGLDPEGYG---------- 2207
Cdd:cd15258     69 LCIAVAVALHYFLLACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLcLVGWGLPALLVTLVLSVRSDNYGpitipngegf 148

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2208 -NPDFCWIsiHDKLVWSF--AGPITVVIVMNGVMFLLVAKMSC--SPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLL 2282
Cdd:cd15258    149 qNDSFCWI--RDPVVFYItvVGYFGLTFLFNMVMLATVLVQICrlREKAQATPRKRALHDLLTLLGLTFLLGLTWGLAFF 226

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1894698391 2283 AVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15258    227 AWGPFNLPFLYLFAIFNSLQGFFIFIWYCSMKENVRKQWR 266
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 4-87 6.41e-25

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 100.50  E-value: 6.41e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391     4 RATEGDSPPNANIRYRFVNERAAHaVFEIDPRSGLITTSGPVDREKMERYSLVVEANDQGrePGPRSATVKVYITVLDEN 83
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDG-LFSIDPETGEITTTKPLDREEQPEYTLTVEATDGG--GPPLSSTATVTITVLDVN 77


                    ....
gi 1894698391    84 DNTP 87
Cdd:smart00112   78 DNAP 81
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 4-85 1.44e-24

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 100.08  E-value: 1.44e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391    4 RATEGDSPPNANIRYRFVNERAAHaVFEIDPRSGLITTSGPVDREKMERYSLVVEANDQGrePGPRSATVKVYITVLDEN 83
Cdd:cd11304     20 SATDPDSGENGEVTYSIVSGNEDG-LFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGG--GPPLSSTATVTITVLDVN 96


                   ..
gi 1894698391   84 DN 85
Cdd:cd11304     97 DN 98
Cadherin pfam00028
Cadherin domain;
200-290 1.53e-24

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 99.68  E-value: 1.53e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  200 FQISVLENAPLGHSVIHIQAVDADYGENSRLEYKLTGVSADTPFVVNSATGWITVSGPLDRESVEHYFFGVEARDHGSPS 279
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|.
gi 1894698391  280 LSASASVTITV 290
Cdd:pfam00028   81 LSSTATVTITV 91
Cadherin pfam00028
Cadherin domain;
510-602 1.82e-24

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 99.68  E-value: 1.82e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  510 YQGMISEDAPPFTSVLQISATDRDAHTNGRVQYTFQNGEDGdGDFTIEPTSGIIRTVRRLDRENVPVYELTAYAVDRGIP 589
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPG-GNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGP 79

                           90
                   ....*....|...
gi 1894698391  590 PQRTPVHIQVTIQ 602
Cdd:pfam00028   80 PLSSTATVTITVL 92
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
 2140-2319 2.04e-24

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: 106.50  E-value: 2.04e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIY---RMQTEARNVNFgaMRFYYAIGWGVPAIITGLAVG----------LDPEGY 2206
Cdd:cd15257     93 CTAVAALLHYFLLVTFMWNAVYSAQLYlllIRMMKPLPEMF--ILQASAIGWGIPAVVVAITLGatyrfptslpVFTRTY 170

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2207 GNPDFCWISIHDK-------LVWSFAGPITVVIVMNGVMFLLVAKMSCSPGQKE--TKKKSVLMTLRSSFVLLLVISTTW 2277
Cdd:cd15257    171 RQEEFCWLAALDKnfdikkpLLWGFLLPVGLILITNVILFIMTSQKVLKKNNKKltTKKRSYMKKIYITVSVAVVFGITW 250

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1894698391 2278 LFG-LLAVNN--SVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVRE 2319
Cdd:cd15257    251 ILGyLMLVNNdlSKLVFSYIFCITNTTQGVQIFILYTWRTPEFRK 295
LamG smart00282
Laminin G domain;
1075-1239 2.05e-24

Laminin G domain;


Pssm-ID: 214598 [Multi-domain]  Cd Length: 132  Bit Score: 100.88  E-value: 2.05e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  1075 TLALSFSTVEPSGLLLYNGRLNeRHDFLAVEIIQGQIQLKYSTGESSTVVSpYLPGGVSDGQWHTLQLHYYNkpkvsalg 1154
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKG-GGDYLALELRDGRLVLRYDLGSGPARLT-SDPTPLNDGQWHRVAVERNG-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  1155 vvqgpskdKVAILTVDECDasvalqfgneignyscAAEGVQTSSKKSLDLTGPLLLGGVPNLPENFPVTHRD-FVGCMRD 1233
Cdd:smart00282   71 --------RSVTLSVDGGN----------------RVSGESPGGLTILNLDGPLYLGGLPEDLKLPPLPVTPgFRGCIRN 126


                    ....*.
gi 1894698391  1234 LYIDSK 1239
Cdd:smart00282  127 LKVNGK 132
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 304-398 2.25e-24

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 99.70  E-value: 2.25e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  304 EYFIRLNEDAAVGTSVLSVTAIDRD--VNSAITYQITGGNTRNRFSISTQggMGLITLSLPLDYKQERRYVLTVTASDR- 380
Cdd:cd11304      1 SYEVSVPENAPPGTVVLTVSATDPDsgENGEVTYSIVSGNEDGLFSIDPS--TGEITTAKPLDREEQSSYTLTVTATDGg 78

                           90       100
                   ....*....|....*....|
gi 1894698391  381 --TLRDNCHVHINITDANTH 398
Cdd:cd11304     79 gpPLSSTATVTITVLDVNDN 98
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
 2139-2322 2.29e-24

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: 105.29  E-value: 2.29e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2139 LCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAI-GWGVPAIITGLAVGLDPEGYG---------- 2207
Cdd:cd15444     70 LCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIvGWGVPAVVVAIVLAVSKDNYGlgsygkspng 149

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2208 -NPDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMSC---SPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLA 2283
Cdd:cd15444    150 sTDDFCWINNNIVFYITVVGYFCVIFLLNISMFIVVLVQLCrikKQKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFA 229

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1894698391 2284 VNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15444    230 WGPVNLAFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWR 268
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
 2130-2322 5.69e-24

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: 104.65  E-value: 5.69e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2130 GINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIY-----RMQTEARNVNFgamrfyYAIGWGVPAIITGLAVGLD-P 2203
Cdd:cd15988     58 GQSQTLSKGVCTMTAAFLHFFFLSSFCWVLTEAWQSYlavigRMRTRLVRKRF------LCLGWGLPALVVAVSVGFTrT 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2204 EGYGNPDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLV-AKMSCSPGQKETKKK------------------------- 2257
Cdd:cd15988    132 KGYGTASYCWLSLEGGLLYAFVGPAAVIVLVNMLIGIIVfNKLMSRDGISDKSKKqragseaepcsslllkcskcgvvss 211

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1894698391 2258 ---------SVLMTLRSSFVLLLVISTTWLFGLLAVNN--SVLaFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15988    212 aamssatasSAMASLWSSCVVLPLLALTWMSAVLAMTDrrSIL-FQVLFAVFNSVQGFVIITVHCFLRREVQDVVK 286
Laminin_G_2 pfam02210
Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G ...
 1080-1239 7.44e-24

Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G subfamily.


Pssm-ID: 460494 [Multi-domain]  Cd Length: 126  Bit Score: 99.03  E-value: 7.44e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1080 FSTVEPSGLLLYNGrlNERHDFLAVEIIQGQIQLKYSTGESSTVVSpYLPGGVSDGQWHTLQLHYynkpkvsalgvvqgp 1159
Cdd:pfam02210    1 FRTRQPNGLLLYAG--GGGSDFLALELVNGRLVLRYDLGSGPESLL-SSGKNLNDGQWHSVRVER--------------- 62

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1160 sKDKVAILTVDECDASVALQFGNEIGnyscaaegvqtsskksLDLTGPLLLGGVPN-LPENFPVTHRDFVGCMRDLYIDS 1238
Cdd:pfam02210   63 -NGNTLTLSVDGQTVVSSLPPGESLL----------------LNLNGPLYLGGLPPlLLLPALPVRAGFVGCIRDVRVNG 125


                   .
gi 1894698391 1239 K 1239
Cdd:pfam02210  126 E 126
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
 2139-2320 1.75e-23

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


Pssm-ID: 320598 [Multi-domain]  Cd Length: 268  Bit Score: 102.78  E-value: 1.75e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2139 LCTVIAILLHCFFLSTFAWLFIQGLHI-YRM----QTEARNVNFGAMrfyYAIGWGVPAIITG--LAVGLDPEGYGNPDF 2211
Cdd:cd15932     75 ACTAATFFIHFFYLALFFWMLTLGLLLfYRLvlvfHDMSKSTMMAIA---FSLGYGCPLIIAIitVAATAPQGGYTRKGV 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2212 CWISIHD-KLVWSFAGPITVVIVMNGVMFLLV-AKM---SCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGL-LAVN 2285
Cdd:cd15932    152 CWLNWDKtKALLAFVIPALAIVVVNFIILIVViFKLlrpSVGERPSKDEKNALVQIGKSVAILTPLLGLTWGFGLgTMID 231

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1894698391 2286 NSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREA 2320
Cdd:cd15932    232 PKSLAFHIIFAILNSFQGFFILVFGTLLDSKVREA 266
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 634-711 2.93e-23

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 95.88  E-value: 2.93e-23
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   634 TAVDPDEGPNAQIMYQIVEGNIPEIFQMDIFSGELTALIDLDYETKPEYVIVVQAT---SAPLVSRATVHIKLIDQNDNS 710
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATdggGPPLSSTATVTITVLDVNDNA 80


                    .
gi 1894698391   711 P 711
Cdd:smart00112   81 P 81
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
 2135-2326 1.61e-22

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


Pssm-ID: 341321 [Multi-domain]  Cd Length: 273  Bit Score: 99.99  E-value: 1.61e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2135 ENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTearNVNFG---AMRFYYAIGWGVPAIITGLAVGLdpEGYGNPDF 2211
Cdd:cd15041     77 QNPVGCKLLSVLKRYFKSANYFWMLCEGLYLHRLIV---VAFFSepsSLKLYYAIGWGLPLVIVVIWAIV--RALLSNES 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2212 CWISIHDK-LVWSFAGPITVVIVMNGVMFL-----LVAKMSCSPGQKETKKKSvlmTLRSSFVLLLVISTTWLFGLLAVN 2285
Cdd:cd15041    152 CWISYNNGhYEWILYGPNLLALLVNLFFLInilriLLTKLRSHPNAEPSNYRK---AVKATLILIPLFGIQYLLTIYRPP 228

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1894698391 2286 NSVLAFH-YLYT--VLCSLQGLAVLVLFCVLNEEVREAWKLACL 2326
Cdd:cd15041    229 DGSEGELvYEYFnaILNSSQGFFVAVIYCFLNGEVQSELKRKWS 272
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
 2130-2322 1.80e-22

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: 100.53  E-value: 1.80e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2130 GINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFyYAIGWGVPAIITGLAVGLD-PEGYGN 2208
Cdd:cd15989     60 GQTQTHNKGICTMTTAFLHFFFLASFCWVLTEAWQSYMAVTGKIRTRLIRKRF-LCLGWGLPALVVAISMGFTkAKGYGT 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2209 PDFCWISIHDKLVWSFAGPITVVIVMNGVMFLLV------------AKMSCSPGQ-----------------------KE 2253
Cdd:cd15989    139 PHYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVfnklvsrdgildKKLKHRAGQmsephsgltlkcakcgvvsttalSA 218

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2254 TKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNS-VLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15989    219 TTASNAMASLWSSCVVLPLLALTWMSAVLAMTDKrSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFR 288
Cadherin pfam00028
Cadherin domain;
407-495 2.05e-22

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 93.90  E-value: 2.05e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  407 YSVSINEDRPVGSTVVVISATDDDVGENARITYY-LEDNVPQ-FRIDPDSGAITLQAELDYEDQVTYTLAITAKDNGIPQ 484
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSiLGGGPGGnFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|.
gi 1894698391  485 KADTTYVEIMV 495
Cdd:pfam00028   81 LSSTATVTITV 91
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
 2138-2320 1.85e-21

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: 96.75  E-value: 1.85e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2138 FLCTVIAILLHCFFLSTFAWLFIQGLHIYRM------QTEARNVnfgaMRFYYAIGWGVPAIITGLAVGL-DPEG-YGNP 2209
Cdd:cd15253     73 PLCLAAAFLCHFFYLATFFWMLVQALMLFHQllfvfhQLAKRSV----LPLMVTLGYLCPLLIAAATVAYyYPKRqYLHE 148

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2210 DFCWISIHDKLVWSFAGPITVVIVMNG-VMFLLVAKM---SCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFGL-LAV 2284
Cdd:cd15253    149 GACWLNGESGAIYAFSIPVLAIVLVNLlVLFVVLMKLmrpSVSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVaTLT 228

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1894698391 2285 NNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREA 2320
Cdd:cd15253    229 GESSQVSHYGFAILNAFQGVFILLFGCLMDKKVREA 264
Cadherin pfam00028
Cadherin domain;
616-704 3.42e-21

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 90.44  E-value: 3.42e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  616 FEVLVKENSIVGSVVAQITAVDPDEGPNAQIMYQIVEGNIPEIFQMDIFSGELTALIDLDYETKPEYVIVVQATSA---P 692
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSggpP 80

                           90
                   ....*....|..
gi 1894698391  693 LVSRATVHIKLI 704
Cdd:pfam00028   81 LSSTATVTITVL 92
Laminin_G_1 pfam00054
Laminin G domain;
1080-1242 4.73e-21

Laminin G domain;


Pssm-ID: 395008 [Multi-domain]  Cd Length: 131  Bit Score: 91.22  E-value: 4.73e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1080 FSTVEPSGLLLYNGRlNERHDFLAVEIIQGQIQLKYSTGESSTVVSPylPGGVSDGQWHTLQLHyYNKpkvsalgvvqgp 1159
Cdd:pfam00054    1 FRTTEPSGLLLYNGT-QTERDFLALELRDGRLEVSYDLGSGAAVVRS--GDKLNDGKWHSVELE-RNG------------ 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1160 skdKVAILTVDECDASVALQfgneignyscaaegvQTSSKKSLDLTGPLLLGGVPNL---PENFPVTHRdFVGCMRDLYI 1236
Cdd:pfam00054   65 ---RSGTLSVDGEARPTGES---------------PLGATTDLDVDGPLYVGGLPSLgvkKRRLAISPS-FDGCIRDVIV 125


                   ....*.
gi 1894698391 1237 DSKRID 1242
Cdd:pfam00054  126 NGKPLD 131
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
 2135-2322 3.11e-20

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: 93.11  E-value: 3.11e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2135 ENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWI 2214
Cdd:cd15260     70 ENPIWCQALHVLLQYFMVCNYFWMFCEGLYLHTVLVVAFISEKSLMRWFIAIGWGVPLVITAIYAGVRASLPDDTERCWM 149

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2215 SiHDKLVWSFAGPITVVIVMN-----GVMFLLVAKMSCSPGQKE--TKKKSVLMTlrssfvLLLVIsttwLFGLLAV--- 2284
Cdd:cd15260    150 E-ESSYQWILIVPVVLSLLINlifliNIVRVLLTKLRATSPNPApaGLRKAVRAT------LILIP----LLGLQFLlip 218

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1894698391 2285 ----NNSVL--AFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15260    219 frpePGAPLetIYQYVSALLTSLQGLCVAVLFCFCNGEVIAAIK 262
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
 2130-2325 3.75e-20

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: 93.09  E-value: 3.75e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2130 GINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGA----------MRFYYAIGwGVPAIITGLAV 2199
Cdd:cd16000     60 GINRTKYPIICQAVGIVLHYSTLSTMLWIGVTARNIYKQVTKKPHLCQDTdqppypkqplLRFYLVSG-GVPFIICGITA 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2200 GLDPEGYGNPD----FCWISIHDKLvWSFAGPITVVIVMNGVMFLLV-AKMSCSPGQK-ETKKK-SVLMTLRSSFVLLLV 2272
Cdd:cd16000    139 ATNINNYGTEDedtpYCWMAWEPSL-GAFYGPVAFIVLVTCIYFLCTyVQLRRHPERKyELKNEhSFKAQLRAAAFTLFL 217

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1894698391 2273 ISTTWLFGLLAVNNSV---LAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWKLAC 2325
Cdd:cd16000    218 FTATWAFGALAVSQGHfldMIFSCLYGAFCVTLGLFILIHHCAKRDDVWHCWWSCC 273
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1303-1456 5.10e-20

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.


Pssm-ID: 238058 [Multi-domain]  Cd Length: 151  Bit Score: 89.01  E-value: 5.10e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1303 YFQGNSVLtwDFKTDVKISVPWYLGLAFRTRQPDGVLLQAHAGQYT-TLLCQLAGGLLSFMVSRGSGRSTslLLDQLRLS 1381
Cdd:cd00110      3 SFSGSSYV--RLPTLPAPRTRLSISFSFRTTSPNGLLLYAGSQNGGdFLALELEDGRLVLRYDLGSGSLV--LSSKTPLN 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1382 DGRWHDLQLElrdvRSGRdsryVITLTVDFGLYQDTVVVGNELHGLKVKHLHVGGVLGSGE-----VQNGLRGCIQGVRL 1456
Cdd:cd00110     79 DGQWHSVSVE----RNGR----SVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDLKspglpVSPGFVGCIRDLKV 150
Laminin_G_2 pfam02210
Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G ...
 1330-1458 6.72e-20

Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G subfamily.


Pssm-ID: 460494 [Multi-domain]  Cd Length: 126  Bit Score: 87.86  E-value: 6.72e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1330 FRTRQPDGVLLQAHAGQYTTLLCQLAGGLLSFMVSRGSGRSTSLLLDQlRLSDGRWHDLQLElrdvRSGRDsryvITLTV 1409
Cdd:pfam02210    1 FRTRQPNGLLLYAGGGGSDFLALELVNGRLVLRYDLGSGPESLLSSGK-NLNDGQWHSVRVE----RNGNT----LTLSV 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1894698391 1410 DFGLYQDTVVVGNELHGLKVKHLHVGGVLGSG-----EVQNGLRGCIQGVRLGD 1458
Cdd:pfam02210   72 DGQTVVSSLPPGESLLLNLNGPLYLGGLPPLLllpalPVRAGFVGCIRDVRVNG 125
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
 2096-2320 1.08e-18

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: 88.97  E-value: 1.08e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2096 FSFLTCLKglksNTrsIHSNISVTLFFSEL----LFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTE 2171
Cdd:cd15263     29 FKDLRCLR----NT--IHTNLMFTYILADLtwilTLTLQVSIGEDQKSCIILVVLLHYFHLTNFFWMFVEGLYLYMLVVE 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2172 ARNVNFGAMRFYYAIGWGVPAI-ITGLAV-----------GLDPEGYgnPDFC-WI--SIHDklvWSFAGPITVVIVMNG 2236
Cdd:cd15263    103 TFSGENIKLRVYAFIGWGIPAVvIVIWAIvkalaptapntALDPNGL--LKHCpWMaeHIVD---WIFQGPAILVLAVNL 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2237 V-----MFLLVAKMSCSPG------QKETKKKSVLMTLRS-SFVLLLVISTTwlfGLLAVnnsvlAFHYLYTVLCSLQGL 2304
Cdd:cd15263    178 VflvriMWVLITKLRSANTvetqqyRKAAKALLVLIPLLGiTYILVIAGPTE---GIAAN-----IFEYVRAVLLSTQGF 249

                          250
                   ....*....|....*.
gi 1894698391 2305 AVLVLFCVLNEEVREA 2320
Cdd:cd15263    250 TVALFYCFLNTEVRNT 265
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
 2136-2322 2.72e-18

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: 87.47  E-value: 2.72e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2136 NQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEArnvnFGA--MRFYY--AIGWGVPAIITgLAVGLDPEGYGNpDF 2211
Cdd:cd15264     69 NQWVCRLIVTVYNYFQVTNFFWMFVEGLYLHTMIVWA----YSAdkIRFWYyiVIGWCIPCPFV-LAWAIVKLLYEN-EH 142

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2212 CWISIH--DKLVWSFAGPITVVIVMNgVMFL------LVAKMSCSPGQkETK--KKSVLMTLrssfVLLLVISTTWLFGL 2281
Cdd:cd15264    143 CWLPKSenSYYDYIYQGPILLVLLIN-FIFLfnivwvLITKLRASNTL-ETIqyRKAVKATL----VLLPLLGITYMLFF 216

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1894698391 2282 LAVNN---SVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15264    217 INPGDdktSRLVFIYFNTFLQSFQGLFVAVFYCFLNGEVRSAIR 260
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
 2132-2322 3.46e-18

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: 87.20  E-value: 3.46e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2132 NRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHI-------YRMQTEARNVNFGamrfyYAIGWGVPAIITGLAVGL-DP 2203
Cdd:cd15994     68 NTALNYPLCVAATFFLHFFYLSLFFWMLTKALLIlygillvFFKITKSVFIATA-----FSIGYGCPLVIAVLTVAItEP 142

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2204 E-GYGNPDFCWISIHD-KLVWSFAGPITVVIVMNGVMFLLVAKMSCSPGQKETKKKSVLMTLRSS---FVLLLVISTTWL 2278
Cdd:cd15994    143 KkGYLRPEACWLNWDEtKALLAFIIPALSIVVVNLIVVGVVVVKTQRSSIGESCKQDVSNIIRISknvAILTPLLGLTWG 222

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1894698391 2279 FGLLA-VNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15994    223 FGLATiIDSRSLPFHIIFALLNAFQGFFILLFGTILDRKIRIALY 267
Cadherin pfam00028
Cadherin domain;
305-393 6.82e-18

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 80.81  E-value: 6.82e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  305 YFIRLNEDAAVGTSVLSVTAIDRD--VNSAITYQITGGNTRNRFSISTQGgmGLITLSLPLDYKQERRYVLTVTASDR-- 380
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDlgPNGRIFYSILGGGPGGNFRIDPDT--GDISTTKPLDRESIGEYELTVEATDSgg 78

                           90
                   ....*....|....
gi 1894698391  381 -TLRDNCHVHINIT 393
Cdd:pfam00028   79 pPLSSTATVTITVL 92
LamG smart00282
Laminin G domain;
1325-1456 8.36e-18

Laminin G domain;


Pssm-ID: 214598 [Multi-domain]  Cd Length: 132  Bit Score: 82.00  E-value: 8.36e-18
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  1325 YLGLAFRTRQPDGVLLQAHAGQYT-TLLCQLAGGLLSFMVSRGSGRsTSLLLDQLRLSDGRWHDLQLElrdvRSGRdsry 1403
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGdYLALELRDGRLVLRYDLGSGP-ARLTSDPTPLNDGQWHRVAVE----RNGR---- 71

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 1894698391  1404 VITLTVDFGLYQDTVVVGNELhGLKVK-HLHVGGVLGSGE-----VQNGLRGCIQGVRL 1456
Cdd:smart00282   72 SVTLSVDGGNRVSGESPGGLT-ILNLDgPLYLGGLPEDLKlpplpVTPGFRGCIRNLKV 129
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
 2132-2320 8.16e-17

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


Pssm-ID: 320382 [Multi-domain]  Cd Length: 275  Bit Score: 83.32  E-value: 8.16e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2132 NRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHI-YRMQTEARNVNFGAMR-FYYAIGWGVPAIIT--GLAVGLDPEGYG 2207
Cdd:cd15254     70 NYAVNGNVCVAATFFIHFFYLCVFFWMLALGLMLfYRLVFILHDTSKTIQKaVAFCLGYGCPLIISviTIAVTLPRDSYT 149

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2208 NPDFCWISIHD-KLVWSFAGPITVVIVMNGVMFLLVAKMSCSP--GQKETK--KKSVLMTLRSSFVLLLVISTTWLFGLL 2282
Cdd:cd15254    150 RKKVCWLNWEDsKALLAFVIPALIIVAVNSIITVVVIVKILRPsiGEKPSKqeRSSLFQIIKSIGVLTPLLGLTWGFGLA 229

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1894698391 2283 AV-NNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREA 2320
Cdd:cd15254    230 TViKGSSIVFHILFTLLNAFQGLFILVFGTLWDKKVQEA 268
HormR smart00008
Domain present in hormone receptors;
1660-1726 1.58e-16

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 76.40  E-value: 1.58e-16
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1894698391  1660 YDGCPKSLKAGVWWPQTKFGFSAAVLCPKGSLGLRGAGAAIRHCDEEKGWLE--PDLFNCTSPAFKELS 1726
Cdd:smart00008    2 DLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFSYKTGASRNCTENGGWSPpfPNYSNCTSNDYEELK 70
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
 2097-2311 1.58e-16

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: 82.50  E-value: 1.58e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2097 SFLTCL------KGLKSNTRSIHSNI--SVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRM 2168
Cdd:cd15443     19 SLLTILlhffsrKQPKDSTTRIHMNLlgSLFLLNGSFLLSPPLATSQSTWLCRAAAALLHYSLLCCLTWMAIEGFHLYLL 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2169 QTEARNVNFgamRFYY----AIGWGVPAIITGLAVGLDPEGYG-----------NPDFCWI---SIHDKLVWSFAGpitV 2230
Cdd:cd15443     99 LVKVYNIYI---RRYVlklcVLGWGLPALIVLLVLIFKREAYGphtiptgtgyqNASMCWItssKVHYVLVLGYAG---L 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2231 VIVMNGVMFLLVAKMSCS-PGQKETKKKSVLMTLRSSFVLLLVISTTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVL 2309
Cdd:cd15443    173 TSLFNLVVLAWVVRMLRRlRSRKQELGERARRDWVTVLGLTCLLGTTWALAFFSFGVFLIPQLFLFTIINSLYGFFICLW 252


                   ..
gi 1894698391 2310 FC 2311
Cdd:cd15443    253 YC 254
Cadherin pfam00028
Cadherin domain;
4-80 1.64e-16

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 76.96  E-value: 1.64e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1894698391    4 RATEGDSPPNANIRYRFVNERAAHaVFEIDPRSGLITTSGPVDREKMERYSLVVEANDQGrePGPRSATVKVYITVL 80
Cdd:pfam00028   19 TATDPDLGPNGRIFYSILGGGPGG-NFRIDPDTGDISTTKPLDRESIGEYELTVEATDSG--GPPLSSTATVTITVL 92
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 323-400 1.81e-16

Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. Cadherin domains occur as repeats in the extracellular regions which are thought to mediate cell-cell contact when bound to calcium.


Pssm-ID: 214520 [Multi-domain]  Cd Length: 81  Bit Score: 76.23  E-value: 1.81e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391   323 TAIDRD--VNSAITYQITGGNTRNRFSISTQGGMglITLSLPLDYKQERRYVLTVTASDR---TLRDNCHVHINITDANT 397
Cdd:smart00112    1 SATDADsgENGKVTYSILSGNDDGLFSIDPETGE--ITTTKPLDREEQPEYTLTVEATDGggpPLSSTATVTITVLDVND 78


                    ...
gi 1894698391   398 HRP 400
Cdd:smart00112   79 NAP 81
EGF_Lam smart00180
Laminin-type epidermal growth factor-like domai;
1611-1656 5.19e-14

Laminin-type epidermal growth factor-like domai;


Pssm-ID: 214543  Cd Length: 46  Bit Score: 68.11  E-value: 5.19e-14
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 1894698391  1611 CDCYPVGSTSRSCDKETGRCHCRPGVIGRQCNSCDSPFAEVTPSGC 1656
Cdd:smart00180    1 CDCDPGGSASGTCDPDTGQCECKPNVTGRRCDRCAPGYYGDGPPGC 46
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 2014-2065 5.45e-14

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


Pssm-ID: 197639  Cd Length: 49  Bit Score: 68.18  E-value: 5.45e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1894698391  2014 SKPLCVQWNHSnltnpSGFWTARDCELVYRNTTHVHCQCSQFGTFGVLMDSS 2065
Cdd:smart00303    1 FNPICVFWDES-----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVP 47
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
 2140-2318 1.23e-13

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: 73.62  E-value: 1.23e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGL--AVGLDPEGYGnpdfCW-ISI 2216
Cdd:cd15930     77 CKASMVFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTVwiVARLYFEDTG----CWdIND 152

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2217 HDKLVWSFAGPITVVIVMNGVMFL-----LVAKMSCspgqKETKKKSVLMTLRSSFVLLLVISttwLFG-------LLAV 2284
Cdd:cd15930    153 ESPYWWIIKGPILISILVNFVLFIniiriLLQKLRS----PDIGGNESSQYKRLARSTLLLIP---LFGihyivfaFFPE 225

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1894698391 2285 NNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15930    226 NISLGIRLYFELCLGSFQGFVVAVLYCFLNGEVQ 259
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
 2130-2318 1.74e-13

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: 73.56  E-value: 1.74e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2130 GINRTEnqFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTearnVNF----GAMRFYYAIGWGVPAIITGLAVGLDPEG 2205
Cdd:cd15261     80 TINSTP--ILCEGFYVLLEYAKTVMFMWMFIEGLYLHNIIV----VSVfsgkPNYLFYYILGWGIPIVHTSAWAIVTLIK 153

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2206 YGNPDfCWISIH-DKLVWSFAGPITVVIVMN-----GVMFLLVAKMSCSPGQKETK-KKSVlmtlRSSFVLLLVISTTWL 2278
Cdd:cd15261    154 MKVNR-CWFGYYlTPYYWILEGPRLAVILINlffllNIIRVLVSKLRESHSREIEQvRKAV----KAAIVLLPLLGITNI 228

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1894698391 2279 FGLLAVN--NSVLAF---HYLYTVLCSLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15261    229 LQMIPPPltSVIVGFavwSYSTHFLTSFQGFFVALIYCFLNGEVK 273
EGF_Lam cd00055
Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous ...
 1610-1648 4.28e-13

Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in tandem arrays; the domain contains 4 disulfide bonds (loops a-d) the first three resemble epidermal growth factor (EGF); the number of copies of this domain in the different forms of laminins is highly variable ranging from 3 up to 22 copies


Pssm-ID: 238012  Cd Length: 50  Bit Score: 65.84  E-value: 4.28e-13
                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1894698391 1610 PCDCYPVGSTSRSCDKETGRCHCRPGVIGRQCNSCDSPF 1648
Cdd:cd00055      1 PCDCNGHGSLSGQCDPGTGQCECKPNTTGRRCDRCAPGY 39
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
 2134-2318 1.31e-12

insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of hormone receptors; member of the class B secretin-like seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Bombyx mori (silk worm) and its closely related proteins from arthropods. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 320390 [Multi-domain]  Cd Length: 270  Bit Score: 70.94  E-value: 1.31e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2134 TENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRM--QTEARNVNFgamRFYYAIGWGV---PAIITGLAVGLDpegygN 2208
Cdd:cd15262     76 NQNAVVCRLLSIFERAARNAVFACMFVEGFYLHRLivAVFAEKSSI---RFLYVIGAVLplfPVIIWAIIRALH-----N 147

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2209 PDFCWISIHDKLVWSFAGPITVVIVMNGVMFL-----LVAKMSCSPGQKETKKksvlmTLRSSFVLLLvisttwLFGLLA 2283
Cdd:cd15262    148 DHSCWVVDIEGVQWVLDTPRLFILLVNTVLLVdiirvLVTKLRNTEENSQTKS-----TTRATLFLVP------LFGLHF 216

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1894698391 2284 V----------NNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15262    217 VitayrpstddCDWEDIYYYANYLIEGLQGFLVAILFCYINKEVH 261
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
 2096-2313 1.51e-12

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: 70.60  E-value: 1.51e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2096 FSFLTCL-KGLKS-NTRSIHSN--ISVTLFFSELLFLLGINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTE 2171
Cdd:cd15442     26 YFFLRFTyQKFKSeDAPKIHVNlsSSLLLLNLAFLLNSGVSSRAHPGLCKALGGVTHYFLLCCFTWMAIEAFHLYLLAIK 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2172 ARNVnfgAMRFYYA----IGWGVPAIITGLAVGLDPEG-YGNPD--------FCWISIHDKLVW--SFAGPITVVIVMNG 2236
Cdd:cd15442    106 VFNT---YIHHYFAklclVGWGFPALVVTITGSINSYGaYTIMDmanrttlhLCWINSKHLTVHyiTVCGYFGLTFLFNT 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2237 VMFLLVAKMSCS-----PGQKETKKKSVLMTLRSSFVLLLVistTWLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFC 2311
Cdd:cd15442    183 VVLGLVAWKIFHlqsatAGKEKCQAWKGGLTVLGLSCLLGV---TWGLAFFTYGSMSVPTVYIFALLNSLQGLFIFIWFV 259


                   ..
gi 1894698391 2312 VL 2313
Cdd:cd15442    260 IL 261
Laminin_EGF pfam00053
Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.
 1611-1644 1.90e-12

Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.


Pssm-ID: 395007  Cd Length: 49  Bit Score: 63.91  E-value: 1.90e-12
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1894698391 1611 CDCYPVGSTSRSCDKETGRCHCRPGVIGRQCNSC 1644
Cdd:pfam00053    1 CDCNPHGSLSDTCDPETGQCLCKPGVTGRHCDRC 34
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
 2130-2325 8.36e-12

G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR124 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, which also includes orphan GPR123 and GPR125. GPR124, also known as tumor endothelial marker 5 (TEM5), is highly expressed in tumor vessels and in the vasculature of the developing embryo. GPR124 is essentially required for proper angiogenic sprouting into neural tissue, CNS-specific vascularization, and formation of the blood-brain barrier. GPR124 interacts with the PDZ domain of DLG1 (discs large homolog 1) through its PDZ-binding motif. Recently, studies of double-knockout mice showed that GPR124 functions as a co-activator of Wnt7a/Wnt7b-dependent beta-catenin signaling in brain endothelium. Moreover, WNT7-stimulated beta-catenin signaling is regulated by GPR124's intracellular PDZ binding motif and leucine-rich repeats (LRR) in its N-terminal extracellular domain. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320664 [Multi-domain]  Cd Length: 268  Bit Score: 68.44  E-value: 8.36e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2130 GINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQT---------EARNVNFGAMRFYYAIGWGVPAIITGLAVG 2200
Cdd:cd15998     60 GITLTNYQMVCQAVGITLHYSSLSTLLWMGVKARVLHKELTwrapppqegDPALPTPRPMLRFYLIAGGIPLIICGITAA 139

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2201 LDPEGY-GNPDFCWisihdkLVW-----SFAGPITVVIVMNGVMFLLVA-KMSCSPGQKET--KKKSVLMTLRSSFVLLL 2271
Cdd:cd15998    140 VNIHNYrDHSPYCW------LVWrpslgAFYIPVALILLVTWIYFLCAGlHLRGPSADGDSvySPGVQLGALVTTHFLYL 213

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1894698391 2272 VIsttWLFGLLAVNNSVL---AFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWKLAC 2325
Cdd:cd15998    214 AM---WACGALAVSQRWLprvVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACC 267
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
 2139-2322 1.56e-11

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


Pssm-ID: 320399 [Multi-domain]  Cd Length: 267  Bit Score: 67.45  E-value: 1.56e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2139 LCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTearnVNFGAMR----FYYAIGWGVPAIITGLAVGL----DPEGygnpd 2210
Cdd:cd15271     76 ACKAAVTFFQFCVLANFFWLLVEGMYLQTLLL----LTFTSDRkyfwWYILIGWGAPSVTVTVWVLTrlqyDNRG----- 146

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2211 fCWISIHDKLVWSFAGPITVVIVMNGVMFL-----LVAKMScSPGQKETKKKSVLMTLRSSFVLLLVISTTW-LFGLLAV 2284
Cdd:cd15271    147 -CWDDLESRIWWIIKTPILLSVFVNFLIFInviriLVQKLK-SPDVGGNDTSHYMRLAKSTLLLIPLFGVHYvVFAFFPE 224

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1894698391 2285 NNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEV-----REAWK 2322
Cdd:cd15271    225 HVGVEARLYFELVLGSFQGFIVALLYCFLNGEVqaeikKRLGK 267
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
 2135-2318 1.84e-11

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: 67.46  E-value: 1.84e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2135 ENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIIT---GLA-VGLDPEGygnpd 2210
Cdd:cd15266     82 ESSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLFVvpwGVAkILLENTG----- 156

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2211 fCW-ISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMSCSpgqketKKKSVLMTLRsSFVLLLVISTTWLFGLLAVNNSVL 2289
Cdd:cd15266    157 -CWgRNENMGIWWIIRGPILLCITVNFYIFLKILKLLLS------KLKAQQMRFT-DYKYRLARSTLVLIPLLGIHEVVF 228

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1894698391 2290 AF--------------HYLYTVLCSLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15266    229 SFitdeqvegfsrhirLFIQLTLSSFQGFLVAVLYCFANGEVK 271
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
 2140-2322 1.85e-11

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


Pssm-ID: 320397 [Multi-domain]  Cd Length: 268  Bit Score: 67.19  E-value: 1.85e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQTearnVNFGAMRFYY----AIGWGVPAI-ITGLAVGldpEGYGNPDFCW- 2213
Cdd:cd15269     77 CKAAMVFFQYCIMANFFWLLVEGLYLHTLLA----VSFFSERKYFwwyiLIGWGAPSVfITAWSVA---RIYFEDVGCWd 149

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2214 ISIHDKLVWSFAGPITVVIVMNGVMFL-----LVAKMSCSP-GQKETKKKSVLMtlRSSFVLLLVISTTW-LFGLLAVNN 2286
Cdd:cd15269    150 TIIESLLWWIIKTPILVSILVNFILFIciiriLVQKLHSPDiGRNESSQYSRLA--KSTLLLIPLFGIHYiMFAFFPDNF 227

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1894698391 2287 SVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15269    228 KAEVKLVFELILGSFQGFVVAVLYCFLNGEVQAELK 263
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
 2140-2322 2.69e-11

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


Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 66.92  E-value: 2.69e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARnvnFGAMRFYY---AIGWGVPAI-ITGLAVgldPEGYGNPDFCW-I 2214
Cdd:cd15987     77 CKAVMVFFHYCVMSNYFWLFIEGLYLFTLLVETF---FPERRYFYwytIIGWGTPTIcVTVWAV---LRLHFDDTGCWdM 150

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2215 SIHDKLVWSFAGPITVVIVMNGVMF-----LLVAKMScSP--GQKEtkkksvlmtlrSSFVLLLVISTTWLFGLLAVNNS 2287
Cdd:cd15987    151 NDNTALWWVIKGPVVGSIMINFVLFigiiiILVQKLQ-SPdiGGNE-----------SSIYLRLARSTLLLIPLFGIHYT 218

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1894698391 2288 VLAF---------HYLYTV-LCSLQGLAVLVLFCVLNEEVREAWK 2322
Cdd:cd15987    219 VFAFspenvskreRLVFELgLGSFQGFVVAVLYCFLNGEVQSEIK 263
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
 2130-2325 4.73e-11

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: 66.81  E-value: 4.73e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2130 GINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQT----------EARNVNFGAMRFYYaIGWGVPAIITGLAV 2199
Cdd:cd15999     60 GINQTRNASVCQAVGIILHYSTLATVLWVGVTARNIYKQVTrkakrcqdpdEPPPPPRPMLRFYL-IGGGIPIIVCGITA 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2200 GLDPEGYG---NPDFCWISIHDKLvWSFAGPITVVIVMNGVMFL-------------------------LVAKMSCSPGQ 2251
Cdd:cd15999    139 AANIKNYGsrpNAPYCWMAWEPSL-GAFYGPAGFIIFVNCMYFLsifiqlkrhperkyelkepteeqqrLAASEHGELNH 217

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2252 KETKKKSVLMTLRSSFVL----------------LLVISTTWLFGLLAVNNSV---LAFHYLYTVLCSLQGLAVLVLFCV 2312
Cdd:cd15999    218 QDSGSSSASCSLVSTSALenehsfqaqllgaslaLFLYVALWIFGALAVSLYYpmdLVFSCLFGATCLSLGAFLVVHHCV 297

                          250
                   ....*....|...
gi 1894698391 2313 LNEEVREAWKLAC 2325
Cdd:cd15999    298 NREDVRRAWIATC 310
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
 2131-2318 8.07e-11

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


Pssm-ID: 320401 [Multi-domain]  Cd Length: 285  Bit Score: 65.47  E-value: 8.07e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2131 INRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITG--LAVGLDPEGygn 2208
Cdd:cd15273     82 IANIGSNWVCKAITSLWQYFIIANYSWILMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFVVpwIVARILFEN--- 158

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2209 pDFCWISIHDKLV-WSFAGPITVVIVMNGVMFL-----LVAKMSCSPGQKETKKKSVLmtlRSSFVL--LLVISTTWLFG 2280
Cdd:cd15273    159 -SLCWTTNSNLLNfLIIRIPIMISVLINFILFLnivrvLLVKLRSSVNEDSRRYKKWA---KSTLVLvpLFGVHYTIFLI 234

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1894698391 2281 LLAVNNSVLAFHYLY----TVLCSLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15273    235 LSYLDDTNEAVELIWlfcdQLFASFQGFFVALLYCFLNGEVR 276
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
 2136-2320 1.10e-10

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


Pssm-ID: 320562 [Multi-domain]  Cd Length: 264  Bit Score: 64.98  E-value: 1.10e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2136 NQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPA-IITGLAVGldpEGYGNPDFCWI 2214
Cdd:cd15446     68 NEVWCRCITTIYNYFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCpIIVAWAIG---KLYYENEQCWF 144

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2215 SIH--DKLVWSFAGPITVVIVMNGVMFLLVAKMSCSPGQKETKKKSVLM--TLRSSFVLLLVISTTWLfgLLAVNN---- 2286
Cdd:cd15446    145 GKEpgKYIDYIYQGPVILVLLINFVFLFNIVRILMTKLRASTTSETIQYrkAVKATLVLLPLLGITYM--LFFVNPgedd 222

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1894698391 2287 -SVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREA 2320
Cdd:cd15446    223 iSQIVFIYFNSFLQSFQGFFVSVFYCFLNGEVRSA 257
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
 2140-2318 1.36e-10

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: 64.76  E-value: 1.36e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQtearNVNFGAMR----FYYAIGWGVPAI-ITGLAVG---LDPEGygnpdf 2211
Cdd:cd15275     77 CKVAMVFSNYCIMANYSWLLVEGLYLHSLL----SISFFSERkhlwWYIALGWGSPLIfIISWAIArylHENEG------ 146

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2212 CW-ISIHDKLVWSFAGPITVVIVMNGVMFL-----LVAKMSCSPGQ-KETKKKSVLMtlRSSFVLLLVISTTW-LFGLLA 2283
Cdd:cd15275    147 CWdTRRNAWIWWIIRGPVILSIFVNFILFLnilriLMRKLRAPDMRgNEFSQYKRLA--KSTLLLIPLFGLHYiLFAFFP 224

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1894698391 2284 VNNSVLAFH---YLYTVLCSLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15275    225 EDVSSGTMEiwlFFELALGSFQGFVVAVLYCFLNGEVQ 262
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 729-810 1.81e-10

Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers.


Pssm-ID: 206637 [Multi-domain]  Cd Length: 98  Bit Score: 60.02  E-value: 1.81e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  729 NTFPSGVIGKVPAYDPDVSD--RLFYTFERGNELHLLIVNQSSGELRLSRKLDNNRPLVASMLVTVTD-GIHSVTAQCVL 805
Cdd:cd11304      9 NAPPGTVVLTVSATDPDSGEngEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDgGGPPLSSTATV 88


                   ....*
gi 1894698391  806 RVIII 810
Cdd:cd11304     89 TITVL 93
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
 2140-2319 2.08e-10

orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR56 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR64, GPR97, GPR112, GPR114, and GPR126. GPR56 is involved in the regulation of oligodendrocyte development and myelination in the central nervous system via coupling to G(12/13) proteins, which leads to the activation of RhoA GTPase. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320661  Cd Length: 269  Bit Score: 64.08  E-value: 2.08e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYY-AIGWGVPAIITGLAVGLD--------------PE 2204
Cdd:cd15995     70 CRAGGMFLHFSLLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLcAVGWGLPIFLVTLIFLVDqdnygpiilavhrsPE 149

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2205 GYGNPDFCWISihDKLVWSFA--GPITVVIVMNGVMFLLVAKMSCSPGQKETKKKSVLMTLRSSfvllLVISTTW--LFG 2280
Cdd:cd15995    150 KVTYATICWIT--DSLISNITnlGLFSLVFLFNMAMLATMVVEILRLRPRTHKWSHVLTLLGLS----LVLGIPWalAFF 223

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1894698391 2281 LLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVRE 2319
Cdd:cd15995    224 SFASGTFQLVIVYLFTIINSLQGFLIFLWYWSMVLQARG 262
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 1660-1720 5.50e-10

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: 57.38  E-value: 5.50e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1894698391 1660 YDGCPKSLKAGVWWPQTKFGFSAAVLCPKGSLGLRGAGAAIRHCDEEKGWLEP---DLFNCTSP 1720
Cdd:pfam02793    1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDPRGNASRNCTEDGTWSEHppsNYSNCTSN 64
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
 2136-2320 8.58e-10

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: 62.26  E-value: 8.58e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2136 NQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVP-AIITGLAVGldpEGYGNPDFCWI 2214
Cdd:cd15445     69 NVVWCRLVTAAYNYFHVTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFICIGWCIPfPIIVAWAIG---KLYYDNEKCWF 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2215 SIHDKLV--WSFAGPITVVIVMNGVMFLLVAKMSCSPGQKETKKKSVLM--TLRSSFVLLLVISTTWLfgLLAVNN---- 2286
Cdd:cd15445    146 GKRAGVYtdYIYQGPMILVLLINFIFLFNIVRILMTKLRASTTSETIQYrkAVKATLVLLPLLGITYM--LFFVNPgede 223

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1894698391 2287 -SVLAFHYLYTVLCSLQGLAVLVLFCVLNEEVREA 2320
Cdd:cd15445    224 iSRIVFIYFNSFLESFQGFFVSVFYCFLNSEVRSA 258
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
 2136-2323 2.33e-09

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: 60.95  E-value: 2.33e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2136 NQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVgLDPEGYGNpDFCWIS 2215
Cdd:cd15274     71 NPVSCKILHFIHQYMMGCNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHA-ITRAVYYN-DNCWLS 148

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2216 IHDKLVWSFAGPITVVIVMNGVMFL-----LVAKMscspgqKETKKKSVLMTL---RSSFVLLLVISTTWLFGLLAVNNS 2287
Cdd:cd15274    149 SETHLLYIIHGPIMAALVVNFFFLLnivrvLVTKL------RETHEAESHMYLkavKATLILVPLLGIQFVLFPWRPSGK 222

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1894698391 2288 VLA--FHYLYTVLCSLQGLAVLVLFCVLNEEVREAWKL 2323
Cdd:cd15274    223 ILGkiYDYVMHSLIHFQGFFVATIFCFCNGEVQATLKR 260
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
 2140-2321 2.43e-09

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: 60.91  E-value: 2.43e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPA--IITGLAVGLDPEGYGnpdfCWISIH 2217
Cdd:cd15929     86 CRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSERSIFRLYLLLGWGAPVlfVVPWGIVKYLYENTG----CWTRND 161

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2218 DKLVW-SFAGPITVVIVMNGVMFLLVAKMSCSpgqketKKKSVLMTlRSSFVLLLVISTTWLFGLLAVNNSVLAF----H 2292
Cdd:cd15929    162 NMAYWwIIRLPILLAILINFFIFVRILKILVS------KLRANQMC-KTDYKFRLAKSTLTLIPLLGVHEVVFAFvtdeQ 234

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1894698391 2293 YLYTV----------LCSLQGLAVLVLFCVLNEEV----REAW 2321
Cdd:cd15929    235 ARGTLrfiklffelfLSSFQGLLVAVLYCFANKEVqselRKKW 277
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
 2139-2318 3.89e-09

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


Pssm-ID: 320398 [Multi-domain]  Cd Length: 268  Bit Score: 60.20  E-value: 3.89e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2139 LCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGldPEGYGNPDFCW-ISIH 2217
Cdd:cd15270     76 LCKVSVVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWIL--CKLYFEDTECWdINND 153

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2218 DKLVWSFAGPITVVIVMNGVMFL-----LVAKMSCSPGQKETKKKSVLMTlRSSFVLLLVISTTWL-FGLLAVNNSVLAF 2291
Cdd:cd15270    154 SPYWWIIKGPIVISVGVNFLLFLniiriLLKKLDPRQINFNNSAQYRRLS-KSTLLLIPLFGTHYIiFNFLPDYAGLGIR 232

                          170       180
                   ....*....|....*....|....*..
gi 1894698391 2292 HYLYTVLCSLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15270    233 LYLELCLGSFQGFIVAVLYCFLNQEVQ 259
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
 2140-2318 1.29e-08

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: 58.66  E-value: 1.29e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGL--HIYRMQTEARNVNFGAmrfYYAIGWGVPA--IITGLAVGLDPEGYGnpdfCWIS 2215
Cdd:cd15986     79 CKVSLVILQYCIMANFYWLLVEGLylHTLLVVIFSENRHFIV---YLLIGWGIPTvfIIAWIVARIYLEDTG----CWDT 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2216 I-HDKLVWSFAGPITVVIVMNGVMFL-----LVAKMSCSP--GQKETKKKSvlmtlrssfvllLVISTTWLFGLLAVNNS 2287
Cdd:cd15986    152 NdHSVPWWVIRIPIIISIILNFILFIsiiriLLQKLRSPDvgGNDQSQYKR------------LAKSTLLLIPLFGVHYI 219

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1894698391 2288 VLAFHYL-----YTV---LC--SLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15986    220 VFVYFPDssssnYQIffeLClgSFQGLVVAILYCFLNSEVQ 260
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 2016-2061 1.40e-08

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: 52.69  E-value: 1.40e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1894698391 2016 PLCVQWNHSNltNPSGFWTARDCELVYRNTTHVHCQCSQFGTFGVL 2061
Cdd:pfam01825    1 PQCVFWDFTN--STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
CA_like cd00031
Cadherin repeat-like domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 508-607 2.51e-08

Cadherin repeat-like domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers. This family also includes the cadherin-like repeats of extracellular alpha-dystroglycan.


Pssm-ID: 206635  Cd Length: 98  Bit Score: 53.89  E-value: 2.51e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  508 PHYQGMISEDAPPFtsVLQIsATDRDAHTNGRVQYTFQNGEDGDGDFTIEPTSGIIRTVRRLDRENVPVYELTAYAVDRG 587
Cdd:cd00031      2 PDGSAVEGRSRGSF--RVSI-PTDLIASSGEIIKISAAGKEALPSWLHWEPHSGILEGLEKLDREDKGVHYISVSAASLG 78

                           90       100
                   ....*....|....*....|
gi 1894698391  588 IPPQRTPVHIQVTIQDVNDN 607
Cdd:cd00031     79 ANVPQTSSVFSIEVYDENDN 98
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
 2140-2318 2.92e-08

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


Pssm-ID: 320400 [Multi-domain]  Cd Length: 285  Bit Score: 57.78  E-value: 2.92e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPA--IITGLAVgldpEGYGNPDFCWISIH 2217
Cdd:cd15272     90 CKLFFTMFNYILGANYMWIFVEGLYLHMLIFVAVFSENSRVKWYILLGWLSPLlfVLPWVFV----RATLEDTLCWNTNT 165

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2218 DKL-VWSFAGPITVVIVMNGVMFL-----LVAKMSCSPGQKETKKKSVLMTlRSSFVLLLvisttwLFG----LLAVNNS 2287
Cdd:cd15272    166 NKGyFWIIRGPIVISIAINFLFFInivrvLFTKLKASNTQESRPFRYRKLA-KSTLVLIP------LFGvhymVFVVLPD 238

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1894698391 2288 VLAFHYLYTVLC-------SLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15272    239 SMSSDEAELVWLyfemffnSFQGFIVALLFCFLNGEVQ 276
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1263-1293 3.73e-08

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.


Pssm-ID: 394967  Cd Length: 31  Bit Score: 51.23  E-value: 3.73e-08
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1894698391 1263 CDSSPCKNGGTCSVSWGTYSCLCPVGFGGKD 1293
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
 2130-2322 3.81e-08

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


Pssm-ID: 341342 [Multi-domain]  Cd Length: 279  Bit Score: 57.27  E-value: 3.81e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2130 GINRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVP---AIITGLAVGL-DPEG 2205
Cdd:cd15268     76 GLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPllfVIPWGIVKYLyEDEG 155

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2206 ygnpdfCWISIHDKLVWSFAG-PITVVIVMNGVMFLLVAKMSCSpgqketKKKSVLMTlRSSFVLLLVISTTWLFGLLAV 2284
Cdd:cd15268    156 ------CWTRNSNMNYWLIIRlPILFAIGVNFLIFIRVICIVVS------KLKANLMC-KTDIKCRLAKSTLTLIPLLGT 222

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1894698391 2285 NNSVLAF----HY--------LYTVL--CSLQGLAVLVLFCVLNEEV----REAWK 2322
Cdd:cd15268    223 HEVIFAFvmdeHArgtlrfvkLFTELsfTSFQGLMVAILYCFVNNEVqmefRKSWE 278
Laminin_G_1 pfam00054
Laminin G domain;
1330-1454 5.93e-08

Laminin G domain;


Pssm-ID: 395008 [Multi-domain]  Cd Length: 131  Bit Score: 53.86  E-value: 5.93e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 1330 FRTRQPDGVLL---QAHAGQYTTLlcQLAGGLLSFMVSRGSGRSTSLLLDqlRLSDGRWHDLQLElrdvRSGRdsryVIT 1406
Cdd:pfam00054    1 FRTTEPSGLLLyngTQTERDFLAL--ELRDGRLEVSYDLGSGAAVVRSGD--KLNDGKWHSVELE----RNGR----SGT 68

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1894698391 1407 LTVDFGLYQD-TVVVGNELHGLKVKHLHVGGVLGSGE------VQNGLRGCIQGV 1454
Cdd:pfam00054   69 LSVDGEARPTgESPLGATTDLDVDGPLYVGGLPSLGVkkrrlaISPSFDGCIRDV 123
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
 2140-2319 8.70e-08

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: 56.37  E-value: 8.70e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPA--IITGLAVGLdpeGYGNPDfCWISIH 2217
Cdd:cd15267     88 CRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPAlfVVPWVVVKC---LYENVQ-CWTSND 163

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2218 D-KLVWSFAGPITVVIVMNGVMF-----LLVAKMScSPGQKETKKKsvlmtlrssfvLLLVISTTWLFGLLAVNNSVLAF 2291
Cdd:cd15267    164 NmGFWWILRFPVFLAILINFFIFvriiqILVSKLR-ARQMHYTDYK-----------FRLAKSTLTLIPLLGIHEVVFAF 231

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1894698391 2292 ----HYLYTV----------LCSLQGLAVLVLFCVLNEEVRE 2319
Cdd:cd15267    232 vtdeHAQGTLrsaklffdlfLSSFQGLLVAVLYCFLNKEVQS 273
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 977-1006 2.80e-07

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.


Pssm-ID: 394967  Cd Length: 31  Bit Score: 48.92  E-value: 2.80e-07
                           10        20        30
                   ....*....|....*....|....*....|
gi 1894698391  977 CYSNPCLNGGICTRKEGGYTCVCRQHFSGE 1006
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGK 30
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1263-1294 3.25e-07

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 48.79  E-value: 3.25e-07
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1894698391 1263 CDS-SPCKNGGTCSVSWGTYSCLCPVGFGGKDC 1294
Cdd:cd00054      5 CASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37
CA_like cd00031
Cadherin repeat-like domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 202-296 6.09e-07

Cadherin repeat-like domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. The cadherin repeat domains occur as tandem repeats in the extracellular regions, which are thought to mediate cell-cell contact when bound to calcium. They play numerous roles in cell fate, signalling, proliferation, differentiation, and migration; members include E-, N-, P-, T-, VE-, CNR-, proto-, and FAT-family cadherin, desmocollin, and desmoglein, a large variety of domain architectures with varying repeat copy numbers. Cadherin-repeat containing proteins exist as monomers, homodimers, or heterodimers. This family also includes the cadherin-like repeats of extracellular alpha-dystroglycan.


Pssm-ID: 206635  Cd Length: 98  Bit Score: 50.04  E-value: 6.09e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391  202 ISVLENAPLGHSVIHIQAvdaDYGENSRLEYKLTGVSADTP---FVVNSATGWITVSGPLDRESVEHYFFGVEARDHGSP 278
Cdd:cd00031      4 GSAVEGRSRGSFRVSIPT---DLIASSGEIIKISAAGKEALpswLHWEPHSGILEGLEKLDREDKGVHYISVSAASLGAN 80

                           90
                   ....*....|....*...
gi 1894698391  279 SLSASASVTITVMDVNDN 296
Cdd:cd00031     81 VPQTSSVFSIEVYDENDN 98
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1484-1516 8.66e-07

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 47.63  E-value: 8.66e-07
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1894698391 1484 CDS-NPCPVNSICKDEWQSYSCVCQPGYYGGDCV 1516
Cdd:cd00054      5 CASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
 2133-2321 2.47e-06

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


Pssm-ID: 320649 [Multi-domain]  Cd Length: 285  Bit Score: 51.85  E-value: 2.47e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2133 RTENQFLCTVIAILLHCFFLST-FAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGL-----DPEgy 2206
Cdd:cd15983     82 GTRLQWVGCKVTVTLFLYFLATnHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVWASVrvslaDTQ-- 159

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2207 gnpdfCWISIHDKLVWSFAGPITVVIVMNGVMFLLVAKMSCS-----------PGQ---KETKKKSVLMTLRS-SFVLLL 2271
Cdd:cd15983    160 -----CWDLSAGNLKWIYQVPILAAILVNFFLFLNIVRVLASklwetntgkldPRQqyrKLLKSTLVLMPLFGvHYVLFM 234

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1894698391 2272 VISTTWLFGLLAvnnsVLAFHYlYTVLCSLQGLAVLVLFCVLNEEV----REAW 2321
Cdd:cd15983    235 AMPYTDVTGLLW----QIQMHY-EMLFNSSQGFFVAFIYCFCNGEVqaeiKKAW 283
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
 2135-2318 2.91e-06

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


Pssm-ID: 320648 [Multi-domain]  Cd Length: 289  Bit Score: 51.86  E-value: 2.91e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2135 ENQFLCTVIAILLHCFFLST-FAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGL-----AVGLDPEgygn 2208
Cdd:cd15982     89 KSQYVGCKIAVVMFIYFLATnYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVFVAAwavvrATLADAR---- 164

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2209 pdfCWISIHDKLVWSFAGPITVVIVMNGVMFL-----LVAKMSCSPGQKETKKKSVLMTLRSSFVLLLVISTTWLFgLLA 2283
Cdd:cd15982    165 ---CWELSAGDIKWIYQAPILAAIGLNFILFLntvrvLATKIWETNAVGYDTRKQYRKLAKSTLVLVLVFGVHYIV-FVC 240

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1894698391 2284 VNNSVLAFHYLYTVLC-----SLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15982    241 LPHTFTGLGWEIRMHCelffnSFQGFFVSIIYCYCNGEVQ 280
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
 2140-2318 3.19e-06

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


Pssm-ID: 320393 [Multi-domain]  Cd Length: 289  Bit Score: 51.61  E-value: 3.19e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAI-----ITGLAVGLDPEgygnpdfCWI 2214
Cdd:cd15265     95 CKVAVTLFLYFLATNYYWILVEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVfvipwASVRATLADTR-------CWD 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2215 SIHDKLVWSFAGPITVVIVMNGVMFL-----LVAKM------SCSPGQKETKkksvlmTLRSSFVLLLvisttwLFGLla 2283
Cdd:cd15265    168 LSAGNYKWIYQVPILAAIVVNFILFLnivrvLATKLretnagRCDTRQQYRK------LAKSTLVLIP------LFGV-- 233

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1894698391 2284 vnnsvlafHYL------YTV--------------LCSLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15265    234 --------HYIvfmgmpYTEvgllwqirmhyelfFNSFQGFFVAIIYCFCNGEVQ 280
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1019-1051 3.48e-06

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 45.71  E-value: 3.48e-06
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1894698391 1019 PGVCRNGGTCTNGaDGGFRCQCPAgGFEMPFCE 1051
Cdd:cd00054      8 GNPCQNGGTCVNT-VGSYRCSCPP-GYTGRNCE 38
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 974-1005 5.47e-06

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 45.32  E-value: 5.47e-06
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1894698391  974 INLCYS-NPCLNGGICTRKEGGYTCVCRQHFSG 1005
Cdd:cd00054      2 IDECASgNPCQNGGTCVNTVGSYRCSCPPGYTG 34
7tmE_cAMP_R_Slime_mold cd14940
slime mold cyclic AMP receptor, member of the class E family of seven-transmembrane G ...
 2134-2317 5.72e-06

slime mold cyclic AMP receptor, member of the class E family of seven-transmembrane G protein-coupled receptors; This family represents the class E of seven-transmembrane G-protein coupled receptors found in soil-living amoebas, commonly referred to as slime molds. The class E family includes cAMP receptors (cAR1-4) and cAMP receptors-like proteins (CrlA-C) from Dictyostelium discoideum, and their highly homologous cAMP receptors (TasA and TasB) from Polysphondylium pallidum. So far, four subtypes of cAMP receptors (cAR1-4) have been identified that play an essential role in the detection and transmit of the periodic extracellular cAMP waves that regulate chemotactic cell movement during Dictyostelium development, from the unicellular amoeba aggregate into many multicellular slugs and then differentiate into a sporocarp, a fruiting body with cells specialized for different functions. These four subtypes differ in their expression levels and patterns during development. cAR1 is high-affinity receptor that is the first one to be expressed highly during early aggregation and continues to be expressed at low levels during later developmental stages. cAR1 detects extracellular cAMP and is coupled to G-alpha2 protein. Cells lacking cAR1 fail to aggregate, demonstrating that cAR1 is responsible for aggregation. During later aggregation the high-affinity cAR3 receptor is expressed at low levels. Nonetheless, cells lacking cAR3 do not show an obviously altered pattern of development and are still able to aggregate into fruiting bodies. In contrast, cAR2 and cAR4 are low affinity receptors expressed predominantly after aggregation in pre-stalk cells. cAR2 is essential for normal tip formation and deletion of the receptor arrests development at the mound stage. On the other hand, CAR4 regulates axial patterning and cellular differentiation, and deletion of the receptor results in defects during culmination. Furthermore, three cAMP receptor-like proteins (CrlA-C) were identified in Dictyostelium that show limited sequence similarity to the cAMP receptors. Of these CrlA is thought to be required for normal cell growth and tip formation in developing aggregates.


Pssm-ID: 320094 [Multi-domain]  Cd Length: 256  Bit Score: 50.43  E-value: 5.72e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2134 TENQFLCTVIAILLHCFFLSTFAWLFIQGLHIY----RMQTEARNVNfgamRFYYAIGWGVPAIITGLAVGLDPEGY-GN 2208
Cdd:cd14940     62 RPDGFLCYLYAIVITYGSLSCWLWTLCLAISIYllivKREPEPEKFE----KYYHFVCWGLPLISTIIMLIKHHYGPvGN 137

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2209 pdFCWIsIHDKLVWSFA---GPITVVIVMNGVMFLLVA-----KMSCSPGQKETKKKSVLMTLRSSFVLLLVIsttWLFG 2280
Cdd:cd14940    138 --WCWI-GNQYTGYRFGlfyGPFFIIFGISAVLVGLTShytyqVIHNWVSDNKDLHKTYQFKLVNYIIVFLLC---WIFA 211

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1894698391 2281 LL-----AVNNSVLAFHYLYTVLCSLQGLAVLVLFcVLNEEV 2317
Cdd:cd14940    212 VInriqnALNPFPFALNLLHTYLSPSHGFYASVVF-IYNNPL 252
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
 2137-2321 1.08e-05

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: 49.95  E-value: 1.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2137 QFLCTVIAILLHCFFLST-FAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGL-----AVGLDPEgygnpd 2210
Cdd:cd15984     91 QFVGCKVAVTFFLYFLATnYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIwasvrATLADTG------ 164

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2211 fCWISIHDKLVWSFAGPITVVIVMNGVMFL-----LVAKMSCSPGQKETKKKSVLMTLRSSFVLLLVISTTWL----FGL 2281
Cdd:cd15984    165 -CWDLSAGNLKWIIQVPILAAIVVNFILFInivrvLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIvfmaMPY 243

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1894698391 2282 LAVNNSVLAFHYLYTVLC-SLQGLAVLVLFCVLNEEV----REAW 2321
Cdd:cd15984    244 TEVSGILWQVQMHYEMLFnSFQGFFVAIIYCFCNGEVqaeiKKSW 288
EGF_CA smart00179
Calcium-binding EGF-like domain;
1019-1051 1.56e-05

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 44.16  E-value: 1.56e-05
                            10        20        30
                    ....*....|....*....|....*....|...
gi 1894698391  1019 PGVCRNGGTCTNGaDGGFRCQCPAGGFEMPFCE 1051
Cdd:smart00179    8 GNPCQNGGTCVNT-VGSYRCECPPGYTDGRNCE 39
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
 1264-1292 1.75e-05

Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large number of proteins, mostly animal; the list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied; the functional significance of EGF-like domains in what appear to be unrelated proteins is not yet clear; a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase); the domain includes six cysteine residues which have been shown to be involved in disulfide bonds; the main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet; Subdomains between the conserved cysteines vary in length; the region between the 5th and 6th cysteine contains two conserved glycines of which at least one is present in most EGF-like domains; a subset of these bind calcium.


Pssm-ID: 238010  Cd Length: 36  Bit Score: 44.00  E-value: 1.75e-05
                           10        20
                   ....*....|....*....|....*....
gi 1894698391 1264 DSSPCKNGGTCSVSWGTYSCLCPVGFGGK 1292
Cdd:cd00053      4 ASNPCSNGGTCVNTPGSYRCVCPPGYTGD 32
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
 2132-2314 4.53e-05

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.


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 47.81  E-value: 4.53e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2132 NRTENQFLCTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVN----FGAMRFYYAIGWGVPAI--ITGLAV-GLDPE 2204
Cdd:cd14964     63 ASSRPQALCYLIYLLWYGANLASIWTTLVLTYHRYFALCGPLKYTrlssPGKTRVIILGCWGVSLLlsIPPLVGkGAIPR 142

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2205 ----GYGNPDFCWISIHDKLV--WSFAGPITVVIVMN--GVMFLLVAKMSCSPGQ-----KETKKKSVLMTLRSSFVLLL 2271
Cdd:cd14964    143 yntlTGSCYLICTTIYLTWGFllVSFLLPLVAFLVIFsrIVLRLRRRVRAIRSAAslntdKNLKATKSLLILVITFLLCW 222

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1894698391 2272 V---ISTTwLFGLLAVNNSVLAFHYLYTVLCSLQGLAVLVLFCVLN 2314
Cdd:cd14964    223 LpfsIVFI-LHALVAAGQGLNLLSILANLLAVLASTLNPFIYCLGN 267
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
 979-1006 5.01e-05

Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large number of proteins, mostly animal; the list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied; the functional significance of EGF-like domains in what appear to be unrelated proteins is not yet clear; a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase); the domain includes six cysteine residues which have been shown to be involved in disulfide bonds; the main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet; Subdomains between the conserved cysteines vary in length; the region between the 5th and 6th cysteine contains two conserved glycines of which at least one is present in most EGF-like domains; a subset of these bind calcium.


Pssm-ID: 238010  Cd Length: 36  Bit Score: 42.46  E-value: 5.01e-05
                           10        20
                   ....*....|....*....|....*...
gi 1894698391  979 SNPCLNGGICTRKEGGYTCVCRQHFSGE 1006
Cdd:cd00053      5 SNPCSNGGTCVNTPGSYRCVCPPGYTGD 32
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
 1483-1512 1.21e-04

Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large number of proteins, mostly animal; the list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied; the functional significance of EGF-like domains in what appear to be unrelated proteins is not yet clear; a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase); the domain includes six cysteine residues which have been shown to be involved in disulfide bonds; the main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet; Subdomains between the conserved cysteines vary in length; the region between the 5th and 6th cysteine contains two conserved glycines of which at least one is present in most EGF-like domains; a subset of these bind calcium.


Pssm-ID: 238010  Cd Length: 36  Bit Score: 41.31  E-value: 1.21e-04
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1894698391 1483 PCD-SNPCPVNSICKDEWQSYSCVCQPGYYG 1512
Cdd:cd00053      1 ECAaSNPCSNGGTCVNTPGSYRCVCPPGYTG 31
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1484-1512 1.53e-04

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.


Pssm-ID: 394967  Cd Length: 31  Bit Score: 41.21  E-value: 1.53e-04
                           10        20
                   ....*....|....*....|....*....
gi 1894698391 1484 CDSNPCPVNSICKDEWQSYSCVCQPGYYG 1512
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTG 29
EGF_CA smart00179
Calcium-binding EGF-like domain;
1263-1294 1.80e-04

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 41.08  E-value: 1.80e-04
                            10        20        30
                    ....*....|....*....|....*....|....
gi 1894698391  1263 CDS-SPCKNGGTCSVSWGTYSCLCPVGF-GGKDC 1294
Cdd:smart00179    5 CASgNPCQNGGTCVNTVGSYRCECPPGYtDGRNC 38
EGF_CA smart00179
Calcium-binding EGF-like domain;
973-1000 2.82e-04

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 40.31  E-value: 2.82e-04
                            10        20
                    ....*....|....*....|....*....
gi 1894698391   973 EINLCYS-NPCLNGGICTRKEGGYTCVCR 1000
Cdd:smart00179    1 DIDECASgNPCQNGGTCVNTVGSYRCECP 29
hEGF pfam12661
Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six ...
 1268-1289 3.07e-04

Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six conserved residues disulfide-bonded into the characteriztic 'ababcc' pattern. They are involved in growth and proliferation of cells, in proteins of the Notch/Delta pathway, neurogulin and selectins. hEGFs are also found in mosaic proteins with four-disulfide laminin EGFs such as aggrecan and perlecan. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal Cys residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In hEGFs the C-terminal thiol resides in the beta-turn, resulting in shorter loop-lengths between the Cys residues of disulfide 'c', typically C[8-9]XC. These shorter loop-lengths are also typical of the four-disulfide EGF domains, laminin ad integrin. Tandem hEGF domains have six linking residues between terminal cysteines of adjacent domains. hEGF domains may or may not bind calcium in the linker region. hEGF domains with the consensus motif CXD4X[F,Y]XCXC are hydroxylated exclusively in the Asp residue.


Pssm-ID: 463660  Cd Length: 22  Bit Score: 40.01  E-value: 3.07e-04
                           10        20
                   ....*....|....*....|..
gi 1894698391 1268 CKNGGTCSVSWGTYSCLCPVGF 1289
Cdd:pfam12661    1 CQNGGTCVDGVNGYKCQCPPGY 22
hEGF pfam12661
Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six ...
 1022-1043 4.38e-04

Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six conserved residues disulfide-bonded into the characteriztic 'ababcc' pattern. They are involved in growth and proliferation of cells, in proteins of the Notch/Delta pathway, neurogulin and selectins. hEGFs are also found in mosaic proteins with four-disulfide laminin EGFs such as aggrecan and perlecan. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal Cys residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In hEGFs the C-terminal thiol resides in the beta-turn, resulting in shorter loop-lengths between the Cys residues of disulfide 'c', typically C[8-9]XC. These shorter loop-lengths are also typical of the four-disulfide EGF domains, laminin ad integrin. Tandem hEGF domains have six linking residues between terminal cysteines of adjacent domains. hEGF domains may or may not bind calcium in the linker region. hEGF domains with the consensus motif CXD4X[F,Y]XCXC are hydroxylated exclusively in the Asp residue.


Pssm-ID: 463660  Cd Length: 22  Bit Score: 39.62  E-value: 4.38e-04
                           10        20
                   ....*....|....*....|..
gi 1894698391 1022 CRNGGTCTNGaDGGFRCQCPAG 1043
Cdd:pfam12661    1 CQNGGTCVDG-VNGYKCQCPPG 21
EGF_CA smart00179
Calcium-binding EGF-like domain;
1484-1516 1.12e-03

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 38.77  E-value: 1.12e-03
                            10        20        30
                    ....*....|....*....|....*....|....*
gi 1894698391  1484 CDS-NPCPVNSICKDEWQSYSCVCQPGYY-GGDCV 1516
Cdd:smart00179    5 CASgNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
 2140-2321 1.41e-03

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


Pssm-ID: 320089  Cd Length: 314  Bit Score: 43.46  E-value: 1.41e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRM-----QTEArnvNFGAMRFYYAIGWGVPAI--ITGLAVGL-DPE------- 2204
Cdd:cd13951     94 CAIVFLLTYYFGMAASIWWVILTLTWFLSaglkwSSEA---IEKKSSYFHLVAWGLPAVltIAVLVLRKvDGDeltgicf 170

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2205 -GYGNPdfcwisihDKLVWSFAGPITVVIVMnGVMFLLVAKMS---CSPGQKETKKKSVLMTLRSsfvlllvisttwlfg 2280
Cdd:cd13951    171 vGNQNL--------DALRGFVLAPLFLYLIL-GTVFLLCGFLSlfrIRSILSNDGKKTDKLEKLM--------------- 226

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1894698391 2281 llavnNSVLAFHYLYTVlcslqgLAVLVLFCVLNEEV-REAW 2321
Cdd:cd13951    227 -----LRIGIFAVLYTL------PALIVIACYFYEYAnRPDW 257
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
 1019-1051 1.79e-03

Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large number of proteins, mostly animal; the list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied; the functional significance of EGF-like domains in what appear to be unrelated proteins is not yet clear; a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase); the domain includes six cysteine residues which have been shown to be involved in disulfide bonds; the main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet; Subdomains between the conserved cysteines vary in length; the region between the 5th and 6th cysteine contains two conserved glycines of which at least one is present in most EGF-like domains; a subset of these bind calcium.


Pssm-ID: 238010  Cd Length: 36  Bit Score: 38.23  E-value: 1.79e-03
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1894698391 1019 PGVCRNGGTCTNGaDGGFRCQCPAGGFEMPFCE 1051
Cdd:cd00053      5 SNPCSNGGTCVNT-PGSYRCVCPPGYTGDRSCE 36
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
 2140-2318 2.72e-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: 42.61  E-value: 2.72e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2140 CTVIAILLHCFFLSTFAWLFIQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPA--IITGLAVGLDPEgygNPDfCWiSIH 2217
Cdd:cd15985     87 CRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYLGWGTPVlfVVPWMLAKYLKE---NKE-CW-ALN 161

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1894698391 2218 DKLV--WSFAGPITVVIVMNGVMFLLVAKMscspgqketkkksVLMTLRSS------FVLLLVISTTWLFGLLAVNNSVL 2289
Cdd:cd15985    162 ENMAywWIIRIPILLASLINLLIFMRILKV-------------ILSKLRANqkgyadYKLRLAKATLTLIPLFGIHEVVF 228

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1894698391 2290 AFH--------------YLYTVLCSLQGLAVLVLFCVLNEEVR 2318
Cdd:cd15985    229 IFAtdeqttgilryikvFFTLFLNSFQGFLVAVLYCFANKEVK 271
EGF_CA pfam07645
Calcium-binding EGF domain;
1021-1043 3.16e-03

Calcium-binding EGF domain;


Pssm-ID: 429571  Cd Length: 32  Bit Score: 37.22  E-value: 3.16e-03
                           10        20
                   ....*....|....*....|...
gi 1894698391 1021 VCRNGGTCTNgADGGFRCQCPAG 1043
Cdd:pfam07645   11 NCPANTVCVN-TIGSFECRCPDG 32
hEGF pfam12661
Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six ...
 982-1003 4.21e-03

Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six conserved residues disulfide-bonded into the characteriztic 'ababcc' pattern. They are involved in growth and proliferation of cells, in proteins of the Notch/Delta pathway, neurogulin and selectins. hEGFs are also found in mosaic proteins with four-disulfide laminin EGFs such as aggrecan and perlecan. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal Cys residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In hEGFs the C-terminal thiol resides in the beta-turn, resulting in shorter loop-lengths between the Cys residues of disulfide 'c', typically C[8-9]XC. These shorter loop-lengths are also typical of the four-disulfide EGF domains, laminin ad integrin. Tandem hEGF domains have six linking residues between terminal cysteines of adjacent domains. hEGF domains may or may not bind calcium in the linker region. hEGF domains with the consensus motif CXD4X[F,Y]XCXC are hydroxylated exclusively in the Asp residue.


Pssm-ID: 463660  Cd Length: 22  Bit Score: 36.93  E-value: 4.21e-03
                           10        20
                   ....*....|....*....|..
gi 1894698391  982 CLNGGICTRKEGGYTCVCRQHF 1003
Cdd:pfam12661    1 CQNGGTCVDGVNGYKCQCPPGY 22
EGF smart00181
Epidermal growth factor-like domain;
1478-1512 4.75e-03

Epidermal growth factor-like domain;


Pssm-ID: 214544  Cd Length: 35  Bit Score: 37.11  E-value: 4.75e-03
                            10        20        30
                    ....*....|....*....|....*....|....*
gi 1894698391  1478 CSVPSPCDsnpcpvNSICKDEWQSYSCVCQPGYYG 1512
Cdd:smart00181    2 CASGGPCS------NGTCINTPGSYTCSCPPGYTG 30
 
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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