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Conserved domains on  [gi|242009018|ref|XP_002425290|]
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class D atypical G-protein coupled receptor GPRsmo1, putative [Pediculus humanus corporis]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
214-539 0e+00

class F smoothened family membrane region, a homolog of frizzled receptors; This group represents smoothened (SMO), a transmembrane G protein-coupled receptor that acts as the transducer of the hedgehog (HH) signaling pathway. SMO is activated by the hedgehog (HH) family of proteins acting on the 12-transmembrane domain receptor patched (PTCH), which constitutively inhibits SMO. Thus, in the absence of HH proteins, PTCH inhibits SMO signaling. On the other hand, binding of HH to the PTCH receptor activates its internalization and degradation, thereby releasing the PTCH inhibition of SMO. This allows SMO to trigger intracellular signaling and the subsequent activation of the Gli family of zinc finger transcriptional factors and induction of HH target gene expression (PTCH, Gli1, cyclin, Bcl-2, etc). SMO is closely related to the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate family of G-protein coupled receptors. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The WNT and HH signaling pathways play critical roles in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


:

Pssm-ID: 320158  Cd Length: 331  Bit Score: 588.11  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 214 PLITKNEYEQIHKMIGWGATASLFCNLFTVVSFLIEWRSGNKYPAVIIFYINICFLLSNLGWLAQFLPKAREDIVCKKDM 293
Cdd:cd15030    1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 294 TLRRSEPSAEENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCRGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASR 373
Cdd:cd15030   81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 374 QIDGNSMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQILSDKASAKIREMIVRIGLFSVFC 453
Cdd:cd15030  161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 454 LTFVIVTFMCHIYEFAHEEDWQKSFRNYIFCSILSS-----KSDPRDCQMESRPSIAMIQLHLLIIFAAGIVMSSWVWIS 528
Cdd:cd15030  241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTiaeqtNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                        330
                 ....*....|.
gi 242009018 529 STAETWRRFFN 539
Cdd:cd15030  321 ATLETWKRFWR 331
CRD_FZ super family cl02447
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
50-190 3.69e-64

CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential component of a number of cell surface receptors, which are involved in multiple signal transduction pathways, particularly in modulating the activity of the Wnt proteins, which play a fundamental role in the early development of metazoans. CRD is also found in secreted frizzled related proteins (SFRPs), which lack the transmembrane segment found in the frizzled protein. The CRD domain is also present in the alpha-1 chain of mouse type XVIII collagen, in carboxypeptidase Z, several receptor tyrosine kinases, and the mosaic transmembrane serine protease corin. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. CRD domains have also been identified in multiple tandem copies in a Dictyostelium discoideum protein. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


The actual alignment was detected with superfamily member cd07451:

Pssm-ID: 413323  Cd Length: 132  Bit Score: 210.69  E-value: 3.69e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  50 CRKSAECTSSNlTCFGVPLPYSDISSDVVVDLfkspelQNFHNLQQELNKWEILRKVPKCWQTLQPFLCALYLPKCEYDT 129
Cdd:cd07451    1 RPAKCEPLKNT-TCLGSKLPYTYTSLDLVPDS------TTQEEVQEKLHLWSGLRNVPKCWAVIQPLLCALYMPKCENGK 73
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 242009018 130 VYLLSQERCKYTMSTCKILKEPLFAATFPsiNCDATEFFPRTCKNDVKDLRSNLSGECISP 190
Cdd:cd07451   74 VELPSQEMCQATRGPCKIVENERGWPDFL--RCDNDRFPPRGCKNDVRELKFNTSGQCESP 132
DUF755 super family cl05192
Domain of unknown function (DUF755); This family is predominated by ORFs from Circoviridae. ...
669-712 2.03e-03

Domain of unknown function (DUF755); This family is predominated by ORFs from Circoviridae. The function of this family remains to be determined.


The actual alignment was detected with superfamily member pfam05501:

Pssm-ID: 368473  Cd Length: 122  Bit Score: 38.95  E-value: 2.03e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 242009018  669 THKTKNHRRRSVRSRGKRRRKDFSRSKKNSSSWTRRGSSTSQES 712
Cdd:pfam05501  77 THKKKRKKSRHVSSRSAKKISAKKRRRSSSSSSSSSSSSSSSSE 120
 
Name Accession Description Interval E-value
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
214-539 0e+00

class F smoothened family membrane region, a homolog of frizzled receptors; This group represents smoothened (SMO), a transmembrane G protein-coupled receptor that acts as the transducer of the hedgehog (HH) signaling pathway. SMO is activated by the hedgehog (HH) family of proteins acting on the 12-transmembrane domain receptor patched (PTCH), which constitutively inhibits SMO. Thus, in the absence of HH proteins, PTCH inhibits SMO signaling. On the other hand, binding of HH to the PTCH receptor activates its internalization and degradation, thereby releasing the PTCH inhibition of SMO. This allows SMO to trigger intracellular signaling and the subsequent activation of the Gli family of zinc finger transcriptional factors and induction of HH target gene expression (PTCH, Gli1, cyclin, Bcl-2, etc). SMO is closely related to the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate family of G-protein coupled receptors. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The WNT and HH signaling pathways play critical roles in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320158  Cd Length: 331  Bit Score: 588.11  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 214 PLITKNEYEQIHKMIGWGATASLFCNLFTVVSFLIEWRSGNKYPAVIIFYINICFLLSNLGWLAQFLPKAREDIVCKKDM 293
Cdd:cd15030    1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 294 TLRRSEPSAEENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCRGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASR 373
Cdd:cd15030   81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 374 QIDGNSMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQILSDKASAKIREMIVRIGLFSVFC 453
Cdd:cd15030  161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 454 LTFVIVTFMCHIYEFAHEEDWQKSFRNYIFCSILSS-----KSDPRDCQMESRPSIAMIQLHLLIIFAAGIVMSSWVWIS 528
Cdd:cd15030  241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTiaeqtNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                        330
                 ....*....|.
gi 242009018 529 STAETWRRFFN 539
Cdd:cd15030  321 ATLETWKRFWR 331
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
215-541 2.89e-129

Frizzled/Smoothened family membrane region; This family contains the membrane spanning region of frizzled and smoothened receptors. This membrane region is predicted to contain seven transmembrane alpha helices. Proteins related to Drosophila frizzled are receptors for Wnt (mediating the beta-catenin signalling pathway), but also the planar cell polarity (PCP) pathway and the Wnt/calcium pathway. The predominantly alpha-helical Cys-rich ligand-binding region (CRD) of Frizzled is both necessary and sufficient for Wnt binding. The smoothened receptor mediates hedgehog signalling.


Pssm-ID: 396219  Cd Length: 321  Bit Score: 389.28  E-value: 2.89e-129
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  215 LITKNEYEQIHKMIGWGATASLFCNLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQFLPkAREDIVCKKDMT 294
Cdd:pfam01534   1 LFTEEEKRFARSWIAVWSILCFVSTLFTVLTFLIDWSR-FRYPERPIIFLSLCYLLVSLGYLIRFVL-GRESIACRKDGT 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  295 LRRSEPSAE--ENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMAS 372
Cdd:pfam01534  79 GRSSYLITQgtENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAA-GLKWGSEAIEKKSSYFHLAAWGIPAVLTITVLAL 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  373 RQIDGNSMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQiLSDKASAKIREMIVRIGLFSVF 452
Cdd:pfam01534 158 GKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLKK-DGARATDKLEKLMVRIGVFSVL 236
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  453 CLTFVIVTFMCHIYEFAHEEDWQKSFrNYIFCSILSSksdprDC--QMESRPSIAMIQLHLLIIFAAGIVMSSWVWISST 530
Cdd:pfam01534 237 YTVPALIVIACYFYEFANRDSWERSW-AYILCRAYGI-----PClpEPESRPSLSVFMLKYFMSLVVGITSGFWVWSGKT 310
                         330
                  ....*....|.
gi 242009018  531 AETWRRFFNRK 541
Cdd:pfam01534 311 LESWRRFFRRL 321
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
50-190 3.69e-64

Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The cysteine-rich domain (CRD) is part of the smoothened receptor (Smo), an integral membrane protein and one of the key players in the Hedgehog (Hh) signaling pathway, critical for development, cell growth and migration, as well as stem cell maintenance. The CRD of Smo is conserved in vertebrates and can also be identified in invertebrates. The precise function of the CRD in Smo is unknown. Mutations in the Drosophila CRD disrupt Smo activity in vivo, while deletion of the CRD in mammalian cells does not seem to affect the activity of overexpressed Smo.


Pssm-ID: 143560  Cd Length: 132  Bit Score: 210.69  E-value: 3.69e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  50 CRKSAECTSSNlTCFGVPLPYSDISSDVVVDLfkspelQNFHNLQQELNKWEILRKVPKCWQTLQPFLCALYLPKCEYDT 129
Cdd:cd07451    1 RPAKCEPLKNT-TCLGSKLPYTYTSLDLVPDS------TTQEEVQEKLHLWSGLRNVPKCWAVIQPLLCALYMPKCENGK 73
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 242009018 130 VYLLSQERCKYTMSTCKILKEPLFAATFPsiNCDATEFFPRTCKNDVKDLRSNLSGECISP 190
Cdd:cd07451   74 VELPSQEMCQATRGPCKIVENERGWPDFL--RCDNDRFPPRGCKNDVRELKFNTSGQCESP 132
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
91-163 2.92e-07

Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell along the anteroposterior axis. Homologues of the N-terminal region of frizzled exist either as transmembrane or secreted molecules. Frizzled homologues are reported to be receptors for the Wnt growth factors. (Not yet in MEDLINE: the FRI domain occurs in several receptor tyrosine kinases [Xu, Y.K. and Nusse, Curr. Biol. 8 R405-R406 (1998); Masiakowski, P. and Yanopoulos, G.D., Curr. Biol. 8, R407 (1998)].


Pssm-ID: 214498  Cd Length: 113  Bit Score: 49.62  E-value: 2.92e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 242009018    91 HNLQQELNKWEILRKVPkCWQTLQPFLCALYLPKCEYD-TVYLLSQERCKYTMSTCkilkEPLFAA-TFP---SINCD 163
Cdd:smart00063  29 EEAGLELEQFHPLLNVQ-CSPDLRFFLCSVYAPICTEDlRPILPCRSLCEAAREGC----EPLMEKfGFPwpeFLRCD 101
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
94-169 6.71e-05

Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups. The domain contains 10 conserved cysteines.


Pssm-ID: 396115  Cd Length: 107  Bit Score: 42.86  E-value: 6.71e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018   94 QQELNKWEILRKVpKCWQTLQPFLCALYLPKC----EYDTVYLLSQERCKYTMSTC-KILKEplFAATFPSI-NCDAtef 167
Cdd:pfam01392  32 ALELEQFEPLVNL-GCHPDLRLFLCSLYFPPCtpsgEGGKPIPPCRSLCEAVRDGCePELLK--FGFSWPEFlDCSK--- 105

                  ..
gi 242009018  168 FP 169
Cdd:pfam01392 106 FP 107
DUF755 pfam05501
Domain of unknown function (DUF755); This family is predominated by ORFs from Circoviridae. ...
669-712 2.03e-03

Domain of unknown function (DUF755); This family is predominated by ORFs from Circoviridae. The function of this family remains to be determined.


Pssm-ID: 368473  Cd Length: 122  Bit Score: 38.95  E-value: 2.03e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 242009018  669 THKTKNHRRRSVRSRGKRRRKDFSRSKKNSSSWTRRGSSTSQES 712
Cdd:pfam05501  77 THKKKRKKSRHVSSRSAKKISAKKRRRSSSSSSSSSSSSSSSSE 120
 
Name Accession Description Interval E-value
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
214-539 0e+00

class F smoothened family membrane region, a homolog of frizzled receptors; This group represents smoothened (SMO), a transmembrane G protein-coupled receptor that acts as the transducer of the hedgehog (HH) signaling pathway. SMO is activated by the hedgehog (HH) family of proteins acting on the 12-transmembrane domain receptor patched (PTCH), which constitutively inhibits SMO. Thus, in the absence of HH proteins, PTCH inhibits SMO signaling. On the other hand, binding of HH to the PTCH receptor activates its internalization and degradation, thereby releasing the PTCH inhibition of SMO. This allows SMO to trigger intracellular signaling and the subsequent activation of the Gli family of zinc finger transcriptional factors and induction of HH target gene expression (PTCH, Gli1, cyclin, Bcl-2, etc). SMO is closely related to the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate family of G-protein coupled receptors. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The WNT and HH signaling pathways play critical roles in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320158  Cd Length: 331  Bit Score: 588.11  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 214 PLITKNEYEQIHKMIGWGATASLFCNLFTVVSFLIEWRSGNKYPAVIIFYINICFLLSNLGWLAQFLPKAREDIVCKKDM 293
Cdd:cd15030    1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 294 TLRRSEPSAEENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCRGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASR 373
Cdd:cd15030   81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 374 QIDGNSMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQILSDKASAKIREMIVRIGLFSVFC 453
Cdd:cd15030  161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 454 LTFVIVTFMCHIYEFAHEEDWQKSFRNYIFCSILSS-----KSDPRDCQMESRPSIAMIQLHLLIIFAAGIVMSSWVWIS 528
Cdd:cd15030  241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTiaeqtNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                        330
                 ....*....|.
gi 242009018 529 STAETWRRFFN 539
Cdd:cd15030  321 ATLETWKRFWR 331
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
215-541 2.89e-129

Frizzled/Smoothened family membrane region; This family contains the membrane spanning region of frizzled and smoothened receptors. This membrane region is predicted to contain seven transmembrane alpha helices. Proteins related to Drosophila frizzled are receptors for Wnt (mediating the beta-catenin signalling pathway), but also the planar cell polarity (PCP) pathway and the Wnt/calcium pathway. The predominantly alpha-helical Cys-rich ligand-binding region (CRD) of Frizzled is both necessary and sufficient for Wnt binding. The smoothened receptor mediates hedgehog signalling.


Pssm-ID: 396219  Cd Length: 321  Bit Score: 389.28  E-value: 2.89e-129
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  215 LITKNEYEQIHKMIGWGATASLFCNLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQFLPkAREDIVCKKDMT 294
Cdd:pfam01534   1 LFTEEEKRFARSWIAVWSILCFVSTLFTVLTFLIDWSR-FRYPERPIIFLSLCYLLVSLGYLIRFVL-GRESIACRKDGT 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  295 LRRSEPSAE--ENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMAS 372
Cdd:pfam01534  79 GRSSYLITQgtENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAA-GLKWGSEAIEKKSSYFHLAAWGIPAVLTITVLAL 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  373 RQIDGNSMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQiLSDKASAKIREMIVRIGLFSVF 452
Cdd:pfam01534 158 GKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLKK-DGARATDKLEKLMVRIGVFSVL 236
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  453 CLTFVIVTFMCHIYEFAHEEDWQKSFrNYIFCSILSSksdprDC--QMESRPSIAMIQLHLLIIFAAGIVMSSWVWISST 530
Cdd:pfam01534 237 YTVPALIVIACYFYEFANRDSWERSW-AYILCRAYGI-----PClpEPESRPSLSVFMLKYFMSLVVGITSGFWVWSGKT 310
                         330
                  ....*....|.
gi 242009018  531 AETWRRFFNRK 541
Cdd:pfam01534 311 LESWRRFFRRL 321
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
214-539 1.50e-74

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


Pssm-ID: 320089  Cd Length: 314  Bit Score: 245.69  E-value: 1.50e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 214 PLITKNEYEQIHKMIG-WGATASLFCnLFTVVSFLIEWRSGNkYPAVIIFYINICFLLSNLGWLAQFLPKaREDIVCKKD 292
Cdd:cd13951    1 GLFTSSEKKFAEIWISaWSALCFLLT-LFTLLTFLIDPSRFR-YPERPIIFLALCYNFYSLGYLVRLVVG-REGIACGKD 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 293 -MTLRRSEPSAEENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMA 371
Cdd:cd13951   78 eGKPYLLLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSA-GLKWSSEAIEKKSSYFHLVAWGLPAVLTIAVLV 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 372 SRQIDGNSMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSV 451
Cdd:cd13951  157 LRKVDGDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSILSN--DGKKTDKLEKLMLRIGIFAV 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 452 FCLTFVIVTFMCHIYEFAHEEDWQKSFRNYIFCSIlssksdprDCQMESRPSIAMIQLHLLIIFAAGIVMSSWVWISSTA 531
Cdd:cd13951  235 LYTLPALIVIACYFYEYANRPDWLRSWEPHSCCSP--------DCEILSRPSLAVFLLKYFMQLVIGITTGVWVWSKKTL 306

                 ....*...
gi 242009018 532 ETWRRFFN 539
Cdd:cd13951  307 LSWRRLLR 314
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
50-190 3.69e-64

Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The cysteine-rich domain (CRD) is part of the smoothened receptor (Smo), an integral membrane protein and one of the key players in the Hedgehog (Hh) signaling pathway, critical for development, cell growth and migration, as well as stem cell maintenance. The CRD of Smo is conserved in vertebrates and can also be identified in invertebrates. The precise function of the CRD in Smo is unknown. Mutations in the Drosophila CRD disrupt Smo activity in vivo, while deletion of the CRD in mammalian cells does not seem to affect the activity of overexpressed Smo.


Pssm-ID: 143560  Cd Length: 132  Bit Score: 210.69  E-value: 3.69e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  50 CRKSAECTSSNlTCFGVPLPYSDISSDVVVDLfkspelQNFHNLQQELNKWEILRKVPKCWQTLQPFLCALYLPKCEYDT 129
Cdd:cd07451    1 RPAKCEPLKNT-TCLGSKLPYTYTSLDLVPDS------TTQEEVQEKLHLWSGLRNVPKCWAVIQPLLCALYMPKCENGK 73
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 242009018 130 VYLLSQERCKYTMSTCKILKEPLFAATFPsiNCDATEFFPRTCKNDVKDLRSNLSGECISP 190
Cdd:cd07451   74 VELPSQEMCQATRGPCKIVENERGWPDFL--RCDNDRFPPRGCKNDVRELKFNTSGQCESP 132
7tmF_FZD4_9_10-like cd15909
class F frizzled subfamilies 4, 9, 10, and related proteins; member of 7-transmembrane G ...
227-539 2.98e-57

class F frizzled subfamilies 4, 9, 10, and related proteins; member of 7-transmembrane G protein-coupled receptors; This group includes subfamilies 4, 9 and 10 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320575  Cd Length: 320  Bit Score: 198.68  E-value: 2.98e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 227 MIGWgATASLFCNLFTVVSFLIEwRSGNKYPAVIIFYINICFLLSNLGWLAQFLpKAREDIVCKKDmtlrRSEPS----- 301
Cdd:cd15909   15 MAVW-ASLCFASTAFTVLTFLID-TSRFRYPERPIIFLSMCYFIYSLGYLIRLF-LGRERIACDSL----NSGVSyliqe 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 302 AEENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMA 381
Cdd:cd15909   88 GLESTWCTIVFLLLYYFGMASALWWVILTFTWYLAA-GRKWGPEAIEAASSYFHLVAWALPAVKTIVILIMHKVDADELT 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 382 GICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLTFVIVTF 461
Cdd:cd15909  167 GLCYVGNHDSDALLGFVLVPLAIYLLIGTLFILAGFVSMFRIRRNLKT--RGTDTSKLEKLMVKIGVFSVLYTVPATCVI 244
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 242009018 462 MCHIYEFAHEEDWQKSfrnYIFCSILSSKSDPRDCQME-SRPSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWRRFFN 539
Cdd:cd15909  245 ACYFYEYLNMDQWRIA---AIECKCQSPNAIGSDCCLQpSIPSVEIYMLKIFMSLVVGITSGMWVWSSKTLQSWQRFIC 320
7tmF_FZD1_2_7-like cd15034
class F frizzled subfamilies 1, 2 and 7; member of 7-transmembrane G protein-coupled receptors; ...
240-538 6.96e-50

class F frizzled subfamilies 1, 2 and 7; member of 7-transmembrane G protein-coupled receptors; This group includes subfamilies 1, 2 and 7 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of G-protein coupled receptors, as well as their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320162  Cd Length: 322  Bit Score: 178.30  E-value: 6.96e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 240 LFTVVSFLIEWRSGnKYPAVIIFYINICFLLSNLGWLAQFLpkAREDIVCKK----DMTLRRSEPSAEEnlSCVVIFVVI 315
Cdd:cd15034   27 LFTVLTFLIDMDRF-RYPERPIIFLSGCYFMVSIAYIVGFF--LGDKVACNGpfppGGPKTVTQGTKKE--GCTILFMML 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 316 YYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGICFVRSSYWGARV 395
Cdd:cd15034  102 YFFSMASSIWWVILTLTWFLAA-GLKWGHEAIEANSQYFHLAAWAVPAIKTIAILAMGKVDGDVLSGVCFVGLSDVDALR 180
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 396 VFLLVPIAVTILMGGYYLVRGLSFLFNVKKdsqqILSDKASA--KIREMIVRIGLFSVFCLTFVIVTFMCHIYEFAHEED 473
Cdd:cd15034  181 GFVLAPLFVYLLIGTSFLLAGFVSLFRIRT----VMKHDGTKtdKLEKLMVRIGVFSVLYTVPATIVIACYFYEQANRES 256
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 242009018 474 WQKSFRNYIFCSILSSKSDPRDCQMESRPSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWRRFF 538
Cdd:cd15034  257 WEKSWLSQNCKKYEDPCPCPPTPHPLDRPDFTVFMIKYLMTLIVGITSGFWIWSGKTLQSWRQFY 321
7tmF_FZD5_FZD8-like cd15035
class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G ...
230-539 8.16e-48

class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G protein-coupled receptors; This group includes subfamilies 5 and 8 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, as well as their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320163  Cd Length: 307  Bit Score: 172.08  E-value: 8.16e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFC---NLFTVVSFLIEwRSGNKYPAVIIFYINICFLLSNLGWLAQfLPKAREDIVCKKDMTLRRSEPSAeenl 306
Cdd:cd15035   14 WIGLWSILCfisTLITVLTFLID-MQRFQYPERPIIFLSFCYFMVSVGYIIR-LIVGHEAVACDGGIIRYATTGPA---- 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 307 SCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGICFV 386
Cdd:cd15035   88 LCTVVFLLTYFFGMASSIWWVILSLTWFLAA-GLKWGNEAISSYSQYFHLVAWLIPAVQTIAILALSAVDGDPISGICYV 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 387 RSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQILSDKASaKIREMIVRIGLFSVfcLTFV--IVTFMCH 464
Cdd:cd15035  167 GNQNLNNLRGFVLAPLVVYLILGTSFLLAGFVSLFRIRNVIKQQGGDKTD-KLEKLMIRIGIFSV--LYTVpaTIVIACY 243
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 242009018 465 IYEFAHEEDWQKSfrnyIFCSilsskSDPRDCQmeSRPSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWRRFFN 539
Cdd:cd15035  244 FYEQHYREIWEKS----LNCP-----CSPGSIK--SRPEYSIFMLKYFMSLVVGITSGFWIWSGKTLDSWKRFCR 307
7tmF_FZD5 cd15249
class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This ...
214-537 6.53e-46

class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 5 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320377  Cd Length: 310  Bit Score: 167.04  E-value: 6.53e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 214 PLITKNEYEQIHKMIGWGATASLFCNLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQFLpKAREDIVCKKDM 293
Cdd:cd15249    1 PYFSQDERTFATFWIGLWSVLCFISTFTTVATFLIDMER-FRYPERPIIFLSACYLFVSLGYIVRLV-VGHESVACNREH 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 294 TLRRSEPSAEEnlSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASR 373
Cdd:cd15249   79 NHIHYETTGPA--LCTIVFLLIYFFGMASSIWWVILSFTWFLAA-GMKWGNEAIAGYSQYFHLAAWLIPSVKSIAVLALS 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 374 QIDGNSMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFC 453
Cdd:cd15249  156 SVDGDPVAGICYVGNQNLNNLRGFVLAPLVVYLFTGTLFLLAGFVSLFRIRSVIKQ--GGTKTDKLEKLMIRIGIFTVLY 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 454 LTFVIVTFMCHIYEFAHEEDWQKSFRnyifCSILSSKSDPRdcqmeSRPSIAMIQLHLLIIFAAGIVMSSWVWISSTAET 533
Cdd:cd15249  234 TVPATIVVACYVYEQHYRESWEAALN----CSCPGDDTQPR-----ARPDYAVFMLKYFMCLVVGITSGVWIWSGKTLES 304

                 ....
gi 242009018 534 WRRF 537
Cdd:cd15249  305 WRRF 308
7tmF_FZD7 cd15246
class F frizzled subfamily 7, member of 7-transmembrane G protein-coupled receptors; This ...
230-540 1.01e-45

class F frizzled subfamily 7, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 7 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of G-protein coupled receptors. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others


Pssm-ID: 320374  Cd Length: 331  Bit Score: 167.12  E-value: 1.01e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFC---NLFTVVSFLIEWRSGNkYPAVIIFYINICFLLSNLGWLAQFLPKAREDIVCKKDMTLRRSEPSAEENL 306
Cdd:cd15246   14 WVGIWSILCcasTLFTVLTYLVDMRRFS-YPERPIIFLSGCYFMVAVAYAAGFLLEDRVVCVERFSDDGYRTVAQGTKKE 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 307 SCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGICFV 386
Cdd:cd15246   93 GCTILFMVLYFFGMASSIWWVILSLTWFLSA-GMKWGHEAIEANSQYFHLAAWAVPAVKTITILAMGQVDGDLLSGVCYV 171
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 387 RSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLTFVIVTFMCHIY 466
Cdd:cd15246  172 GIYSVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKH--DGTKTEKLEKLMVRIGVFSVLYTVPATIVLACYFY 249
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 242009018 467 EFAHEEDWQKSFRNYIfCSILSSKSDPRDCQMESrPSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWRRFFNR 540
Cdd:cd15246  250 EQAFRETWEKTWLLQT-CKRYAVPCPNNNFAPMS-PDFTVFMIKYLMTMIVGITSGFWIWSGKTLQSWRRFYHR 321
7tmF_FZD4 cd15038
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This ...
230-539 9.84e-45

class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 4 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320166  Cd Length: 304  Bit Score: 163.40  E-value: 9.84e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFC---NLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQfLPKAREDIVCKKDMTLRRSEPSAE--E 304
Cdd:cd15038   14 WMAIWAGLCfisTLFTVLTFLIDSGR-FKYPERPIIFLSMCYNIYSIAYIVR-LLAGRESISCDLDSQTAVSILIQEglE 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 305 NLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGIC 384
Cdd:cd15038   92 NTGCAIVFLLLYFFGMASSIWWVILTLTWFLAA-GLKWGHEAIQMHSSYFHIAAWALPAVKTIVILVMRVVDADELTGLC 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 385 FVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLTFVIVTFMCH 464
Cdd:cd15038  171 YVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQLQR--DGTKTDKLERLMVRIGIFSVLYTVPATCVIACY 248
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 242009018 465 IYEFAHEEDWqksfrnyifcsilssksdpRDCQMESRPSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWRRFFN 539
Cdd:cd15038  249 FYEYSNRDLW-------------------YYGGSAARPNMEVFMLKIFMSLVVGITSGMWIWSAKTLSSWRNFFN 304
7tmF_FZD10 cd15037
class F frizzled subfamily 10, member of 7-transmembrane G protein-coupled receptors; This ...
230-539 1.16e-44

class F frizzled subfamily 10, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 10 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320165  Cd Length: 320  Bit Score: 163.62  E-value: 1.16e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFC---NLFTVVSFLIEwRSGNKYPAVIIFYINICFLLSNLGWLAQFLPKArEDIVCKKDMTLRRSEPSAEENL 306
Cdd:cd15037   14 WIAIWSILCffsSAFTVLTFLID-PQRFKYPERPIIFLSMCYCVYSVGYIIRLFAGA-ESIACDRDSGQLYVIQEGLEST 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 307 SCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGICFV 386
Cdd:cd15037   92 GCTIVFLILYYFGMASSLWWVILTLTWFLAA-GKKWGHEAIEANSSYFHLAAWAIPAVKTIMILVMRRVAGDELTGVCYV 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 387 RSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLTFVIVTFMCHIY 466
Cdd:cd15037  171 GSMDVNALTGFVLIPLACYLIIGTSFILSGFVALFHIRRVMKT--GGENTDKLEKLMVRIGVFSVLYTVPATCVIACYFY 248
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 242009018 467 EFAHEEDWqKSFRNYIFCSiLSSKSDPRDCQMESR-PSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWRRFFN 539
Cdd:cd15037  249 ERLNMDYW-KILATQQKCK-MDNQTKTLDCVMTSSiPAVEIFMVKIFMLLVVGITSGMWIWTSKTLQSWQNVFS 320
7tmF_FZD1_insect cd15248
class F insect frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
230-540 2.12e-44

class F insect frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 1 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of G-protein coupled receptors, found in insects such as Drosophila melanogaster. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320376  Cd Length: 332  Bit Score: 163.45  E-value: 2.12e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFCnLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQFlpKAREDIVCKK---------DMTLRRSEP 300
Cdd:cd15248   18 WAAVCMASC-LFTVLTFLIDSSR-FRYPERPIVFLSVCYLMVAAAYVAGL--GAGDSVSCNEpfpppvklgRLQMVSTIT 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 301 SAEENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSM 380
Cdd:cd15248   94 QGTKTESCTVLFMVLYFFSMAASIWWVVLTLTWFLAA-GLKWGHEAIEAKSHYFHLVAWAVPALKTISILAMGKVEGDVL 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 381 AGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLTFVIVT 460
Cdd:cd15248  173 SGVCYVGLWDMHALRGFVLAPLCVYLSLGTIFLLAGFISLFRIRTVMKH--DGTKTDKLEKLMLRIGIFSFLYTLPALIV 250
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 461 FMCHIYEFAHEEDWQKSFRNYIfCS--ILSSKSDPRDCQMESRPSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWRRFF 538
Cdd:cd15248  251 LACLFYEQAHFDSWMLQWHRDI-CKppSWSIPACRATGSPEARPEFQVFMIKYLMSMIVGITSSVWIWSSKTLVSWRNFY 329

                 ..
gi 242009018 539 NR 540
Cdd:cd15248  330 ER 331
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
230-535 2.20e-44

class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 9 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320164  Cd Length: 320  Bit Score: 162.82  E-value: 2.20e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFC---NLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQFLPKArEDIVCKKDMTLRRSEPSAEENL 306
Cdd:cd15036   14 WMAVWSTLCfvsTAFTVLTFLLDPHR-FQYPERPIIFLSMCYNVYSVAFLIRAVAGA-ESIACDRENGALYIIQEGLEST 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 307 SCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGICFV 386
Cdd:cd15036   92 GCTLVFLILYYFGMASSLWWVVLTLTWFLAA-GKKWGHEAIESHGSYFHMAAWGIPALKTIVILTMRKVAGDELTGLCYV 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 387 RSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLTFVIVTFMCHIY 466
Cdd:cd15036  171 GSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVALFHIRKVMKT--GGTNTEKLEKLMVKIGVFSILYTVPATCVIVCYFY 248
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 467 EFAHEEDWQKSFRNYIfCSILSSKSDPrDCQME-SRPSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWR 535
Cdd:cd15036  249 ERLNMDYWDLRALEES-CRTVPGRRRP-DCSLPhSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTLQTWQ 316
7tmF_FZD1 cd15247
class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
230-550 9.12e-43

class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 1 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of G-protein coupled receptors. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320375  Cd Length: 341  Bit Score: 159.05  E-value: 9.12e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFC---NLFTVVSFLIEWRSGNkYPAVIIFYINICFLLSNLGWLAQFLPKARedIVCKKDMTLR--RSEPSAEE 304
Cdd:cd15247   24 WIGIWSVLCcasTLFTVLTYLVDMKRFS-YPERPIIFLSGCYTMVAIAYIAGFLLEDK--VVCNDKFAEDgiKTVAQGTK 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 305 NLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGIC 384
Cdd:cd15247  101 KEGCTILFMMLYFFSMASSIWWVILSLTWFLAA-GMKWGHEAIEANSQYFHLAAWAVPAIKTITILAVGQVDGDVLSGVC 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 385 FVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLTFVIVTFMCH 464
Cdd:cd15247  180 FVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKH--DGTKTEKLEKLMVRIGIFSVLYTVPATIVIACY 257
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 465 IYEFAHEEDWQKSFRNYifcsilSSKSDPRDCQMESRPSIA----MIQLHLLIIFAAGIVMSSWVWISSTAETWRRFFNR 540
Cdd:cd15247  258 FYEQAFREQWERSWISQ------SCKTYAIPCPAHSHPPMSpdftVFMIKYLMTLIVGITSGFWIWSGKTLNSWRKFYTR 331
                        330
                 ....*....|
gi 242009018 541 KILKKEIEES 550
Cdd:cd15247  332 LTNSKQGETT 341
7tmF_FZD3 cd15033
class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This ...
228-538 1.00e-40

class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 3 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320161  Cd Length: 321  Bit Score: 152.41  E-value: 1.00e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 228 IGWGATASLFCNLFTVVSFLIEwRSGNKYPAVIIFYINICFLLSNLGWLAQFLPKARedIVCKKDMTLRRSEPSAEE--- 304
Cdd:cd15033   15 IGVISIVCLSATLFTFLTFLID-VTRFRYPERPIIFYAVCYMMVSLIFFIGFLLEDR--VACNAASPGQYKASTVTQgsh 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 305 NLSCVVIFVVIYYFLMAACVWFVIFTYAWHLScrGLAKI-QERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGI 383
Cdd:cd15033   92 NKACTMLFMVLYFFTMAGSVWWVILTITWFLA--AVPKWgSEAIEKKALLFHASAWGIPGTLTIILLAMNKIEGDNISGV 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 384 CFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQqiLSDKASAKIREMIVRIGLFSVFCLTFVIVTFMC 463
Cdd:cd15033  170 CFVGLYDVDALRYFVLAPLCLDVVVGVSLLLAGIISLNRVRIEIP--LEKENQDKLVKFMIRIGVFSVLYLVPLLVVIGC 247
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 464 HIYEFAHEEDWQKSF-----RNY-IFCsilssksdPRDCQMESRPSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWRRF 537
Cdd:cd15033  248 YFYEQAYRGVWETTWvqercREYhIPC--------PYKVTQTSRPDLILFLMKYLMALVVGIPSVFWVGSKKTCFEWASF 319

                 .
gi 242009018 538 F 538
Cdd:cd15033  320 F 320
7tmF_FZD2 cd15245
class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This ...
230-540 1.15e-40

class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 2 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of G-protein coupled receptors. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320373  Cd Length: 330  Bit Score: 152.48  E-value: 1.15e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFC---NLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQFLpkAREDIVCKKDMTLR--RSEPSAEE 304
Cdd:cd15245   14 WILIWSVLCcasTFFTVTTYLVDMQR-FRYPERPIIFLSGCYTMVSVAYIAGFV--LGDKVVCNERFSEDgyKTVVQGTK 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 305 NLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGIC 384
Cdd:cd15245   91 KEGCTILFMMLYFFSMASSIWWVILSLTWFLAA-GMKWGHEAIEANSQYFHLAAWAVPAVKTITILAMGQIDGDLLSGVC 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 385 FVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLTFVIVTFMCH 464
Cdd:cd15245  170 FVGLNNIDPLRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKH--DGTKTEKLERLMVRIGVFSVLYTVPATIVIACY 247
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 465 IYEFAHEEDWQKSFRNyifcsiLSSKSDPRDCQMESRPSI----AMIQLHLLIIFAAGIVMSSWVWISSTAETWRRFFNR 540
Cdd:cd15245  248 FYEQAFRQHWERSWIS------QNCKSLAIPCPLQYTPRMtpdfTVYMIKYLMTLIVGITSGFWIWSGKTLHSWRKFYTR 321
7tmF_FZD8 cd15250
class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This ...
230-537 2.50e-39

class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 8 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320378  Cd Length: 314  Bit Score: 148.15  E-value: 2.50e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFC---NLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQfLPKAREDIVCKkdmtlrRSEPSAEENL 306
Cdd:cd15250   14 WIGLWSVLCflsTFATVSTFLIDMER-FKYPERPIIFLSACYLFVSLGYLVR-LIAGHEKVACS------RGALAEVEHI 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 307 S--------CVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGN 378
Cdd:cd15250   86 HyettgpalCTVVFLLIYFFGMASSIWWVILSLTWFLAA-GMKWGNEAIAGYSQYFHLAAWLIPSVKSIAVLALSSVDGD 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 379 SMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLTFVI 458
Cdd:cd15250  165 PVAGICYVGNQNLDNLRGFVLAPLVIYLFIGTMFLLAGFVSLFRIRSVIKQ--GGTKTDKLEKLMIRIGIFTVLYTVPAT 242
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 242009018 459 VTFMCHIYEFAHEEDWQKSFRnyifCSILSSKSDprdcqMESRPSIAMIQLHLLIIFAAGIVMSSWVWISSTAETWRRF 537
Cdd:cd15250  243 IVVACYFYEQHNRQRWEITHN----CNCLRDQPD-----QARRPDYAVFMLKYFMCLVVGITSGVWTWSGKTLESWRAL 312
7tmF_FZD6 cd15032
class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This ...
216-539 1.16e-35

class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 6 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320160  Cd Length: 321  Bit Score: 137.67  E-value: 1.16e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 216 ITKNEYEQIHKMIGwgaTASLFC---NLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQFLPKARedIVC-KK 291
Cdd:cd15032    3 FKSDELDFAKSFIG---IVSIFClcaTLFTFLTFLIDVKR-FRYPERPIIYYSVCYSIVSLMYFIGFLLGNS--TACnKA 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 292 DMTLRRSEPS--AEENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITV 369
Cdd:cd15032   77 DEKLELGDTVvlGSQNKACTVLFMLLYFFTMAGTIWWVILTITWFLAA-GRKWSCEAIEQKALWFHAVAWGIPGFLTIML 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 370 MASRQIDGNSMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLF 449
Cdd:cd15032  156 LAMNKVEGDNISGVCFVGLYDLDASRYFVLLPLCLCVFVGLSLLLAGIISLNHVRQVIQH--DGRNQEKLKKFMIRIGVF 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 450 SVFCLTFVIVTFMCHIYEFAHEEDWQKSFRN------YIFCsilssksdPRDCQMESRPSIAMIQLHLLIIFAAGIVMSS 523
Cdd:cd15032  234 SGLYLVPLVTLLGCYVYEQVYRRTWEITWVSdhcqqyHIPC--------PYQAKAVARPELALFLIKYLMTLIVGISAVF 305
                        330
                 ....*....|....*.
gi 242009018 524 WVWISSTAETWRRFFN 539
Cdd:cd15032  306 WVGSKKTCSEWASFFN 321
7tmF_FZD3_FZD6-like cd15910
class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G ...
218-538 1.29e-35

class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G protein-coupled receptors; This group includes subfamilies 3 and 6 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320576  Cd Length: 321  Bit Score: 137.68  E-value: 1.29e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 218 KNEYEQIHKMIGWGATASLFCNLFTVVSFLIEWRSgNKYPAVIIFYINICFLLSNLGWLAQFLpkAREDIVCKK-DMTLR 296
Cdd:cd15910    5 DDELMFARYFIGVVSILCLLATLFTFLTFLIDVNR-FRYPERPIIFYAVCYFVVSLIFFVGFL--LGDDVACNHaIMDEN 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 297 RSEPSAE--ENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCrGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQ 374
Cdd:cd15910   82 NGATVVEgsRNKACTILFMILYFFTMAGTVWWVILTITWFLAA-GFKWGSEAIEKKALYFHALAWGIPGVLTMVLLATNK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 375 IDGNSMAGICFVRSSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQqiLSDKASAKIREMIVRIGLFSVFCL 454
Cdd:cd15910  161 IEGDNISGVCFVGLYDSDGLRFFVLLPLCLYVLVGMSLLLAGIICLNRVRKSIH--DDETNQEKLAKFMIRIGVFSILYL 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 455 TFVIVTFMCHIYEFAHEEDWQKSF------RNYIFCsilssksdPRDCQMESRPSIAMIQLHLLIIFAAGIVMSSWVWIS 528
Cdd:cd15910  239 VPLLTLIGCYAYEQSNRKSWESTWvvrncrRYHIPC--------PQLAQGNPRPGLFLFCIKYLMTLIVGIPPVFWVGSK 310
                        330
                 ....*....|
gi 242009018 529 STAETWRRFF 538
Cdd:cd15910  311 KTCAEWAGFF 320
7tmF_FZD3_insect cd15031
class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; ...
230-536 1.34e-21

class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This group represents subfamily 3 of the frizzled (FZD) family of seven transmembrane-spanning G protein-coupled proteins that is found in insects such as Drosophila melanogaster. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320159  Cd Length: 311  Bit Score: 96.38  E-value: 1.34e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 230 WGATASLFC---NLFTVVSFLIEwRSGNKYPAVIIFYINICFLLSNL-----GWLAQFLP-KAREDIVCKKDMTLRrseP 300
Cdd:cd15031   14 WMLVLSAVSfilTLFALVTFWAE-PTRFGYPERPVLFMALCYNLISLcylerGILGTFTNcSARSLAIDCDDRYLR---Q 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 301 SAEENLSCVVIFVVIYYFLMAACVWFVIFTYAWHLSCRgLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSM 380
Cdd:cd15031   90 DCLLTPQCLASFIITYYLSLSAASWWLIFALCWYLSSA-KKWSSEALEKKSGLFHVLAWVPPLAPPIAALLLERVSASEL 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 381 AGIC----FVRSSywgarvvFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQILsdkASAKiREMIVRIGLFSVFCLTF 456
Cdd:cd15031  169 TGTCtasgFVESS-------ISELPALILLLLGLYLTIAALRSLLSLQQQLQSRL---AHAP-QRILARVSIFSLLYLIP 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 457 VIVTFMCHIYEFAHEEDwQKSFRNYIFCSILSSKSDPrdcqMESRPSIAMIQLHLLiifaAGIVMSSWVWISSTAETWRR 536
Cdd:cd15031  238 AAAALICKLCERWLQPV-PECNALQEDCAPPATDNEF----LSALPALLRVFFFLI----GGTATGLWLWSRKSCESWRS 308
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
234-461 7.41e-15

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


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 75.54  E-value: 7.41e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 234 ASLFCNLFTVVSFLIEWRSGnKYPAVIIFYINICFLLSNLGWLAQFlpkaredivckkdMTLRRSEPSAEENLSCVVIFV 313
Cdd:cd14964   11 LGLLGNLLVLLSLVRLRKRP-RSTRLLLASLAACDLLASLVVLVLF-------------FLLGLTEASSRPQALCYLIYL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 314 VIYYFLMAACVWFVIFTYAWHLSCRGLAKIQE-RIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGI--CFVRSSY 390
Cdd:cd14964   77 LWYGANLASIWTTLVLTYHRYFALCGPLKYTRlSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRYNTLTgsCYLICTT 156
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 242009018 391 WGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQILSDKASAKIRE---MIVRIGLFSVFCLTFVIVTF 461
Cdd:cd14964  157 IYLTWGFLLVSFLLPLVAFLVIFSRIVLRLRRRVRAIRSAASLNTDKNLKAtksLLILVITFLLCWLPFSIVFI 230
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
235-489 1.38e-10

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  Cd Length: 253  Bit Score: 62.59  E-value: 1.38e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 235 SLFCNLFTVVSFLIEWRSGNKYPAVIIFYINICFLLSNLGWLAqflpkaredivckkdmtlrrSEPSAEENLSCVVIFVV 314
Cdd:cd15040   15 SLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFLF--------------------GINSTDNPVLCTAVAAL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 315 IYYFLMAACVWFviFTYAWHLSCRGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAGICFVRSS---YW 391
Cdd:cd15040   75 LHYFLLASFMWM--LVEALLLYLRLVKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYCWLSNGnglYY 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 392 GarvvfLLVPIAVTILMGGYYLVRglsFLFNVKKDSQQILSDKASAKIREMIVRIGLFSVFCLT--FVIVTFMchiyefa 469
Cdd:cd15040  153 A-----FLGPVLLIILVNLVIFVL---VLRKLLRLSAKRNKKKRKKTKAQLRAAVSLFFLLGLTwiFGILAIF------- 217
                        250       260
                 ....*....|....*....|
gi 242009018 470 heeDWQKSFrNYIFCsILSS 489
Cdd:cd15040  218 ---GARVVF-QYLFA-IFNS 232
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
235-462 6.00e-10

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  Cd Length: 260  Bit Score: 60.69  E-value: 6.00e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 235 SLFCNLFTVVSFLI--EWRsgnKYPAVIIFYINICFLLSNLGWLaqflpkaredivckkdmtLRRSEPSAEENLSCVVIF 312
Cdd:cd13952   15 SLVGLLLTIITYLLfpKLR---NLRGKILINLCLSLLLAQLLFL------------------IGQLLTSSDRPVLCKALA 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 313 VVIYYFLMAACVW-FVIftyAWHLSCRGLAKIQERIDKKGAYFHLVAWSLPVVLTITVMASRQIDGNSMAG----ICFVr 387
Cdd:cd13952   74 ILLHYFLLASFFWmLVE---AFDLYRTFVKVFGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSPGyggeYCWL- 149
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 242009018 388 sSYWGARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQilSDKASAKIREMIVRIGLFSVFCLT--FVIVTFM 462
Cdd:cd13952  150 -SNGNALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETPK--QSERKSDRKQLRAYLKLFPLMGLTwiFGILAPF 223
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
91-163 2.92e-07

Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell along the anteroposterior axis. Homologues of the N-terminal region of frizzled exist either as transmembrane or secreted molecules. Frizzled homologues are reported to be receptors for the Wnt growth factors. (Not yet in MEDLINE: the FRI domain occurs in several receptor tyrosine kinases [Xu, Y.K. and Nusse, Curr. Biol. 8 R405-R406 (1998); Masiakowski, P. and Yanopoulos, G.D., Curr. Biol. 8, R407 (1998)].


Pssm-ID: 214498  Cd Length: 113  Bit Score: 49.62  E-value: 2.92e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 242009018    91 HNLQQELNKWEILRKVPkCWQTLQPFLCALYLPKCEYD-TVYLLSQERCKYTMSTCkilkEPLFAA-TFP---SINCD 163
Cdd:smart00063  29 EEAGLELEQFHPLLNVQ-CSPDLRFFLCSVYAPICTEDlRPILPCRSLCEAAREGC----EPLMEKfGFPwpeFLRCD 101
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
308-463 2.39e-06

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  Cd Length: 270  Bit Score: 49.92  E-value: 2.39e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 308 CVVIFVVIYYFLMAACVWFVIFTYAWHLSCRGLAKIQERID--KKGAYFHLVAWSLPVVLTITVMASRQIDGNS--MAGI 383
Cdd:cd15039   68 CVALGILLHFFFLAAFFWLNVMSFDIWRTFRGKRSSSSRSKerKRFLRYSLYAWGVPLLLVAVTIIVDFSPNTDslRPGY 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 384 ----CFVRSSYwgARVVFLLVPIAVTILMGGYYLVRGLSFLFNVKKDSQQILSDKASAKIReMIVRIGLFSVFCLTFV-- 457
Cdd:cd15039  148 gegsCWISNPW--ALLLYFYGPVALLLLFNIILFILTAIRIRKVKKETAKVQSRLRSDKQR-FRLYLKLFVIMGVTWIle 224

                 ....*.
gi 242009018 458 IVTFMC 463
Cdd:cd15039  225 IISWFV 230
CRD_FZ3 cd07449
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich ...
108-186 4.00e-06

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 3 (Fz3) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz3 plays a vital role in the anterior-posterior guidance of commissural axons. Knockout mice without Fz3 show defects in fiber tracts in the rostral CNS.


Pssm-ID: 143558  Cd Length: 127  Bit Score: 46.93  E-value: 4.00e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018 108 KCWQTLQPFLCALYLPKC-EYDTVYLLSQERCKYTMSTCKILKEpLFAATFP-SINC----DATEFFPRtckndVKDLrs 181
Cdd:cd07449   49 ECSRDFRPFLCALYAPVCmEYGRVTLPCRRLCQRAYSECSKLME-MFGVPWPeDMECsrfpDCDEPYPR-----LVDL-- 120

                 ....*
gi 242009018 182 NLSGE 186
Cdd:cd07449  121 SLSGE 125
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
94-169 6.71e-05

Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups. The domain contains 10 conserved cysteines.


Pssm-ID: 396115  Cd Length: 107  Bit Score: 42.86  E-value: 6.71e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018   94 QQELNKWEILRKVpKCWQTLQPFLCALYLPKC----EYDTVYLLSQERCKYTMSTC-KILKEplFAATFPSI-NCDAtef 167
Cdd:pfam01392  32 ALELEQFEPLVNL-GCHPDLRLFLCSLYFPPCtpsgEGGKPIPPCRSLCEAVRDGCePELLK--FGFSWPEFlDCSK--- 105

                  ..
gi 242009018  168 FP 169
Cdd:pfam01392 106 FP 107
CRD_FZ cd07066
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
91-191 4.12e-04

CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential component of a number of cell surface receptors, which are involved in multiple signal transduction pathways, particularly in modulating the activity of the Wnt proteins, which play a fundamental role in the early development of metazoans. CRD is also found in secreted frizzled related proteins (SFRPs), which lack the transmembrane segment found in the frizzled protein. The CRD domain is also present in the alpha-1 chain of mouse type XVIII collagen, in carboxypeptidase Z, several receptor tyrosine kinases, and the mosaic transmembrane serine protease corin. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. CRD domains have also been identified in multiple tandem copies in a Dictyostelium discoideum protein. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143549  Cd Length: 119  Bit Score: 40.95  E-value: 4.12e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 242009018  91 HNLQQELNKWEILRKVpKCWQTLQPFLCALYLPKCEYDT--VYLLSQERCKYTMSTCKILKEPLFAATFPSINCDAtefF 168
Cdd:cd07066   30 EEAEQELESFTPLVNS-GCHPDLRFFLCSLYFPECTPDGdrPIPPCRSLCEEVRDSCEPLMLAFGFPWPEPLDCDR---F 105
                         90       100
                 ....*....|....*....|...
gi 242009018 169 PrtckndvkdlRSNLSGECISPL 191
Cdd:cd07066  106 P----------DSNEEGLCISPP 118
PMT_4TMC pfam16192
C-terminal four TMM region of protein-O-mannosyltransferase; PMT_4TMC is the C-terminal four ...
223-281 1.77e-03

C-terminal four TMM region of protein-O-mannosyltransferase; PMT_4TMC is the C-terminal four membrane-pass region of protein-O-mannosyltransferases and similar enzymes.


Pssm-ID: 406576  Cd Length: 198  Bit Score: 40.22  E-value: 1.77e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 242009018  223 QIHkMIG-----WGATASLFCNLFTVVSFLIEWRSG----NKYPAVIIFYINICFLLsnLGWLAQFLP 281
Cdd:pfam16192  48 QIY-LLGnpviwWSSTAAILVFVLLLLAYLLRWQRGyydlSDDDTRSRFYYSGGFLL--LGWALHYLP 112
DUF755 pfam05501
Domain of unknown function (DUF755); This family is predominated by ORFs from Circoviridae. ...
669-712 2.03e-03

Domain of unknown function (DUF755); This family is predominated by ORFs from Circoviridae. The function of this family remains to be determined.


Pssm-ID: 368473  Cd Length: 122  Bit Score: 38.95  E-value: 2.03e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 242009018  669 THKTKNHRRRSVRSRGKRRRKDFSRSKKNSSSWTRRGSSTSQES 712
Cdd:pfam05501  77 THKKKRKKSRHVSSRSAKKISAKKRRRSSSSSSSSSSSSSSSSE 120
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.19
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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