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Conserved domains on  [gi|7656967|ref|NP_055061|]
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cadherin EGF LAG seven-pass G-type receptor 1 isoform 2 precursor [Homo sapiens]

Protein Classification

Cadherin_repeat and GAIN domain-containing protein( domain architecture ID 11588071)

protein containing domains Cadherin_repeat, LamG, GAIN, and GPS

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
 2465-2718 1.97e-145

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


The actual alignment was detected with superfamily member cd15991:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 254  Bit Score: 452.76  E-value: 1.97e-145
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2465 VLPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMS 2544
Cdd:cd15991    1 VLPLKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIGINQTENPFVCTVVAILLHYFYMS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVII 2624
Cdd:cd15991   81 TFAWMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWGIPAIITGLAVGLDPQGYGNPDFCWLSVQDTLIWSFAGPIGIVVI 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2625 INTVTSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFHCVL 2704
Cdd:cd15991  161 INTVIFVLAAKASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLGLMAVNSDTLSFHYLFAIFSCLQGIFIFFFHCIF 240

                        250
                 ....*....|....
gi 7656967  2705 NQEVRKHLKGVLGG 2718
Cdd:cd15991  241 NKEVRKHLKNVLTG 254
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
 2130-2381 5.36e-62

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: 211.36  E-value: 5.36e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2130 RALQLVRALRSATQHtGTLFGNDVRTAYQLLGHVlqheswqqgFDLAATQDA----DFHEDVIHSGSALLAPATRAAWEQ 2205
Cdd:pfam16489    1 GAKELARELRNATRH-GPLYGGDVLTAVELLSQL---------FDLLATQDAtlsnAFLENFVQTVSNLLDPENRESWED 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2206 IQRSEGGTAQ--LLRRLEGYFSNVARNVRrtYLRPFVIVTANMILAVDIFDKFNFTGARVPRFDTIHEEFPRelESSVSF 2283
Cdd:pfam16489   71 LQQTERGTAAtkLLRTLEEYALLLAQNMK--YLTPFTIVTPNIVLSVDRLDTHNFKGARFPRFPMKGERPKD--EDSVKL 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2284 PADFFRPPeekegpllrpagrrttpqttrpgpgtereapisrrrrhpdDAGQFAVALVIIYRTLGQLLPE--RYDPDRRS 2361
Cdd:pfam16489  147 PPKAFKPP----------------------------------------DSNGTVVVVFILYRNLGSLLPPssRYDPDRRS 186

                          250       260
                   ....*....|....*....|
gi 7656967    2362 LRLPHRpIINTPMVSTLVYS 2381
Cdd:pfam16489  187 LRLPRR-VVNSPVVSASVHS 205
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 793-888 4.60e-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: 130.13  E-value: 4.60e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   793 HYTVSVSEDRPVGTSIATLSANDEDTGENARITYVIQDPVPQ--FRIDPDSGTMYTMMELDYENQVAYTLTIMAQDNGIP 870
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDglFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                         90
                 ....*....|....*...
gi 7656967   871 QKSDTTTLEILILDANDN 888
Cdd:cd11304   81 PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 464-561 1.06e-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: 126.27  E-value: 1.06e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   464 YVVQVPEDVGLNTAVLRVQATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGILDVINPLDFEDVQKYSLSIKAQDGGRPP 543
Cdd:cd11304    2 YEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGPP 81

                         90
                 ....*....|....*...
gi 7656967   544 LiNSSGVVSVQVLDVNDN 561
Cdd:cd11304   82 L-SSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 357-455 2.28e-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: 125.12  E-value: 2.28e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   357 EYRERVRENLEVGYEVLTIRASDRDSPINANLRYRVLGG-AWDVFQLNESSGVVSTRAVLDREEAAEYQLLVEANDQGRN 435
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGnEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                         90       100
                 ....*....|....*....|
gi 7656967   436 pgPLSATATVYIEVEDENDN 455
Cdd:cd11304   81 --PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 897-995 2.85e-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: 125.12  E-value: 2.85e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   897 YQGSIFEDAPPSTSILQVSATDRDSGPNGRLLYTFQgGDDGDGDFYIEPTSGVIRTQRRLDRENVAVYNLWALAVDRGSP 976
Cdd:cd11304    2 YEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIV-SGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                         90
                 ....*....|....*....
gi 7656967   977 tPLSASVEIQVTILDINDN 995
Cdd:cd11304   81 -PLSSTATVTITVLDVNDN 98
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1444-1627 1.73e-31

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: 121.76  E-value: 1.73e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1444 TRSFPPQSFVTFRGLR-QRFHFTISLTFATQERNGLLLYNGRFNeKHDFIALEIVDEQVQLTFSAGETTTTVAPKVPsgV 1522
Cdd:cd00110    1 GVSFSGSSYVRLPTLPaPRTRLSISFSFRTTSPNGLLLYAGSQN-GGDFLALELEDGRLVLRYDLGSGSLVLSSKTP--L 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1523 SDGRWHSVQVQYYNkpnighlglphgpsgeKMAVVTVDDCDTtmavrfgkdignyscaAQGTQTGSKKSLDLTGPLLLGG 1602
Cdd:cd00110   78 NDGQWHSVSVERNG----------------RSVTLSVDGERV----------------VESGSPGGSALLNLDGPLYLGG 125

                        170       180
                 ....*....|....*....|....*.
gi 7656967  1603 VPNLPEDFPVHNRQ-FVGCMRNLSVD 1627
Cdd:cd00110  126 LPEDLKSPGLPVSPgFVGCIRDLKVN 151
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 1003-1097 7.37e-29

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: 112.41  E-value: 7.37e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1003 ELELFVEENNPVGSVVAKIRANDPDEGPNAQIMYQIVEGDMRHFFQLDLLNGDLRAMVELDFEVRREYVLVVQAT---SA 1079
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATdggGP 80

                         90
                 ....*....|....*...
gi 7656967  1080 PLVSRATVHILLVDQNDN 1097
Cdd:cd11304   81 PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 569-683 2.44e-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: 99.31  E-value: 2.44e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   569 PFQATVLENVPLGYPVVHIQAVDADSGENARLHYRLVDtastflgggsagpknpaPTPDFPFQIHNSSGWITVCAELDRE 648
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVS-----------------GNEDGLFSIDPSTGEITTAKPLDRE 63

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 7656967   649 EVEHYSFGVEAVDHGSPPMSSSTSVSITVLDVNDN 683
Cdd:cd11304   64 EQSSYTLTVTATDGGGPPLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 250-349 8.29e-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: 98.15  E-value: 8.29e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   250 YQVALFENEPAGTLILQLHAHytiEGEEERVSYYmegLFDERSRGYFRIDSATGAVSTDSVLDRETKETHVLRVKAVDYS 329
Cdd:cd11304    2 YEVSVPENAPPGTVVLTVSATdpdSGENGEVTYS---IVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGG 78

                         90       100
                 ....*....|....*....|
gi 7656967   330 TPPRSATTYITVLVKDTNDH 349
Cdd:cd11304   79 GPPLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 691-785 5.91e-23

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: 95.46  E-value: 5.91e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   691 TYELRLNEDAAVGSSVLTLQARDRD--ANSVITYQLTGGNTRNRFALSSQRggGLITLALPLDYKQEQQYVLAVTASDG- 767
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDsgENGEVTYSIVSGNEDGLFSIDPST--GEITTAKPLDREEQSSYTLTVTATDGg 78

                         90       100
                 ....*....|....*....|
gi 7656967   768 --TRSHTAHVLINVTDANTH 785
Cdd:cd11304   79 gpPLSSTATVTITVLDVNDN 98
Laminin_G_2 pfam02210
Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G ...
 1719-1849 3.83e-22

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: 94.41  E-value: 3.83e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1719 FRTRKEDSVLMEATSGGPTSFRLQILNNYLQFEVSHGpSDVESVMLSGLRVTDGEWHHLLIELKNvkedsemkHLVTMTL 1798
Cdd:pfam02210    1 FRTRQPNGLLLYAGGGGSDFLALELVNGRLVLRYDLG-SGPESLLSSGKNLNDGQWHSVRVERNG--------NTLTLSV 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 7656967    1799 DYGMDQNKADIGGMLPGLTVRSVVVGGA----SEDKVSVRRGFRGCMQGVRMGGT 1849
Cdd:pfam02210   72 DGQTVVSSLPPGESLLLNLNGPLYLGGLppllLLPALPVRAGFVGCIRDVRVNGE 126
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 2407-2460 2.37e-18

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: 80.89  E-value: 2.37e-18
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 7656967     2407 TKPVCVFWNHSlavggTGGWSARGCELLSRNRTHVACQCSHTASFAVLMDISRR 2460
Cdd:smart00303    1 FNPICVFWDES-----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPPI 49
HormR smart00008
Domain present in hormone receptors;
2052-2113 6.96e-16

Domain present in hormone receptors;


:

Pssm-ID: 214468  Cd Length: 70  Bit Score: 74.47  E-value: 6.96e-16
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7656967     2052 YNGCPKAFEAGIWWPQTKFGQPAAVPCPKGSVG-----NAVRHCSGEKGWLP--PELFNCTTISFVDLR 2113
Cdd:smart00008    2 DLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGfsyktGASRNCTENGGWSPpfPNYSNCTSNDYEELK 70
EGF_Lam cd00055
Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous ...
 2002-2040 6.64e-14

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: 68.15  E-value: 6.64e-14
                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 7656967  2002 PCDCFPHGSHSRTCDMATGQCACKPGVIGRQCNRCDNPF 2040
Cdd:cd00055    1 PCDCNGHGSLSGQCDPGTGQCECKPNTTGRRCDRCAPGY 39
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 1117-1198 1.39e-09

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: 57.32  E-value: 1.39e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1117 NSFPTGVIGCIPAHDPDVSD--SLNYTFVQGNELRLLLLDPATGELQLSRDLDNNRPLEALMEVSVSD-GIHSVTAFCTL 1193
Cdd:cd11304    9 NAPPGTVVLTVSATDPDSGEngEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDgGGPPLSSTATV 88


                 ....*
gi 7656967  1194 RVTII 1198
Cdd:cd11304   89 TITVL 93
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1407-1441 7.13e-08

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: 50.71  E-value: 7.13e-08
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1407 CA-NGVCKNGGTCVNLlIGGFHCVCPPGeYERPYCE 1441
Cdd:cd00054    5 CAsGNPCQNGGTCVNT-VGSYRCSCPPG-YTGRNCE 38
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1364-1399 7.42e-08

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: 50.71  E-value: 7.42e-08
                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 7656967  1364 IDLCYS-DPCGANGRCRSREGGYTCECFEDFTGEHCE 1399
Cdd:cd00054    2 IDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1651-1685 2.87e-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: 2.87e-07
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1651 NFCD-GRRCQNGGTCVNRWNMYLCECPLRFGGKNCE 1685
Cdd:cd00054    3 DECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1874-1908 2.57e-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: 46.09  E-value: 2.57e-06
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1874 DPCTS-SPCPPNSRCHDAWEDYSCVCDKGYLGINCV 1908
Cdd:cd00054    3 DECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
TNFRSF super family cl22855
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
 1881-2011 8.20e-04

Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) interactions with TNF superfamily (TNFSF) ligands (TNFL) control key cellular processes such as differentiation, proliferation, apoptosis, and cell growth. Dysregulation of these pathways has been shown to result in a wide range of pathological conditions, including autoimmune diseases, inflammation, cancer, and viral infection. There are 29 very diverse family members of TNFRSF reported in humans: 22 are type I transmembrane receptors (single pass with the N terminus on extracellular side of the cell membrane) and have a clear signal peptide; the remaining 7 members are either type III transmembrane receptors (single pass with the N terminus on extracellular side of the membrane but no signal sequence; TNFR13B, TNFR13C, TNFR17, and XEDAR), or attached to the membrane via a glycosylphosphatidylinositol (GPI) linker (TNFR10C), or secreted as soluble receptors (TNFR11B and TNFR6B). All TNFRs contain relatively short cysteine-rich domains (CRDs) in the ectodomain, and are involved in interaction with the TNF homology domain (THD) of their ligands. TNFRs often have multiple CRDs (between one and six), with the most frequent configurations of three or four copies; most CRDs possess three disulfide bridges, but could have between one and four. Localized or genome-wide duplication and evolution of the TNFRSF members appear to have paralleled the emergence of the adaptive immune system; teleosts (i.e. ray-finned, bony fish), which possess an immune system with B and T cells, possess primary and secondary lymphoid organs, and are capable of adaptive responses to pathogens also display several characteristics that are different from the mammalian immune system, making teleost TNFSF orthologs and paralogs of interest to better understand immune system evolution and the immunological pathways elicited to pathogens.


The actual alignment was detected with superfamily member cd15834:

Pssm-ID: 473981 [Multi-domain]  Cd Length: 150  Bit Score: 42.48  E-value: 8.20e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1881 CPPNSR----CHDAWEDYSCV-CDKG-YLG-INCVDAC-HLNPCENMGACVRSPGSP-QGYVCECGPSHYgpycENKLDl 1951
Cdd:cd15834   17 CHPGYKlkeeCTAPGERSQCTpCPEGtYLEqINYSPNCrRCTLCKVKNEEEVSPCKKsSNTVCRCKKGYY----KSRID- 91

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7656967  1952 pcPRGWwgnpVCGPChcavsKGFDPD------CNK-TNGQCQCKENYYKLlaQDTCLPCD-CFPHGSH 2011
Cdd:cd15834   92 --SETR----ECLKC-----KTCGPGeieiqpCTPeSNTVCECKDNYYRN--NNKCKPCQkCSLDCQH 146
 
Name Accession Description Interval E-value
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
 2465-2718 1.97e-145

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: 452.76  E-value: 1.97e-145
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2465 VLPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMS 2544
Cdd:cd15991    1 VLPLKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIGINQTENPFVCTVVAILLHYFYMS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVII 2624
Cdd:cd15991   81 TFAWMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWGIPAIITGLAVGLDPQGYGNPDFCWLSVQDTLIWSFAGPIGIVVI 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2625 INTVTSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFHCVL 2704
Cdd:cd15991  161 INTVIFVLAAKASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLGLMAVNSDTLSFHYLFAIFSCLQGIFIFFFHCIF 240

                        250
                 ....*....|....
gi 7656967  2705 NQEVRKHLKGVLGG 2718
Cdd:cd15991  241 NKEVRKHLKNVLTG 254
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 2466-2697 1.89e-74

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: 249.12  E-value: 1.89e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTEN--------PFLCTVVAIL 2537
Cdd:pfam00002    2 LSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNkqdldhcsWVGCKVVAVF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2538 LHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAG 2617
Cdd:pfam00002   82 LHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYGEDDGCWLSNENGLWWIIRG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2618 PIGAVIIINTVTSVLSAKVSCQRKHHYYGKKGIvsllrTAFLLLLLISA---------TWLLGLLAVNRDALS---FHYL 2685
Cdd:pfam00002  162 PILLIILVNFIIFINIVRILVQKLRETNMGKSD-----LKQYRRLAKSTllllpllgiTWVFGLFAFNPENTLrvvFLYL 236

                          250
                   ....*....|..
gi 7656967    2686 FAIFSGLQGPFV 2697
Cdd:pfam00002  237 FLILNSFQGFFV 248
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
 2130-2381 5.36e-62

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: 211.36  E-value: 5.36e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2130 RALQLVRALRSATQHtGTLFGNDVRTAYQLLGHVlqheswqqgFDLAATQDA----DFHEDVIHSGSALLAPATRAAWEQ 2205
Cdd:pfam16489    1 GAKELARELRNATRH-GPLYGGDVLTAVELLSQL---------FDLLATQDAtlsnAFLENFVQTVSNLLDPENRESWED 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2206 IQRSEGGTAQ--LLRRLEGYFSNVARNVRrtYLRPFVIVTANMILAVDIFDKFNFTGARVPRFDTIHEEFPRelESSVSF 2283
Cdd:pfam16489   71 LQQTERGTAAtkLLRTLEEYALLLAQNMK--YLTPFTIVTPNIVLSVDRLDTHNFKGARFPRFPMKGERPKD--EDSVKL 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2284 PADFFRPPeekegpllrpagrrttpqttrpgpgtereapisrrrrhpdDAGQFAVALVIIYRTLGQLLPE--RYDPDRRS 2361
Cdd:pfam16489  147 PPKAFKPP----------------------------------------DSNGTVVVVFILYRNLGSLLPPssRYDPDRRS 186

                          250       260
                   ....*....|....*....|
gi 7656967    2362 LRLPHRpIINTPMVSTLVYS 2381
Cdd:pfam16489  187 LRLPRR-VVNSPVVSASVHS 205
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 793-888 4.60e-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: 130.13  E-value: 4.60e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   793 HYTVSVSEDRPVGTSIATLSANDEDTGENARITYVIQDPVPQ--FRIDPDSGTMYTMMELDYENQVAYTLTIMAQDNGIP 870
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDglFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                         90
                 ....*....|....*...
gi 7656967   871 QKSDTTTLEILILDANDN 888
Cdd:cd11304   81 PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 464-561 1.06e-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: 126.27  E-value: 1.06e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   464 YVVQVPEDVGLNTAVLRVQATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGILDVINPLDFEDVQKYSLSIKAQDGGRPP 543
Cdd:cd11304    2 YEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGPP 81

                         90
                 ....*....|....*...
gi 7656967   544 LiNSSGVVSVQVLDVNDN 561
Cdd:cd11304   82 L-SSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 357-455 2.28e-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: 125.12  E-value: 2.28e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   357 EYRERVRENLEVGYEVLTIRASDRDSPINANLRYRVLGG-AWDVFQLNESSGVVSTRAVLDREEAAEYQLLVEANDQGRN 435
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGnEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                         90       100
                 ....*....|....*....|
gi 7656967   436 pgPLSATATVYIEVEDENDN 455
Cdd:cd11304   81 --PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 897-995 2.85e-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: 125.12  E-value: 2.85e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   897 YQGSIFEDAPPSTSILQVSATDRDSGPNGRLLYTFQgGDDGDGDFYIEPTSGVIRTQRRLDRENVAVYNLWALAVDRGSP 976
Cdd:cd11304    2 YEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIV-SGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                         90
                 ....*....|....*....
gi 7656967   977 tPLSASVEIQVTILDINDN 995
Cdd:cd11304   81 -PLSSTATVTITVLDVNDN 98
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1444-1627 1.73e-31

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: 121.76  E-value: 1.73e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1444 TRSFPPQSFVTFRGLR-QRFHFTISLTFATQERNGLLLYNGRFNeKHDFIALEIVDEQVQLTFSAGETTTTVAPKVPsgV 1522
Cdd:cd00110    1 GVSFSGSSYVRLPTLPaPRTRLSISFSFRTTSPNGLLLYAGSQN-GGDFLALELEDGRLVLRYDLGSGSLVLSSKTP--L 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1523 SDGRWHSVQVQYYNkpnighlglphgpsgeKMAVVTVDDCDTtmavrfgkdignyscaAQGTQTGSKKSLDLTGPLLLGG 1602
Cdd:cd00110   78 NDGQWHSVSVERNG----------------RSVTLSVDGERV----------------VESGSPGGSALLNLDGPLYLGG 125

                        170       180
                 ....*....|....*....|....*.
gi 7656967  1603 VPNLPEDFPVHNRQ-FVGCMRNLSVD 1627
Cdd:cd00110  126 LPEDLKSPGLPVSPgFVGCIRDLKVN 151
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 1003-1097 7.37e-29

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: 112.41  E-value: 7.37e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1003 ELELFVEENNPVGSVVAKIRANDPDEGPNAQIMYQIVEGDMRHFFQLDLLNGDLRAMVELDFEVRREYVLVVQAT---SA 1079
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATdggGP 80

                         90
                 ....*....|....*...
gi 7656967  1080 PLVSRATVHILLVDQNDN 1097
Cdd:cd11304   81 PLSSTATVTITVLDVNDN 98
LamG smart00282
Laminin G domain;
1465-1629 3.26e-27

Laminin G domain;


Pssm-ID: 214598 [Multi-domain]  Cd Length: 132  Bit Score: 108.97  E-value: 3.26e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     1465 TISLTFATQERNGLLLYNGrFNEKHDFIALEIVDEQVQLTFSAGETTTTVAPKVPSgVSDGRWHSVQVQYYNkpnighlg 1544
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAG-SKGGGDYLALELRDGRLVLRYDLGSGPARLTSDPTP-LNDGQWHRVAVERNG-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     1545 lphgpsgeKMAVVTVDDCDTTMAVRFgkdignyscaaqgtqtGSKKSLDLTGPLLLGGVPNLPEDFPVHNRQ-FVGCMRN 1623
Cdd:smart00282   71 --------RSVTLSVDGGNRVSGESP----------------GGLTILNLDGPLYLGGLPEDLKLPPLPVTPgFRGCIRN 126


                    ....*.
gi 7656967     1624 LSVDGK 1629
Cdd:smart00282  127 LKVNGK 132
Cadherin pfam00028
Cadherin domain;
794-883 1.40e-26

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 105.85  E-value: 1.40e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     794 YTVSVSEDRPVGTSIATLSANDEDTGENARITYVI--QDPVPQFRIDPDSGTMYTMMELDYENQVAYTLTIMAQDNGIPQ 871
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSIlgGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|..
gi 7656967     872 KSDTTTLEILIL 883
Cdd:pfam00028   81 LSSTATVTITVL 92
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 812-890 1.12e-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: 102.81  E-value: 1.12e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      812 SANDEDTGENARITYVI--QDPVPQFRIDPDSGTMYTMMELDYENQVAYTLTIMAQDNGIPQKSDTTTLEILILDANDNA 889
Cdd:smart00112    1 SATDADSGENGKVTYSIlsGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDNA 80


                    .
gi 7656967      890 P 890
Cdd:smart00112   81 P 81
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 482-563 2.07e-24

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: 98.96  E-value: 2.07e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      482 QATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGILDVINPLDFEDVQKYSLSIKAQDGGRPPLiNSSGVVSVQVLDVNDN 561
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPL-SSTATVTITVLDVNDN 79


                    ..
gi 7656967      562 EP 563
Cdd:smart00112   80 AP 81
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 569-683 2.44e-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: 99.31  E-value: 2.44e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   569 PFQATVLENVPLGYPVVHIQAVDADSGENARLHYRLVDtastflgggsagpknpaPTPDFPFQIHNSSGWITVCAELDRE 648
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVS-----------------GNEDGLFSIDPSTGEITTAKPLDRE 63

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 7656967   649 EVEHYSFGVEAVDHGSPPMSSSTSVSITVLDVNDN 683
Cdd:cd11304   64 EQSSYTLTVTATDGGGPPLSSTATVTITVLDVNDN 98
Cadherin pfam00028
Cadherin domain;
464-556 2.77e-24

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 99.30  E-value: 2.77e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     464 YVVQVPEDVGLNTAVLRVQATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGILDVINPLDFEDVQKYSLSIKAQDGGRPP 543
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|...
gi 7656967     544 LiNSSGVVSVQVL 556
Cdd:pfam00028   81 L-SSTATVTITVL 92
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 376-457 3.56e-24

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: 98.58  E-value: 3.56e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      376 RASDRDSPINANLRYRVLGG-AWDVFQLNESSGVVSTRAVLDREEAAEYQLLVEANDQGrnPGPLSATATVYIEVEDEND 454
Cdd:smart00112    1 SATDADSGENGKVTYSILSGnDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGG--GPPLSSTATVTITVLDVND 78


                    ...
gi 7656967      455 NYP 457
Cdd:smart00112   79 NAP 81
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 915-997 6.14e-24

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: 97.81  E-value: 6.14e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      915 SATDRDSGPNGRLLYTFqGGDDGDGDFYIEPTSGVIRTQRRLDRENVAVYNLWALAVDRGSPtPLSASVEIQVTILDIND 994
Cdd:smart00112    1 SATDADSGENGKVTYSI-LSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGP-PLSSTATVTITVLDVND 78


                    ...
gi 7656967      995 NAP 997
Cdd:smart00112   79 NAP 81
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 250-349 8.29e-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: 98.15  E-value: 8.29e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   250 YQVALFENEPAGTLILQLHAHytiEGEEERVSYYmegLFDERSRGYFRIDSATGAVSTDSVLDRETKETHVLRVKAVDYS 329
Cdd:cd11304    2 YEVSVPENAPPGTVVLTVSATdpdSGENGEVTYS---IVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGG 78

                         90       100
                 ....*....|....*....|
gi 7656967   330 TPPRSATTYITVLVKDTNDH 349
Cdd:cd11304   79 GPPLSSTATVTITVLDVNDN 98
Laminin_G_2 pfam02210
Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G ...
 1470-1629 1.09e-23

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: 98.65  E-value: 1.09e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1470 FATQERNGLLLYNGrfNEKHDFIALEIVDEQVQLTFSAGETTTTVAPKvPSGVSDGRWHSVQVQYYNkpnighlglphgp 1549
Cdd:pfam02210    1 FRTRQPNGLLLYAG--GGGSDFLALELVNGRLVLRYDLGSGPESLLSS-GKNLNDGQWHSVRVERNG------------- 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1550 sgeKMAVVTVDDCDTTMAVRFGKDIGnyscaaqgtqtgskksLDLTGPLLLGGVPN-LPEDFPVHNRQFVGCMRNLSVDG 1628
Cdd:pfam02210   65 ---NTLTLSVDGQTVVSSLPPGESLL----------------LNLNGPLYLGGLPPlLLLPALPVRAGFVGCIRDVRVNG 125


                   .
gi 7656967    1629 K 1629
Cdd:pfam02210  126 E 126
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 691-785 5.91e-23

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: 95.46  E-value: 5.91e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   691 TYELRLNEDAAVGSSVLTLQARDRD--ANSVITYQLTGGNTRNRFALSSQRggGLITLALPLDYKQEQQYVLAVTASDG- 767
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDsgENGEVTYSIVSGNEDGLFSIDPST--GEITTAKPLDREEQSSYTLTVTATDGg 78

                         90       100
                 ....*....|....*....|
gi 7656967   768 --TRSHTAHVLINVTDANTH 785
Cdd:cd11304   79 gpPLSSTATVTITVLDVNDN 98
Laminin_G_2 pfam02210
Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G ...
 1719-1849 3.83e-22

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: 94.41  E-value: 3.83e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1719 FRTRKEDSVLMEATSGGPTSFRLQILNNYLQFEVSHGpSDVESVMLSGLRVTDGEWHHLLIELKNvkedsemkHLVTMTL 1798
Cdd:pfam02210    1 FRTRQPNGLLLYAGGGGSDFLALELVNGRLVLRYDLG-SGPESLLSSGKNLNDGQWHSVRVERNG--------NTLTLSV 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 7656967    1799 DYGMDQNKADIGGMLPGLTVRSVVVGGA----SEDKVSVRRGFRGCMQGVRMGGT 1849
Cdd:pfam02210   72 DGQTVVSSLPPGESLLLNLNGPLYLGGLppllLLPALPVRAGFVGCIRDVRVNGE 126
Cadherin pfam00028
Cadherin domain;
897-990 1.28e-21

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 91.59  E-value: 1.28e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     897 YQGSIFEDAPPSTSILQVSATDRDSGPNGRLLYTFQGGDDGDGdFYIEPTSGVIRTQRRLDRENVAVYNLWALAVDRGSP 976
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGN-FRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGP 79

                           90
                   ....*....|....
gi 7656967     977 tPLSASVEIQVTIL 990
Cdd:pfam00028   80 -PLSSTATVTITVL 92
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 1022-1099 1.47e-21

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: 90.87  E-value: 1.47e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     1022 RANDPDEGPNAQIMYQIVEGDMRHFFQLDLLNGDLRAMVELDFEVRREYVLVVQAT---SAPLVSRATVHILLVDQNDNP 1098
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATdggGPPLSSTATVTITVLDVNDNA 80


                    .
gi 7656967     1099 P 1099
Cdd:smart00112   81 P 81
Cadherin pfam00028
Cadherin domain;
358-450 2.87e-21

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 90.44  E-value: 2.87e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     358 YRERVRENLEVGYEVLTIRASDRDSPINANLRYRVL-GGAWDVFQLNESSGVVSTRAVLDREEAAEYQLLVEANDQGrnP 436
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILgGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSG--G 78

                           90
                   ....*....|....
gi 7656967     437 GPLSATATVYIEVE 450
Cdd:pfam00028   79 PPLSSTATVTITVL 92
Cadherin pfam00028
Cadherin domain;
1008-1091 9.33e-21

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 88.90  E-value: 9.33e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1008 VEENNPVGSVVAKIRANDPDEGPNAQIMYQIVEGDMRHFFQLDLLNGDLRAMVELDFEVRREYVLVVQATSA---PLVSR 1084
Cdd:pfam00028    5 VPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSggpPLSST 84


                   ....*..
gi 7656967    1085 ATVHILL 1091
Cdd:pfam00028   85 ATVTITV 91
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1694-1846 1.71e-18

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: 84.78  E-value: 1.71e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1694 FSGESVVSWSDLNIIiSVPWYLGLMFRTRKEDSVLMEATSGGPTSF-RLQILNNYLQFEVSHGPSDVesVMLSGLRVTDG 1772
Cdd:cd00110    4 FSGSSYVRLPTLPAP-RTRLSISFSFRTTSPNGLLLYAGSQNGGDFlALELEDGRLVLRYDLGSGSL--VLSSKTPLNDG 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7656967  1773 EWHHLLIELKNvkedsemkHLVTMTLDYGMDQNKADIGGMLPGLTVRSVVVGGASED----KVSVRRGFRGCMQGVRM 1846
Cdd:cd00110   81 QWHSVSVERNG--------RSVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDlkspGLPVSPGFVGCIRDLKV 150
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 2407-2460 2.37e-18

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: 80.89  E-value: 2.37e-18
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 7656967     2407 TKPVCVFWNHSlavggTGGWSARGCELLSRNRTHVACQCSHTASFAVLMDISRR 2460
Cdd:smart00303    1 FNPICVFWDES-----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPPI 49
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 274-351 4.02e-18

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: 81.24  E-value: 4.02e-18
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7656967      274 EGEEERVSYYmegLFDERSRGYFRIDSATGAVSTDSVLDRETKETHVLRVKAVDYSTPPRSATTYITVLVKDTNDHSP 351
Cdd:smart00112    7 SGENGKVTYS---ILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDNAP 81
Cadherin pfam00028
Cadherin domain;
570-667 5.31e-18

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 81.19  E-value: 5.31e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     570 FQATVLENVPLGYPVVHIQAVDADSGENARLHYRLvdtastfLGGGSAGPknpaptpdfpFQIHNSSGWITVCAELDREE 649
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSI-------LGGGPGGN----------FRIDPDTGDISTTKPLDRES 63

                           90
                   ....*....|....*...
gi 7656967     650 VEHYSFGVEAVDHGSPPM 667
Cdd:pfam00028   64 IGEYELTVEATDSGGPPL 81
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 588-685 7.40e-17

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: 77.39  E-value: 7.40e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      588 QAVDADSGENARLHYRLVDtastflgggsagpknpaPTPDFPFQIHNSSGWITVCAELDREEVEHYSFGVEAVDHGSPPM 667
Cdd:smart00112    1 SATDADSGENGKVTYSILS-----------------GNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPL 63

                            90
                    ....*....|....*...
gi 7656967      668 SSSTSVSITVLDVNDNDP 685
Cdd:smart00112   64 SSTATVTITVLDVNDNAP 81
Cadherin pfam00028
Cadherin domain;
250-343 1.21e-16

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 77.34  E-value: 1.21e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     250 YQVALFENEPAGTLILQLHAHYTIEGEEERVSYYMegLFDErSRGYFRIDSATGAVSTDSVLDRETKETHVLRVKAVDYS 329
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSI--LGGG-PGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSG 77

                           90
                   ....*....|....
gi 7656967     330 TPPRSATTYITVLV 343
Cdd:pfam00028   78 GPPLSSTATVTITV 91
LamG smart00282
Laminin G domain;
1714-1848 3.64e-16

Laminin G domain;


Pssm-ID: 214598 [Multi-domain]  Cd Length: 132  Bit Score: 77.38  E-value: 3.64e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     1714 YLGLMFRTRKEDSVLMEATSGGPTSF-RLQILNNYLQFEVSHGpSDVESVMLSGLRVTDGEWHHLLIELKNvkedsemkH 1792
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGDYlALELRDGRLVLRYDLG-SGPARLTSDPTPLNDGQWHRVAVERNG--------R 71

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7656967     1793 LVTMTLDYGMDQNKADIGGmLPGLTVRS-VVVGGASED----KVSVRRGFRGCMQGVRMGG 1848
Cdd:smart00282   72 SVTLSVDGGNRVSGESPGG-LTILNLDGpLYLGGLPEDlklpPLPVTPGFRGCIRNLKVNG 131
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 2409-2454 5.93e-16

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: 73.88  E-value: 5.93e-16
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 7656967    2409 PVCVFWNHSLavGGTGGWSARGCELLSRNRTHVACQCSHTASFAVL 2454
Cdd:pfam01825    1 PQCVFWDFTN--STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
HormR smart00008
Domain present in hormone receptors;
2052-2113 6.96e-16

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 74.47  E-value: 6.96e-16
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7656967     2052 YNGCPKAFEAGIWWPQTKFGQPAAVPCPKGSVG-----NAVRHCSGEKGWLP--PELFNCTTISFVDLR 2113
Cdd:smart00008    2 DLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGfsyktGASRNCTENGGWSPpfPNYSNCTSNDYEELK 70
Cadherin pfam00028
Cadherin domain;
692-780 1.01e-15

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 74.64  E-value: 1.01e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     692 YELRLNEDAAVGSSVLTLQARDRD--ANSVITYQLTGGNTRNRFALSSQrgGGLITLALPLDYKQEQQYVLAVTASDG-- 767
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDlgPNGRIFYSILGGGPGGNFRIDPD--TGDISTTKPLDRESIGEYELTVEATDSgg 78

                           90
                   ....*....|....
gi 7656967     768 -TRSHTAHVLINVT 780
Cdd:pfam00028   79 pPLSSTATVTITVL 92
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 710-787 2.28e-14

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: 70.46  E-value: 2.28e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      710 QARDRD--ANSVITYQLTGGNTRNRFALSSQrgGGLITLALPLDYKQEQQYVLAVTASDG---TRSHTAHVLINVTDANT 784
Cdd:smart00112    1 SATDADsgENGKVTYSILSGNDDGLFSIDPE--TGEITTTKPLDREEQPEYTLTVEATDGggpPLSSTATVTITVLDVND 78


                    ...
gi 7656967      785 HRP 787
Cdd:smart00112   79 NAP 81
EGF_Lam cd00055
Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous ...
 2002-2040 6.64e-14

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: 68.15  E-value: 6.64e-14
                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 7656967  2002 PCDCFPHGSHSRTCDMATGQCACKPGVIGRQCNRCDNPF 2040
Cdd:cd00055    1 PCDCNGHGSLSGQCDPGTGQCECKPNTTGRRCDRCAPGY 39
EGF_Lam smart00180
Laminin-type epidermal growth factor-like domai;
2003-2048 1.14e-13

Laminin-type epidermal growth factor-like domai;


Pssm-ID: 214543  Cd Length: 46  Bit Score: 67.34  E-value: 1.14e-13
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 7656967     2003 CDCFPHGSHSRTCDMATGQCACKPGVIGRQCNRCDNPFAEVTTLGC 2048
Cdd:smart00180    1 CDCDPGGSASGTCDPDTGQCECKPNVTGRRCDRCAPGYYGDGPPGC 46
Laminin_EGF pfam00053
Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.
 2003-2036 1.27e-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: 64.30  E-value: 1.27e-12
                           10        20        30
                   ....*....|....*....|....*....|....
gi 7656967    2003 CDCFPHGSHSRTCDMATGQCACKPGVIGRQCNRC 2036
Cdd:pfam00053    1 CDCNPHGSLSDTCDPETGQCLCKPGVTGRHCDRC 34
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 2052-2107 3.07e-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: 58.15  E-value: 3.07e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7656967    2052 YNGCPKAFEAGIWWPQTKFGQPAAVPCPKG-----SVGNAVRHCSGEKGWL---PPELFNCTTI 2107
Cdd:pfam02793    1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYfsgfdPRGNASRNCTEDGTWSehpPSNYSNCTSN 64
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 1117-1198 1.39e-09

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: 57.32  E-value: 1.39e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1117 NSFPTGVIGCIPAHDPDVSD--SLNYTFVQGNELRLLLLDPATGELQLSRDLDNNRPLEALMEVSVSD-GIHSVTAFCTL 1193
Cdd:cd11304    9 NAPPGTVVLTVSATDPDSGEngEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDgGGPPLSSTATV 88


                 ....*
gi 7656967  1194 RVTII 1198
Cdd:cd11304   89 TITVL 93
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1407-1441 7.13e-08

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: 50.71  E-value: 7.13e-08
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1407 CA-NGVCKNGGTCVNLlIGGFHCVCPPGeYERPYCE 1441
Cdd:cd00054    5 CAsGNPCQNGGTCVNT-VGSYRCSCPPG-YTGRNCE 38
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1364-1399 7.42e-08

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: 50.71  E-value: 7.42e-08
                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 7656967  1364 IDLCYS-DPCGANGRCRSREGGYTCECFEDFTGEHCE 1399
Cdd:cd00054    2 IDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
EGF_CA smart00179
Calcium-binding EGF-like domain;
1407-1441 1.24e-07

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 49.94  E-value: 1.24e-07
                            10        20        30
                    ....*....|....*....|....*....|....*.
gi 7656967     1407 CA-NGVCKNGGTCVNLlIGGFHCVCPPGEYERPYCE 1441
Cdd:smart00179    5 CAsGNPCQNGGTCVNT-VGSYRCECPPGYTDGRNCE 39
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1651-1685 2.87e-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: 2.87e-07
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1651 NFCD-GRRCQNGGTCVNRWNMYLCECPLRFGGKNCE 1685
Cdd:cd00054    3 DECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1653-1683 2.09e-06

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: 46.22  E-value: 2.09e-06
                           10        20        30
                   ....*....|....*....|....*....|.
gi 7656967    1653 CDGRRCQNGGTCVNRWNMYLCECPLRFGGKN 1683
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1874-1908 2.57e-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: 46.09  E-value: 2.57e-06
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1874 DPCTS-SPCPPNSRCHDAWEDYSCVCDKGYLGINCV 1908
Cdd:cd00054    3 DECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
EGF_CA smart00179
Calcium-binding EGF-like domain;
1363-1399 1.18e-05

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 44.55  E-value: 1.18e-05
                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 7656967     1363 EIDLCYS-DPCGANGRCRSREGGYTCECFEDFT-GEHCE 1399
Cdd:smart00179    1 DIDECASgNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1367-1397 1.40e-05

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: 43.91  E-value: 1.40e-05
                           10        20        30
                   ....*....|....*....|....*....|.
gi 7656967    1367 CYSDPCGANGRCRSREGGYTCECFEDFTGEH 1397
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31
EGF_CA smart00179
Calcium-binding EGF-like domain;
1658-1685 1.77e-05

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 43.77  E-value: 1.77e-05
                            10        20
                    ....*....|....*....|....*....
gi 7656967     1658 CQNGGTCVNRWNMYLCECPLRF-GGKNCE 1685
Cdd:smart00179   11 CQNGGTCVNTVGSYRCECPPGYtDGRNCE 39
hEGF pfam12661
Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six ...
 1412-1433 1.41e-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: 41.17  E-value: 1.41e-04
                           10        20
                   ....*....|....*....|..
gi 7656967    1412 CKNGGTCVNLlIGGFHCVCPPG 1433
Cdd:pfam12661    1 CQNGGTCVDG-VNGYKCQCPPG 21
EGF_CA smart00179
Calcium-binding EGF-like domain;
1871-1908 2.88e-04

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 40.31  E-value: 2.88e-04
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|
gi 7656967     1871 DVDDpCTS-SPCPPNSRCHDAWEDYSCVCDKGY-LGINCV 1908
Cdd:smart00179    1 DIDE-CASgNPCQNGGTCVNTVGSYRCECPPGYtDGRNCE 39
TNFRSF1A_teleost cd15834
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as ...
 1881-2011 8.20e-04

Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as TNFR1; This subfamily of TNFRSF1 ((also known as type I TNFR, TNFR1, DR1, TNFRSF1A, CD120a, p55) is found in teleosts. It binds TNF-alpha, through the death domain (DD), and activates NF-kappaB, mediates apoptosis and activates signaling pathways controlling inflammatory, immune, and stress responses. It mediates signal transduction by interacting with antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRAF2 and TRADD that play regulatory roles. The human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS), or periodic fever syndrome, is associated with germline mutations of the extracellular domains of this receptor, possibly due to impaired receptor clearance. Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder, and high levels are also associated with cognitive impairment and dementia. Knockout studies in zebrafish embryos have shown that a signaling balance between TNFRSF1A and TNFRSF1B is required for endothelial cell integrity. TNFRSF1A signals apoptosis through caspase-8, whereas TNFRSF1B signals survival via NF-kappaB in endothelial cells. Thus, this apoptotic pathway seems to be evolutionarily conserved, as TNFalpha promotes apoptosis of human endothelial cells and triggers caspase-2 and P53 activation in these cells via TNFRSF1A.


Pssm-ID: 276930 [Multi-domain]  Cd Length: 150  Bit Score: 42.48  E-value: 8.20e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1881 CPPNSR----CHDAWEDYSCV-CDKG-YLG-INCVDAC-HLNPCENMGACVRSPGSP-QGYVCECGPSHYgpycENKLDl 1951
Cdd:cd15834   17 CHPGYKlkeeCTAPGERSQCTpCPEGtYLEqINYSPNCrRCTLCKVKNEEEVSPCKKsSNTVCRCKKGYY----KSRID- 91

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7656967  1952 pcPRGWwgnpVCGPChcavsKGFDPD------CNK-TNGQCQCKENYYKLlaQDTCLPCD-CFPHGSH 2011
Cdd:cd15834   92 --SETR----ECLKC-----KTCGPGeieiqpCTPeSNTVCECKDNYYRN--NNKCKPCQkCSLDCQH 146
 
Name Accession Description Interval E-value
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
 2465-2718 1.97e-145

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: 452.76  E-value: 1.97e-145
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2465 VLPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMS 2544
Cdd:cd15991    1 VLPLKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIGINQTENPFVCTVVAILLHYFYMS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVII 2624
Cdd:cd15991   81 TFAWMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWGIPAIITGLAVGLDPQGYGNPDFCWLSVQDTLIWSFAGPIGIVVI 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2625 INTVTSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFHCVL 2704
Cdd:cd15991  161 INTVIFVLAAKASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLGLMAVNSDTLSFHYLFAIFSCLQGIFIFFFHCIF 240

                        250
                 ....*....|....
gi 7656967  2705 NQEVRKHLKGVLGG 2718
Cdd:cd15991  241 NKEVRKHLKNVLTG 254
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
 2465-2713 4.36e-116

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: 368.50  E-value: 4.36e-116
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2465 VLPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMS 2544
Cdd:cd15441    1 VLLLKIVTYIGIGISLVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLLAELLFLLGINQTENLFPCKLIAILLHYFYLS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVII 2624
Cdd:cd15441   81 AFSWLLVESLHLYRMLTEPRDINHGHMRFYYLLGYGIPAIIVGLSVGLRPDGYGNPDFCWLSVNETLIWSFAGPIAFVIV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2625 INTVTSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFHCVL 2704
Cdd:cd15441  161 ITLIIFILALRASCTLKRHVLEKASVRTDLRSSFLLLPLLGATWVFGLLAVNEDSELLHYLFAGLNFLQGLFIFLFYCIF 240


                 ....*....
gi 7656967  2705 NQEVRKHLK 2713
Cdd:cd15441  241 NKKVRRELK 249
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
 2465-2718 1.46e-106

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: 341.42  E-value: 1.46e-106
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2465 VLPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMS 2544
Cdd:cd15992    1 ILPLKTLTWSSVGVTLGFLLLTFLFLLCLRALRSNKTSIRKNGATALFLSELVFILGINQADNPFACTVIAILLHFFYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVII 2624
Cdd:cd15992   81 TFSWLFLEGLHIYRMLSEVRDINYGPMRFYYLIGWGVPAFITGLAVGLDPEGYGNPDFCWLSIYDTLIWSFAGPVAFAVS 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2625 INTVTSVLSAKVSCQRKHH-YYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFHCV 2703
Cdd:cd15992  161 MNVFLYILSSRASCSAQQQsFEKKKGPVSGLRTAFTVLLLVSVTCLLALLSVNSDVILFHYLFAGFNCLQGPFIFLSHVV 240

                        250
                 ....*....|....*
gi 7656967  2704 LNQEVRKHLKGVLGG 2718
Cdd:cd15992  241 LLKEVRKALKTLCGP 255
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
 2468-2713 4.78e-100

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: 322.56  E-value: 4.78e-100
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTFA 2547
Cdd:cd15993    4 LAIVTYSSVSASLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELLFLLGINRTENQFLCTVVAILLHYFFLSTFA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2548 WTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIINT 2627
Cdd:cd15993   84 WLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEGYGNPDFCWISIHDKLVWSFAGPIVVVIVMNG 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2628 VTSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFHCVLNQE 2707
Cdd:cd15993  164 VMFLLVARMSCSPGQKETKKTSVLMTLRSSFLLLLLISATWLFGLLAVNNSVLAFHYLHAILCCLQGLAVLLLFCVLNEE 243


                 ....*.
gi 7656967  2708 VRKHLK 2713
Cdd:cd15993  244 VQEAWK 249
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
 2468-2711 8.58e-77

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: 255.96  E-value: 8.58e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHS-IHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTF 2546
Cdd:cd15040    4 LSIITYIGCGLSLLGLLLTIITYILFRKLRKRKPTkILLNLCLALLLANLLFLFGINSTDNPVLCTAVAALLHYFLLASF 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2547 AWTLVESLHVYRMLTEVRNIDTG-PMRFYYVVGWGIPAIVTGLAVGLDPQGYGN-PDFCWLSLQDTLIWSFAGPIGAVII 2624
Cdd:cd15040   84 MWMLVEALLLYLRLVKVFGTYPRhFILKYALIGWGLPLIIVIITLAVDPDSYGNsSGYCWLSNGNGLYYAFLGPVLLIIL 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2625 INTVTSVLSAKVSCQRKHH--YYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFHC 2702
Cdd:cd15040  164 VNLVIFVLVLRKLLRLSAKrnKKKRKKTKAQLRAAVSLFFLLGLTWIFGILAIFGARVVFQYLFAIFNSLQGFFIFIFHC 243


                 ....*....
gi 7656967  2703 VLNQEVRKH 2711
Cdd:cd15040  244 LRNKEVRKA 252
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
 2467-2710 1.35e-75

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: 252.25  E-value: 1.35e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2467 PLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTF 2546
Cdd:cd15933    3 ALSIISYIGCGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQILLLAGEWAEGNKVACKVVAILLHFFFMAAF 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2547 AWTLVESLHVYRMLTEVRNIDTGpMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIIN 2626
Cdd:cd15933   83 SWMLVEGLHLYLMIVKVFNYKSK-MRYYYFIGWGLPAIIVAISLAILFDDYGSPNVCWLSLDDGLIWAFVGPVIFIITVN 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2627 TVTSVLSAKVSCQ-----RKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFH 2701
Cdd:cd15933  162 TVILILVVKITVSlstndAKKSQGTLAQIKSTAKASVVLLPILGLTWLFGVLVVNSQTIVFQYIFVILNSLQGLMIFLFH 241


                 ....*....
gi 7656967  2702 CVLNQEVRK 2710
Cdd:cd15933  242 CVLNSEVRS 250
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 2466-2697 1.89e-74

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: 249.12  E-value: 1.89e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTEN--------PFLCTVVAIL 2537
Cdd:pfam00002    2 LSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNkqdldhcsWVGCKVVAVF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2538 LHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAG 2617
Cdd:pfam00002   82 LHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYGEDDGCWLSNENGLWWIIRG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2618 PIGAVIIINTVTSVLSAKVSCQRKHHYYGKKGIvsllrTAFLLLLLISA---------TWLLGLLAVNRDALS---FHYL 2685
Cdd:pfam00002  162 PILLIILVNFIIFINIVRILVQKLRETNMGKSD-----LKQYRRLAKSTllllpllgiTWVFGLFAFNPENTLrvvFLYL 236

                          250
                   ....*....|..
gi 7656967    2686 FAIFSGLQGPFV 2697
Cdd:pfam00002  237 FLILNSFQGFFV 248
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
 2466-2713 8.14e-73

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: 244.86  E-value: 8.14e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMST 2545
Cdd:cd15440    2 SALTFITYIGCIISIVCLLLAFITFTCFRNLQCDRNTIHKNLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFLAA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2546 FAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIII 2625
Cdd:cd15440   82 FSWMLLEGFQLYVMLVEVFEPEKSRIKWYYLFGYGLPALIVAVSAGVDPTGYGTEDHCWLSTENGFIWSFVGPVIVVLLA 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2626 NTVTSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLIS------ATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLL 2699
Cdd:cd15440  162 NLVFLGMAIYVMCRHSSRSASKKDASKLKNIRGWLKGSIVlvvllgLTWTFGLLFINQESIVMAYIFTILNSLQGLFIFI 241

                        250
                 ....*....|....
gi 7656967  2700 FHCVLNQEVRKHLK 2713
Cdd:cd15440  242 FHCVLNEKVRKELR 255
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
 2468-2712 3.41e-64

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: 220.16  E-value: 3.41e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTEN--PFLCTVVAILLHYIYMST 2545
Cdd:cd13952    4 LSIITYIGCSLSLVGLLLTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIGQLLTSSdrPVLCKALAILLHYFLLAS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2546 FAWTLVESLHVYRMLTEVRNIDTG-PMRFYYVVGWGIPAIVTGLAVGLDPQGYGNP-----DFCWLSLQDTLIWSFAGPI 2619
Cdd:cd13952   84 FFWMLVEAFDLYRTFVKVFGSSERrRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSpgyggEYCWLSNGNALLWAFYGPV 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2620 GAVIIINTVTSVLSA-KVSCQRKHHYYGKKgivsllrtAFLLLLLISA----------TWLLGLLAVNRDA-LSFHYLFA 2687
Cdd:cd13952  164 LLILLVNLVFFILTVrILLRKLRETPKQSE--------RKSDRKQLRAylklfplmglTWIFGILAPFVGGsLVFWYLFD 235

                        250       260
                 ....*....|....*....|....*
gi 7656967  2688 IFSGLQGPFVLLFHCVLNQEVRKHL 2712
Cdd:cd13952  236 ILNSLQGFFIFLIFCLKNKEVRRLL 260
GAIN pfam16489
GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and ...
 2130-2381 5.36e-62

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: 211.36  E-value: 5.36e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2130 RALQLVRALRSATQHtGTLFGNDVRTAYQLLGHVlqheswqqgFDLAATQDA----DFHEDVIHSGSALLAPATRAAWEQ 2205
Cdd:pfam16489    1 GAKELARELRNATRH-GPLYGGDVLTAVELLSQL---------FDLLATQDAtlsnAFLENFVQTVSNLLDPENRESWED 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2206 IQRSEGGTAQ--LLRRLEGYFSNVARNVRrtYLRPFVIVTANMILAVDIFDKFNFTGARVPRFDTIHEEFPRelESSVSF 2283
Cdd:pfam16489   71 LQQTERGTAAtkLLRTLEEYALLLAQNMK--YLTPFTIVTPNIVLSVDRLDTHNFKGARFPRFPMKGERPKD--EDSVKL 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2284 PADFFRPPeekegpllrpagrrttpqttrpgpgtereapisrrrrhpdDAGQFAVALVIIYRTLGQLLPE--RYDPDRRS 2361
Cdd:pfam16489  147 PPKAFKPP----------------------------------------DSNGTVVVVFILYRNLGSLLPPssRYDPDRRS 186

                          250       260
                   ....*....|....*....|
gi 7656967    2362 LRLPHRpIINTPMVSTLVYS 2381
Cdd:pfam16489  187 LRLPRR-VVNSPVVSASVHS 205
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
 2466-2709 3.65e-58

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: 202.96  E-value: 3.65e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMST 2545
Cdd:cd15439    2 LALTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQLSLCLFLADLLFLVGIDRTDNKVLCSIIAGFLHYLFLAC 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2546 FAWTLVESLHVYRMlteVRNID----TGP----MRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAG 2617
Cdd:cd15439   82 FAWMFLEAVHLFLT---VRNLKvvnyFSShrfkKRFMYPVGYGLPAVIVAISAAVNPQGYGTPKHCWLSMEKGFIWSFLG 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2618 PIGAVIIINTV------------TSVLSAKVSCQRKHHYYGKKGIVSllrtafllLLLISATWLLGLLAVNRDALSFHYL 2685
Cdd:cd15439  159 PVCVIIVINLVlfcltlwilrekLSSLNAEVSTLKNTRLLTFKAIAQ--------LFILGCTWILGLFQVGPVATVMAYL 230

                        250       260
                 ....*....|....*....|....
gi 7656967  2686 FAIFSGLQGPFVLLFHCVLNQEVR 2709
Cdd:cd15439  231 FTITNSLQGVFIFLVHCLLNRQVR 254
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
 2468-2710 1.42e-56

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: 198.11  E-value: 1.42e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTFA 2547
Cdd:cd15252    4 LTRITQVGIIISLVCLAICIFTFWFFRGLQSDRTTIHKNLCISLFLAELVFLIGINTTTNKIFCSVIAGLLHYFFLAAFA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2548 WTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIINT 2627
Cdd:cd15252   84 WMFIEGIQLYLMLVEVFENEGSRHKNFYIFGYGSPAVIVGVSAALGYRYYGTTKVCWLSTENYFIWSFIGPATLIILLNL 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2628 V------------TSVLSAKVSCQRKHHYYGKKGIVsllrtaflLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGP 2695
Cdd:cd15252  164 IflgvaiykmfrhTAGLKPEVSCLENIRSWARGAIA--------LLFLLGLTWIFGVLHINHASVVMAYLFTVSNSLQGM 235

                        250
                 ....*....|....*
gi 7656967  2696 FVLLFHCVLNQEVRK 2710
Cdd:cd15252  236 FIFLFHCVLSRKVRK 250
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 2467-2709 2.27e-53

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: 188.82  E-value: 2.27e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2467 PLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTF 2546
Cdd:cd15438    3 PLTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNNQVACAVVAGLLHYFFLAAF 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2547 AWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIIN 2626
Cdd:cd15438   83 CWMSLEGVELYLMVVQVFNTQSLKKRYLLLIGYGVPLVIVAISAAVNSKGYGTQRHCWLSLERGFLWSFLGPVCLIILVN 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2627 T---VTSV--LSAKVSCQRKHHYYGKKgIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFH 2701
Cdd:cd15438  163 AiifVITVwkLAEKFSSINPDMEKLRK-IRALTITAIAQLCILGCTWIFGFFQFSDSTLVMSYLFTILNSLQGLFIFLLH 241


                 ....*...
gi 7656967  2702 CVLNQEVR 2709
Cdd:cd15438  242 CLLSKQVR 249
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
 2468-2713 1.20e-50

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: 181.28  E-value: 1.20e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLS---LAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMS 2544
Cdd:cd15256    4 LSSITYVGCSLSifcLAITLVTFAVLSSVSTIRNQRYHIHANLSFAVLVAQILLLISFRFEPGTLPCKIMAILLHFFFLS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVII 2624
Cdd:cd15256   84 AFAWMLVEGLHLYSMVIKVFGSEESKHFYYYGIGWGSPLLICIISLTSALDSYGESDNCWLSLENGAIWAFVAPALFVIV 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2625 IN-----TVTSVLSAKVSCQRKHHyyGKKGIVSLLRTAFLLLLLI-SATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVL 2698
Cdd:cd15256  164 VNigiliAVTRVISRISADNYKVH--GDANAFKLTAKAVAVLLPIlGSSWVFGVLAVNTHALVFQYMFAIFNSLQGFFIF 241

                        250
                 ....*....|....*
gi 7656967  2699 LFHCVLNQEVRKHLK 2713
Cdd:cd15256  242 LFHCLLNSEVRAAFK 256
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 2466-2710 3.95e-50

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: 179.60  E-value: 3.95e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMST 2545
Cdd:cd15436    2 LLLFVITWVGIVISLVCLLICIFTFCFFRGLQTDRNTIHKNLCINLFIAELLFLIGINRTQYTIACPIFAGLLHFFFLAA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2546 FAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIII 2625
Cdd:cd15436   82 FCWLCLEGVQLYLLLVEVFESEYSRRKYFYLCGYSFPALVVAVSAAIDYRSYGTEKACWLRVDNYFIWSFIGPVTFVITL 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2626 NTVTSVLSAkvsCQRKHHYYGKK-------GIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVL 2698
Cdd:cd15436  162 NLVFLVITL---HKMVSHSDLLKpdssrldNIKSWALGAIALLFLLGLTWSFGLMFINEESVVMAYLFTIFNAFQGVFIF 238

                        250
                 ....*....|..
gi 7656967  2699 LFHCVLNQEVRK 2710
Cdd:cd15436  239 IFHCALQKKVRK 250
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
 2466-2716 1.38e-49

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: 177.81  E-value: 1.38e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMST 2545
Cdd:cd16007    2 LLLSVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLIGIDKTQYQIACPIFAGLLHFFFLAA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2546 FAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIII 2625
Cdd:cd16007   82 FSWLCLEGVQLYLMLVEVFESEYSRKKYYYLCGYCFPALVVGISAAIDYRSYGTEKACWLRVDNYFIWSFIGPVSFVIVV 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2626 NTVTSVLS----AKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFH 2701
Cdd:cd16007  162 NLVFLMVTlhkmIRSSSVLKPDSSRLDNIKSWALGAITLLFLLGLTWAFGLLFINKESVVMAYLFTTFNAFQGMFIFIFH 241

                        250
                 ....*....|....*
gi 7656967  2702 CVLNQEVRKHLKGVL 2716
Cdd:cd16007  242 CALQKKVHKEYSKCL 256
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
 2466-2710 1.69e-49

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: 177.80  E-value: 1.69e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMST 2545
Cdd:cd16006    2 LLLTVITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIGIDKTEYKIACPIFAGLLHFFFLAA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2546 FAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIII 2625
Cdd:cd16006   82 FAWMCLEGVQLYLMLVEVFESEYSRKKYYYVAGYLFPATVVGVSAAIDYKSYGTEKACWLRVDNYFIWSFIGPVTFIILL 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2626 NTVTSVLS----AKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGPFVLLFH 2701
Cdd:cd16006  162 NLIFLVITlckmVKHSNTLKPDSSRLENIKSWVLGAFALLCLLGLTWSFGLLFINEETIVMAYLFTIFNAFQGMFIFIFH 241


                 ....*....
gi 7656967  2702 CVLNQEVRK 2710
Cdd:cd16006  242 CALQKKVRK 250
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
 2466-2710 2.05e-49

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: 177.44  E-value: 2.05e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMST 2545
Cdd:cd16005    2 LLLDVITWVGILLSLVCLLICIFTFCFFRGLQSDRNTIHKNLCISLFVAELLFLIGINRTDQPIACAVFAALLHFFFLAA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2546 FAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIII 2625
Cdd:cd16005   82 FTWMFLEGVQLYIMLVEVFESEHSRRKYFYLVGYGMPALIVAVSAAVDYRSYGTDKVCWLRLDTYFIWSFIGPATLIIML 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2626 NTV------------TSVLSAKVSCQRKhhyygkkgIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQ 2693
Cdd:cd16005  162 NVIflgialykmfhhTAILKPESGCLDN--------IKSWVIGAIALLCLLGLTWAFGLMYINESTVIMAYLFTIFNSLQ 233

                        250
                 ....*....|....*..
gi 7656967  2694 GPFVLLFHCVLNQEVRK 2710
Cdd:cd16005  234 GMFIFIFHCVLQKKVRK 250
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
 2468-2713 1.51e-45

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: 166.54  E-value: 1.51e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTFA 2547
Cdd:cd15931    4 LEWINRVGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHLCLCLSMSHTLFLAGIEYVENELACTVMAGLLHYLFLASFV 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2548 WTLVESLHVY---RMLTEVRNI--DTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAV 2622
Cdd:cd15931   84 WMLLEALQLHllvRRLTKVQVIqrDGLPRPLLCLIGYGVPFLIVGVSALVYSDGYGEAKMCWLSQERGFNWSFLGPVIAI 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2623 IIINTVtsVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLIS------ATWLLGLLAVNRDALSFHYLFAIFSGLQGPF 2696
Cdd:cd15931  164 IGINWI--LFCATLWCLRQTLSNMNSDISQLKDTRLLTFKAVAqlfilgCTWVLGLFQTNPVALVFQYLFTILNSLQGAF 241

                        250
                 ....*....|....*..
gi 7656967  2697 VLLFHCVLNQEVRKHLK 2713
Cdd:cd15931  242 LFLVHCLLNKEVREEYI 258
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
 2468-2709 4.60e-40

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: 150.41  E-value: 4.60e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTFA 2547
Cdd:cd15437    4 LTRITQLGIIISLICLSMCIFTFWFFSEIQSTRTTIHKNLCCSLFLAELIFLIGINMNANKLFCSIIAGLLHYFFLAAFA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2548 WTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIINT 2627
Cdd:cd15437   84 WMCIEGIHLYLIVVGVIYNKGFLHKNFYIFGYGSPAVVVGISAALGYKYYGTTKVCWLSTENNFIWSFIGPACLIILVNL 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2628 V------------TSVLSAKVSCQrkhhyygkKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYLFAIFSGLQGP 2695
Cdd:cd15437  164 LafgviiykvfrhTAMLKPEVSCY--------ENIRSCARGALALLFLLGATWIFGVLHVVYGSVVTAYLFTISNAFQGM 235

                        250
                 ....*....|....
gi 7656967  2696 FVLLFHCVLNQEVR 2709
Cdd:cd15437  236 FIFIFLCVLSRKIQ 249
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 793-888 4.60e-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: 130.13  E-value: 4.60e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   793 HYTVSVSEDRPVGTSIATLSANDEDTGENARITYVIQDPVPQ--FRIDPDSGTMYTMMELDYENQVAYTLTIMAQDNGIP 870
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDglFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                         90
                 ....*....|....*...
gi 7656967   871 QKSDTTTLEILILDANDN 888
Cdd:cd11304   81 PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 464-561 1.06e-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: 126.27  E-value: 1.06e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   464 YVVQVPEDVGLNTAVLRVQATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGILDVINPLDFEDVQKYSLSIKAQDGGRPP 543
Cdd:cd11304    2 YEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGPP 81

                         90
                 ....*....|....*...
gi 7656967   544 LiNSSGVVSVQVLDVNDN 561
Cdd:cd11304   82 L-SSTATVTITVLDVNDN 98
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
 2467-2709 1.39e-33

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: 131.73  E-value: 1.39e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2467 PLKIVTYAAVSLSLAALLVAF----VLLSLVRMLRSNLHSIhKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIY 2542
Cdd:cd15259    3 LLHPVVYAGAALCLLCLLATIityiVFHRLIRISRKGRHML-VNLCLHLLLTCVVFVGGINRTANQLVCQAVGILLHYST 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2543 MSTFAWTLVESLHVYRMLTEVRNIDTG---------PMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIw 2613
Cdd:cd15259   82 LCTLLWVGVTARNMYKQVTKTAKPPQDedqpprppkPMLRFYLIGWGIPLIICGITAAVNLDNYSTYDYCWLAWDPSLG- 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2614 SFAGPIGAVIIINTvtsVLSAKVSCQRKHHYygkKGIVSLLRTAFLLLLLISATWLLGLLAVNRDA---LSFHYLFAIFS 2690
Cdd:cd15259  161 AFYGPAALIVLVNC---IYFLRIYCQLKGAP---VSFQSQLRGAVITLFLYVAMWACGALAVSQRYfldLVFSCLYGATC 234

                        250
                 ....*....|....*....
gi 7656967  2691 GLQGPFVLLFHCVLNQEVR 2709
Cdd:cd15259  235 SSLGLFVLIHHCLSREDVR 253
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 357-455 2.28e-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: 125.12  E-value: 2.28e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   357 EYRERVRENLEVGYEVLTIRASDRDSPINANLRYRVLGG-AWDVFQLNESSGVVSTRAVLDREEAAEYQLLVEANDQGRN 435
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGnEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                         90       100
                 ....*....|....*....|
gi 7656967   436 pgPLSATATVYIEVEDENDN 455
Cdd:cd11304   81 --PLSSTATVTITVLDVNDN 98
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 897-995 2.85e-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: 125.12  E-value: 2.85e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   897 YQGSIFEDAPPSTSILQVSATDRDSGPNGRLLYTFQgGDDGDGDFYIEPTSGVIRTQRRLDRENVAVYNLWALAVDRGSP 976
Cdd:cd11304    2 YEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIV-SGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGGGP 80

                         90
                 ....*....|....*....
gi 7656967   977 tPLSASVEIQVTILDINDN 995
Cdd:cd11304   81 -PLSSTATVTITVLDVNDN 98
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
 2467-2713 7.20e-33

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: 130.04  E-value: 7.20e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2467 PLKIVTYAAVSLSLAALLVAFVLLSLVRMLRsNLHSIHK-HLAVALFLSQLVFVIGINQTEN-PFLCTVVAILLHYIYMS 2544
Cdd:cd15039    3 ILGILTLIGLIISLVFLLLTLAVYALLPELR-NLHGKCLmCLVLSLFVAYLLLLIGQLLSSGdSTLCVALGILLHFFFLA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNIDTG-----PMRFYYVVGWGIPAIVTGLAVGLD---PQGYGNPDF----CWLSLQDTLI 2612
Cdd:cd15039   82 AFFWLNVMSFDIWRTFRGKRSSSSRskerkRFLRYSLYAWGVPLLLVAVTIIVDfspNTDSLRPGYgegsCWISNPWALL 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2613 WSFAGPIGAVIIINTVTSVLSA----------KVSCQRKHHY------YGKKGIVsllrtaflllllISATWLLGLLAVN 2676
Cdd:cd15039  162 LYFYGPVALLLLFNIILFILTAirirkvkketAKVQSRLRSDkqrfrlYLKLFVI------------MGVTWILEIISWF 229

                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 7656967  2677 RDALS-FHYLFAIFSGLQGPFV-LLFhcVLNQEVRKHLK 2713
Cdd:cd15039  230 VGGSSvLWYIFDILNGLQGVFIfLIF--VCKRRVLRLLK 266
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
 2468-2716 7.71e-33

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: 129.97  E-value: 7.71e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTFA 2547
Cdd:cd15255    4 LRTLSFIGCGVSLCALIVTFILFLAVGVPKSERTTVHKNLIFALAAAEFLLMFSEWAKGNQVACWAVTALLHLFFLAAFS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2548 WTLVESLHVYRMLTEVrNIDTGP-MRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIIN 2626
Cdd:cd15255   84 WMLVEGLLLWSKVVAV-NMSEDRrMKFYYVTGWGLPVVIVAVTLATSFNKYVADQHCWLNVQTDIIWAFVGPVLFVLTVN 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2627 TVT--SVLSAKVSCQRKHhyygKKGIVSLLRTAFLLLLLISA--------------TWLLGLLAVNRDALSfhYLFAIFS 2690
Cdd:cd15255  163 TFVlfRVVMVTVSSARRR----AKMLTPSSDLEKQIGIQIWAtakpvlvllpvlglTWLCGVLVHLSDVWA--YVFITLN 236

                        250       260
                 ....*....|....*....|....*.
gi 7656967  2691 GLQGPFVLLFHCVLNQEVRKHLKGVL 2716
Cdd:cd15255  237 SFQGLYIFLVYAIYNSEVRNAIQRMQ 262
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
 2479-2717 1.08e-32

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: 128.91  E-value: 1.08e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2479 SLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTFAWTLVESLHVYR 2558
Cdd:cd15251   16 CLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNILILVGQTQTLNKGVCTMTAAFLHFFFLSSFCWVLTEAWQSYM 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2559 MLtevrnidTGPMRF------YYVVGWGIPAIVTGLAVGLD-PQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIINTVTSV 2631
Cdd:cd15251   96 AV-------TGRMRTrlirkrFLCLGWGLPALVVAVSVGFTrTKGYGTSSYCWLSLEGGLLYAFVGPAAAVVLVNMVIGI 168

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2632 LSAkvscqrkHHYYGKKGIVSLLRTAFLLLLLI----SATWLLGLLAV-NRDALSFHYLFAIFSGLQGPFVLLFHCVLNQ 2706
Cdd:cd15251  169 LVF-------NKLVSRDGISDNAMASLWSSCVVlpllALTWMSAVLAMtDRRSVLFQILFAVFDSLQGFVIVMVHCILRR 241

                        250
                 ....*....|.
gi 7656967  2707 EVRKHLKGVLG 2717
Cdd:cd15251  242 EVQDAVKCRMG 252
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1444-1627 1.73e-31

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: 121.76  E-value: 1.73e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1444 TRSFPPQSFVTFRGLR-QRFHFTISLTFATQERNGLLLYNGRFNeKHDFIALEIVDEQVQLTFSAGETTTTVAPKVPsgV 1522
Cdd:cd00110    1 GVSFSGSSYVRLPTLPaPRTRLSISFSFRTTSPNGLLLYAGSQN-GGDFLALELEDGRLVLRYDLGSGSLVLSSKTP--L 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1523 SDGRWHSVQVQYYNkpnighlglphgpsgeKMAVVTVDDCDTtmavrfgkdignyscaAQGTQTGSKKSLDLTGPLLLGG 1602
Cdd:cd00110   78 NDGQWHSVSVERNG----------------RSVTLSVDGERV----------------VESGSPGGSALLNLDGPLYLGG 125

                        170       180
                 ....*....|....*....|....*.
gi 7656967  1603 VPNLPEDFPVHNRQ-FVGCMRNLSVD 1627
Cdd:cd00110  126 LPEDLKSPGLPVSPgFVGCIRDLKVN 151
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
 2479-2720 4.35e-31

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: 124.72  E-value: 4.35e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2479 SLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTFAWTLVESLHVYR 2558
Cdd:cd15990   19 SLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYM 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2559 MLT-EVRNIDTgpMRFYYVVGWGIPAIVTGLAVGL-DPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIINTVTSVLSAkv 2636
Cdd:cd15990   99 AVTgRLRNRII--RKRFLCLGWGLPALVVAISVGFtKAKGYGTVNYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVF-- 174

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2637 scqrkHHYYGKKGIVSLLRTAFLLLLLISA---------TWLLGLLAV-NRDALSFHYLFAIFSGLQGPFVLLFHCVLNQ 2706
Cdd:cd15990  175 -----NKLVSKDGITDKKLKERAGASLWSScvvlpllalTWMSAVLAItDRRSALFQILFAVFDSLEGFVIVMVHCILRR 249

                        250
                 ....*....|....
gi 7656967  2707 EVRKHLKGVLGGRK 2720
Cdd:cd15990  250 EVQDAVKCRVVDRQ 263
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 1003-1097 7.37e-29

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: 112.41  E-value: 7.37e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1003 ELELFVEENNPVGSVVAKIRANDPDEGPNAQIMYQIVEGDMRHFFQLDLLNGDLRAMVELDFEVRREYVLVVQAT---SA 1079
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATdggGP 80

                         90
                 ....*....|....*...
gi 7656967  1080 PLVSRATVHILLVDQNDN 1097
Cdd:cd11304   81 PLSSTATVTITVLDVNDN 98
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
 2477-2718 4.77e-28

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: 116.98  E-value: 4.77e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2477 SLSLAALLVAFVLLSLV-RMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTFAWTLVESLH 2555
Cdd:cd15988   13 AVSCMALLILLAIYAAFwRFIRSERSIILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFLSSFCWVLTEAWQ 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2556 VYrmLTEVRNIDTGPMRFYYV-VGWGIPAIVTGLAVGLD-PQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIINTVTSV-- 2631
Cdd:cd15988   93 SY--LAVIGRMRTRLVRKRFLcLGWGLPALVVAVSVGFTrTKGYGTASYCWLSLEGGLLYAFVGPAAVIVLVNMLIGIiv 170

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2632 ---LSAK--VSCQRKHHYYGKK--------------GIVSLLRTAFLLLLLISA--------------TWLLGLLAV-NR 2677
Cdd:cd15988  171 fnkLMSRdgISDKSKKQRAGSEaepcsslllkcskcGVVSSAAMSSATASSAMAslwsscvvlpllalTWMSAVLAMtDR 250

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 7656967  2678 DALSFHYLFAIFSGLQGPFVLLFHCVLNQEVRKHLKGVLGG 2718
Cdd:cd15988  251 RSILFQVLFAVFNSVQGFVIITVHCFLRREVQDVVKCQMGG 291
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
 2480-2713 1.16e-27

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: 115.55  E-value: 1.16e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2480 LAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIYMSTFAWTLVESLHVYRM 2559
Cdd:cd15989   19 LALITLAVVYAALWRYIRSERSIILINFCLSIISSNILILVGQTQTHNKGICTMTTAFLHFFFLASFCWVLTEAWQSYMA 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2560 LTEvrNIDTGPMRFYYV-VGWGIPAIVTGLAVGLD-PQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIINTVTSVLSAKVS 2637
Cdd:cd15989   99 VTG--KIRTRLIRKRFLcLGWGLPALVVAISMGFTkAKGYGTPHYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKL 176

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2638 CQRK-------HHYYG--------------KKGIVSLLRTAFLLLLL--------------ISATWLLGLLAV-NRDALS 2681
Cdd:cd15989  177 VSRDgildkklKHRAGqmsephsgltlkcaKCGVVSTTALSATTASNamaslwsscvvlplLALTWMSAVLAMtDKRSIL 256

                        250       260       270
                 ....*....|....*....|....*....|..
gi 7656967  2682 FHYLFAIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15989  257 FQILFAVFDSLQGFVIVMVHCILRREVQDAFR 288
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
 2467-2710 1.28e-27

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: 114.82  E-value: 1.28e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2467 PLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHS-IHKHLAVALFLSQLVFVI--GINQTENPFLCTVVAILLHYIYM 2543
Cdd:cd15258    3 ILTFISYVGCGISAIFLAITILTYIAFRKLRRDYPSkIHMNLCAALLLLNLAFLLssWIASFGSDGLCIAVAVALHYFLL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2544 STFAWTLVESLHVYRMLTEVRNIDTGPMRFYY-VVGWGIPAIVTGLAVGLDPQGYG-----------NPDFCWLslQDTL 2611
Cdd:cd15258   83 ACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLcLVGWGLPALLVTLVLSVRSDNYGpitipngegfqNDSFCWI--RDPV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2612 IWSF--AGPIGAVIIIN---------TVTSVLSAKVSCQRKHHYYGKKGIVSLLRTaflllllISATWLLGLLAVNRDAL 2680
Cdd:cd15258  161 VFYItvVGYFGLTFLFNmvmlatvlvQICRLREKAQATPRKRALHDLLTLLGLTFL-------LGLTWGLAFFAWGPFNL 233

                        250       260       270
                 ....*....|....*....|....*....|
gi 7656967  2681 SFHYLFAIFSGLQGPFVLLFHCVLNQEVRK 2710
Cdd:cd15258  234 PFLYLFAIFNSLQGFFIFIWYCSMKENVRK 263
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
 2468-2713 3.13e-27

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: 113.86  E-value: 3.13e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVAL-------FLSQLVFV--------IGINQTENPFLCT 2532
Cdd:cd15041    4 VYYIYLVGYSLSLVALLPAIVIFLYFRSLRCTRIRLHINLFLSFilravfwIIWDLLVVydrltssgVETVLMQNPVGCK 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2533 VVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLdpQGYGNPDFCWLSLQDTLI 2612
Cdd:cd15041   84 LLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSEPSSLKLYYAIGWGLPLVIVVIWAIV--RALLSNESCWISYNNGHY 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2613 -WSFAGPIGAVIIINTVT-----SVLSAKVSCQ---RKHHYygKKGivsllrtaflllllISATW----LLG---LLAVN 2676
Cdd:cd15041  162 eWILYGPNLLALLVNLFFlinilRILLTKLRSHpnaEPSNY--RKA--------------VKATLilipLFGiqyLLTIY 225

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 7656967  2677 R----DALSFHYLF--AIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15041  226 RppdgSEGELVYEYfnAILNSSQGFFVAVIYCFLNGEVQSELK 268
LamG smart00282
Laminin G domain;
1465-1629 3.26e-27

Laminin G domain;


Pssm-ID: 214598 [Multi-domain]  Cd Length: 132  Bit Score: 108.97  E-value: 3.26e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     1465 TISLTFATQERNGLLLYNGrFNEKHDFIALEIVDEQVQLTFSAGETTTTVAPKVPSgVSDGRWHSVQVQYYNkpnighlg 1544
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAG-SKGGGDYLALELRDGRLVLRYDLGSGPARLTSDPTP-LNDGQWHRVAVERNG-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     1545 lphgpsgeKMAVVTVDDCDTTMAVRFgkdignyscaaqgtqtGSKKSLDLTGPLLLGGVPNLPEDFPVHNRQ-FVGCMRN 1623
Cdd:smart00282   71 --------RSVTLSVDGGNRVSGESP----------------GGLTILNLDGPLYLGGLPEDLKLPPLPVTPgFRGCIRN 126


                    ....*.
gi 7656967     1624 LSVDGK 1629
Cdd:smart00282  127 LKVNGK 132
Cadherin pfam00028
Cadherin domain;
794-883 1.40e-26

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 105.85  E-value: 1.40e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     794 YTVSVSEDRPVGTSIATLSANDEDTGENARITYVI--QDPVPQFRIDPDSGTMYTMMELDYENQVAYTLTIMAQDNGIPQ 871
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSIlgGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|..
gi 7656967     872 KSDTTTLEILIL 883
Cdd:pfam00028   81 LSSTATVTITVL 92
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
 2468-2710 1.43e-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: 111.68  E-value: 1.43e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVL-LSLVRMLRSNLHSIHKHLAVALFLSQLVFVIG--INQTENPFLCTVVAILLHYIYMS 2544
Cdd:cd15997    4 LTLITYLGCGISSIFLGITLVTyLAFEKLRRDYPSKILINLCTALLMLNLVFLLNswLSSFNNYGLCITVAAFLHYFLLA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNIDtgpMRFYY----VVGWGIPAIVTGLAVGLDPQGYGN----------PDFCWLslQDT 2610
Cdd:cd15997   84 SFTWMGLEAVHMYFALVKVFNIY---IPNYIlkfcIAGWGIPAVVVALVLAINKDFYGNelssdslhpsTPFCWI--QDD 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2611 LIW--SFAGPIGAVIIINT---VTSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYL 2685
Cdd:cd15997  159 VVFyiSVVAYFCLIFLCNIsmfITVLIQIRSMKAKKPSRNWKQGFLHDLKSVASLTFLLGLTWGFAFFAWGPVRIFFLYL 238

                        250       260
                 ....*....|....*....|....*
gi 7656967  2686 FAIFSGLQGPFVLLFHCVLNQEVRK 2710
Cdd:cd15997  239 FSICNTLQGFFIFVFHCLMKENVRK 263
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 812-890 1.12e-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: 102.81  E-value: 1.12e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      812 SANDEDTGENARITYVI--QDPVPQFRIDPDSGTMYTMMELDYENQVAYTLTIMAQDNGIPQKSDTTTLEILILDANDNA 889
Cdd:smart00112    1 SATDADSGENGKVTYSIlsGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDNA 80


                    .
gi 7656967      890 P 890
Cdd:smart00112   81 P 81
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
 2466-2716 4.16e-25

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: 107.60  E-value: 4.16e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHS-IHKHLAVALFLSQLVFVIG--INQTEN-PFLCTVVAILLHYI 2541
Cdd:cd15444    2 LILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDYPSkILIQLCVALLLLNLVFLLDswIALYKDiVGLCISVAVFLHYF 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2542 YMSTFAWTLVESLHVYRMLTEVRN--IDTGPMRFYyVVGWGIPAIVTGLAVGLDPQGYG-----------NPDFCWLSLQ 2608
Cdd:cd15444   82 LLVSFTWMGLEAFHMYLALVKVFNtyIRKYILKFC-IVGWGVPAVVVAIVLAVSKDNYGlgsygkspngsTDDFCWINNN 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2609 DTLIWSFAGPIGAVIIINTVTSVLSAKVSCQ---RKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHYL 2685
Cdd:cd15444  161 IVFYITVVGYFCVIFLLNISMFIVVLVQLCRikkQKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFAWGPVNLAFMYL 240

                        250       260       270
                 ....*....|....*....|....*....|.
gi 7656967  2686 FAIFSGLQGPFVLLFHCVLNQEVRKHLKGVL 2716
Cdd:cd15444  241 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 271
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 482-563 2.07e-24

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: 98.96  E-value: 2.07e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      482 QATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGILDVINPLDFEDVQKYSLSIKAQDGGRPPLiNSSGVVSVQVLDVNDN 561
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPL-SSTATVTITVLDVNDN 79


                    ..
gi 7656967      562 EP 563
Cdd:smart00112   80 AP 81
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 569-683 2.44e-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: 99.31  E-value: 2.44e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   569 PFQATVLENVPLGYPVVHIQAVDADSGENARLHYRLVDtastflgggsagpknpaPTPDFPFQIHNSSGWITVCAELDRE 648
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDSGENGEVTYSIVS-----------------GNEDGLFSIDPSTGEITTAKPLDRE 63

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 7656967   649 EVEHYSFGVEAVDHGSPPMSSSTSVSITVLDVNDN 683
Cdd:cd11304   64 EQSSYTLTVTATDGGGPPLSSTATVTITVLDVNDN 98
Cadherin pfam00028
Cadherin domain;
464-556 2.77e-24

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 99.30  E-value: 2.77e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     464 YVVQVPEDVGLNTAVLRVQATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGILDVINPLDFEDVQKYSLSIKAQDGGRPP 543
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGPP 80

                           90
                   ....*....|...
gi 7656967     544 LiNSSGVVSVQVL 556
Cdd:pfam00028   81 L-SSTATVTITVL 92
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 376-457 3.56e-24

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: 98.58  E-value: 3.56e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      376 RASDRDSPINANLRYRVLGG-AWDVFQLNESSGVVSTRAVLDREEAAEYQLLVEANDQGrnPGPLSATATVYIEVEDEND 454
Cdd:smart00112    1 SATDADSGENGKVTYSILSGnDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGG--GPPLSSTATVTITVLDVND 78


                    ...
gi 7656967      455 NYP 457
Cdd:smart00112   79 NAP 81
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 915-997 6.14e-24

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: 97.81  E-value: 6.14e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      915 SATDRDSGPNGRLLYTFqGGDDGDGDFYIEPTSGVIRTQRRLDRENVAVYNLWALAVDRGSPtPLSASVEIQVTILDIND 994
Cdd:smart00112    1 SATDADSGENGKVTYSI-LSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGP-PLSSTATVTITVLDVND 78


                    ...
gi 7656967      995 NAP 997
Cdd:smart00112   79 NAP 81
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
 2466-2713 7.54e-24

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


Pssm-ID: 320598 [Multi-domain]  Cd Length: 268  Bit Score: 103.93  E-value: 7.54e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLV-RMLRSNLHSIHKHL-----AVALFLSQLVFVIG--INQTENPF-LCTVVAI 2536
Cdd:cd15932    2 PALDYITYVGLGISILSLVLCLIIEALVwKSVTKNKTSYMRHVclvniALSLLIADIWFIIGaaISTPPNPSpACTAATF 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2537 LLHYIYMSTFAWTLVESLH-VYRMLTEVRNIDTGPMR-FYYVVGWGIPAIVTGLAVGL-DPQG-YGNPDFCWLSLQDTL- 2611
Cdd:cd15932   82 FIHFFYLALFFWMLTLGLLlFYRLVLVFHDMSKSTMMaIAFSLGYGCPLIIAIITVAAtAPQGgYTRKGVCWLNWDKTKa 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2612 IWSFAGPIGAVIIINTVTsVLSAKVSCQR-----KHHYYGKKGIVSLLRTAFLLLLLISATWLLGL-LAVNRDALSFHYL 2685
Cdd:cd15932  162 LLAFVIPALAIVVVNFII-LIVVIFKLLRpsvgeRPSKDEKNALVQIGKSVAILTPLLGLTWGFGLgTMIDPKSLAFHII 240

                        250       260
                 ....*....|....*....|....*...
gi 7656967  2686 FAIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15932  241 FAILNSFQGFFILVFGTLLDSKVREALL 268
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 250-349 8.29e-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: 98.15  E-value: 8.29e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   250 YQVALFENEPAGTLILQLHAHytiEGEEERVSYYmegLFDERSRGYFRIDSATGAVSTDSVLDRETKETHVLRVKAVDYS 329
Cdd:cd11304    2 YEVSVPENAPPGTVVLTVSATdpdSGENGEVTYS---IVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDGG 78

                         90       100
                 ....*....|....*....|
gi 7656967   330 TPPRSATTYITVLVKDTNDH 349
Cdd:cd11304   79 GPPLSSTATVTITVLDVNDN 98
Laminin_G_2 pfam02210
Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G ...
 1470-1629 1.09e-23

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: 98.65  E-value: 1.09e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1470 FATQERNGLLLYNGrfNEKHDFIALEIVDEQVQLTFSAGETTTTVAPKvPSGVSDGRWHSVQVQYYNkpnighlglphgp 1549
Cdd:pfam02210    1 FRTRQPNGLLLYAG--GGGSDFLALELVNGRLVLRYDLGSGPESLLSS-GKNLNDGQWHSVRVERNG------------- 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1550 sgeKMAVVTVDDCDTTMAVRFGKDIGnyscaaqgtqtgskksLDLTGPLLLGGVPN-LPEDFPVHNRQFVGCMRNLSVDG 1628
Cdd:pfam02210   65 ---NTLTLSVDGQTVVSSLPPGESLL----------------LNLNGPLYLGGLPPlLLLPALPVRAGFVGCIRDVRVNG 125


                   .
gi 7656967    1629 K 1629
Cdd:pfam02210  126 E 126
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 691-785 5.91e-23

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: 95.46  E-value: 5.91e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967   691 TYELRLNEDAAVGSSVLTLQARDRD--ANSVITYQLTGGNTRNRFALSSQRggGLITLALPLDYKQEQQYVLAVTASDG- 767
Cdd:cd11304    1 SYEVSVPENAPPGTVVLTVSATDPDsgENGEVTYSIVSGNEDGLFSIDPST--GEITTAKPLDREEQSSYTLTVTATDGg 78

                         90       100
                 ....*....|....*....|
gi 7656967   768 --TRSHTAHVLINVTDANTH 785
Cdd:cd11304   79 gpPLSSTATVTITVLDVNDN 98
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
 2468-2711 6.78e-23

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: 101.12  E-value: 6.78e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSL---AALLVAFVLLSLVRmlRSNLHSIHKHLAVALFLSQLVFVIG--INQTENPFLCTVVAILLHYIY 2542
Cdd:cd15996    4 LTFITYIGCGISAifsAATLLTYIAFEKLR--RDYPSKILMNLSTALLFLNLVFLLDgwIASFEIDELCITVAVLLHFFL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2543 MSTFAWTLVESLHVYRMLTEVRNidTGPMRF---YYVVGWGIPAIVTGLAV------------GLDPQGYGNPDFCWLSL 2607
Cdd:cd15996   82 LATFTWMGLEAIHMYIALVKVFN--TYIRRYilkFCIIGWGLPALIVSIVLastndnygygyyGKDKDGQGGDEFCWIKN 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2608 QDTLIWSFAGPIGAVIIINTVTSVLSAKVSCQR---KHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHY 2684
Cdd:cd15996  160 PVVFYVTCAAYFGIMFLMNVAMFIVVMVQICGRngkRSNRTLREEILRNLRSVVSLTFLLGMTWGFAFFAWGPVNLAFMY 239

                        250       260
                 ....*....|....*....|....*..
gi 7656967  2685 LFAIFSGLQGPFVLLFHCVLNQEVRKH 2711
Cdd:cd15996  240 LFTIFNSLQGLFIFVFHCALKENVQKQ 266
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
 2468-2708 1.58e-22

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: 100.03  E-value: 1.58e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLL----SLVRMLRSNLHSI-----HKHLAVAlflsqlVFVIGINQTENPFLCTVVAILL 2538
Cdd:cd16000    4 LHPVVYACTAVMLLCLFASIITYivhhSTIRISRKGWHMLlnfcfHTALTFA------VFAGGINRTKYPIICQAVGIVL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2539 HYIYMSTFAWTLVESLHVYRMLTE----VRNIDTGP------MRFYYVVGwGIPAIVTGLAVGLDPQGYGNPD----FCW 2604
Cdd:cd16000   78 HYSTLSTMLWIGVTARNIYKQVTKkphlCQDTDQPPypkqplLRFYLVSG-GVPFIICGITAATNINNYGTEDedtpYCW 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2605 LSLQDTLiWSFAGPIGAVIIINTV---TSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDals 2681
Cdd:cd16000  157 MAWEPSL-GAFYGPVAFIVLVTCIyflCTYVQLRRHPERKYELKNEHSFKAQLRAAAFTLFLFTATWAFGALAVSQG--- 232

                        250       260       270
                 ....*....|....*....|....*....|....
gi 7656967  2682 fHYLFAIFSGLQGP-------FVLLFHCVLNQEV 2708
Cdd:cd16000  233 -HFLDMIFSCLYGAfcvtlglFILIHHCAKRDDV 265
Laminin_G_2 pfam02210
Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G ...
 1719-1849 3.83e-22

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: 94.41  E-value: 3.83e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1719 FRTRKEDSVLMEATSGGPTSFRLQILNNYLQFEVSHGpSDVESVMLSGLRVTDGEWHHLLIELKNvkedsemkHLVTMTL 1798
Cdd:pfam02210    1 FRTRQPNGLLLYAGGGGSDFLALELVNGRLVLRYDLG-SGPESLLSSGKNLNDGQWHSVRVERNG--------NTLTLSV 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 7656967    1799 DYGMDQNKADIGGMLPGLTVRSVVVGGA----SEDKVSVRRGFRGCMQGVRMGGT 1849
Cdd:pfam02210   72 DGQTVVSSLPPGESLLLNLNGPLYLGGLppllLLPALPVRAGFVGCIRDVRVNGE 126
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
 2468-2717 9.22e-22

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


Pssm-ID: 320381 [Multi-domain]  Cd Length: 271  Bit Score: 97.91  E-value: 9.22e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLV--RMLRSNL----HSIHKHLAVALFLSQLVFVIGINQTENP--FLCTVVAILLH 2539
Cdd:cd15253    4 LDFLSQVGLGASILALLLCLGIYRLVwrSVVRNKIsyfrHMTLVNIAFSLLLADTCFLGATFLSAGHesPLCLAAAFLCH 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2540 YIYMSTFAWTLVESLHVYRMLTEV-----RNIDTGPMRFyyvVGWGIPAIVTGLAVGL-DPQG-YGNPDFCWLSLQDTLI 2612
Cdd:cd15253   84 FFYLATFFWMLVQALMLFHQLLFVfhqlaKRSVLPLMVT---LGYLCPLLIAAATVAYyYPKRqYLHEGACWLNGESGAI 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2613 WSFAGPIGAVIIINTVTSVLS----AKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALS-FHYLFA 2687
Cdd:cd15253  161 YAFSIPVLAIVLVNLLVLFVVlmklMRPSVSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVATLTGESSQvSHYGFA 240

                        250       260       270
                 ....*....|....*....|....*....|
gi 7656967  2688 IFSGLQGPFVLLFHCVLNQEVRKHLKGVLG 2717
Cdd:cd15253  241 ILNAFQGVFILLFGCLMDKKVREALLKRLC 270
Cadherin pfam00028
Cadherin domain;
897-990 1.28e-21

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 91.59  E-value: 1.28e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     897 YQGSIFEDAPPSTSILQVSATDRDSGPNGRLLYTFQGGDDGDGdFYIEPTSGVIRTQRRLDRENVAVYNLWALAVDRGSP 976
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGN-FRIDPDTGDISTTKPLDRESIGEYELTVEATDSGGP 79

                           90
                   ....*....|....
gi 7656967     977 tPLSASVEIQVTIL 990
Cdd:pfam00028   80 -PLSSTATVTITVL 92
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 1022-1099 1.47e-21

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: 90.87  E-value: 1.47e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     1022 RANDPDEGPNAQIMYQIVEGDMRHFFQLDLLNGDLRAMVELDFEVRREYVLVVQAT---SAPLVSRATVHILLVDQNDNP 1098
Cdd:smart00112    1 SATDADSGENGKVTYSILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATdggGPPLSSTATVTITVLDVNDNA 80


                    .
gi 7656967     1099 P 1099
Cdd:smart00112   81 P 81
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
 2470-2714 1.71e-21

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: 96.72  E-value: 1.71e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2470 IVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVI------GINQTENPFLCTVVAILLHYIYM 2543
Cdd:cd15264    6 IIYYLGFSISLVALAVALIIFLYFRSLRCLRNNIHCNLIVTFILRNVTWFImqntltEIHHQSNQWVCRLIVTVYNYFQV 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2544 STFAWTLVESLHVYRMLTEVRNIDTgpMRFYY--VVGWGIPAIVTgLAVGLDPQGYGNpDFCWLSLQDTLIWSF--AGPI 2619
Cdd:cd15264   86 TNFFWMFVEGLYLHTMIVWAYSADK--IRFWYyiVIGWCIPCPFV-LAWAIVKLLYEN-EHCWLPKSENSYYDYiyQGPI 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2620 GAVIIIN-----TVTSVLSAKV--SCQRKHHYYGK--KGIVsllrtafLLLLLISATWLLGLLAVNRDALS---FHYLFA 2687
Cdd:cd15264  162 LLVLLINfiflfNIVWVLITKLraSNTLETIQYRKavKATL-------VLLPLLGITYMLFFINPGDDKTSrlvFIYFNT 234

                        250       260
                 ....*....|....*....|....*..
gi 7656967  2688 IFSGLQGPFVLLFHCVLNQEVRKHLKG 2714
Cdd:cd15264  235 FLQSFQGLFVAVFYCFLNGEVRSAIRK 261
Cadherin pfam00028
Cadherin domain;
358-450 2.87e-21

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 90.44  E-value: 2.87e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     358 YRERVRENLEVGYEVLTIRASDRDSPINANLRYRVL-GGAWDVFQLNESSGVVSTRAVLDREEAAEYQLLVEANDQGrnP 436
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSILgGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSG--G 78

                           90
                   ....*....|....
gi 7656967     437 GPLSATATVYIEVE 450
Cdd:pfam00028   79 PPLSSTATVTITVL 92
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
 2467-2716 8.99e-21

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: 95.71  E-value: 8.99e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2467 PLKIVTYAAVSLSLAALLVAFVLLSLVRMLR-SNLHSIHKHLAVALFLSQLVFVIGINQTENPF---------------- 2529
Cdd:cd15257    3 TLDIISTIGCVLSIAGLVITIIFHLHTRKLRkSSVTWVLLNLCSSLLLFNIIFTSGVENTNNDYeistvpdretntvlls 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2530 ---------LCTVVAILLHYIYMSTFAWTLVESLHVYRMLteVRNIDTGP---MRFYYVVGWGIPAIVTGLAVG------ 2591
Cdd:cd15257   83 eeyvepdtdVCTAVAALLHYFLLVTFMWNAVYSAQLYLLL--IRMMKPLPemfILQASAIGWGIPAVVVAITLGatyrfp 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2592 ----LDPQGYGNPDFCWLSLQDT-------LIWSFAGPIGAVIIINTVTSVLSAKVSCQR-------KHHYYGKKGIVSl 2653
Cdd:cd15257  161 tslpVFTRTYRQEEFCWLAALDKnfdikkpLLWGFLLPVGLILITNVILFIMTSQKVLKKnnkklttKKRSYMKKIYIT- 239

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7656967  2654 lrtaFLLLLLISATWLLG-LLAVNRDA--LSFHYLFAIFSGLQGPFVLLFHCVLNQEVRKHLKGVL 2716
Cdd:cd15257  240 ----VSVAVVFGITWILGyLMLVNNDLskLVFSYIFCITNTTQGVQIFILYTWRTPEFRKLVSKLS 301
Cadherin pfam00028
Cadherin domain;
1008-1091 9.33e-21

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 88.90  E-value: 9.33e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1008 VEENNPVGSVVAKIRANDPDEGPNAQIMYQIVEGDMRHFFQLDLLNGDLRAMVELDFEVRREYVLVVQATSA---PLVSR 1084
Cdd:pfam00028    5 VPENAPVGTEVLTVTATDPDLGPNGRIFYSILGGGPGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSggpPLSST 84


                   ....*..
gi 7656967    1085 ATVHILL 1091
Cdd:pfam00028   85 ATVTITV 91
Laminin_G_1 pfam00054
Laminin G domain;
1470-1632 3.50e-20

Laminin G domain;


Pssm-ID: 395008 [Multi-domain]  Cd Length: 131  Bit Score: 88.91  E-value: 3.50e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1470 FATQERNGLLLYNGRfNEKHDFIALEIVDEQVQLTFSAGETTTTVAPKVPsgVSDGRWHSVQVQYynkpnIGHLGlphgp 1549
Cdd:pfam00054    1 FRTTEPSGLLLYNGT-QTERDFLALELRDGRLEVSYDLGSGAAVVRSGDK--LNDGKWHSVELER-----NGRSG----- 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1550 sgekmaVVTVDDCDTTMavrfgkdignyscaaqGTQ-TGSKKSLDLTGPLLLGGVPNL---PEDFPvHNRQFVGCMRNLS 1625
Cdd:pfam00054   68 ------TLSVDGEARPT----------------GESpLGATTDLDVDGPLYVGGLPSLgvkKRRLA-ISPSFDGCIRDVI 124


                   ....*..
gi 7656967    1626 VDGKNVD 1632
Cdd:pfam00054  125 VNGKPLD 131
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
 2470-2709 8.90e-20

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: 92.05  E-value: 8.90e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2470 IVTYAAVSLSLAALLVA-FVLLSL--VRMLRSNlhsIHKHLAVALFLSQLVFVI-----GINQTENPfLCTVVAILLHYI 2541
Cdd:cd15263    6 TIYFIGYSLSLVALSLAlWIFLYFkdLRCLRNT---IHTNLMFTYILADLTWILtltlqVSIGEDQK-SCIILVVLLHYF 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2542 YMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIV------------TGLAVGLDPQGYgnPDFCWLSLQD 2609
Cdd:cd15263   82 HLTNFFWMFVEGLYLYMLVVETFSGENIKLRVYAFIGWGIPAVViviwaivkalapTAPNTALDPNGL--LKHCPWMAEH 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2610 TLIWSFAGPIGAVIIINTV----------TSVLSAKVSCQRKHHYYGKKGIVsllrtaflLLLLISATWLLGLLAVNRD- 2678
Cdd:cd15263  160 IVDWIFQGPAILVLAVNLVflvrimwvliTKLRSANTVETQQYRKAAKALLV--------LIPLLGITYILVIAGPTEGi 231

                        250       260       270
                 ....*....|....*....|....*....|..
gi 7656967  2679 -ALSFHYLFAIFSGLQGPFVLLFHCVLNQEVR 2709
Cdd:cd15263  232 aANIFEYVRAVLLSTQGFTVALFYCFLNTEVR 263
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
 2467-2712 8.06e-19

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: 89.48  E-value: 8.06e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2467 PLKIVTYAAVSLSLAALLVAFVLLSLV-RMLRSNLHSIHKH-----LAVALFLSQLVFVI--GINQTENPF---LCTVVA 2535
Cdd:cd15254    3 ELDYITYIGLSISILSLAICIVIESLVwKSVTKNRTSYMRHvcilnIAVSLLIADIWFIVvaAIQDQNYAVngnVCVAAT 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2536 ILLHYIYMSTFAWTLVESLHV-YRMLTEVRNIDTGPMR-FYYVVGWGIPAI--VTGLAVGLDPQGYGNPDFCWLSLQDT- 2610
Cdd:cd15254   83 FFIHFFYLCVFFWMLALGLMLfYRLVFILHDTSKTIQKaVAFCLGYGCPLIisVITIAVTLPRDSYTRKKVCWLNWEDSk 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2611 LIWSFAGPIGAVIIINT-VTSVLSAKV---SCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDA-LSFHYL 2685
Cdd:cd15254  163 ALLAFVIPALIIVAVNSiITVVVIVKIlrpSIGEKPSKQERSSLFQIIKSIGVLTPLLGLTWGFGLATVIKGSsIVFHIL 242

                        250       260
                 ....*....|....*....|....*..
gi 7656967  2686 FAIFSGLQGPFVLLFHCVLNQEVRKHL 2712
Cdd:cd15254  243 FTLLNAFQGLFILVFGTLWDKKVQEAL 269
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
 2477-2716 8.62e-19

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


Pssm-ID: 320388 [Multi-domain]  Cd Length: 267  Bit Score: 88.87  E-value: 8.62e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2477 SLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVI--------GINQTENPFLCTVVAILLHYIYMSTFAW 2548
Cdd:cd15260   13 SVSLIALIISLAIFFSFRSLRCTRITIHMNLFISFALNNLLWIVwyklvvdnPEVLLENPIWCQALHVLLQYFMVCNYFW 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2549 TLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDFCWLSlQDTLIWSFAGPIGAVIIIN-- 2626
Cdd:cd15260   93 MFCEGLYLHTVLVVAFISEKSLMRWFIAIGWGVPLVITAIYAGVRASLPDDTERCWME-ESSYQWILIVPVVLSLLINli 171

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2627 ---TVTSVLSAKVSCQrkhhyygkkgivSLLRTAFLLLLLISATW----LLGL----LAVNRDALS-----FHYLFAIFS 2690
Cdd:cd15260  172 fliNIVRVLLTKLRAT------------SPNPAPAGLRKAVRATLilipLLGLqfllIPFRPEPGApletiYQYVSALLT 239

                        250       260
                 ....*....|....*....|....*.
gi 7656967  2691 GLQGPFVLLFHCVLNQEVRKHLKGVL 2716
Cdd:cd15260  240 SLQGLCVAVLFCFCNGEVIAAIKRKW 265
LamG cd00110
Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have ...
 1694-1846 1.71e-18

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: 84.78  E-value: 1.71e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1694 FSGESVVSWSDLNIIiSVPWYLGLMFRTRKEDSVLMEATSGGPTSF-RLQILNNYLQFEVSHGPSDVesVMLSGLRVTDG 1772
Cdd:cd00110    4 FSGSSYVRLPTLPAP-RTRLSISFSFRTTSPNGLLLYAGSQNGGDFlALELEDGRLVLRYDLGSGSL--VLSSKTPLNDG 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7656967  1773 EWHHLLIELKNvkedsemkHLVTMTLDYGMDQNKADIGGMLPGLTVRSVVVGGASED----KVSVRRGFRGCMQGVRM 1846
Cdd:cd00110   81 QWHSVSVERNG--------RSVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDlkspGLPVSPGFVGCIRDLKV 150
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
 2467-2626 1.83e-18

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: 89.15  E-value: 1.83e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2467 PLKIVTYAAVSLSLAALLVAFVLL----SLVRMLRSNLHSIhKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHYIY 2542
Cdd:cd15999    3 LLHPVVYATAVVLLLCLLTIIVSYiyhhSLVRISRKSWHML-VNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYST 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2543 MSTFAWTLVESLHVYRMLTE----VRNIDT-----GPMRFYYVVGWGIPAIVTGLAVGLDPQGYG---NPDFCWLSLQDT 2610
Cdd:cd15999   82 LATVLWVGVTARNIYKQVTRkakrCQDPDEpppppRPMLRFYLIGGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWEPS 161

                        170
                 ....*....|....*.
gi 7656967  2611 LiWSFAGPIGAVIIIN 2626
Cdd:cd15999  162 L-GAFYGPAGFIIFVN 176
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 2407-2460 2.37e-18

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: 80.89  E-value: 2.37e-18
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 7656967     2407 TKPVCVFWNHSlavggTGGWSARGCELLSRNRTHVACQCSHTASFAVLMDISRR 2460
Cdd:smart00303    1 FNPICVFWDES-----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPPI 49
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 274-351 4.02e-18

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: 81.24  E-value: 4.02e-18
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7656967      274 EGEEERVSYYmegLFDERSRGYFRIDSATGAVSTDSVLDRETKETHVLRVKAVDYSTPPRSATTYITVLVKDTNDHSP 351
Cdd:smart00112    7 SGENGKVTYS---ILSGNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPLSSTATVTITVLDVNDNAP 81
Cadherin pfam00028
Cadherin domain;
570-667 5.31e-18

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 81.19  E-value: 5.31e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     570 FQATVLENVPLGYPVVHIQAVDADSGENARLHYRLvdtastfLGGGSAGPknpaptpdfpFQIHNSSGWITVCAELDREE 649
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSI-------LGGGPGGN----------FRIDPDTGDISTTKPLDRES 63

                           90
                   ....*....|....*...
gi 7656967     650 VEHYSFGVEAVDHGSPPM 667
Cdd:pfam00028   64 IGEYELTVEATDSGGPPL 81
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
 2468-2713 3.88e-17

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


Pssm-ID: 320660 [Multi-domain]  Cd Length: 267  Bit Score: 84.12  E-value: 3.88e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLV--RMLRSNL----HSIHKHLAVALFLSQLVFVIGI---NQTENPFLCTVVAILL 2538
Cdd:cd15994    4 LDYITRIGLGLSIFSLALCLTIEAVVwsHVTKTEItymrHVCIVNIATSLLIADVWFILASivhNTALNYPLCVAATFFL 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2539 HYIYMSTFAWTLVESLH-------VYRMLTEVRNIDTGpmrfyYVVGWGIPAIVTGLAVGL-DP-QGYGNPDFCWLSLQD 2609
Cdd:cd15994   84 HFFYLSLFFWMLTKALLilygillVFFKITKSVFIATA-----FSIGYGCPLVIAVLTVAItEPkKGYLRPEACWLNWDE 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2610 T-LIWSFAGPIGAVIIINTVTsVLSAKVSCQRKHHYYGKK----GIVSLLRTAFLLLLLISATWLLGLLAVNRD-ALSFH 2683
Cdd:cd15994  159 TkALLAFIIPALSIVVVNLIV-VGVVVVKTQRSSIGESCKqdvsNIIRISKNVAILTPLLGLTWGFGLATIIDSrSLPFH 237

                        250       260       270
                 ....*....|....*....|....*....|
gi 7656967  2684 YLFAIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15994  238 IIFALLNAFQGFFILLFGTILDRKIRIALY 267
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 588-685 7.40e-17

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: 77.39  E-value: 7.40e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      588 QAVDADSGENARLHYRLVDtastflgggsagpknpaPTPDFPFQIHNSSGWITVCAELDREEVEHYSFGVEAVDHGSPPM 667
Cdd:smart00112    1 SATDADSGENGKVTYSILS-----------------GNDDGLFSIDPETGEITTTKPLDREEQPEYTLTVEATDGGGPPL 63

                            90
                    ....*....|....*...
gi 7656967      668 SSSTSVSITVLDVNDNDP 685
Cdd:smart00112   64 SSTATVTITVLDVNDNAP 81
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
 2478-2713 1.04e-16

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: 83.19  E-value: 1.04e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2478 LSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVA----------LFLSQLVFV-------------IGINQTenPFLCTVV 2534
Cdd:cd15261   14 LSLVSLIISLFIFSYFRTLRNHRTRIHKNLFLAillqviirlvLYIDQAITRsrgshtnaattegRTINST--PILCEGF 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2535 AILLHYIYMSTFAWTLVESLHVYRMLTeVRNIDTGP-MRFYYVVGWGIPAIVTGLAVGLDPQGYGNPDfCWLSLQDTLI- 2612
Cdd:cd15261   92 YVLLEYAKTVMFMWMFIEGLYLHNIIV-VSVFSGKPnYLFYYILGWGIPIVHTSAWAIVTLIKMKVNR-CWFGYYLTPYy 169

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2613 WSFAGPIGAVIIIN-----TVTSVLSAKVSCQRKHHYYGKKGIVSllrtafllllliSATWLLGLLAV-----------N 2676
Cdd:cd15261  170 WILEGPRLAVILINlffllNIIRVLVSKLRESHSREIEQVRKAVK------------AAIVLLPLLGItnilqmippplT 237

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 7656967  2677 RDALSF---HYLFAIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15261  238 SVIVGFavwSYSTHFLTSFQGFFVALIYCFLNGEVKNVLK 277
Cadherin pfam00028
Cadherin domain;
250-343 1.21e-16

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 77.34  E-value: 1.21e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     250 YQVALFENEPAGTLILQLHAHYTIEGEEERVSYYMegLFDErSRGYFRIDSATGAVSTDSVLDRETKETHVLRVKAVDYS 329
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDLGPNGRIFYSI--LGGG-PGGNFRIDPDTGDISTTKPLDRESIGEYELTVEATDSG 77

                           90
                   ....*....|....
gi 7656967     330 TPPRSATTYITVLV 343
Cdd:pfam00028   78 GPPLSSTATVTITV 91
LamG smart00282
Laminin G domain;
1714-1848 3.64e-16

Laminin G domain;


Pssm-ID: 214598 [Multi-domain]  Cd Length: 132  Bit Score: 77.38  E-value: 3.64e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     1714 YLGLMFRTRKEDSVLMEATSGGPTSF-RLQILNNYLQFEVSHGpSDVESVMLSGLRVTDGEWHHLLIELKNvkedsemkH 1792
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGDYlALELRDGRLVLRYDLG-SGPARLTSDPTPLNDGQWHRVAVERNG--------R 71

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7656967     1793 LVTMTLDYGMDQNKADIGGmLPGLTVRS-VVVGGASED----KVSVRRGFRGCMQGVRMGG 1848
Cdd:smart00282   72 SVTLSVDGGNRVSGESPGG-LTILNLDGpLYLGGLPEDlklpPLPVTPGFRGCIRNLKVNG 131
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
 2471-2704 5.11e-16

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: 81.00  E-value: 5.11e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2471 VTYAAVSLSLAALLVAFVLLSLVRMLRSNLHS-----IHKHLAVALFLSQLVFVI--GINQTENPFLCTVVAILLHYIYM 2543
Cdd:cd15442    7 ISSAGCGVSMVFLIFTIILYFFLRFTYQKFKSedapkIHVNLSSSLLLLNLAFLLnsGVSSRAHPGLCKALGGVTHYFLL 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2544 STFAWTLVESLHVYRMLTEVRNIdtgPMRFYYV----VGWGIPAIVTGLAVGLDPQG-YGNPD--------FCWLSLQDT 2610
Cdd:cd15442   87 CCFTWMAIEAFHLYLLAIKVFNT---YIHHYFAklclVGWGFPALVVTITGSINSYGaYTIMDmanrttlhLCWINSKHL 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2611 LIW--SFAGPIGAVIIINTVTSVLSA-KV-SCQR----KHHYYGKKGIVSllrtAFLLLLLISATWLLGLLAVNRDALSF 2682
Cdd:cd15442  164 TVHyiTVCGYFGLTFLFNTVVLGLVAwKIfHLQSatagKEKCQAWKGGLT----VLGLSCLLGVTWGLAFFTYGSMSVPT 239

                        250       260
                 ....*....|....*....|..
gi 7656967  2683 HYLFAIFSGLQGPFVLLFHCVL 2704
Cdd:cd15442  240 VYIFALLNSLQGLFIFIWFVIL 261
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 2409-2454 5.93e-16

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: 73.88  E-value: 5.93e-16
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 7656967    2409 PVCVFWNHSLavGGTGGWSARGCELLSRNRTHVACQCSHTASFAVL 2454
Cdd:pfam01825    1 PQCVFWDFTN--STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
HormR smart00008
Domain present in hormone receptors;
2052-2113 6.96e-16

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 74.47  E-value: 6.96e-16
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7656967     2052 YNGCPKAFEAGIWWPQTKFGQPAAVPCPKGSVG-----NAVRHCSGEKGWLP--PELFNCTTISFVDLR 2113
Cdd:smart00008    2 DLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGfsyktGASRNCTENGGWSPpfPNYSNCTSNDYEELK 70
Cadherin pfam00028
Cadherin domain;
692-780 1.01e-15

Cadherin domain;


Pssm-ID: 394985 [Multi-domain]  Cd Length: 92  Bit Score: 74.64  E-value: 1.01e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967     692 YELRLNEDAAVGSSVLTLQARDRD--ANSVITYQLTGGNTRNRFALSSQrgGGLITLALPLDYKQEQQYVLAVTASDG-- 767
Cdd:pfam00028    1 YSASVPENAPVGTEVLTVTATDPDlgPNGRIFYSILGGGPGGNFRIDPD--TGDISTTKPLDRESIGEYELTVEATDSgg 78

                           90
                   ....*....|....
gi 7656967     768 -TRSHTAHVLINVT 780
Cdd:pfam00028   79 pPLSSTATVTITVL 92
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
 2467-2702 4.27e-15

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: 78.26  E-value: 4.27e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2467 PLKIVTYAAVSLSLAALLVAfVLLSLV--RMLRSNLHSIHKHLAVALFLSQLVFVIG--INQTENPFLCTVVAILLHYIY 2542
Cdd:cd15443    3 PLTYISIVGCSISAAASLLT-ILLHFFsrKQPKDSTTRIHMNLLGSLFLLNGSFLLSppLATSQSTWLCRAAAALLHYSL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2543 MSTFAWTLVESLHVYRMLTEVRNIdtgPMRFYY----VVGWGIPAIVTGLAVGLDPQGYG-----------NPDFCWL-- 2605
Cdd:cd15443   82 LCCLTWMAIEGFHLYLLLVKVYNI---YIRRYVlklcVLGWGLPALIVLLVLIFKREAYGphtiptgtgyqNASMCWIts 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2606 -SLQDTLIWSFAgpiGAVIIINTVTSVLSAKVSCQ---RKHHYYG--KKGIVSllrtAFLLLLLISATWLLGLLAVNRDA 2679
Cdd:cd15443  159 sKVHYVLVLGYA---GLTSLFNLVVLAWVVRMLRRlrsRKQELGEraRRDWVT----VLGLTCLLGTTWALAFFSFGVFL 231

                        250       260
                 ....*....|....*....|...
gi 7656967  2680 LSFHYLFAIFSGLQGPFVLLFHC 2702
Cdd:cd15443  232 IPQLFLFTIINSLYGFFICLWYC 254
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
 2470-2709 1.42e-14

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


Pssm-ID: 320561 [Multi-domain]  Cd Length: 265  Bit Score: 76.51  E-value: 1.42e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2470 IVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVAL-------FLSQLVFVIGINQTeNPFLCTVVAILLHYIY 2542
Cdd:cd15445    6 IINYLGHCISLVALLVAFVLFLRLRSIRCLRNIIHWNLITAFilrnatwFVVQLTMSPEVHQS-NVVWCRLVTAAYNYFH 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2543 MSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIP-AIVTGLAVGldpQGYGNPDFCWLSLQDTLI--WSFAGPI 2619
Cdd:cd15445   85 VTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFICIGWCIPfPIIVAWAIG---KLYYDNEKCWFGKRAGVYtdYIYQGPM 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2620 GAVIIIN-----TVTSVLSAKVSCQRKHHYYGKKGIVSllrTAFLLLLLISATWLLGLLAVNRDALS---FHYLFAIFSG 2691
Cdd:cd15445  162 ILVLLINfiflfNIVRILMTKLRASTTSETIQYRKAVK---ATLVLLPLLGITYMLFFVNPGEDEISrivFIYFNSFLES 238

                        250
                 ....*....|....*...
gi 7656967  2692 LQGPFVLLFHCVLNQEVR 2709
Cdd:cd15445  239 FQGFFVSVFYCFLNSEVR 256
CA smart00112
Cadherin repeats; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell adhesion. ...
 710-787 2.28e-14

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: 70.46  E-value: 2.28e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967      710 QARDRD--ANSVITYQLTGGNTRNRFALSSQrgGGLITLALPLDYKQEQQYVLAVTASDG---TRSHTAHVLINVTDANT 784
Cdd:smart00112    1 SATDADsgENGKVTYSILSGNDDGLFSIDPE--TGEITTTKPLDREEQPEYTLTVEATDGggpPLSSTATVTITVLDVND 78


                    ...
gi 7656967      785 HRP 787
Cdd:smart00112   79 NAP 81
EGF_Lam cd00055
Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous ...
 2002-2040 6.64e-14

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: 68.15  E-value: 6.64e-14
                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 7656967  2002 PCDCFPHGSHSRTCDMATGQCACKPGVIGRQCNRCDNPF 2040
Cdd:cd00055    1 PCDCNGHGSLSGQCDPGTGQCECKPNTTGRRCDRCAPGY 39
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
 2466-2713 1.04e-13

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: 74.33  E-value: 1.04e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPL-KIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVAL-------------------FLSQLVFVIG---- 2521
Cdd:cd15273    1 LPIiKGISQIGYIVSLITLIIAFAIFLSFKKLHCARNKLHMHLFASFilrafmtllkdslfidglgLLADIVERNGggne 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2522 -INQTENPFLCTVVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVgLDPQGYGNp 2600
Cdd:cd15273   81 vIANIGSNWVCKAITSLWQYFIIANYSWILMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFVVPWI-VARILFEN- 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2601 DFCWLSLQDTLI-WSFAGPIGAVIIINTV-----TSVLSAKVSC---QRKHHYygKKGIVSLLRTAFLLLLLISATWLLG 2671
Cdd:cd15273  159 SLCWTTNSNLLNfLIIRIPIMISVLINFIlflniVRVLLVKLRSsvnEDSRRY--KKWAKSTLVLVPLFGVHYTIFLILS 236

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 7656967  2672 LLAVNRDALSFHYLF--AIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15273  237 YLDDTNEAVELIWLFcdQLFASFQGFFVALLYCFLNGEVRAEIQ 280
EGF_Lam smart00180
Laminin-type epidermal growth factor-like domai;
2003-2048 1.14e-13

Laminin-type epidermal growth factor-like domai;


Pssm-ID: 214543  Cd Length: 46  Bit Score: 67.34  E-value: 1.14e-13
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 7656967     2003 CDCFPHGSHSRTCDMATGQCACKPGVIGRQCNRCDNPFAEVTTLGC 2048
Cdd:smart00180    1 CDCDPGGSASGTCDPDTGQCECKPNVTGRRCDRCAPGYYGDGPPGC 46
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
 2466-2713 3.48e-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: 72.46  E-value: 3.48e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIG---INQTENPFLCTV-------VA 2535
Cdd:cd15930    2 LTVKIIYTVGYSLSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAVFIKdavLFSSEDVDHCFVstvgckaSM 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2536 ILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLdpQGYGNPDFCWLSLQDTLI-WS 2614
Cdd:cd15930   82 VFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTVWIVA--RLYFEDTGCWDINDESPYwWI 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2615 FAGPIGAVIIIN-----TVTSVLSAKVSCQRkhhyygkkgiVSLLRTAFLLLLLISATWLLGLLAVnrdalsfHYL-FAI 2688
Cdd:cd15930  160 IKGPILISILVNfvlfiNIIRILLQKLRSPD----------IGGNESSQYKRLARSTLLLIPLFGI-------HYIvFAF 222

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 7656967  2689 F----------------SGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15930  223 FpenislgirlyfelclGSFQGFVVAVLYCFLNGEVQAEIK 263
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
 2468-2713 1.02e-12

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: 71.35  E-value: 1.02e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYaavSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVI-----GINQ---TENPFLCTVVAILLH 2539
Cdd:cd15274    7 LAIVGH---SLSIATLLISLGIFFFFRSLSCQRVTLHKNLFLSYILNSIIIIIhlvavVPNGelvARNPVSCKILHFIHQ 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2540 YIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVgLDPQGYGNpDFCWLSLQDTLIWSFAGPI 2619
Cdd:cd15274   84 YMMGCNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHA-ITRAVYYN-DNCWLSSETHLLYIIHGPI 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2620 GAVIIIN-----TVTSVLSAK--VSCQRKHHYYGKkgivsllrtafllllLISATW----LLGLLAV-------NRDALS 2681
Cdd:cd15274  162 MAALVVNfffllNIVRVLVTKlrETHEAESHMYLK---------------AVKATLilvpLLGIQFVlfpwrpsGKILGK 226

                        250       260       270
                 ....*....|....*....|....*....|...
gi 7656967  2682 -FHYLFAIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15274  227 iYDYVMHSLIHFQGFFVATIFCFCNGEVQATLK 259
Laminin_EGF pfam00053
Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.
 2003-2036 1.27e-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: 64.30  E-value: 1.27e-12
                           10        20        30
                   ....*....|....*....|....*....|....
gi 7656967    2003 CDCFPHGSHSRTCDMATGQCACKPGVIGRQCNRC 2036
Cdd:pfam00053    1 CDCNPHGSLSDTCDPETGQCLCKPGVTGRHCDRC 34
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
 2477-2713 1.39e-12

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: 70.65  E-value: 1.39e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2477 SLSLAALLVAFVLLSLVRMLRSNLHSIHKHL-------AVALFLSQLVFVIGINQ---TENPFLCTVVAILLHYIYMSTF 2546
Cdd:cd15269   13 SLSLISLTAAMIILCLFRKLHCTRNYIHMHLfmsfilrAIAVFIKDAVLFESGEEdhcSVASVGCKAAMVFFQYCIMANF 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2547 AWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAI-VTGLAVGldpQGYGNPDFCW-LSLQDTLIWSFAGPIGAVII 2624
Cdd:cd15269   93 FWLLVEGLYLHTLLAVSFFSERKYFWWYILIGWGAPSVfITAWSVA---RIYFEDVGCWdTIIESLLWWIIKTPILVSIL 169

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2625 INTVTSVLSAKVSCQRKHhyygkKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSF---------HYLFAIFSG-LQG 2694
Cdd:cd15269  170 VNFILFICIIRILVQKLH-----SPDIGRNESSQYSRLAKSTLLLIPLFGIHYIMFAFfpdnfkaevKLVFELILGsFQG 244

                        250
                 ....*....|....*....
gi 7656967  2695 PFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15269  245 FVVAVLYCFLNGEVQAELK 263
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
 2474-2713 1.62e-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: 70.55  E-value: 1.62e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2474 AAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVI-------------GINQ--TENPFLCTVVAILL 2538
Cdd:cd15262   10 AALSVSVVTSLPAVFIFYSYKRLRITRVILHRNLLISIIIRNILVIIskvfvildaltssGDDTvmNQNAVVCRLLSIFE 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2539 HYIYMSTFAWTLVESLHVYRMLTEVRNiDTGPMRFYYVVGWGIPAIVTGLAVGLdpQGYGNPDFCWLSLQDTLIWSFAGP 2618
Cdd:cd15262   90 RAARNAVFACMFVEGFYLHRLIVAVFA-EKSSIRFLYVIGAVLPLFPVIIWAII--RALHNDHSCWVVDIEGVQWVLDTP 166

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2619 IGAVIIINTVTSVLSAKVscqrkhhyygkkgIVSLLRTAFLLLLLISATW-------LLGL---LAVNR------DALSF 2682
Cdd:cd15262  167 RLFILLVNTVLLVDIIRV-------------LVTKLRNTEENSQTKSTTRatlflvpLFGLhfvITAYRpstddcDWEDI 233

                        250       260       270
                 ....*....|....*....|....*....|..
gi 7656967  2683 HYLF-AIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15262  234 YYYAnYLIEGLQGFLVAILFCYINKEVHYLIK 265
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
 2463-2709 1.21e-11

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: 68.06  E-value: 1.21e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2463 GEVL-PLKIVTYAAVSLSLAALLVAFVL-LSLVRMLRSNLHSIhKHLAVALFLSQLVFVIGINQTENPFLCTVVAILLHY 2540
Cdd:cd15998    1 GAGLhPVVYPCTALLLLCLFSTIITYILnHSSIHVSRKGWHML-LNLCFHIAMTSAVFAGGITLTNYQMVCQAVGITLHY 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2541 IYMSTFAWTLVESLHVYRMLT---------EVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGY-GNPDFCWLSLQDT 2610
Cdd:cd15998   80 SSLSTLLWMGVKARVLHKELTwrapppqegDPALPTPRPMLRFYLIAGGIPLIICGITAAVNIHNYrDHSPYCWLVWRPS 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2611 LiWSFAGPIgAVIIINTVTSVLSAKVSCQrkHHYYGKKGIVSLLRTAFLLLLLIS---ATWLLGLLAVNRDALS---FHY 2684
Cdd:cd15998  160 L-GAFYIPV-ALILLVTWIYFLCAGLHLR--GPSADGDSVYSPGVQLGALVTTHFlylAMWACGALAVSQRWLPrvvCSC 235

                        250       260
                 ....*....|....*....|....*
gi 7656967  2685 LFAIFSGLQGPFVLLFHCVLNQEVR 2709
Cdd:cd15998  236 LYGVAASALGLFVFTHHCARRRDVR 260
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
 2470-2713 1.36e-11

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


Pssm-ID: 320562 [Multi-domain]  Cd Length: 264  Bit Score: 67.68  E-value: 1.36e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2470 IVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVI------GINQTENPFlCTVVAILLHYIYM 2543
Cdd:cd15446    6 IINYLGHCISVGALVVAFLLFLCLRSIRCLRNIIHWNLITTFILRNVMWFLlqmidhNIHESNEVW-CRCITTIYNYFVV 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2544 STFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPA-IVTGLAVGldpQGYGNPDFCWLSLQ--DTLIWSFAGPIG 2620
Cdd:cd15446   85 TNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCpIIVAWAIG---KLYYENEQCWFGKEpgKYIDYIYQGPVI 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2621 AVIIIN-----TVTSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLlllISATWLLGLLAVNRDALS---FHYLFAIFSGL 2692
Cdd:cd15446  162 LVLLINfvflfNIVRILMTKLRASTTSETIQYRKAVKATLVLLPL---LGITYMLFFVNPGEDDISqivFIYFNSFLQSF 238

                        250       260
                 ....*....|....*....|.
gi 7656967  2693 QGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15446  239 QGFFVSVFYCFLNGEVRSAAR 259
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
 2468-2717 1.38e-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: 67.83  E-value: 1.38e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQL-VFVI--------GINQ-TENPFLCTVVAIL 2537
Cdd:cd15271    4 VKLLYTVGYGTSLTSLITAVLIFCTFRKLHCTRNYIHINLFVSFILRALaVFIKdavlfadeSVDHcTMSTVACKAAVTF 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2538 LHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVgLDPQGYGNPDfCWLSLQDTLIWSFAG 2617
Cdd:cd15271   84 FQFCVLANFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILIGWGAPSVTVTVWV-LTRLQYDNRG-CWDDLESRIWWIIKT 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2618 PIGAVIIIN-----TVTSVLSAKVSCQRkhhyygkkgiVSLLRTAFLLLLLISATWLLGLLAVnrdalsfHY-LFAIF-- 2689
Cdd:cd15271  162 PILLSVFVNflifiNVIRILVQKLKSPD----------VGGNDTSHYMRLAKSTLLLIPLFGV-------HYvVFAFFpe 224

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 7656967  2690 --------------SGLQGPFVLLFHCVLNQEVRKHLKGVLG 2717
Cdd:cd15271  225 hvgvearlyfelvlGSFQGFIVALLYCFLNGEVQAEIKKRLG 266
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
 2468-2713 2.77e-11

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: 67.07  E-value: 2.77e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQL-VFVI---------GINQTENPFL------- 2530
Cdd:cd15929    4 LQVMYTVGYSLSLAALVLALAILLGLRKLHCTRNYIHANLFASFILRALsVLVKdallprrysQKGDQDLWSTllsnqas 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2531 --CTVVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTgLAVGLDPQGYGNPDfCWLSLQ 2608
Cdd:cd15929   84 lgCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSERSIFRLYLLLGWGAPVLFV-VPWGIVKYLYENTG-CWTRND 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2609 DTLIW-SFAGPIGAVIIIN---------TVTSVLSAKVSCQRKHHYYGKKgivsllrtafllllliSATWLLGLLAVN-- 2676
Cdd:cd15929  162 NMAYWwIIRLPILLAILINffifvrilkILVSKLRANQMCKTDYKFRLAK----------------STLTLIPLLGVHev 225

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 7656967  2677 ----------RDALSFHYLFA--IFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15929  226 vfafvtdeqaRGTLRFIKLFFelFLSSFQGLLVAVLYCFANKEVQSELR 274
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
 2466-2628 3.25e-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: 66.53  E-value: 3.25e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2466 LPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVI--GINQTE--------NPFLCTVVA 2535
Cdd:cd15987    2 LSVKALYTVGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIkdGVLYAEqdsdhcfvSTVECKAVM 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2536 ILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAI-VTGLAVgldPQGYGNPDFCWLSLQDT-LIW 2613
Cdd:cd15987   82 VFFHYCVMSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTIcVTVWAV---LRLHFDDTGCWDMNDNTaLWW 158

                        170
                 ....*....|....*
gi 7656967  2614 SFAGPIGAVIIINTV 2628
Cdd:cd15987  159 VIKGPVVGSIMINFV 173
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
 2468-2626 3.68e-11

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: 66.30  E-value: 3.68e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIG---INQTEN-------PFLCTVVAIL 2537
Cdd:cd15275    4 LKTMYTVGYSVSLVSLAIALAILCSFRRLHCTRNYIHMQLFLSFILRAISIFIKdavLFSSEDdnhcdiyTVGCKVAMVF 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2538 LHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTgLAVGLDPQGYGNPDfCWLSLQDTLI-WSFA 2616
Cdd:cd15275   84 SNYCIMANYSWLLVEGLYLHSLLSISFFSERKHLWWYIALGWGSPLIFI-ISWAIARYLHENEG-CWDTRRNAWIwWIIR 161

                        170
                 ....*....|
gi 7656967  2617 GPIGAVIIIN 2626
Cdd:cd15275  162 GPVILSIFVN 171
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 2052-2107 3.07e-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: 58.15  E-value: 3.07e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7656967    2052 YNGCPKAFEAGIWWPQTKFGQPAAVPCPKG-----SVGNAVRHCSGEKGWL---PPELFNCTTI 2107
Cdd:pfam02793    1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYfsgfdPRGNASRNCTEDGTWSehpPSNYSNCTSN 64
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
 2468-2713 4.18e-10

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: 63.61  E-value: 4.18e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHL-------AVALFLSQLVF-------------VIGINQTEN 2527
Cdd:cd15266    4 LQLIYTIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLfasfilrALAVLIKDIVLystyskrpddetgWISYLSEES 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2528 PFLCTVVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAI-VTGLAVG---LDPQGygnpdfC 2603
Cdd:cd15266   84 STSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLfVVPWGVAkilLENTG------C 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2604 WLSLQDTLI-WSFAGPIGAVIIINTVT---------SVLSAKVSCQRKHHYYGKKgivsllrtafllllliSATWLLGLL 2673
Cdd:cd15266  158 WGRNENMGIwWIIRGPILLCITVNFYIflkilklllSKLKAQQMRFTDYKYRLAR----------------STLVLIPLL 221

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 7656967  2674 AVNRDALSF--------------HYLFAIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15266  222 GIHEVVFSFitdeqvegfsrhirLFIQLTLSSFQGFLVAVLYCFANGEVKAELK 275
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
 2468-2626 1.26e-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: 61.74  E-value: 1.26e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHL-------AVALFLSQLVFVIGINQTENPF---LCTVVAIL 2537
Cdd:cd15270    4 VKIIYTVGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLfftfilkAIAVFIKDAALFQEDDTDHCSMstvLCKVSVVF 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2538 LHYIYMSTFAWTLVESLHVYRMLteVRNIDTGPMRFYYVV--GWGIPAIVTGLAVGldPQGYGNPDFCW-LSLQDTLIWS 2614
Cdd:cd15270   84 CHYCVMTNFFWLLVEAVYLNCLL--ASSFPRGKRYFWWLVllGWGLPTLCTGTWIL--CKLYFEDTECWdINNDSPYWWI 159

                        170
                 ....*....|..
gi 7656967  2615 FAGPIGAVIIIN 2626
Cdd:cd15270  160 IKGPIVISVGVN 171
Cadherin_repeat cd11304
Cadherin tandem repeat domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 1117-1198 1.39e-09

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: 57.32  E-value: 1.39e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1117 NSFPTGVIGCIPAHDPDVSD--SLNYTFVQGNELRLLLLDPATGELQLSRDLDNNRPLEALMEVSVSD-GIHSVTAFCTL 1193
Cdd:cd11304    9 NAPPGTVVLTVSATDPDSGEngEVTYSIVSGNEDGLFSIDPSTGEITTAKPLDREEQSSYTLTVTATDgGGPPLSSTATV 88


                 ....*
gi 7656967  1194 RVTII 1198
Cdd:cd11304   89 TITVL 93
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
 2468-2710 1.96e-09

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: 61.38  E-value: 1.96e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLS-LAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVIG--INQTENPFLCTVVAILLHYIYMS 2544
Cdd:cd15995    4 LTILTYVGCIISaLASVFTIAFYLCSRRKPRDYTIYVHMNLLLAIFLLDTSFLISepLALTGSEAACRAGGMFLHFSLLA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNIDTGPMRFYY-VVGWGIPAIVTGLAVGLD--------------PQGYGNPDFCWLSlqD 2609
Cdd:cd15995   84 CLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLcAVGWGLPIFLVTLIFLVDqdnygpiilavhrsPEKVTYATICWIT--D 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2610 TLIWSFA--GPIGAVIIINTVtsVLSAKVSCQRKHHYYGKKgiVSLLRTAFLLLLLISATWLLGLLAVNRDA--LSFHYL 2685
Cdd:cd15995  162 SLISNITnlGLFSLVFLFNMA--MLATMVVEILRLRPRTHK--WSHVLTLLGLSLVLGIPWALAFFSFASGTfqLVIVYL 237

                        250       260
                 ....*....|....*....|....*
gi 7656967  2686 FAIFSGLQGPFVLLFHCVLNQEVRK 2710
Cdd:cd15995  238 FTIINSLQGFLIFLWYWSMVLQARG 262
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
 2477-2713 1.28e-08

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: 59.17  E-value: 1.28e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2477 SLSLAALLVAFVLLSLVRMLRSNLHSIHKHL-------AVALFLSQLVFVIGINQTE---------------NPFL-CTV 2533
Cdd:cd15983   13 SISLAALLVAVCILCYFKRLHCTRNYIHIHLfasficrAGSIFVKDAVLYSGTNEGEaldekiefglspgtrLQWVgCKV 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2534 VAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGL-----DPQgygnpdfCWLSLQ 2608
Cdd:cd15983   93 TVTLFLYFLATNHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVWASVrvslaDTQ-------CWDLSA 165

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2609 DTLIWSFAGPIGAVIIIN-----TVTSVLSAKV---------SCQRkhhyYGK--KG---IVSLLRTAFLLLLLISATWL 2669
Cdd:cd15983  166 GNLKWIYQVPILAAILVNfflflNIVRVLASKLwetntgkldPRQQ----YRKllKStlvLMPLFGVHYVLFMAMPYTDV 241

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 7656967  2670 LGLLAvnrdALSFHYLFaIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15983  242 TGLLW----QIQMHYEM-LFNSSQGFFVAFIYCFCNGEVQAEIK 280
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
 2477-2713 2.54e-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: 58.17  E-value: 2.54e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2477 SLSLAALLVAFVLLSLVRMLRSNLHSIHKHL-------AVALFLSQLVFVIGI-----NQTENPFL-----------CTV 2533
Cdd:cd15272   13 GLSLVSLLIAVIIMLYFKKLHCPRNTIHINLfvsfilrAVLSFIKENLLVQGVgfpgdVYYDSNGViefkdegshweCKL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2534 VAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPA--IVTGLAVgldpQGYGNPDFCWLSLQDTL 2611
Cdd:cd15272   93 FFTMFNYILGANYMWIFVEGLYLHMLIFVAVFSENSRVKWYILLGWLSPLlfVLPWVFV----RATLEDTLCWNTNTNKG 168

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2612 -IWSFAGPIGAVIIIN-----TVTSVLSAKVSC-----QRKHHY-------------YGKKGIVSLLRTAFLLLLLISAT 2667
Cdd:cd15272  169 yFWIIRGPIVISIAINflffiNIVRVLFTKLKAsntqeSRPFRYrklakstlvliplFGVHYMVFVVLPDSMSSDEAELV 248

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 7656967  2668 WLlgllavnrdalsfhYLFAIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15272  249 WL--------------YFEMFFNSFQGFIVALLFCFLNGEVQSEIK 280
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
 2468-2713 4.70e-08

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: 57.26  E-value: 4.70e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHL-------AVALFLSQLVFVIGINQTENPFL---------- 2530
Cdd:cd15984    4 LYLIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGSALEEMERIteedlksite 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2531 -----------CTVVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVtgLAVGLDPQGYGN 2599
Cdd:cd15984   84 appadkaqfvgCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVF--VTIWASVRATLA 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2600 PDFCWLSLQDTLIWSFAGPIGAVIIIN-----TVTSVLSAKV------SCQRKHHY-------------YGKKGIVsllr 2655
Cdd:cd15984  162 DTGCWDLSAGNLKWIIQVPILAAIVVNfilfiNIVRVLATKLretnagRCDTRQQYrkllkstlvlmplFGVHYIV---- 237

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 7656967  2656 tafllLLLISATWLLGLLAvnrdALSFHYLFaIFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15984  238 -----FMAMPYTEVSGILW----QVQMHYEM-LFNSFQGFFVAIIYCFCNGEVQAEIK 285
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1407-1441 7.13e-08

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: 50.71  E-value: 7.13e-08
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1407 CA-NGVCKNGGTCVNLlIGGFHCVCPPGeYERPYCE 1441
Cdd:cd00054    5 CAsGNPCQNGGTCVNT-VGSYRCSCPPG-YTGRNCE 38
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1364-1399 7.42e-08

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: 50.71  E-value: 7.42e-08
                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 7656967  1364 IDLCYS-DPCGANGRCRSREGGYTCECFEDFTGEHCE 1399
Cdd:cd00054    2 IDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
7tmE_cAMP_R_Slime_mold cd14940
slime mold cyclic AMP receptor, member of the class E family of seven-transmembrane G ...
 2469-2628 9.06e-08

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: 56.21  E-value: 9.06e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2469 KIVTYAAVSLSLAALLVAFVLLsLVRMLRSNLHSIHKHLAVALFLSQLVFVIG---INQTENPFLCTVVAILLHYIYMST 2545
Cdd:cd14940    4 AILLFADFSSIIGCLFVLVGFW-LLKLLRNHITRVISCFCLTSLLKDIIYTMLtltQSARPDGFLCYLYAIVITYGSLSC 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2546 FAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDPQGY-GNpdFCWLSLQDTlIWSFA---GPIGA 2621
Cdd:cd14940   83 WLWTLCLAISIYLLIVKREPEPEKFEKYYHFVCWGLPLISTIIMLIKHHYGPvGN--WCWIGNQYT-GYRFGlfyGPFFI 159


                 ....*..
gi 7656967  2622 VIIINTV 2628
Cdd:cd14940  160 IFGISAV 166
EGF_CA smart00179
Calcium-binding EGF-like domain;
1407-1441 1.24e-07

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 49.94  E-value: 1.24e-07
                            10        20        30
                    ....*....|....*....|....*....|....*.
gi 7656967     1407 CA-NGVCKNGGTCVNLlIGGFHCVCPPGEYERPYCE 1441
Cdd:smart00179    5 CAsGNPCQNGGTCVNT-VGSYRCECPPGYTDGRNCE 39
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
 2477-2626 1.76e-07

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


Pssm-ID: 320393 [Multi-domain]  Cd Length: 289  Bit Score: 55.46  E-value: 1.76e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2477 SLSLAALLVAFVLLSLVRMLRSNLHSIHKHL-------AVALFLSQLVFVIGINQTENPFL------------------- 2530
Cdd:cd15265   13 SISLVSLTVAVFILGYFRRLHCTRNYIHMHLfvsfmlrAVSIFVKDAVLYSGSGLDELERPsmedlksiveappvdksqy 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2531 --CTVVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAI-----VTGLAVGLDPQgygnpdfC 2603
Cdd:cd15265   93 vgCKVAVTLFLYFLATNYYWILVEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVfvipwASVRATLADTR-------C 165

                        170       180
                 ....*....|....*....|...
gi 7656967  2604 WLSLQDTLIWSFAGPIGAVIIIN 2626
Cdd:cd15265  166 WDLSAGNYKWIYQVPILAAIVVN 188
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
 2473-2627 2.19e-07

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: 55.13  E-value: 2.19e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2473 YAAVSLSLAALLVAFVLLSLVRMLR--SNLHSIHKHLAVALFLSQLVFVIGIN---QTENP----FLCTVVAILLHYIYM 2543
Cdd:cd14964    4 ILSLLTCLGLLGNLLVLLSLVRLRKrpRSTRLLLASLAACDLLASLVVLVLFFllgLTEASsrpqALCYLIYLLWYGANL 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2544 STFAWTLVESLHVYRMLTEVRNIDT----GPMRFYYVVGWGIPAIVTGL-AVGLDPQG---YGNPDFCWLSLQDTLIW-- 2613
Cdd:cd14964   84 ASIWTTLVLTYHRYFALCGPLKYTRlsspGKTRVIILGCWGVSLLLSIPpLVGKGAIPrynTLTGSCYLICTTIYLTWgf 163

                        170
                 ....*....|....*..
gi 7656967  2614 ---SFAGPIGAVIIINT 2627
Cdd:cd14964  164 llvSFLLPLVAFLVIFS 180
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1651-1685 2.87e-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: 2.87e-07
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1651 NFCD-GRRCQNGGTCVNRWNMYLCECPLRFGGKNCE 1685
Cdd:cd00054    3 DECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1653-1683 2.09e-06

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: 46.22  E-value: 2.09e-06
                           10        20        30
                   ....*....|....*....|....*....|.
gi 7656967    1653 CDGRRCQNGGTCVNRWNMYLCECPLRFGGKN 1683
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 1874-1908 2.57e-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: 46.09  E-value: 2.57e-06
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1874 DPCTS-SPCPPNSRCHDAWEDYSCVCDKGYLGINCV 1908
Cdd:cd00054    3 DECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
 2468-2713 2.70e-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: 2.70e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQL-VFV--------IGINQTENPFL-------- 2530
Cdd:cd15982    4 LYIMYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAAsIFVkdkvvhthIGVKELDAVLMndfqnavd 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2531 -----------CTVVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAI-VTGLAVGLDPQGYG 2598
Cdd:cd15982   84 appvdksqyvgCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVfVAAWAVVRATLADA 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2599 NpdfCWLSLQDTLIWSFAGPIGAVI------IINTVtSVLSAKVSCQRKHHYYGKKgivsllrtaflLLLLISATWLLGL 2672
Cdd:cd15982  164 R---CWELSAGDIKWIYQAPILAAIglnfilFLNTV-RVLATKIWETNAVGYDTRK-----------QYRKLAKSTLVLV 228

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 7656967  2673 LAVNRDALSFHYLFAIFSGL---------------QGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15982  229 LVFGVHYIVFVCLPHTFTGLgweirmhcelffnsfQGFFVSIIYCYCNGEVQTEIK 284
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
 2465-2713 4.37e-06

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: 51.11  E-value: 4.37e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2465 VLPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVI-------------------GINQT 2525
Cdd:cd15268    1 LLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIkdaalkwmystaaqqhqwdGLLSY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2526 ENPFLCTVVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTgLAVGLDPQGYGNpDFCWL 2605
Cdd:cd15268   81 QDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPLLFV-IPWGIVKYLYED-EGCWT 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2606 SLQDTLIWSFAG-PIGAVIIIN---------TVTSVLSAKVSCQRKHHYYGKKGIVSllrtaflllllisatwLLGLLAV 2675
Cdd:cd15268  159 RNSNMNYWLIIRlPILFAIGVNflifirvicIVVSKLKANLMCKTDIKCRLAKSTLT----------------LIPLLGT 222

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 7656967  2676 N------------RDALSFHYLFA--IFSGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15268  223 HevifafvmdehaRGTLRFVKLFTelSFTSFQGLMVAILYCFVNNEVQMEFR 274
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
 2468-2712 5.92e-06

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: 50.98  E-value: 5.92e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2468 LKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQL-VFVIGI------------------NQTENP 2528
Cdd:cd15267    6 FQVMYTVGYSLSLGALLLALAILGGFSKLHCMRNAIHMNLFASFILKASsVLVIDGllrtrysqkieddlsstwLSDEAV 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2529 FLCTVVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPA--IVTGLAVGLdpqGYGNPDfCWlS 2606
Cdd:cd15267   86 AGCRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPAlfVVPWVVVKC---LYENVQ-CW-T 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2607 LQDTL--IWSFAGPIGAVIIIN-----TVTSVLSAKVSCQRKHHYYGKKGIVSllrtafllllliSATWLLGLLAVN--- 2676
Cdd:cd15267  161 SNDNMgfWWILRFPVFLAILINffifvRIIQILVSKLRARQMHYTDYKFRLAK------------STLTLIPLLGIHevv 228

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 7656967  2677 -------------RDALSFHYLFaiFSGLQGPFVLLFHCVLNQEVRKHL 2712
Cdd:cd15267  229 fafvtdehaqgtlRSAKLFFDLF--LSSFQGLLVAVLYCFLNKEVQSEL 275
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
 2477-2713 1.04e-05

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: 49.80  E-value: 1.04e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2477 SLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVI----------GINQTENPFL--CTVVAILLHYIYMS 2544
Cdd:cd15986   13 SVSLIALTTGSTILCLFRKLHCTRNYIHLNLFFSFILRAISVLVkddilysssnTEHCTVPPSLigCKVSLVILQYCIMA 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2545 TFAWTLVESLHVYRMLTEVRNidtgPMR---FYYVVGWGIPAIVTGL----AVGLDPQGygnpdfCW-LSLQDTLIWSFA 2616
Cdd:cd15986   93 NFYWLLVEGLYLHTLLVVIFS----ENRhfiVYLLIGWGIPTVFIIAwivaRIYLEDTG------CWdTNDHSVPWWVIR 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2617 GPIGAVIIIN-----TVTSVLSAKVSC-------QRKHHYYGKkgivsllrtafllllliSATWLLGLLAVnrdalsfHY 2684
Cdd:cd15986  163 IPIIISIILNfilfiSIIRILLQKLRSpdvggndQSQYKRLAK-----------------STLLLIPLFGV-------HY 218

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 7656967  2685 L-FAIF----------------SGLQGPFVLLFHCVLNQEVRKHLK 2713
Cdd:cd15986  219 IvFVYFpdssssnyqiffelclGSFQGLVVAILYCFLNSEVQGELK 264
EGF_CA smart00179
Calcium-binding EGF-like domain;
1363-1399 1.18e-05

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 44.55  E-value: 1.18e-05
                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 7656967     1363 EIDLCYS-DPCGANGRCRSREGGYTCECFEDFT-GEHCE 1399
Cdd:smart00179    1 DIDECASgNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39
Laminin_G_1 pfam00054
Laminin G domain;
1719-1850 1.32e-05

Laminin G domain;


Pssm-ID: 395008 [Multi-domain]  Cd Length: 131  Bit Score: 46.93  E-value: 1.32e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    1719 FRTRKEDSVLM-EATSGGPTSFRLQILNNYLQFEVSHGpSDVESVMlSGLRVTDGEWHHLLIElknvkedsEMKHLVTMT 1797
Cdd:pfam00054    1 FRTTEPSGLLLyNGTQTERDFLALELRDGRLEVSYDLG-SGAAVVR-SGDKLNDGKWHSVELE--------RNGRSGTLS 70

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7656967    1798 LDygmdqNKADIGGMLPG------LTVRSVVVGGASEDKVS-----VRRGFRGCMQGVRMGGTP 1850
Cdd:pfam00054   71 VD-----GEARPTGESPLgattdlDVDGPLYVGGLPSLGVKkrrlaISPSFDGCIRDVIVNGKP 129
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1367-1397 1.40e-05

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: 43.91  E-value: 1.40e-05
                           10        20        30
                   ....*....|....*....|....*....|.
gi 7656967    1367 CYSDPCGANGRCRSREGGYTCECFEDFTGEH 1397
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
 1407-1441 1.67e-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: 1.67e-05
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1407 CA-NGVCKNGGTCVNLlIGGFHCVCPPGEYERPYCE 1441
Cdd:cd00053    2 CAaSNPCSNGGTCVNT-PGSYRCVCPPGYTGDRSCE 36
EGF_CA smart00179
Calcium-binding EGF-like domain;
1658-1685 1.77e-05

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 43.77  E-value: 1.77e-05
                            10        20
                    ....*....|....*....|....*....
gi 7656967     1658 CQNGGTCVNRWNMYLCECPLRF-GGKNCE 1685
Cdd:smart00179   11 CQNGGTCVNTVGSYRCECPPGYtDGRNCE 39
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
 1369-1399 3.60e-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: 42.85  E-value: 3.60e-05
                         10        20        30
                 ....*....|....*....|....*....|..
gi 7656967  1369 SDPCGANGRCRSREGGYTCECFEDFTGE-HCE 1399
Cdd:cd00053    5 SNPCSNGGTCVNTPGSYRCVCPPGYTGDrSCE 36
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
 2465-2584 8.81e-05

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


Pssm-ID: 320651 [Multi-domain]  Cd Length: 280  Bit Score: 47.23  E-value: 8.81e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2465 VLPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIHKHLAVALFLSQLVFVI---------GINQTENPFL----- 2530
Cdd:cd15985    1 MVSFRMLYTVGYTLSLLTLVSALLILTSIRKLHCTRNYIHANLFASFILRAVSVIVkdtllerrwGREIMRVADWgells 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2531 ------CTVVAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAI 2584
Cdd:cd15985   81 hkaaigCRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYLGWGTPVL 140
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
 1658-1685 9.98e-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: 41.69  E-value: 9.98e-05
                         10        20
                 ....*....|....*....|....*....
gi 7656967  1658 CQNGGTCVNRWNMYLCECPLRF-GGKNCE 1685
Cdd:cd00053    8 CSNGGTCVNTPGSYRCVCPPGYtGDRSCE 36
hEGF pfam12661
Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six ...
 1412-1433 1.41e-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: 41.17  E-value: 1.41e-04
                           10        20
                   ....*....|....*....|..
gi 7656967    1412 CKNGGTCVNLlIGGFHCVCPPG 1433
Cdd:pfam12661    1 CQNGGTCVDG-VNGYKCQCPPG 21
EGF_CA pfam07645
Calcium-binding EGF domain;
1407-1433 2.58e-04

Calcium-binding EGF domain;


Pssm-ID: 429571  Cd Length: 32  Bit Score: 40.30  E-value: 2.58e-04
                           10        20
                   ....*....|....*....|....*....
gi 7656967    1407 CANG--VCKNGGTCVNLlIGGFHCVCPPG 1433
Cdd:pfam07645    5 CATGthNCPANTVCVNT-IGSFECRCPDG 32
EGF_CA smart00179
Calcium-binding EGF-like domain;
1871-1908 2.88e-04

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 40.31  E-value: 2.88e-04
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|
gi 7656967     1871 DVDDpCTS-SPCPPNSRCHDAWEDYSCVCDKGY-LGINCV 1908
Cdd:smart00179    1 DIDE-CASgNPCQNGGTCVNTVGSYRCECPPGYtDGRNCE 39
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 1407-1433 5.60e-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: 39.67  E-value: 5.60e-04
                           10        20
                   ....*....|....*....|....*..
gi 7656967    1407 CANGVCKNGGTCVNLLiGGFHCVCPPG 1433
Cdd:pfam00008    1 CAPNPCSNGGTCVDTP-GGYTCICPEG 26
TNFRSF1A_teleost cd15834
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as ...
 1881-2011 8.20e-04

Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as TNFR1; This subfamily of TNFRSF1 ((also known as type I TNFR, TNFR1, DR1, TNFRSF1A, CD120a, p55) is found in teleosts. It binds TNF-alpha, through the death domain (DD), and activates NF-kappaB, mediates apoptosis and activates signaling pathways controlling inflammatory, immune, and stress responses. It mediates signal transduction by interacting with antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRAF2 and TRADD that play regulatory roles. The human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS), or periodic fever syndrome, is associated with germline mutations of the extracellular domains of this receptor, possibly due to impaired receptor clearance. Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder, and high levels are also associated with cognitive impairment and dementia. Knockout studies in zebrafish embryos have shown that a signaling balance between TNFRSF1A and TNFRSF1B is required for endothelial cell integrity. TNFRSF1A signals apoptosis through caspase-8, whereas TNFRSF1B signals survival via NF-kappaB in endothelial cells. Thus, this apoptotic pathway seems to be evolutionarily conserved, as TNFalpha promotes apoptosis of human endothelial cells and triggers caspase-2 and P53 activation in these cells via TNFRSF1A.


Pssm-ID: 276930 [Multi-domain]  Cd Length: 150  Bit Score: 42.48  E-value: 8.20e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  1881 CPPNSR----CHDAWEDYSCV-CDKG-YLG-INCVDAC-HLNPCENMGACVRSPGSP-QGYVCECGPSHYgpycENKLDl 1951
Cdd:cd15834   17 CHPGYKlkeeCTAPGERSQCTpCPEGtYLEqINYSPNCrRCTLCKVKNEEEVSPCKKsSNTVCRCKKGYY----KSRID- 91

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7656967  1952 pcPRGWwgnpVCGPChcavsKGFDPD------CNK-TNGQCQCKENYYKLlaQDTCLPCD-CFPHGSH 2011
Cdd:cd15834   92 --SETR----ECLKC-----KTCGPGeieiqpCTPeSNTVCECKDNYYRN--NNKCKPCQkCSLDCQH 146
CA_like cd00031
Cadherin repeat-like domain; Cadherins are glycoproteins involved in Ca2+-mediated cell-cell ...
 941-995 1.16e-03

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: 40.79  E-value: 1.16e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 7656967   941 FYIEPTSGVIRTQRRLDRENVAVYNLWALAVDRGSPTPLSaSVEIQVTILDINDN 995
Cdd:cd00031   45 LHWEPHSGILEGLEKLDREDKGVHYISVSAASLGANVPQT-SSVFSIEVYDENDN 98
Dicty_CAR pfam05462
Slime mold cyclic AMP receptor; This family consists of cyclic AMP receptor (CAR) proteins ...
 2472-2635 1.54e-03

Slime mold cyclic AMP receptor; This family consists of cyclic AMP receptor (CAR) proteins from slime molds. CAR proteins are responsible for controlling development in Dictyostelium discoideum.


Pssm-ID: 283188  Cd Length: 305  Bit Score: 43.62  E-value: 1.54e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2472 TYAAVSLSLAALLVA---------FVLLSLVRM--LRSNLHSIHKHLAVALFLSQLVFVIGI---NQTENPFLCTVVAIL 2537
Cdd:pfam05462    3 TQQEIDLSYSVLLIAdfssiigcfLVLIGFWRLklLRNHITKVISCFCATSLLKDLISTILTltnSAQSGGFPCYLYAIV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967    2538 LHYIYMSTFAWTLVESLHVYRMLTEVRNIDTGPMRFYYVVGWGIPAIVTGLAVGLDP-QGYGNpdFCWLSLQDT--LIWS 2614
Cdd:pfam05462   83 ITYGSLACWLWTLCLAFSIYNLIVKREPEPEKFEKYYFFVCWGLPLISTIVMLSKDTiEFVGN--WCWIGEQYTgyRFGL 160

                          170       180
                   ....*....|....*....|.
gi 7656967    2615 FAGPIGAVIIINTVTSVLSAK 2635
Cdd:pfam05462  161 FYGPFFAIWGISAVLVGLTSR 181
hEGF pfam12661
Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six ...
 1658-1676 2.00e-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: 37.70  E-value: 2.00e-03
                           10
                   ....*....|....*....
gi 7656967    1658 CQNGGTCVNRWNMYLCECP 1676
Cdd:pfam12661    1 CQNGGTCVDGVNGYKCQCP 19
RET_CLD1 pfam17756
RET Cadherin like domain 1; RET is a single transmembrane-spanning receptor tyrosine kinase ...
 243-314 2.58e-03

RET Cadherin like domain 1; RET is a single transmembrane-spanning receptor tyrosine kinase (RTK) that plays critical roles in the development of vertebrates. Structural analysis indicate that RET contains four consecutive cadherin-like domains (CLD). This entry relates to the first CLD at the N-terminal. Several regions within RET-CLD1 have been shown to be important for ligand-coreceptor binding. CLD1 and CLD2 have a distinctive clamshell shape and CLD1 is essential for CLD2 folding. CLD1 contains 2 sites for GDNF receptor alpha 1 binding.


Pssm-ID: 465485  Cd Length: 124  Bit Score: 40.37  E-value: 2.58e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 7656967     243 LKFPMPNYQVALFENEPAGTLILQLHAhyTIEGEEERVSYYMEGLFDERSRG-----YFRIDSATGAVSTDSVLDRE 314
Cdd:pfam17756    1 LYFPQKEYSENVYVGQPAGTPLLQVHA--LRDSPSEVPHFYLCQHLGIYRRRphynsWFHIDEDTGLLYLNKTLDRS 75
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
 2528-2649 3.28e-03

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


Pssm-ID: 320089  Cd Length: 314  Bit Score: 42.31  E-value: 3.28e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7656967  2528 PFLCTVVAILLHYIYMSTFAWTLVESLHVYRML-----TEvrnIDTGPMRFYYVVGWGIPAI--VTGLAVGL-DPQGYGN 2599
Cdd:cd13951   91 NAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAglkwsSE---AIEKKSSYFHLVAWGLPAVltIAVLVLRKvDGDELTG 167

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 7656967  2600 pdFCWLSLQDT--LIWSFAGPIGAVIIINTVTSvLSAKVSCQRKHHYYGKKG 2649
Cdd:cd13951  168 --ICFVGNQNLdaLRGFVLAPLFLYLILGTVFL-LCGFLSLFRIRSILSNDG 216
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
 1875-1908 3.37e-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: 37.46  E-value: 3.37e-03
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 7656967  1875 PC-TSSPCPPNSRCHDAWEDYSCVCDKGYLG-INCV 1908
Cdd:cd00053    1 ECaASNPCSNGGTCVNTPGSYRCVCPPGYTGdRSCE 36
EGF smart00181
Epidermal growth factor-like domain;
1369-1399 5.85e-03

Epidermal growth factor-like domain;


Pssm-ID: 214544  Cd Length: 35  Bit Score: 36.73  E-value: 5.85e-03
                            10        20        30
                    ....*....|....*....|....*....|..
gi 7656967     1369 SDPCGaNGRCRSREGGYTCECFEDFTG-EHCE 1399
Cdd:smart00181    5 GGPCS-NGTCINTPGSYTCSCPPGYTGdKRCE 35
EGF smart00181
Epidermal growth factor-like domain;
1407-1441 6.46e-03

Epidermal growth factor-like domain;


Pssm-ID: 214544  Cd Length: 35  Bit Score: 36.73  E-value: 6.46e-03
                            10        20        30
                    ....*....|....*....|....*....|....*.
gi 7656967     1407 CA-NGVCKNGgTCVNLlIGGFHCVCPPGEYERPYCE 1441
Cdd:smart00181    2 CAsGGPCSNG-TCINT-PGSYTCSCPPGYTGDKRCE 35
 
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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