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Conserved domains on  [gi|187952901|gb|AAI38452|]
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G protein-coupled receptor 124 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
 757-1075 0e+00

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: 551.10  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  757 GAGLHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYS 836
Cdd:cd15998     1 GAGLHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHIAMTSAVFAGGITLTNYQMVCQAVGITLHYS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  837 SLSSLLWMGVKARVLHKELSWRAPPLEEGEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSPYCWLVWRPSL 916
Cdd:cd15998    81 SLSTLLWMGVKARVLHKELTWRAPPPQEGDPALPTPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSPYCWLVWRPSL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  917 GAFYIPVALILPITWIYFLCAGLHLRSHVAqnpkqgnrislepgeelrgstrlrssgvllndsgsllatvsagvgtpapp 996
Cdd:cd15998   161 GAFYIPVALILLVTWIYFLCAGLHLRGPSA-------------------------------------------------- 190

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187952901  997 eDGDGVYSPGVQLGALMTTHFLYLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACCP 1075
Cdd:cd15998   191 -DGDSVYSPGVQLGALVTTHFLYLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACCP 268
LRR_8 pfam13855
Leucine rich repeat;
81-137 5.93e-16

Leucine rich repeat;


:

Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 73.33  E-value: 5.93e-16
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 187952901    81 TLLLSNNKITGLRNGSFLGLSLLEKLDLRSNVISTVQPGAFLGLGELKRLDLSNNRI 137
Cdd:pfam13855    5 SLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
65-210 7.80e-12

Leucine-rich repeat (LRR) protein [Transcription];


:

Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 69.19  E-value: 7.80e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   65 DLPEPPDPglLPNgTITLLLSNNKITGLRNgSFLGLSLLEKLDLRSNVISTVqPGAFLGLGELKRLDLSNNRIGCLTSet 144
Cdd:COG4886   173 DLPEELGN--LTN-LKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLTDLPE-- 245

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 187952901  145 FQGLPRLLRLNISGNIYSSLQPGVfdELPALKIVDFGTEFLTcDCRLRWLLPWARNHSLQLSERTL 210
Cdd:COG4886   246 LGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLT-DLKLKELELLLGLNSLLLLLLLL 308
HRM super family cl02422
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 344-410 1.45e-06

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


The actual alignment was detected with superfamily member smart00008:

Pssm-ID: 413313  Cd Length: 70  Bit Score: 47.12  E-value: 1.45e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187952901    344 SYCPAErvtnNRGDFRWPRTLAGITAYQSCLQYpftsvpLSGGAPGTRASRRCDRAGRWEPG--DYSHC 410
Cdd:smart00008    3 LGCPAT----WDGIICWPQTPAGQLVEVPCPKY------FSGFSYKTGASRNCTENGGWSPPfpNYSNC 61
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 702-743 4.53e-06

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: 44.61  E-value: 4.53e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 187952901   702 PMAAWWNQ--DGPGGWSSEGCRLRYSQPNVSSLYCQHLGNVAVL 743
Cdd:pfam01825    1 PQCVFWDFtnSTTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 250-336 7.47e-04

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam00047:

Pssm-ID: 472250  Cd Length: 86  Bit Score: 39.87  E-value: 7.47e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   250 VVFQGDRLPFQCSASYLGNDTRIHWYHNGapMESDEQAGIVLAENLIHdctfiTSELTLSHIGVWASGEWECSVSTVQGN 329
Cdd:pfam00047    7 TVLEGDSATLTCSASTGSPGPDVTWSKEG--GTLIESLKVKHDNGRTT-----QSSLLISNVTKEDAGTYTCVVNNPGGS 79


                   ....*..
gi 187952901   330 TSKKVEI 336
Cdd:pfam00047   80 ATLSTSL 86
PHA03307 super family cl33723
transcriptional regulator ICP4; Provisional
 1075-1286 8.16e-04

transcriptional regulator ICP4; Provisional


The actual alignment was detected with superfamily member PHA03307:

Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 44.01  E-value: 8.16e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1075 PPASPSAShVPARALPTATEDGSPVLGEGPASLKSSPSGSSGRAP--PPPCKLTNLQVAQSQVCEASVAARGDGEPEPTG 1152
Cdd:PHA03307  185 APSSPPAE-PPPSTPPAAASPRPPRRSSPISASASSPAPAPGRSAadDAGASSSDSSSSESSGCGWGPENECPLPRPAPI 263

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1153 SRGSLAPRHHNNLHHGRRVHKSRAKGHRAGETGGKSRLKALRAGTSPGAPELLSSESGSLHNSPSDSYPGSSRNSPGDGL 1232
Cdd:PHA03307  264 TLPTRIWEASGWNGPSSRPGPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSP 343

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 187952901 1233 PLEGEPMLTPSEGSDTSAAPiaetgRPGQRRSASRDNLKGSGSALERESKRRSY 1286
Cdd:PHA03307  344 GPSPSRSPSPSRPPPPADPS-----SPRKRPRPSRAPSSPAASAGRPTRRRARA 392
 
Name Accession Description Interval E-value
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
 757-1075 0e+00

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: 551.10  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  757 GAGLHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYS 836
Cdd:cd15998     1 GAGLHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHIAMTSAVFAGGITLTNYQMVCQAVGITLHYS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  837 SLSSLLWMGVKARVLHKELSWRAPPLEEGEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSPYCWLVWRPSL 916
Cdd:cd15998    81 SLSTLLWMGVKARVLHKELTWRAPPPQEGDPALPTPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSPYCWLVWRPSL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  917 GAFYIPVALILPITWIYFLCAGLHLRSHVAqnpkqgnrislepgeelrgstrlrssgvllndsgsllatvsagvgtpapp 996
Cdd:cd15998   161 GAFYIPVALILLVTWIYFLCAGLHLRGPSA-------------------------------------------------- 190

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187952901  997 eDGDGVYSPGVQLGALMTTHFLYLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACCP 1075
Cdd:cd15998   191 -DGDSVYSPGVQLGALVTTHFLYLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACCP 268
LRR_8 pfam13855
Leucine rich repeat;
81-137 5.93e-16

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 73.33  E-value: 5.93e-16
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 187952901    81 TLLLSNNKITGLRNGSFLGLSLLEKLDLRSNVISTVQPGAFLGLGELKRLDLSNNRI 137
Cdd:pfam13855    5 SLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
81-179 2.90e-12

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 70.35  E-value: 2.90e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   81 TLLLSNNKITGLRNgSFLGLSLLEKLDLRSNVISTVqPGAFLGLGELKRLDLSNNRIGCLtSETFQGLPRLLRLNISGNI 160
Cdd:COG4886   140 ELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDL-PEPLGNLTNLEELDLSGNQ 216

                          90
                  ....*....|....*....
gi 187952901  161 YSSLqPGVFDELPALKIVD 179
Cdd:COG4886   217 LTDL-PEPLANLTNLETLD 234
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
65-210 7.80e-12

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 69.19  E-value: 7.80e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   65 DLPEPPDPglLPNgTITLLLSNNKITGLRNgSFLGLSLLEKLDLRSNVISTVqPGAFLGLGELKRLDLSNNRIGCLTSet 144
Cdd:COG4886   173 DLPEELGN--LTN-LKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLTDLPE-- 245

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 187952901  145 FQGLPRLLRLNISGNIYSSLQPGVfdELPALKIVDFGTEFLTcDCRLRWLLPWARNHSLQLSERTL 210
Cdd:COG4886   246 LGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLT-DLKLKELELLLGLNSLLLLLLLL 308
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 769-976 5.12e-11

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: 64.61  E-value: 5.12e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   769 ALLLLCLFSTIITYILnHSSIHVSRKGWHMllNLCFHMAMTSAVFVGGVTLTNYQ--------MVCQAVGITLHYSSLSS 840
Cdd:pfam00002   13 SLSLVALLLAIAIFLL-FRKLHCTRNYIHL--NLFASFILRALLFLVGDAVLFNKqdldhcswVGCKVVAVFLHYFFLAN 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   841 LLWMGVKARVLHKELswrappleeGEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSpYCWLVWRPSLgaFY 920
Cdd:pfam00002   90 FFWMLVEGLYLYTLL---------VEVFFSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYGEDD-GCWLSNENGL--WW 157

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   921 I---PVALILPITWIYFLCAGLHLRSHVaqnpkqgnRISLEPGEELRGSTRL-RSSGVLL 976
Cdd:pfam00002  158 IirgPILLIILVNFIIFINIVRILVQKL--------RETNMGKSDLKQYRRLaKSTLLLL 209
LRR_8 pfam13855
Leucine rich repeat;
126-179 6.29e-09

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 53.30  E-value: 6.29e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 187952901   126 ELKRLDLSNNRIGCLTSETFQGLPRLLRLNISGNIYSSLQPGVFDELPALKIVD 179
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLD 55
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 82-179 2.24e-07

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 55.62  E-value: 2.24e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   82 LLLSNNKITGLRNGSFlGLSLLEKLDLRSNVISTVQPGAFLGLGELKRLDLSNNRIGCLTSETFQGLPRLLRLNISGNIY 161
Cdd:PLN00113  457 LSLARNKFFGGLPDSF-GSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQL 535

                          90
                  ....*....|....*...
gi 187952901  162 SSLQPGVFDELPALKIVD 179
Cdd:PLN00113  536 SGQIPASFSEMPVLSQLD 553
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 82-180 9.82e-07

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 51.33  E-value: 9.82e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   82 LLLSNNKITGLRNgsFLGLSLLEKLDLRSNVISTV---------------------------QPGAFLGLGE-LKRLDLS 133
Cdd:cd21340    51 LYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVVeglenltnleelhienqrlppgekltfDPRSLAALSNsLRVLNIS 128

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 187952901  134 NNRIGCLTSetFQGLPRLLRLNISGNIYSSLQP--GVFDELPALKIVDF 180
Cdd:cd21340   129 GNNIDSLEP--LAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRELDL 175
HormR smart00008
Domain present in hormone receptors;
344-410 1.45e-06

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 47.12  E-value: 1.45e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187952901    344 SYCPAErvtnNRGDFRWPRTLAGITAYQSCLQYpftsvpLSGGAPGTRASRRCDRAGRWEPG--DYSHC 410
Cdd:smart00008    3 LGCPAT----WDGIICWPQTPAGQLVEVPCPKY------FSGFSYKTGASRNCTENGGWSPPfpNYSNC 61
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 702-743 4.53e-06

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: 44.61  E-value: 4.53e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 187952901   702 PMAAWWNQ--DGPGGWSSEGCRLRYSQPNVSSLYCQHLGNVAVL 743
Cdd:pfam01825    1 PQCVFWDFtnSTTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 360-410 1.43e-05

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


Pssm-ID: 397086  Cd Length: 64  Bit Score: 43.90  E-value: 1.43e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 187952901   360 WPRTLAGITAYQSCLQYpftsvpLSGGAPGTRASRRCDRAGRWE---PGDYSHC 410
Cdd:pfam02793   14 WPRTPAGETVEVPCPDY------FSGFDPRGNASRNCTEDGTWSehpPSNYSNC 61
LRRCT smart00082
Leucine rich repeat C-terminal domain;
185-218 2.28e-05

Leucine rich repeat C-terminal domain;


Pssm-ID: 214507 [Multi-domain]  Cd Length: 51  Bit Score: 42.80  E-value: 2.28e-05
                            10        20        30
                    ....*....|....*....|....*....|....*
gi 187952901    185 LTCDCRLRWLLPWARNHS-LQLSERTLCAYPSALH 218
Cdd:smart00082    3 FICDCELRWLLRWLQANEhLQDPVDLRCASPSSLR 37
PCC TIGR00864
polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) ...
 155-222 8.12e-05

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.


Pssm-ID: 188093 [Multi-domain]  Cd Length: 2740  Bit Score: 47.38  E-value: 8.12e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   155 NISGNIYSSLQPGVFDELPALKIVDFGTEFLTCDCRLRWLLPWARNHSLQL--SERTLCAYPSALHAHAL 222
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVrqPEAALCAGPGALAGQPL 70
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 250-336 7.47e-04

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 39.87  E-value: 7.47e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   250 VVFQGDRLPFQCSASYLGNDTRIHWYHNGapMESDEQAGIVLAENLIHdctfiTSELTLSHIGVWASGEWECSVSTVQGN 329
Cdd:pfam00047    7 TVLEGDSATLTCSASTGSPGPDVTWSKEG--GTLIESLKVKHDNGRTT-----QSSLLISNVTKEDAGTYTCVVNNPGGS 79


                   ....*..
gi 187952901   330 TSKKVEI 336
Cdd:pfam00047   80 ATLSTSL 86
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
 1075-1286 8.16e-04

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 44.01  E-value: 8.16e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1075 PPASPSAShVPARALPTATEDGSPVLGEGPASLKSSPSGSSGRAP--PPPCKLTNLQVAQSQVCEASVAARGDGEPEPTG 1152
Cdd:PHA03307  185 APSSPPAE-PPPSTPPAAASPRPPRRSSPISASASSPAPAPGRSAadDAGASSSDSSSSESSGCGWGPENECPLPRPAPI 263

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1153 SRGSLAPRHHNNLHHGRRVHKSRAKGHRAGETGGKSRLKALRAGTSPGAPELLSSESGSLHNSPSDSYPGSSRNSPGDGL 1232
Cdd:PHA03307  264 TLPTRIWEASGWNGPSSRPGPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSP 343

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 187952901 1233 PLEGEPMLTPSEGSDTSAAPiaetgRPGQRRSASRDNLKGSGSALERESKRRSY 1286
Cdd:PHA03307  344 GPSPSRSPSPSRPPPPADPS-----SPRKRPRPSRAPSSPAASAGRPTRRRARA 392
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 706-744 1.03e-03

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: 38.14  E-value: 1.03e-03
                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 187952901    706 WWNQDGpGGWSSEGCRLRYSQPNVSSLYCQHLGNVAVLM 744
Cdd:smart00303    7 FWDESS-GEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
 
Name Accession Description Interval E-value
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
 757-1075 0e+00

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: 551.10  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  757 GAGLHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYS 836
Cdd:cd15998     1 GAGLHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHIAMTSAVFAGGITLTNYQMVCQAVGITLHYS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  837 SLSSLLWMGVKARVLHKELSWRAPPLEEGEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSPYCWLVWRPSL 916
Cdd:cd15998    81 SLSTLLWMGVKARVLHKELTWRAPPPQEGDPALPTPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSPYCWLVWRPSL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  917 GAFYIPVALILPITWIYFLCAGLHLRSHVAqnpkqgnrislepgeelrgstrlrssgvllndsgsllatvsagvgtpapp 996
Cdd:cd15998   161 GAFYIPVALILLVTWIYFLCAGLHLRGPSA-------------------------------------------------- 190

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187952901  997 eDGDGVYSPGVQLGALMTTHFLYLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACCP 1075
Cdd:cd15998   191 -DGDSVYSPGVQLGALVTTHFLYLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACCP 268
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
 757-1074 3.35e-122

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: 379.41  E-value: 3.35e-122
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  757 GAGLHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYS 836
Cdd:cd15259     1 FELLHPVVYAGAALCLLCLLATIITYIVFHRLIRISRKGRHMLVNLCLHLLLTCVVFVGGINRTANQLVCQAVGILLHYS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  837 SLSSLLWMGVKARVLHKELSWRAPPLEEGEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNYrDHSPYCWLVWRPSL 916
Cdd:cd15259    81 TLCTLLWVGVTARNMYKQVTKTAKPPQDEDQPPRPPKPMLRFYLIGWGIPLIICGITAAVNLDNY-STYDYCWLAWDPSL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  917 GAFYIPVALILPITWIYFLCAGLHLRSHVAqnpkqgnrislepgeelrgstrlrssgvllndsgsllatvsagvgtpapp 996
Cdd:cd15259   160 GAFYGPAALIVLVNCIYFLRIYCQLKGAPV-------------------------------------------------- 189

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 187952901  997 edgdgvySPGVQLGALMTTHFLYLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACC 1074
Cdd:cd15259   190 -------SFQSQLRGAVITLFLYVAMWACGALAVSQRYFLDLVFSCLYGATCSSLGLFVLIHHCLSREDVRQSWRQCC 260
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
 757-1076 1.28e-98

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: 316.51  E-value: 1.28e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  757 GAGLHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYS 836
Cdd:cd16000     1 GEFLHPVVYACTAVMLLCLFASIITYIVHHSTIRISRKGWHMLLNFCFHTALTFAVFAGGINRTKYPIICQAVGIVLHYS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  837 SLSSLLWMGVKARVLHKELSWRAPPLEEGEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNY---RDHSPYCWLVWR 913
Cdd:cd16000    81 TLSTMLWIGVTARNIYKQVTKKPHLCQDTDQPPYPKQPLLRFYLVSGGVPFIICGITAATNINNYgteDEDTPYCWMAWE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  914 PSLGAFYIPVALILPITWIYFLCAGLHLRSHVAQNPKQGNRISLEpgeelrgstrlrssgvllndsgsllatvsagvgtp 993
Cdd:cd16000   161 PSLGAFYGPVAFIVLVTCIYFLCTYVQLRRHPERKYELKNEHSFK----------------------------------- 205

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  994 appedgdgvyspgVQLGALMTTHFLYLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRAC 1073
Cdd:cd16000   206 -------------AQLRAAAFTLFLFTATWAFGALAVSQGHFLDMIFSCLYGAFCVTLGLFILIHHCAKRDDVWHCWWSC 272


                  ...
gi 187952901 1074 CPP 1076
Cdd:cd16000   273 CPS 275
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
 760-1075 6.28e-93

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: 302.17  E-value: 6.28e-93
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  760 LHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLS 839
Cdd:cd15999     4 LHPVVYATAVVLLLCLLTIIVSYIYHHSLVRISRKSWHMLVNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYSTLA 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  840 SLLWMGVKARVLHKELSWRAPPLEEGEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNY--RDHSPYCWLVWRPSLG 917
Cdd:cd15999    84 TVLWVGVTARNIYKQVTRKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYgsRPNAPYCWMAWEPSLG 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  918 AFYIPVALILPITWIYFLCAGLHLRSHvaqnPKQGNRISlEPGEELRGSTRLRSSGVLLNDSGSLLATVSAgVGTPAPPE 997
Cdd:cd15999   164 AFYGPAGFIIFVNCMYFLSIFIQLKRH----PERKYELK-EPTEEQQRLAASEHGELNHQDSGSSSASCSL-VSTSALEN 237

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187952901  998 DgdgvYSPGVQLGALMTTHFLYLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASW-RACCP 1075
Cdd:cd15999   238 E----HSFQAQLLGASLALFLYVALWIFGALAVSLYYPMDLVFSCLFGATCLSLGAFLVVHHCVNREDVRRAWiATCCP 312
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
 760-1070 3.07e-61

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: 210.12  E-value: 3.07e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  760 LHPVVYPCTALLLLCLFSTIITYILNHSSIhvSRKGWHMLLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLS 839
Cdd:cd15040     4 LSIITYIGCGLSLLGLLLTIITYILFRKLR--KRKPTKILLNLCLALLLANLLFLFGINSTDNPVLCTAVAALLHYFLLA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  840 SLLWMGVKARVLHKELSWRAPpleegeaaPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSPYCWL-VWRPSLGA 918
Cdd:cd15040    82 SFMWMLVEALLLYLRLVKVFG--------TYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYCWLsNGNGLYYA 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  919 FYIPVALILPITWIYFLCAGLHLRSHVAQNPKqgnrislepgeELRGSTRlrssgvllndsgsllatvsagvgtpapped 998
Cdd:cd15040   154 FLGPVLLIILVNLVIFVLVLRKLLRLSAKRNK-----------KKRKKTK------------------------------ 192

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 187952901  999 gdgvyspgVQLGALMTTHFLYLAMWACGALAVSQRwlpRVVCSCLYGVAASALGLFVFTHHCARRRDVRASW 1070
Cdd:cd15040   193 --------AQLRAAVSLFFLLGLTWIFGILAIFGA---RVVFQYLFAIFNSLQGFFIFIFHCLRNKEVRKAW 253
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
 760-1070 3.97e-37

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: 140.81  E-value: 3.97e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  760 LHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKgwhMLLNLCFHMAMTSAVFVGGVTLTNYQM--VCQAVGITLHYSS 837
Cdd:cd13952     4 LSIITYIGCSLSLVGLLLTIITYLLFPKLRNLRGK---ILINLCLSLLLAQLLFLIGQLLTSSDRpvLCKALAILLHYFL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  838 LSSLLWMGVKARVLHKELSWRAPPLEegeaappgPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSPY----CWL-VW 912
Cdd:cd13952    81 LASFFWMLVEAFDLYRTFVKVFGSSE--------RRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSPGYggeyCWLsNG 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  913 RPSLGAFYIPVALILPITWIYFLCAGLHLRSHVAQNPKQGNRISLepgeelrgSTRLRSSGVLLndsgSLLatvsagvgt 992
Cdd:cd13952   153 NALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKSD--------RKQLRAYLKLF----PLM--------- 211

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 187952901  993 pappedgdgvyspGVQlgalmtthflylamWACGALAVSQRWlpRVVCSCLYGVAASALGLFVFTHHCARRRDVRASW 1070
Cdd:cd13952   212 -------------GLT--------------WIFGILAPFVGG--SLVFWYLFDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
 769-1074 2.02e-18

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: 86.54  E-value: 2.02e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  769 ALLLLCLFSTIITyilNHSSIHVsrkgwhmllNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMGVKA 848
Cdd:cd15441    22 AFLVLSCLRGLQS---NSNSIHK---------NLVACLLLAELLFLLGINQTENLFPCKLIAILLHYFYLSAFSWLLVES 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  849 rvLHkelSWRAppLEEGEAAPPGprPMLRFYLIAGGIPLIICGITAAVNIHNYrDHSPYCWL-VWRPSLGAFYIPVALIL 927
Cdd:cd15441    90 --LH---LYRM--LTEPRDINHG--HMRFYYLLGYGIPAIIVGLSVGLRPDGY-GNPDFCWLsVNETLIWSFAGPIAFVI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  928 PITWIYF---LCAGLHLRSHVaqnPKQGNrislepgeeLRgsTRLRSSGVLLndsgsllatvsagvgtpappedgdgvys 1004
Cdd:cd15441   160 VITLIIFilaLRASCTLKRHV---LEKAS---------VR--TDLRSSFLLL---------------------------- 197

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1005 pgvqlgalmtthFLYLAMWACGALAVSQrwlPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACC 1074
Cdd:cd15441   198 ------------PLLGATWVFGLLAVNE---DSELLHYLFAGLNFLQGLFIFLFYCIFNKKVRRELKNAL 252
LRR_8 pfam13855
Leucine rich repeat;
81-137 5.93e-16

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 73.33  E-value: 5.93e-16
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 187952901    81 TLLLSNNKITGLRNGSFLGLSLLEKLDLRSNVISTVQPGAFLGLGELKRLDLSNNRI 137
Cdd:pfam13855    5 SLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
 763-1070 4.85e-15

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: 76.60  E-value: 4.85e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  763 VVYPCTALLLLCLFSTIITYIlnhsSIHVSRKGWHML-LNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSL 841
Cdd:cd15933     7 ISYIGCGISIACLALTLIIFL----VLRVLSSDRFQIhKNLCVALLLAQILLLAGEWAEGNKVACKVVAILLHFFFMAAF 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  842 LWMGVKARVLHKELswrappleegeAAPPGPRPMLRFYLIAG-GIPLIICGITAAVNIHNYRDHSpYCWL------VWrp 914
Cdd:cd15933    83 SWMLVEGLHLYLMI-----------VKVFNYKSKMRYYYFIGwGLPAIIVAISLAILFDDYGSPN-VCWLslddglIW-- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  915 slgAFYIPVALILPITWIYFLCAgLHLrshvaqnpkqgnrislepgeelrgstRLRSSGVLLNDSGSLLATVSAGVGtpa 994
Cdd:cd15933   149 ---AFVGPVIFIITVNTVILILV-VKI--------------------------TVSLSTNDAKKSQGTLAQIKSTAK--- 195

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 187952901  995 ppedgdgvyspgvqlGALMTTHFLYLAmWACGALAVSQRwlpRVVCSCLYGVAASALGLFVFTHHCARRRDVRASW 1070
Cdd:cd15933   196 ---------------ASVVLLPILGLT-WLFGVLVVNSQ---TIVFQYIFVILNSLQGLMIFLFHCVLNSEVRSAF 252
LRR_8 pfam13855
Leucine rich repeat;
103-159 1.62e-14

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 69.09  E-value: 1.62e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 187952901   103 LEKLDLRSNVISTVQPGAFLGLGELKRLDLSNNRIGCLTSETFQGLPRLLRLNISGN 159
Cdd:pfam13855    3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGN 59
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
 772-1074 1.11e-13

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: 72.68  E-value: 1.11e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  772 LLCLFSTIITYILNHS------SIHVsrkgwhmllNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMG 845
Cdd:cd15440    16 IVCLLLAFITFTCFRNlqcdrnTIHK---------NLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFLAAFSWML 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  846 VKARVLHKELSwrappleegEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNYrDHSPYCWL------VWrpslgAF 919
Cdd:cd15440    87 LEGFQLYVMLV---------EVFEPEKSRIKWYYLFGYGLPALIVAVSAGVDPTGY-GTEDHCWLstengfIW-----SF 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  920 YIPVALILPITWIYF---LCAGLHLRSHVAQNPKQGNRISLepgeelrgSTRLRSSGVLLndsgSLLatvsaGVgtpapp 996
Cdd:cd15440   152 VGPVIVVLLANLVFLgmaIYVMCRHSSRSASKKDASKLKNI--------RGWLKGSIVLV----VLL-----GL------ 208

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 187952901  997 edgdgvyspgvqlgalmtthflylaMWACGALAVSQRwlpRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRACC 1074
Cdd:cd15440   209 -------------------------TWTFGLLFINQE---SIVMAYIFTILNSLQGLFIFIFHCVLNEKVRKELRRWL 258
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
 767-944 3.50e-13

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: 71.49  E-value: 3.50e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  767 CTALLLLCLFSTIITYIL--NHSSIHvsrkgWHMLLNLCFHMAMTSAVFVGGVTLTNYQM-VCQAVGITLHYSSLSSLLW 843
Cdd:cd15039    11 GLIISLVFLLLTLAVYALlpELRNLH-----GKCLMCLVLSLFVAYLLLLIGQLLSSGDStLCVALGILLHFFFLAAFFW 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  844 MGVKARVLHKELS-WRAPPLEEGEAappgpRPMLRFYLIAGGIPLIICGITAAVNIHNYRDH-SP-----YCWLV-WRPS 915
Cdd:cd15039    86 LNVMSFDIWRTFRgKRSSSSRSKER-----KRFLRYSLYAWGVPLLLVAVTIIVDFSPNTDSlRPgygegSCWISnPWAL 160

                         170       180
                  ....*....|....*....|....*....
gi 187952901  916 LGAFYIPVALILPITWIYFLCAGLHLRSH 944
Cdd:cd15039   161 LLYFYGPVALLLLFNIILFILTAIRIRKV 189
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
 767-934 1.78e-12

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: 69.08  E-value: 1.78e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  767 CTALLLLCLFSTIITYILNhSSIHVSRKGWHmlLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMGV 846
Cdd:cd15931    11 GVIVSLFCLGLAIFTFLLC-RWIPKINTTAH--LHLCLCLSMSHTLFLAGIEYVENELACTVMAGLLHYLFLASFVWMLL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  847 KARVLHkelsWRAPPLEEGEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSpYCWLVW-RPSLGAFYIPVAL 925
Cdd:cd15931    88 EALQLH----LLVRRLTKVQVIQRDGLPRPLLCLIGYGVPFLIVGVSALVYSDGYGEAK-MCWLSQeRGFNWSFLGPVIA 162


                  ....*....
gi 187952901  926 ILPITWIYF 934
Cdd:cd15931   163 IIGINWILF 171
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
81-179 2.90e-12

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 70.35  E-value: 2.90e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   81 TLLLSNNKITGLRNgSFLGLSLLEKLDLRSNVISTVqPGAFLGLGELKRLDLSNNRIGCLtSETFQGLPRLLRLNISGNI 160
Cdd:COG4886   140 ELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDL-PEPLGNLTNLEELDLSGNQ 216

                          90
                  ....*....|....*....
gi 187952901  161 YSSLqPGVFDELPALKIVD 179
Cdd:COG4886   217 LTDL-PEPLANLTNLETLD 234
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
 772-946 7.69e-12

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: 67.37  E-value: 7.69e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  772 LLCLFSTIITYILNHSsIHVSRKGWHMLLNLCFHMAMTsaVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMGVKArvL 851
Cdd:cd15439    16 LLCLFLAILTFLLCRS-IRNTSTSLHLQLSLCLFLADL--LFLVGIDRTDNKVLCSIIAGFLHYLFLACFAWMFLEA--V 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  852 HKELSWRAPPLEEGEAAppgPRPMLRF-YLIAGGIPLIICGITAAVNIHNYRDHSpYCWL------VWrpslgAFYIPVA 924
Cdd:cd15439    91 HLFLTVRNLKVVNYFSS---HRFKKRFmYPVGYGLPAVIVAISAAVNPQGYGTPK-HCWLsmekgfIW-----SFLGPVC 161

                         170       180
                  ....*....|....*....|..
gi 187952901  925 LILPITWIYFLCAGLHLRSHVA 946
Cdd:cd15439   162 VIIVINLVLFCLTLWILREKLS 183
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
65-210 7.80e-12

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 69.19  E-value: 7.80e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   65 DLPEPPDPglLPNgTITLLLSNNKITGLRNgSFLGLSLLEKLDLRSNVISTVqPGAFLGLGELKRLDLSNNRIGCLTSet 144
Cdd:COG4886   173 DLPEELGN--LTN-LKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLTDLPE-- 245

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 187952901  145 FQGLPRLLRLNISGNIYSSLQPGVfdELPALKIVDFGTEFLTcDCRLRWLLPWARNHSLQLSERTL 210
Cdd:COG4886   246 LGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLT-DLKLKELELLLGLNSLLLLLLLL 308
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 769-1073 8.80e-12

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: 67.10  E-value: 8.80e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  769 ALLLLCLFSTIITYILNHSsIHVSRKGWHmlLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMGVKA 848
Cdd:cd15438    13 SVSLFCLFLCILTFLFCRS-IRGTRNTIH--LHLCLSLFLAHLIFLLGINNTNNQVACAVVAGLLHYFFLAAFCWMSLEG 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  849 RVLHKELswrappLEEGEAAPPGPRPMLrfyLIAGGIPLIICGITAAVNIHNYRDHSpYCWLVWRPS-LGAFYIPVALIL 927
Cdd:cd15438    90 VELYLMV------VQVFNTQSLKKRYLL---LIGYGVPLVIVAISAAVNSKGYGTQR-HCWLSLERGfLWSFLGPVCLII 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  928 PITWIYFLCAGLHLRSHVAQ-NPKQGnrislepgeelrgstRLRSSGVLlndsgsllaTVSAgvgtpappedgdgvyspG 1006
Cdd:cd15438   160 LVNAIIFVITVWKLAEKFSSiNPDME---------------KLRKIRAL---------TITA-----------------I 198

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 187952901 1007 VQLGALMTThflylamWACGALAVSQRWLprvVCSCLYGVAASALGLFVFTHHCARRRDVRASWRAC 1073
Cdd:cd15438   199 AQLCILGCT-------WIFGFFQFSDSTL---VMSYLFTILNSLQGLFIFLLHCLLSKQVREEYSRW 255
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 769-976 5.12e-11

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: 64.61  E-value: 5.12e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   769 ALLLLCLFSTIITYILnHSSIHVSRKGWHMllNLCFHMAMTSAVFVGGVTLTNYQ--------MVCQAVGITLHYSSLSS 840
Cdd:pfam00002   13 SLSLVALLLAIAIFLL-FRKLHCTRNYIHL--NLFASFILRALLFLVGDAVLFNKqdldhcswVGCKVVAVFLHYFFLAN 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   841 LLWMGVKARVLHKELswrappleeGEAAPPGPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHSpYCWLVWRPSLgaFY 920
Cdd:pfam00002   90 FFWMLVEGLYLYTLL---------VEVFFSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYGEDD-GCWLSNENGL--WW 157

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   921 I---PVALILPITWIYFLCAGLHLRSHVaqnpkqgnRISLEPGEELRGSTRL-RSSGVLL 976
Cdd:pfam00002  158 IirgPILLIILVNFIIFINIVRILVQKL--------RETNMGKSDLKQYRRLaKSTLLLL 209
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
 773-1072 1.90e-10

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: 63.14  E-value: 1.90e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  773 LCLFSTIITYIlnhsSIHVSRKGW--HMLLNLCFHMAMTSAVFVGGVTLTNYQM--VCQAVGITLHYSSLSSLLWMGVKA 848
Cdd:cd15997    17 IFLGITLVTYL----AFEKLRRDYpsKILINLCTALLMLNLVFLLNSWLSSFNNygLCITVAAFLHYFLLASFTWMGLEA 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  849 --------RVLHKELswrappleegeaappgPRPMLRFYLIAGGIPLIICGITAAVNIHNYRDHS---------PYCWLv 911
Cdd:cd15997    93 vhmyfalvKVFNIYI----------------PNYILKFCIAGWGIPAVVVALVLAINKDFYGNELssdslhpstPFCWI- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  912 wrPSLGAFYIPV----ALILPITWIYFLCAGLHLRSHVAQNPKQGNRislepgeelrgstrlrssGVLLNDsgsllatvs 987
Cdd:cd15997   156 --QDDVVFYISVvayfCLIFLCNISMFITVLIQIRSMKAKKPSRNWK------------------QGFLHD--------- 206

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  988 agvgtpappedgdgvyspgvqLGALMTTHFLYLAMWACGALAvsqrWLP-RVVCSCLYGVAASALGLFVFTHHCARRRDV 1066
Cdd:cd15997   207 ---------------------LKSVASLTFLLGLTWGFAFFA----WGPvRIFFLYLFSICNTLQGFFIFVFHCLMKENV 261


                  ....*.
gi 187952901 1067 RASWRA 1072
Cdd:cd15997   262 RKQWRI 267
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
 772-1073 4.38e-10

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: 61.86  E-value: 4.38e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  772 LLCLFSTIITYILnHSSIHVSRKGWHMllNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMGVKARVL 851
Cdd:cd16007    16 LVCLAICISTFCF-LRGLQTDRNTIHK--NLCINLFLAELLFLIGIDKTQYQIACPIFAGLLHFFFLAAFSWLCLEGVQL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  852 HKELSwrapPLEEGEAAPPgprpmlRFYLIAGGI-PLIICGITAAVNIHNYRDHSPyCWL------VWrpslgAFYIPVA 924
Cdd:cd16007    93 YLMLV----EVFESEYSRK------KYYYLCGYCfPALVVGISAAIDYRSYGTEKA-CWLrvdnyfIW-----SFIGPVS 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  925 LILPITWIyFLCAGLHlrshvaqnpkqgnrislepgeelrgsTRLRSSGVLLNDSGSLlatvsagvgtpappedgDGVYS 1004
Cdd:cd16007   157 FVIVVNLV-FLMVTLH--------------------------KMIRSSSVLKPDSSRL-----------------DNIKS 192

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187952901 1005 pgVQLGALmTTHFLYLAMWACGALAVSQRwlpRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRAC 1073
Cdd:cd16007   193 --WALGAI-TLLFLLGLTWAFGLLFINKE---SVVMAYLFTTFNAFQGMFIFIFHCALQKKVHKEYSKC 255
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
81-227 2.96e-09

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 60.72  E-value: 2.96e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   81 TLLLSNNKitglrngSFLGLSLLEKLDLRSNVISTVqPGAFLGLGELKRLDLSNNRIGCLTSEtFQGLPRLLRLNISGNI 160
Cdd:COG4886   100 ELDLSGNE-------ELSNLTNLESLDLSGNQLTDL-PEELANLTNLKELDLSNNQLTDLPEP-LGNLTNLKSLDLSNNQ 170

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 187952901  161 YSSLqPGVFDELPALK--------IVDFGTEFltcdCRLRWLlpwarnHSLQLSERTLCAYPSALhaHALSSLQE 227
Cdd:COG4886   171 LTDL-PEELGNLTNLKeldlsnnqITDLPEPL----GNLTNL------EELDLSGNQLTDLPEPL--ANLTNLET 232
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 772-1073 3.78e-09

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: 59.04  E-value: 3.78e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  772 LLCLFSTIITYIL------NHSSIHVsrkgwhmllNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWM- 844
Cdd:cd15436    16 LVCLLICIFTFCFfrglqtDRNTIHK---------NLCINLFIAELLFLIGINRTQYTIACPIFAGLLHFFFLAAFCWLc 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  845 --GVKARVLHKELSwrappleEGEAAPPGprpmlRFYLIAGGIPLIICGITAAVNIHNYRDHSPyCWL------VWrpsl 916
Cdd:cd15436    87 leGVQLYLLLVEVF-------ESEYSRRK-----YFYLCGYSFPALVVAVSAAIDYRSYGTEKA-CWLrvdnyfIW---- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  917 gAFYIPVALILPITWIyFLCAGLHlrshvaqnpkqgnrislepgeelrgstRLRSSGVLLNDSGSLLATVSAGVgtpapp 996
Cdd:cd15436   150 -SFIGPVTFVITLNLV-FLVITLH---------------------------KMVSHSDLLKPDSSRLDNIKSWA------ 194

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 187952901  997 edgdgvyspgvqLGALmTTHFLYLAMWACGALAVSQrwlPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRAC 1073
Cdd:cd15436   195 ------------LGAI-ALLFLLGLTWSFGLMFINE---ESVVMAYLFTIFNAFQGVFIFIFHCALQKKVRKEYSKC 255
LRR_8 pfam13855
Leucine rich repeat;
126-179 6.29e-09

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 53.30  E-value: 6.29e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 187952901   126 ELKRLDLSNNRIGCLTSETFQGLPRLLRLNISGNIYSSLQPGVFDELPALKIVD 179
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLD 55
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
 772-1073 1.74e-08

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: 57.13  E-value: 1.74e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  772 LLCLFSTIITYILnHSSIHVSRKGWHMllNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWM---GVKA 848
Cdd:cd15252    16 LVCLAICIFTFWF-FRGLQSDRTTIHK--NLCISLFLAELVFLIGINTTTNKIFCSVIAGLLHYFFLAAFAWMfieGIQL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  849 RVLHKELSWRAPPLEEgeaappgprpmlRFYLIAGGIPLIICGITAAVNIHNYrDHSPYCWL------VWrpslgAFYIP 922
Cdd:cd15252    93 YLMLVEVFENEGSRHK------------NFYIFGYGSPAVIVGVSAALGYRYY-GTTKVCWLstenyfIW-----SFIGP 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  923 VALILPITWIYFLCAGLHLRSHVAqnpkqgnriSLEPGEELRGSTRLRSSGVLlndsgsllatvsagvgtpappedgdgv 1002
Cdd:cd15252   155 ATLIILLNLIFLGVAIYKMFRHTA---------GLKPEVSCLENIRSWARGAI--------------------------- 198

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 187952901 1003 yspgvqlgALMtthFLYLAMWACGALAVSQRwlpRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRAC 1073
Cdd:cd15252   199 --------ALL---FLLGLTWIFGVLHINHA---SVVMAYLFTVSNSLQGMFIFLFHCVLSRKVRKEYYKL 255
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
 763-1072 2.02e-08

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: 56.78  E-value: 2.02e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  763 VVYPCTALLLLCLFSTIityilnHSSIHVSRKgwhmllNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLL 842
Cdd:cd15991    16 LVALLITFILLVLIRTL------RSNLHSIHK------NLVAALFFSELIFLIGINQTENPFVCTVVAILLHYFYMSTFA 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  843 WMGVKARVLHKELSwrappleEGEAAPPGPrpmLRFYLIAG-GIPLIICGITAAVNIHNYrDHSPYCWLVWRPSL-GAFY 920
Cdd:cd15991    84 WMFVEGLHIYRMLT-------EVRNINTGH---MRFYYVVGwGIPAIITGLAVGLDPQGY-GNPDFCWLSVQDTLiWSFA 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  921 IPVALILPI-TWIYFLCAGLHLRSHVAQNPKQGnRISLepgeelrgstrLRSSGVLLndsgsLLATVSAGVGTPAPPEDg 999
Cdd:cd15991   153 GPIGIVVIInTVIFVLAAKASCGRRQRYFEKSG-VISM-----------LRTAFLLL-----LLISATWLLGLMAVNSD- 214

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 187952901 1000 dgvyspgvqlgaLMTTHFLYLAMwacgalavsqrwlprvvcSCLYgvaasalGLFVFTHHCARRRDVRASWRA 1072
Cdd:cd15991   215 ------------TLSFHYLFAIF------------------SCLQ-------GIFIFFFHCIFNKEVRKHLKN 250
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
 769-935 4.55e-08

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: 56.42  E-value: 4.55e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  769 ALLLLCLFSTIITYILNHSsIHVSRKGWhMLLNLCFHMAMTSAVFVGGVTLTNYQM------------------------ 824
Cdd:cd15257    13 VLSIAGLVITIIFHLHTRK-LRKSSVTW-VLLNLCSSLLLFNIIFTSGVENTNNDYeistvpdretntvllseeyvepdt 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  825 -VCQAVGITLHYSSLSSLLWMGVKARVLHKELSWRAPPLEegeaappgPRPMLRFYLIAGGIPLIICGITAAVNI----- 898
Cdd:cd15257    91 dVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLP--------EMFILQASAIGWGIPAVVVAITLGATYrfpts 162

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 187952901  899 -----HNYRDHSpYCWL--------VWRPSLGAFYIPVALILPITWIYFL 935
Cdd:cd15257   163 lpvftRTYRQEE-FCWLaaldknfdIKKPLLWGFLLPVGLILITNVILFI 211
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 82-179 2.24e-07

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 55.62  E-value: 2.24e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   82 LLLSNNKITGLRNGSFlGLSLLEKLDLRSNVISTVQPGAFLGLGELKRLDLSNNRIGCLTSETFQGLPRLLRLNISGNIY 161
Cdd:PLN00113  457 LSLARNKFFGGLPDSF-GSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQL 535

                          90
                  ....*....|....*...
gi 187952901  162 SSLQPGVFDELPALKIVD 179
Cdd:PLN00113  536 SGQIPASFSEMPVLSQLD 553
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
81-243 2.61e-07

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 54.55  E-value: 2.61e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   81 TLLLSNNKITGLRngSFLGLSLLEKLDLRSNVISTVQPGAflGLGELKRLDLSNNRIGCLTSETFQGLPRL--LRLNISG 158
Cdd:COG4886   232 TLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLTDLKLKELELLLGLnsLLLLLLL 307

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  159 NIYSSLQPGVFDELPALKIVDFGTEFLTCDCRLRWLLPWARNHSLQLSERTLCAYPSALHAHALSSLQESQLRCEGALEL 238
Cdd:COG4886   308 LNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATLLTLALLLL 387


                  ....*
gi 187952901  239 HTHYL 243
Cdd:COG4886   388 TLLLL 392
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 82-180 9.82e-07

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 51.33  E-value: 9.82e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   82 LLLSNNKITGLRNgsFLGLSLLEKLDLRSNVISTV---------------------------QPGAFLGLGE-LKRLDLS 133
Cdd:cd21340    51 LYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVVeglenltnleelhienqrlppgekltfDPRSLAALSNsLRVLNIS 128

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 187952901  134 NNRIGCLTSetFQGLPRLLRLNISGNIYSSLQP--GVFDELPALKIVDF 180
Cdd:cd21340   129 GNNIDSLEP--LAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRELDL 175
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
 769-1073 1.23e-06

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: 51.45  E-value: 1.23e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  769 ALLLLCLFSTIITYILnHSSIHVSRKGWHMllNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMGVKA 848
Cdd:cd16006    13 VISLVCLAICIFTFCF-FRGLQSDRNTIHK--NLCINLFIAEFIFLIGIDKTEYKIACPIFAGLLHFFFLAAFAWMCLEG 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  849 RVLHKELSwrapPLEEGEAAPPgprpmlRFYLIAGG-IPLIICGITAAVNIHNYRDHSPyCWL------VWrpslgAFYI 921
Cdd:cd16006    90 VQLYLMLV----EVFESEYSRK------KYYYVAGYlFPATVVGVSAAIDYKSYGTEKA-CWLrvdnyfIW-----SFIG 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  922 PVALILPITWIYFLCAGLHLRSHVAqnpkqgnriSLEPgeelrGSTRLrssgvllndsGSLLATVSagvgtpappedgdg 1001
Cdd:cd16006   154 PVTFIILLNLIFLVITLCKMVKHSN---------TLKP-----DSSRL----------ENIKSWVL-------------- 195

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 187952901 1002 vyspgvqlGALMTTHFLYLAmWACGALAVSQRwlpRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRAC 1073
Cdd:cd16006   196 --------GAFALLCLLGLT-WSFGLLFINEE---TIVMAYLFTIFNAFQGMFIFIFHCALQKKVRKEYSKC 255
HormR smart00008
Domain present in hormone receptors;
344-410 1.45e-06

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 47.12  E-value: 1.45e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187952901    344 SYCPAErvtnNRGDFRWPRTLAGITAYQSCLQYpftsvpLSGGAPGTRASRRCDRAGRWEPG--DYSHC 410
Cdd:smart00008    3 LGCPAT----WDGIICWPQTPAGQLVEVPCPKY------FSGFSYKTGASRNCTENGGWSPPfpNYSNC 61
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 702-743 4.53e-06

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: 44.61  E-value: 4.53e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 187952901   702 PMAAWWNQ--DGPGGWSSEGCRLRYSQPNVSSLYCQHLGNVAVL 743
Cdd:pfam01825    1 PQCVFWDFtnSTTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
 770-1073 7.87e-06

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: 49.17  E-value: 7.87e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  770 LLLLCLFSTIITYILnHSSIHVSRKGWHMllNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMGVKAR 849
Cdd:cd16005    14 LSLVCLLICIFTFCF-FRGLQSDRNTIHK--NLCISLFVAELLFLIGINRTDQPIACAVFAALLHFFFLAAFTWMFLEGV 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  850 VLHKELswrappLEEGEAAPPGPRpmlRFYLIAGGIPLIICGITAAVNIHNYRDHSpYCWL------VWrpslgAFYIPV 923
Cdd:cd16005    91 QLYIML------VEVFESEHSRRK---YFYLVGYGMPALIVAVSAAVDYRSYGTDK-VCWLrldtyfIW-----SFIGPA 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  924 ALILPITWIYFLCAGLHLRSHVAqnpkqgnrislepgeelrgstrlrssgVLLNDSGSlLATVSAGVgtpappedgdgvy 1003
Cdd:cd16005   156 TLIIMLNVIFLGIALYKMFHHTA---------------------------ILKPESGC-LDNIKSWV------------- 194

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1004 spgvqLGALMTTHFLYLAmWACGALAVSQRwlpRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRAC 1073
Cdd:cd16005   195 -----IGAIALLCLLGLT-WAFGLMYINES---TVIMAYLFTIFNSLQGMFIFIFHCVLQKKVRKEYGKC 255
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
 767-924 7.91e-06

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: 48.95  E-value: 7.91e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  767 CTALLLLCLFsTIITYILNH-------SSIHVSRKGWHMLLNLCFHMAmtsavfvGGVTLTNYQMVCQAVGITLHYSSLS 839
Cdd:cd15258    12 CGISAIFLAI-TILTYIAFRklrrdypSKIHMNLCAALLLLNLAFLLS-------SWIASFGSDGLCIAVAVALHYFLLA 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  840 SLLWMGVKA--------RVLHKELswrappleegeaappgPRPMLRFYLIAGGIPLIICGITAAVNIHNY---------- 901
Cdd:cd15258    84 CLTWMGLEAfhlylllvKVFNTYI----------------RRYILKLCLVGWGLPALLVTLVLSVRSDNYgpitipngeg 147

                         170       180
                  ....*....|....*....|...
gi 187952901  902 RDHSPYCWLvwRPSLgAFYIPVA 924
Cdd:cd15258   148 FQNDSFCWI--RDPV-VFYITVV 167
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
 760-1071 1.41e-05

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: 48.38  E-value: 1.41e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  760 LHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLS 839
Cdd:cd15256     4 LSSITYVGCSLSIFCLAITLVTFAVLSSVSTIRNQRYHIHANLSFAVLVAQILLLISFRFEPGTLPCKIMAILLHFFFLS 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  840 SLLWMGVKARVLHkELSWRAPPLEEGEaappgprpMLRFYLIAGGIPLIICGITAAVNIHNYRDhSPYCWL-VWRPSLGA 918
Cdd:cd15256    84 AFAWMLVEGLHLY-SMVIKVFGSEESK--------HFYYYGIGWGSPLLICIISLTSALDSYGE-SDNCWLsLENGAIWA 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  919 FYIPvALILPITWIYFLCAGLHLRSHV-AQNPKqgnrislepgeelrgstrlrssgvLLNDSGSLLATVSAgvgtpappe 997
Cdd:cd15256   154 FVAP-ALFVIVVNIGILIAVTRVISRIsADNYK------------------------VHGDANAFKLTAKA--------- 199

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 187952901  998 dgdgvysPGVQLGALMTThflylamWACGALAVSQRwlpRVVCSCLYGVAASALGLFVFTHHCARRRDVRASWR 1071
Cdd:cd15256   200 -------VAVLLPILGSS-------WVFGVLAVNTH---ALVFQYMFAIFNSLQGFFIFLFHCLLNSEVRAAFK 256
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 360-410 1.43e-05

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


Pssm-ID: 397086  Cd Length: 64  Bit Score: 43.90  E-value: 1.43e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 187952901   360 WPRTLAGITAYQSCLQYpftsvpLSGGAPGTRASRRCDRAGRWE---PGDYSHC 410
Cdd:pfam02793   14 WPRTPAGETVEVPCPDY------FSGFDPRGNASRNCTEDGTWSehpPSNYSNC 61
LRRCT smart00082
Leucine rich repeat C-terminal domain;
185-218 2.28e-05

Leucine rich repeat C-terminal domain;


Pssm-ID: 214507 [Multi-domain]  Cd Length: 51  Bit Score: 42.80  E-value: 2.28e-05
                            10        20        30
                    ....*....|....*....|....*....|....*
gi 187952901    185 LTCDCRLRWLLPWARNHS-LQLSERTLCAYPSALH 218
Cdd:smart00082    3 FICDCELRWLLRWLQANEhLQDPVDLRCASPSSLR 37
LRR_8 pfam13855
Leucine rich repeat;
80-113 3.34e-05

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 42.90  E-value: 3.34e-05
                           10        20        30
                   ....*....|....*....|....*....|....
gi 187952901    80 ITLLLSNNKITGLRNGSFLGLSLLEKLDLRSNVI 113
Cdd:pfam13855   28 KVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
PCC TIGR00864
polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) ...
 155-222 8.12e-05

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.


Pssm-ID: 188093 [Multi-domain]  Cd Length: 2740  Bit Score: 47.38  E-value: 8.12e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   155 NISGNIYSSLQPGVFDELPALKIVDFGTEFLTCDCRLRWLLPWARNHSLQL--SERTLCAYPSALHAHAL 222
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVrqPEAALCAGPGALAGQPL 70
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
 812-936 1.36e-04

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: 45.34  E-value: 1.36e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  812 VFVGGVTLTNyQMVCQAVGITLHYSSLSSLLWMGVKARVLHKELSWrappleegeAAPPGPRPMLRFYLIAGGIPLIICG 891
Cdd:cd15260    62 VDNPEVLLEN-PIWCQALHVLLQYFMVCNYFWMFCEGLYLHTVLVV---------AFISEKSLMRWFIAIGWGVPLVITA 131

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 187952901  892 ITAAVNiHNYRDHSPYCWLVWRPSLGAFYIPVALILPITWIyFLC 936
Cdd:cd15260   132 IYAGVR-ASLPDDTERCWMEESSYQWILIVPVVLSLLINLI-FLI 174
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
 772-934 2.34e-04

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: 44.48  E-value: 2.34e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  772 LLCLFSTIITYILnHSSIHVSRKGWHMllNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMGVKArvL 851
Cdd:cd15437    16 LICLSMCIFTFWF-FSEIQSTRTTIHK--NLCCSLFLAELIFLIGINMNANKLFCSIIAGLLHYFFLAAFAWMCIEG--I 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  852 HKELSWRAPPLEEGEAAPpgprpmlRFYLIAGGIPLIICGITAAVNiHNYRDHSPYCWL------VWrpslgAFYIPVAL 925
Cdd:cd15437    91 HLYLIVVGVIYNKGFLHK-------NFYIFGYGSPAVVVGISAALG-YKYYGTTKVCWLstennfIW-----SFIGPACL 157


                  ....*....
gi 187952901  926 ILPITWIYF 934
Cdd:cd15437   158 IILVNLLAF 166
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 81-170 3.32e-04

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 43.62  E-value: 3.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   81 TLLLSNNKITGLRNgsFLGLSLLEKLDLRSNVISTVQPgaFLGLGELKRLDLSNNRIGCLtsETFQGLPRLLRLNISgni 160
Cdd:cd21340    28 VLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVV--EGLENLTNLEELHIE--- 98

                          90
                  ....*....|...
gi 187952901  161 YSSLQPGV---FD 170
Cdd:cd21340    99 NQRLPPGEkltFD 111
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
 801-929 3.74e-04

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: 44.07  E-value: 3.74e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  801 NLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMGVKARVLhkelsWRappleEGEAAPPGPRPMLRFYL 880
Cdd:cd15255    42 NLIFALAAAEFLLMFSEWAKGNQVACWAVTALLHLFFLAAFSWMLVEGLLL-----WS-----KVVAVNMSEDRRMKFYY 111

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 187952901  881 IAG-GIPLIICGITAAVNIHNYRDHSpYCWL-VWRPSLGAFYIPVALILPI 929
Cdd:cd15255   112 VTGwGLPVVIVAVTLATSFNKYVADQ-HCWLnVQTDIIWAFVGPVLFVLTV 161
LRR_RI cd00116
Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 ...
 81-159 5.39e-04

Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond to structural units consisting of a beta strand (LxxLxLxxN/CxL conserved pattern) and an alpha helix. This alignment contains 12 strands corresponding to 11 full repeats, consistent with the extent observed in the subfamily acting as Ran GTPase Activating Proteins (RanGAP1).


Pssm-ID: 238064 [Multi-domain]  Cd Length: 319  Bit Score: 43.88  E-value: 5.39e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   81 TLLLSNNKITGLrNGSFLGLSL-----LEKLDLRSNVI-----STVQPGAFLGLGELKRLDLSNNRIGCLTSETF-QGL- 148
Cdd:cd00116   197 VLDLNNNGLTDE-GASALAETLaslksLEVLNLGDNNLtdagaAALASALLSPNISLLTLSLSCNDITDDGAKDLaEVLa 275

                          90
                  ....*....|...
gi 187952901  149 --PRLLRLNISGN 159
Cdd:cd00116   276 ekESLLELDLRGN 288
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
 767-1067 6.31e-04

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: 43.40  E-value: 6.31e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  767 CTALL-LLCLFSTIITYILNHSSIhvsrkgwhMLLNLCFHMAMTSAVFVGGVTLTNYQMVCQAVGITLHYSSLSSLLWMG 845
Cdd:cd15988    16 CMALLiLLAIYAAFWRFIRSERSI--------ILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFLSSFCWVL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  846 VKArvlhkelsWRAPPLEEGEAAPPGPRPmlRFYLIAGGIPLIICGITAAVNIHNYRDHSPYCWLVWRPS-LGAFYIPVA 924
Cdd:cd15988    88 TEA--------WQSYLAVIGRMRTRLVRK--RFLCLGWGLPALVVAVSVGFTRTKGYGTASYCWLSLEGGlLYAFVGPAA 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901  925 LILPITWIYFLCA--GLHLRSHVAQNPKQgNRISLEPgeELRGSTRLRSS--GVLlndSGSLLATVSAGVGTPAppedgd 1000
Cdd:cd15988   158 VIVLVNMLIGIIVfnKLMSRDGISDKSKK-QRAGSEA--EPCSSLLLKCSkcGVV---SSAAMSSATASSAMAS------ 225

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 187952901 1001 gVYSPGVQLGALMTThflylamWACGALAVSQRwlPRVVCSCLYGVAASALGLFVFTHHCARRRDVR 1067
Cdd:cd15988   226 -LWSSCVVLPLLALT-------WMSAVLAMTDR--RSILFQVLFAVFNSVQGFVIITVHCFLRREVQ 282
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 250-336 7.47e-04

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 39.87  E-value: 7.47e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   250 VVFQGDRLPFQCSASYLGNDTRIHWYHNGapMESDEQAGIVLAENLIHdctfiTSELTLSHIGVWASGEWECSVSTVQGN 329
Cdd:pfam00047    7 TVLEGDSATLTCSASTGSPGPDVTWSKEG--GTLIESLKVKHDNGRTT-----QSSLLISNVTKEDAGTYTCVVNNPGGS 79


                   ....*..
gi 187952901   330 TSKKVEI 336
Cdd:pfam00047   80 ATLSTSL 86
LRR_4 pfam12799
Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a ...
 127-159 7.92e-04

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.


Pssm-ID: 463713 [Multi-domain]  Cd Length: 44  Bit Score: 38.38  E-value: 7.92e-04
                           10        20        30
                   ....*....|....*....|....*....|...
gi 187952901   127 LKRLDLSNNRIGCLtsETFQGLPRLLRLNISGN 159
Cdd:pfam12799    3 LEVLDLSNNQITDI--PPLAKLPNLETLDLSGN 33
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
 1075-1286 8.16e-04

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 44.01  E-value: 8.16e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1075 PPASPSAShVPARALPTATEDGSPVLGEGPASLKSSPSGSSGRAP--PPPCKLTNLQVAQSQVCEASVAARGDGEPEPTG 1152
Cdd:PHA03307  185 APSSPPAE-PPPSTPPAAASPRPPRRSSPISASASSPAPAPGRSAadDAGASSSDSSSSESSGCGWGPENECPLPRPAPI 263

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1153 SRGSLAPRHHNNLHHGRRVHKSRAKGHRAGETGGKSRLKALRAGTSPGAPELLSSESGSLHNSPSDSYPGSSRNSPGDGL 1232
Cdd:PHA03307  264 TLPTRIWEASGWNGPSSRPGPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSP 343

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 187952901 1233 PLEGEPMLTPSEGSDTSAAPiaetgRPGQRRSASRDNLKGSGSALERESKRRSY 1286
Cdd:PHA03307  344 GPSPSRSPSPSRPPPPADPS-----SPRKRPRPSRAPSSPAASAGRPTRRRARA 392
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
 1075-1299 8.30e-04

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 44.01  E-value: 8.30e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1075 PPASPSASHVPARALPTATEDGSPVLGEGPaslksspSGSSGRAPPPPCKLTNLQVAQSQVCEASVAARGDGEPEPTGSR 1154
Cdd:PHA03307  165 DAASSRQAALPLSSPEETARAPSSPPAEPP-------PSTPPAAASPRPPRRSSPISASASSPAPAPGRSAADDAGASSS 237

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901 1155 GSLAPRHHNNLHHGRrvhkSRAKGHRAGETGGKSRLKALRAGTSPGAPELLSSESGSlhnsPSDSYPGSSRNSPGDGLP- 1233
Cdd:PHA03307  238 DSSSSESSGCGWGPE----NECPLPRPAPITLPTRIWEASGWNGPSSRPGPASSSSS----PRERSPSPSPSSPGSGPAp 309

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 187952901 1234 --------LEGEPMLTPSEGSDTSAAPIAETGRPGQRRSASRDNLKGSGSALERESKRRSYPLNTTSLNGAPKG 1299
Cdd:PHA03307  310 ssprasssSSSSRESSSSSTSSSSESSRGAAVSPGPSPSRSPSPSRPPPPADPSSPRKRPRPSRAPSSPAASAG 383
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 84-186 1.03e-03

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 43.68  E-value: 1.03e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   84 LSNNKITGLRNGSFLGLSLLEKLDLRSNVISTVQPGA-FLGLGELKRLDLSNNRigcLTSETFQG-LPRLLRLNISGNIY 161
Cdd:PLN00113   76 LSGKNISGKISSAIFRLPYIQTINLSNNQLSGPIPDDiFTTSSSLRYLNLSNNN---FTGSIPRGsIPNLETLDLSNNML 152

                          90       100
                  ....*....|....*....|....*
gi 187952901  162 SSLQPGVFDELPALKIVDFGTEFLT 186
Cdd:PLN00113  153 SGEIPNDIGSFSSLKVLDLGGNVLV 177
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 706-744 1.03e-03

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: 38.14  E-value: 1.03e-03
                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 187952901    706 WWNQDGpGGWSSEGCRLRYSQPNVSSLYCQHLGNVAVLM 744
Cdd:smart00303    7 FWDESS-GEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 244-324 2.59e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 37.93  E-value: 2.59e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   244 IPSLRQVVFQGDRLPFQCSASylGNDT-RIHWYHNGAPMESDEQAGIVLAENlihdctfiTSELTLSHIGVWASGEWECS 322
Cdd:pfam13927    6 VSPSSVTVREGETVTLTCEAT--GSPPpTITWYKNGEPISSGSTRSRSLSGS--------NSTLTISNVTRSDAGTYTCV 75


                   ..
gi 187952901   323 VS 324
Cdd:pfam13927   76 AS 77
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 64-166 3.36e-03

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 41.76  E-value: 3.36e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   64 GDLPEPPDPGLLPNgtitLLLSNNKITGLRNGSFLGLSLLEKLDLRSNVISTVQPGAFLGLGELKRLDLSNNRIGCLTSE 143
Cdd:PLN00113  466 GGLPDSFGSKRLEN----LDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSGQIPA 541

                          90       100
                  ....*....|....*....|...
gi 187952901  144 TFQGLPRLLRLNISGNIYSSLQP 166
Cdd:PLN00113  542 SFSEMPVLSQLDLSQNQLSGEIP 564
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
74-181 5.36e-03

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 40.69  E-value: 5.36e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187952901   74 LLPNGTITLLLSNNKITGLRNGSFLGLSLLEKLDLRSNVISTVQPGAFLGLGELKRLDLSNNrigcltsETFQGLPRLLR 153
Cdd:COG4886    45 LLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNLTELDLSGN-------EELSNLTNLES 117

                          90       100
                  ....*....|....*....|....*...
gi 187952901  154 LNISGNIYSSLqPGVFDELPALKIVDFG 181
Cdd:COG4886   118 LDLSGNQLTDL-PEELANLTNLKELDLS 144
 
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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