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Conserved domains on  [gi|45551429|ref|NP_727170|]
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frizzled 4, isoform B [Drosophila melanogaster]

Protein Classification

frizzled family protein; olfactory receptor subfamily 6B-like( domain architecture ID 11575542)

frizzled family protein similar to the ten frizzleds (Fzd1-10) and smoothened (Smo), which are involved in transmitting the signals of Wnts and hedgehog proteins and are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors; contains an N-terminal extracellular cysteine-rich domain (CRD) associated with their role in binding to Wnt ligands| olfactory receptor subfamily 6B-like such as human olfactory receptor 6B, 6A, 6Y, 6P, and related proteins in other mammals, sauropsids, and amphibians; belong to the class A rhodopsin-like family of seven-transmembrane G protein-coupled receptors (7TM GPCRs)

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
222-557 3.01e-107

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: 328.51  E-value: 3.01e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 222 ILFTPAEKHLAEIWVSTWAYAALGLALVATVCLLASDGSRLasaKWSRLLSPLIWCHNMVTLGWAVRFMVGRTGTACGTD 301
Cdd:cd13951   1 GLFTSSEKKFAEIWISAWSALCFLLTLFTLLTFLIDPSRFR---YPERPIIFLALCYNFYSLGYLVRLVVGREGIACGKD 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 302 PQAPneSLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRDIRRHSPDskghvvipsnfggspakrnsaktaQQ 381
Cdd:cd13951  78 EGKP--YLLLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSS------------------------EA 131
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 382 DLTQNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRTKEI 461
Cdd:cd13951 132 IEKKSSYFHLVAWGLPAVLTIAVLVLRKVDGDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSI 211
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 462 LRNSNALSVqqqlqqLSAHSSSGIGIFLFIYGLACAMLLLAVIYEFANIDVWLGSGD------------TNTPLWPFLLR 529
Cdd:cd13951 212 LSNDGKKTD------KLEKLMLRIGIFAVLYTLPALIVIACYFYEYANRPDWLRSWEphsccspdceilSRPSLAVFLLK 285
                       330       340
                ....*....|....*....|....*...
gi 45551429 530 AFMELMLGICCFAWVLGPSISTLYKRQV 557
Cdd:cd13951 286 YFMQLVIGITTGVWVWSKKTLLSWRRLL 313
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
43-169 1.27e-83

Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 4 (Fz4) 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 the 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. Frizzled 4 (Fz4) activates the Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C of the Wnt/Ca(2+) signaling pathway during retinal angiogenesis. Mutations in Fz4 lead to familial exudative vitreoretinopathy (FEVR), a hereditary ocular disorder characterized by failure of the peripheral retinal vascularization. In addition, the interplay between Fz4 and norrin as a receptor-ligand pair plays an important role in vascular development in the retina and inner ear in a Wnt-independent manner.


:

Pssm-ID: 143557  Cd Length: 126  Bit Score: 260.09  E-value: 1.27e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  43 FRQCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVhAIGPCRSL 122
Cdd:cd07448   1 DRRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPV-PIGPCRPL 79
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 45551429 123 CESVRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCMEGPGELHQ 169
Cdd:cd07448  80 CLSVKKRCLPVLKEFGFPWPEALNCSKFPPQNNHNHMCMEGPGDEEV 126
 
Name Accession Description Interval E-value
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
222-557 3.01e-107

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: 328.51  E-value: 3.01e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 222 ILFTPAEKHLAEIWVSTWAYAALGLALVATVCLLASDGSRLasaKWSRLLSPLIWCHNMVTLGWAVRFMVGRTGTACGTD 301
Cdd:cd13951   1 GLFTSSEKKFAEIWISAWSALCFLLTLFTLLTFLIDPSRFR---YPERPIIFLALCYNFYSLGYLVRLVVGREGIACGKD 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 302 PQAPneSLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRDIRRHSPDskghvvipsnfggspakrnsaktaQQ 381
Cdd:cd13951  78 EGKP--YLLLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSS------------------------EA 131
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 382 DLTQNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRTKEI 461
Cdd:cd13951 132 IEKKSSYFHLVAWGLPAVLTIAVLVLRKVDGDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSI 211
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 462 LRNSNALSVqqqlqqLSAHSSSGIGIFLFIYGLACAMLLLAVIYEFANIDVWLGSGD------------TNTPLWPFLLR 529
Cdd:cd13951 212 LSNDGKKTD------KLEKLMLRIGIFAVLYTLPALIVIACYFYEYANRPDWLRSWEphsccspdceilSRPSLAVFLLK 285
                       330       340
                ....*....|....*....|....*...
gi 45551429 530 AFMELMLGICCFAWVLGPSISTLYKRQV 557
Cdd:cd13951 286 YFMQLVIGITTGVWVWSKKTLLSWRRLL 313
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
43-169 1.27e-83

Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 4 (Fz4) 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 the 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. Frizzled 4 (Fz4) activates the Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C of the Wnt/Ca(2+) signaling pathway during retinal angiogenesis. Mutations in Fz4 lead to familial exudative vitreoretinopathy (FEVR), a hereditary ocular disorder characterized by failure of the peripheral retinal vascularization. In addition, the interplay between Fz4 and norrin as a receptor-ligand pair plays an important role in vascular development in the retina and inner ear in a Wnt-independent manner.


Pssm-ID: 143557  Cd Length: 126  Bit Score: 260.09  E-value: 1.27e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  43 FRQCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVhAIGPCRSL 122
Cdd:cd07448   1 DRRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPV-PIGPCRPL 79
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 45551429 123 CESVRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCMEGPGELHQ 169
Cdd:cd07448  80 CLSVKKRCLPVLKEFGFPWPEALNCSKFPPQNNHNHMCMEGPGDEEV 126
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
223-544 2.98e-44

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: 460242  Cd Length: 321  Bit Score: 161.62  E-value: 2.98e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429   223 LFTPAEKHLAEIWVSTWAYAALGLALVaTVCLLASDgsrlasakWSRLLSP---LIW---CHNMVTLGWAVRFMVGRTGT 296
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLF-TVLTFLID--------WSRFRYPerpIIFlslCYLLVSLGYLIRFVLGREDI 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429   297 ACGTDPqAPNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHrdirrHSPDSK-GHVVIpsnfggspakrns 375
Cdd:pfam01534  72 ACRKDG-TGRGSYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWF-----LAAGLKwGSEAI------------- 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429   376 AKTAQqdltqnnFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVH 455
Cdd:pfam01534 133 EKKSS-------YFHLAAWGIPAVLTITVLALGKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSL 205
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429   456 CRTKEILRNSnalsvqqqlqqlSAHSSSG-------IGIFLFIYGLACAMLLLAVIYEFANIDVWLGS------------ 516
Cdd:pfam01534 206 FRIRRVLKKD------------GARATDKleklmvrIGVFSVLYTVPALIVIACYFYEYANRDSWELSwqyincraygip 273
                         330       340       350
                  ....*....|....*....|....*....|..
gi 45551429   517 --GDTNTP--LWPFLLRAFMELMLGICCFAWV 544
Cdd:pfam01534 274 clDEPESRpsFSVFMLKYFMSLVVGITSGFWV 305
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
46-163 1.34e-43

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: 152.46  E-value: 1.34e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429     46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKapVHAIGPCRSLCES 125
Cdd:smart00063   1 CEPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTED--LRPILPCRSLCEA 78
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 45551429    126 VRIRCHPVLQGFGFPWPPALDCDKFPRennHETMCMEG 163
Cdd:smart00063  79 AREGCEPLMEKFGFPWPEFLRCDRFPV---QEELCMDP 113
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
46-151 1.96e-34

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: 460190  Cd Length: 116  Bit Score: 126.91  E-value: 1.96e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429    46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYT-----LQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVHAIG-PC 119
Cdd:pfam01392   1 CEPITLPMCLGLGYNATVFPNLLGHQTQEEAELSlaylvLSEFEPLVDLSCSPSLRLFLCSLYFPPCTLGPSPKPVCpPC 80
                          90       100       110
                  ....*....|....*....|....*....|....
gi 45551429   120 RSLCESVRIRCHPVLQG--FGFPWPPALDCDKFP 151
Cdd:pfam01392  81 RSLCEEVRYGCEPLLEEakFGFSWPEFLDCDSLP 114
 
Name Accession Description Interval E-value
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
222-557 3.01e-107

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: 328.51  E-value: 3.01e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 222 ILFTPAEKHLAEIWVSTWAYAALGLALVATVCLLASDGSRLasaKWSRLLSPLIWCHNMVTLGWAVRFMVGRTGTACGTD 301
Cdd:cd13951   1 GLFTSSEKKFAEIWISAWSALCFLLTLFTLLTFLIDPSRFR---YPERPIIFLALCYNFYSLGYLVRLVVGREGIACGKD 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 302 PQAPneSLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRDIRRHSPDskghvvipsnfggspakrnsaktaQQ 381
Cdd:cd13951  78 EGKP--YLLLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSS------------------------EA 131
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 382 DLTQNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRTKEI 461
Cdd:cd13951 132 IEKKSSYFHLVAWGLPAVLTIAVLVLRKVDGDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSI 211
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 462 LRNSNALSVqqqlqqLSAHSSSGIGIFLFIYGLACAMLLLAVIYEFANIDVWLGSGD------------TNTPLWPFLLR 529
Cdd:cd13951 212 LSNDGKKTD------KLEKLMLRIGIFAVLYTLPALIVIACYFYEYANRPDWLRSWEphsccspdceilSRPSLAVFLLK 285
                       330       340
                ....*....|....*....|....*...
gi 45551429 530 AFMELMLGICCFAWVLGPSISTLYKRQV 557
Cdd:cd13951 286 YFMQLVIGITTGVWVWSKKTLLSWRRLL 313
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
43-169 1.27e-83

Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 4 (Fz4) 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 the 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. Frizzled 4 (Fz4) activates the Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C of the Wnt/Ca(2+) signaling pathway during retinal angiogenesis. Mutations in Fz4 lead to familial exudative vitreoretinopathy (FEVR), a hereditary ocular disorder characterized by failure of the peripheral retinal vascularization. In addition, the interplay between Fz4 and norrin as a receptor-ligand pair plays an important role in vascular development in the retina and inner ear in a Wnt-independent manner.


Pssm-ID: 143557  Cd Length: 126  Bit Score: 260.09  E-value: 1.27e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  43 FRQCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVhAIGPCRSL 122
Cdd:cd07448   1 DRRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPV-PIGPCRPL 79
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 45551429 123 CESVRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCMEGPGELHQ 169
Cdd:cd07448  80 CLSVKKRCLPVLKEFGFPWPEALNCSKFPPQNNHNHMCMEGPGDEEV 126
7tmF_FZD4 cd15038
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This ...
222-544 1.56e-48

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: 173.03  E-value: 1.56e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 222 ILFTPAEKHLAEIWVSTWAyaalGLALVAT---VCLLASDGSRLASAKwsrllSPLIW---CHNMVTLGWAVRFMVGRTG 295
Cdd:cd15038   1 GLFTQSDKEFADIWMAIWA----GLCFISTlftVLTFLIDSGRFKYPE-----RPIIFlsmCYNIYSIAYIVRLLAGRES 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 296 TACGTDPQApNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGW---------HRDIRRHSpdSKGHvvipsnf 366
Cdd:cd15038  72 ISCDLDSQT-AVSILIQEGLENTGCAIVFLLLYFFGMASSIWWVILTLTWflaaglkwgHEAIQMHS--SYFH------- 141
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 367 ggspakrnsaktaqqdltqnnfvcFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSM 446
Cdd:cd15038 142 ------------------------IAAWALPAVKTIVILVMRVVDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTL 197
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 447 NLISGYLVHCRTKEILRNSNALSVQQQLQQLSahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWLGSGDTNTP-LWP 525
Cdd:cd15038 198 FLIAGFVALFRIRSQLQRDGTKTDKLERLMVR------IGIFSVLYTVPATCVIACYFYEYSNRDLWYYGGSAARPnMEV 271
                       330
                ....*....|....*....
gi 45551429 526 FLLRAFMELMLGICCFAWV 544
Cdd:cd15038 272 FMLKIFMSLVVGITSGMWI 290
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
223-544 2.98e-44

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: 460242  Cd Length: 321  Bit Score: 161.62  E-value: 2.98e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429   223 LFTPAEKHLAEIWVSTWAYAALGLALVaTVCLLASDgsrlasakWSRLLSP---LIW---CHNMVTLGWAVRFMVGRTGT 296
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLF-TVLTFLID--------WSRFRYPerpIIFlslCYLLVSLGYLIRFVLGREDI 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429   297 ACGTDPqAPNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHrdirrHSPDSK-GHVVIpsnfggspakrns 375
Cdd:pfam01534  72 ACRKDG-TGRGSYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWF-----LAAGLKwGSEAI------------- 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429   376 AKTAQqdltqnnFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVH 455
Cdd:pfam01534 133 EKKSS-------YFHLAAWGIPAVLTITVLALGKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSL 205
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429   456 CRTKEILRNSnalsvqqqlqqlSAHSSSG-------IGIFLFIYGLACAMLLLAVIYEFANIDVWLGS------------ 516
Cdd:pfam01534 206 FRIRRVLKKD------------GARATDKleklmvrIGVFSVLYTVPALIVIACYFYEYANRDSWELSwqyincraygip 273
                         330       340       350
                  ....*....|....*....|....*....|..
gi 45551429   517 --GDTNTP--LWPFLLRAFMELMLGICCFAWV 544
Cdd:pfam01534 274 clDEPESRpsFSVFMLKYFMSLVVGITSGFWV 305
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
46-163 1.34e-43

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: 152.46  E-value: 1.34e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429     46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKapVHAIGPCRSLCES 125
Cdd:smart00063   1 CEPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTED--LRPILPCRSLCEA 78
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 45551429    126 VRIRCHPVLQGFGFPWPPALDCDKFPRennHETMCMEG 163
Cdd:smart00063  79 AREGCEPLMEKFGFPWPEFLRCDRFPV---QEELCMDP 113
CRD_FZ9_like cd07457
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich ...
46-164 1.94e-43

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 9 (Fz9) and frizzled 10 (Fz10) receptors, and similar proteins. This domain 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. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143566  Cd Length: 121  Bit Score: 152.26  E-value: 1.94e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVhAIGPCRSLCES 125
Cdd:cd07457   3 CERITIPMCQGIGYNMTRMPNLLGHESQSEAAISIHEFAPLVQYGCAEHLRFFLCSLYAPMCTEQVSI-PIPACRSMCEQ 81
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCMEGP 164
Cdd:cd07457  82 ARDKCSPIMEQFSFSWPDSLDCDRLPRKNDPKDLCMEAP 120
CRD_FZ10 cd07462
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 10 (Fz10) receptor; The cysteine-rich ...
45-164 2.14e-40

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 10 (Fz10) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 10 (Fz10) 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. The cellular functon of Fz10 is unknown.


Pssm-ID: 143571  Cd Length: 127  Bit Score: 144.01  E-value: 2.14e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVhAIGPCRSLCE 124
Cdd:cd07462   4 RCQPIEIPMCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQVST-PIPACRVMCE 82
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 45551429 125 SVRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCMEGP 164
Cdd:cd07462  83 QARLKCSPIMEQFNFKWPDSLDCSKLPNKNDPNYLCMEAP 122
CRD_FZ9 cd07463
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich ...
45-164 1.56e-39

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 9 (Fz9) 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. Fz9 may play a signaling role in lymphoid development and maturation, particularly at points where B cells undergo self-renewal prior to further differentiation.


Pssm-ID: 143572  Cd Length: 127  Bit Score: 141.70  E-value: 1.56e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVhAIGPCRSLCE 124
Cdd:cd07463   4 KCQPVVIPMCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMCTDQVST-SIPACRPMCE 82
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 45551429 125 SVRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCMEGP 164
Cdd:cd07463  83 QARQKCSPIMEQFNFGWPESLDCSRLPTRNDPNALCMEAP 122
7tmF_FZD4_9_10-like cd15909
class F frizzled subfamilies 4, 9, 10, and related proteins; member of 7-transmembrane G ...
222-547 6.39e-39

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: 146.68  E-value: 6.39e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 222 ILFTPAEKHLAEIWVSTWAYAALGLALVaTVCLLASDGSRLASAKwsrllSPLIW---CHNMVTLGWAVRFMVGRTGTAC 298
Cdd:cd15909   1 VMFSRSDKNFAEIWMAVWASLCFASTAF-TVLTFLIDTSRFRYPE-----RPIIFlsmCYFIYSLGYLIRLFLGRERIAC 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 299 GTDPQApnESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRDIRRHSpdskGHVVIPSNfggspakrnsakt 378
Cdd:cd15909  75 DSLNSG--VSYLIQEGLESTWCTIVFLLLYYFGMASALWWVILTFTWYLAAGRKW----GPEAIEAA------------- 135
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 379 aqqdltqNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRT 458
Cdd:cd15909 136 -------SSYFHLVAWALPAVKTIVILIMHKVDADELTGLCYVGNHDSDALLGFVLVPLAIYLLIGTLFILAGFVSMFRI 208
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 459 KEILRNSNA-------LSVQqqlqqlsahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWL--------------GSG 517
Cdd:cd15909 209 RRNLKTRGTdtsklekLMVK-------------IGVFSVLYTVPATCVIACYFYEYLNMDQWRiaaieckcqspnaiGSD 275
                       330       340       350
                ....*....|....*....|....*....|....
gi 45551429 518 DTNTPLWP----FLLRAFMELMLGICCFAWVLGP 547
Cdd:cd15909 276 CCLQPSIPsveiYMLKIFMSLVVGITSGMWVWSS 309
CRD_FZ cd07066
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
45-165 2.72e-37

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: 135.33  E-value: 2.72e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKaPVHAIGPCRSLCE 124
Cdd:cd07066   1 KCEPIPLPLCRGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNSGCHPDLRFFLCSLYFPECTPD-GDRPIPPCRSLCE 79
                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 45551429 125 SVRIRCHPVLQGFGFPWPPALDCDKFPrENNHETMCMEGPG 165
Cdd:cd07066  80 EVRDSCEPLMLAFGFPWPEPLDCDRFP-DSNEEGLCISPPG 119
CRD_FZ1_like cd07458
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 1; The cysteine-rich ...
44-162 3.47e-37

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 1; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 1 (Fz1), frizzled 2 (Fz2), and frizzled 7 (Fz7) receptors, and similar proteins. This domain 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. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143567  Cd Length: 119  Bit Score: 134.85  E-value: 3.47e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  44 RQCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKApvHAIGPCRSLC 123
Cdd:cd07458   1 GKCEPITIPLCTDIPYNMTIFPNLLGHTKQEDAGLEVHQFYPLVKVQCSPDLKFFLCSVYAPVCTVLE--RPIPPCRSLC 78
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 45551429 124 ESVRIRCHPVLQGFGFPWPPALDCDKFPrENNHETMCME 162
Cdd:cd07458  79 ESARQGCEALMNKFGFQWPESLDCEKFP-VHGAGDLCVG 116
CRD_FZ5_like cd07456
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich ...
46-165 4.25e-35

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 5 (Fz5) and frizzled 8 (Fz8) receptors, and similar proteins. This domain 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. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143565  Cd Length: 120  Bit Score: 129.06  E-value: 4.25e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPvHAIGPCRSLCES 125
Cdd:cd07456   2 CEEITIPMCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEDYD-KPLPPCRSVCER 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCMEGPG 165
Cdd:cd07456  81 ARDGCAPIMRQYGFAWPERMSCDALPEGGDPDNLCMDRNN 120
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
46-151 1.96e-34

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: 460190  Cd Length: 116  Bit Score: 126.91  E-value: 1.96e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429    46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYT-----LQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVHAIG-PC 119
Cdd:pfam01392   1 CEPITLPMCLGLGYNATVFPNLLGHQTQEEAELSlaylvLSEFEPLVDLSCSPSLRLFLCSLYFPPCTLGPSPKPVCpPC 80
                          90       100       110
                  ....*....|....*....|....*....|....
gi 45551429   120 RSLCESVRIRCHPVLQG--FGFPWPPALDCDKFP 151
Cdd:pfam01392  81 RSLCEEVRYGCEPLLEEakFGFSWPEFLDCDSLP 114
CRD_FZ8 cd07461
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich ...
44-162 2.69e-34

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 8 (Fz8) 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. Xenopus Fz8 is important in Wnt/beta-catenin signaling pathways controlling the transcriptional activation of target genes Siamois and Xnr3 in the animal caps of late blastula.


Pssm-ID: 143570  Cd Length: 125  Bit Score: 127.02  E-value: 2.69e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  44 RQCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTP--KAPvhaIGPCRS 121
Cdd:cd07461   3 LQCQEITVPLCKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEdyKKP---LPPCRS 79
                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 45551429 122 LCESVRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCME 162
Cdd:cd07461  80 VCERAKAGCAPLMRQYGFPWPDRMRCDLLPEQGNPDTLCMD 120
CRD_FZ5 cd07460
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 5 (Fz5) receptor.proteins; The ...
46-162 4.63e-33

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 5 (Fz5) receptor.proteins; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 5 (Fz5) 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. Fz5 plays critical regulating roles in the yolk sac and placental angiogenesis, in the maturation of the Paneth cell phenotype, in governing the neural potential of progenitors in the developing retina, and in neuronal survival in the parafascicular nucleus.


Pssm-ID: 143569 [Multi-domain]  Cd Length: 127  Bit Score: 123.59  E-value: 4.63e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPvHAIGPCRSLCES 125
Cdd:cd07460   5 CQEITVPMCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLPDYR-KPLPPCRSVCER 83
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCME 162
Cdd:cd07460  84 AKAGCSPLMRQYGFAWPERMNCDRLPVLGDPETLCMD 120
7tmF_FZD5_FZD8-like cd15035
class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G ...
224-545 4.13e-31

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: 123.93  E-value: 4.13e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 224 FTPAEKHLAEIWVSTWAyaalGLALVATVCLLAS---DGSRLASAKwsrllSPLIW---CHNMVTLGWAVRFMVGRTGTA 297
Cdd:cd15035   3 FSEDEKTFATFWIGLWS----ILCFISTLITVLTfliDMQRFQYPE-----RPIIFlsfCYFMVSVGYIIRLIVGHEAVA 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 298 CGTDpqapnesLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWhrdirrhspdskghvvipsnFGGSPAKRNS-- 375
Cdd:cd15035  74 CDGG-------IIRYATTGPALCTVVFLLTYFFGMASSIWWVILSLTW--------------------FLAAGLKWGNea 126
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 376 -AKTAQqdltqnnFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLV 454
Cdd:cd15035 127 iSSYSQ-------YFHLVAWLIPAVQTIAILALSAVDGDPISGICYVGNQNLNNLRGFVLAPLVVYLILGTSFLLAGFVS 199
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 455 HCRTKEILRNSNAlsvqqqlqqLSAHSS----SGIGIFLFIYGLACAMLLLAVIYEFANIDVWL--------GSGDTNTP 522
Cdd:cd15035 200 LFRIRNVIKQQGG---------DKTDKLeklmIRIGIFSVLYTVPATIVIACYFYEQHYREIWEkslncpcsPGSIKSRP 270
                       330       340
                ....*....|....*....|....
gi 45551429 523 LWP-FLLRAFMELMLGICCFAWVL 545
Cdd:cd15035 271 EYSiFMLKYFMSLVVGITSGFWIW 294
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
222-544 1.83e-28

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: 116.60  E-value: 1.83e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 222 ILFTPAEKHLAEIWVSTWAyaalGLALVAT---VCLLASDGSRLASAKwsrllSPLIW---CHNMVTLGWAVRFMVGRTG 295
Cdd:cd15036   1 VYWSRGDKDFALVWMAVWS----TLCFVSTaftVLTFLLDPHRFQYPE-----RPIIFlsmCYNVYSVAFLIRAVAGAES 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 296 TACGTDPQAPnesLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRDIRRhspdSKGHVVIPSNfggspakrns 375
Cdd:cd15036  72 IACDRENGAL---YIIQEGLESTGCTLVFLILYYFGMASSLWWVVLTLTWFLAAGK----KWGHEAIESH---------- 134
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 376 aktaqqdltqNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVH 455
Cdd:cd15036 135 ----------GSYFHMAAWGIPALKTIVILTMRKVAGDELTGLCYVGSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVAL 204
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 456 CRTKEILR----NSNALSVQQQLqqlsahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVW--------------LGSG 517
Cdd:cd15036 205 FHIRKVMKtggtNTEKLEKLMVK----------IGVFSILYTVPATCVIVCYFYERLNMDYWdlraleescrtvpgRRRP 274
                       330       340       350
                ....*....|....*....|....*....|..
gi 45551429 518 DTNTP-----LWPFLLRAFMELMLGICCFAWV 544
Cdd:cd15036 275 DCSLPhsvptVAVFMLKIFMSLVVGITSGVWV 306
CRD_FZ2 cd07464
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich ...
46-161 2.82e-28

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 2 (Fz2) 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. Fz2 is involved in the Wnt/beta-catenin signaling pathway and in the activation of protein kinase C and calcium/calmodulin-dependent protein kinase (CaM kinase).


Pssm-ID: 143573  Cd Length: 127  Bit Score: 109.79  E-value: 2.82e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTpkAPVHAIGPCRSLCES 125
Cdd:cd07464   5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSLELRFFLCSMYAPVCT--VLEQAIPPCRSICER 82
                        90       100       110
                ....*....|....*....|....*....|....*.
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFPReNNHETMCM 161
Cdd:cd07464  83 ARQGCEALMNKFGFQWPERLRCENFPR-HGAEQICV 117
CRD_FZ1 cd07465
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich ...
46-175 1.01e-27

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 1 (Fz1) 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.


Pssm-ID: 143574  Cd Length: 127  Bit Score: 108.22  E-value: 1.01e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTpkAPVHAIGPCRSLCES 125
Cdd:cd07465   5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSAELKFFLCSMYAPVCT--VLEQALPPCRSLCER 82
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFPrennhetmcMEGPGELHQPQQEQD 175
Cdd:cd07465  83 ARQGCEALMNKFGFQWPDTLRCEKFP---------VHGAGELCVGQNTSE 123
CRD_FZ7 cd07466
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich ...
46-175 1.10e-27

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 7 (Fz7) 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. Xenopus Fz7 is important in Wnt/beta-catenin signaling pathways controlling the transcriptional activation of target genes Siamois and Xnr3 in the animal caps of late blastula.


Pssm-ID: 143575 [Multi-domain]  Cd Length: 125  Bit Score: 108.25  E-value: 1.10e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTpkAPVHAIGPCRSLCES 125
Cdd:cd07466   5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSPELKFFLCSMYAPVCT--VLEQAIPPCRSLCER 82
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFPrennhetmcMEGPGELHQPQQEQD 175
Cdd:cd07466  83 ARQGCEALMNKFGFQWPERLRCENFP---------VHGAGEICVGQNTSD 123
7tmF_FZD10 cd15037
class F frizzled subfamily 10, member of 7-transmembrane G protein-coupled receptors; This ...
222-544 2.06e-26

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: 110.46  E-value: 2.06e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 222 ILFTPAEKHLAEIWVSTWAYAALgLALVATVCLLASDGSRLASAKwsRLLSPLIWCHNMVTLGWAVRFMVGRTGTACGTD 301
Cdd:cd15037   1 VYWSKDDKRFAVVWIAIWSILCF-FSSAFTVLTFLIDPQRFKYPE--RPIIFLSMCYCVYSVGYIIRLFAGAESIACDRD 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 302 PqapNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRDIRRhspdSKGHVVIPSNfggspakrnsaktaqq 381
Cdd:cd15037  78 S---GQLYVIQEGLESTGCTIVFLILYYFGMASSLWWVILTLTWFLAAGK----KWGHEAIEAN---------------- 134
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 382 dltqNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRTKEI 461
Cdd:cd15037 135 ----SSYFHLAAWAIPAVKTIMILVMRRVAGDELTGVCYVGSMDVNALTGFVLIPLACYLIIGTSFILSGFVALFHIRRV 210
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 462 LR----NSNALSVQQQLqqlsahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVW---------LGSGDTNTP------ 522
Cdd:cd15037 211 MKtggeNTDKLEKLMVR----------IGVFSVLYTVPATCVIACYFYERLNMDYWkilatqqkcKMDNQTKTLdcvmts 280
                       330       340
                ....*....|....*....|....*.
gi 45551429 523 ----LWPFLLRAFMELMLGICCFAWV 544
Cdd:cd15037 281 sipaVEIFMVKIFMLLVVGITSGMWI 306
CRD_SFRP2 cd07446
Cysteine-rich domain of the secreted frizzled-related protein 2 (SFRP2), a regulator of Wnt ...
46-155 3.45e-26

Cysteine-rich domain of the secreted frizzled-related protein 2 (SFRP2), a regulator of Wnt activity; The cysteine-rich-domain (CRD) is an essential part of the secreted frizzled related protein 2 (SFRP2), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to CRD domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs. As a Wnt antagonist, SFRP2 regulates Nkx2.2 expression in the ventral spinal cord and anteroposterior axis elongation. SFRP2 also has a Wnt-independent function as an enhancer of procollagen cleavage by the TLD proteinases. SFRP2 binds both procollagen and TLD, thus facilitating the enzymatic reaction by bringing together the proteinase and its substrate.


Pssm-ID: 143555  Cd Length: 128  Bit Score: 104.22  E-value: 3.45e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETI--RIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPvHAIGPCRSLC 123
Cdd:cd07446   5 CKPIpaNMLLCHGIEYTNMRLPNLLGHETMKEVLQQAGSWIPLVQKQCHPDTKKFLCSLFAPVCLDDLD-EAIQPCRSLC 83
                        90       100       110
                ....*....|....*....|....*....|..
gi 45551429 124 ESVRIRCHPVLQGFGFPWPPALDCDKFPRENN 155
Cdd:cd07446  84 EAVKDGCAPVMSAFGFPWPDMLDCTRFPLDND 115
CRD_FZ3 cd07449
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich ...
46-151 4.61e-26

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 [Multi-domain]  Cd Length: 127  Bit Score: 103.55  E-value: 4.61e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVHAigPCRSLCES 125
Cdd:cd07449   5 CEPITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEYGRVTL--PCRRLCQR 82
                        90       100
                ....*....|....*....|....*.
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFP 151
Cdd:cd07449  83 AYSECSKLMEMFGVPWPEDMECSRFP 108
CRD_corin_2 cd07888
One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ...
45-161 1.61e-25

One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ; The cysteine-rich domain (CRD) is an essential component of corin, a type II transmembrane serine protease which functions as the convertase of the pro-atrial natriuretic peptide (pro-ANP) in the heart. Corin contains two CRDs in its extracellular region, which play an important role in recognition of the physiological substrate, pro-ANP. This model characterizes the second (C-terminal) CRD.


Pssm-ID: 143579 [Multi-domain]  Cd Length: 122  Bit Score: 102.02  E-value: 1.61e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETIRIEMCRKIGYNETSMPNLVGNEMQ--TDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPvHAIGPCRSL 122
Cdd:cd07888   1 QCEPITLELCMNLPYNTTRYPNYLGHRTQkeASISWESSLFPALVQTNCYKYLMFFACTILVPKCDPVTQ-QRIPPCRSL 79
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 45551429 123 CESVRIRCHPVLQGFGFPWPPALDCDKFPRENNHETMCM 161
Cdd:cd07888  80 CRNSKERCESVLGIVGLQWPEDTDCAQFPEENSDNQTCL 118
7tmF_FZD1_2_7-like cd15034
class F frizzled subfamilies 1, 2 and 7; member of 7-transmembrane G protein-coupled receptors; ...
223-544 7.40e-25

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: 105.89  E-value: 7.40e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 223 LFTPAEKHLAEIWVSTWAYAALGLALVaTVCLLASDGSRLASAkwSRLLSPLIWCHNMVTLGWAVRFMVGRTgTACgTDP 302
Cdd:cd15034   2 FFTEKEREFARLWIGIWSVLCAASTLF-TVLTFLIDMDRFRYP--ERPIIFLSGCYFMVSIAYIVGFFLGDK-VAC-NGP 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 303 QAPNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRDIRRHSpdskGHVVIPSNfggspakrnsaktAQqd 382
Cdd:cd15034  77 FPPGGPKTVTQGTKKEGCTILFMMLYFFSMASSIWWVILTLTWFLAAGLKW----GHEAIEAN-------------SQ-- 137
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 383 ltqnnFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRTKEIL 462
Cdd:cd15034 138 -----YFHLAAWAVPAIKTIAILAMGKVDGDVLSGVCFVGLSDVDALRGFVLAPLFVYLLIGTSFLLAGFVSLFRIRTVM 212
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 463 RNSNA-------LSVQqqlqqlsahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWLGS---------------GDTN 520
Cdd:cd15034 213 KHDGTktdklekLMVR-------------IGVFSVLYTVPATIVIACYFYEQANRESWEKSwlsqnckkyedpcpcPPTP 279
                       330       340
                ....*....|....*....|....*....
gi 45551429 521 TPL-WP----FLLRAFMELMLGICCFAWV 544
Cdd:cd15034 280 HPLdRPdftvFMIKYLMTLIVGITSGFWI 308
CRD_SFRP5 cd07444
Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt ...
45-155 1.18e-24

Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related Protein 5 (SFRP5), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to the CRD domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs.


Pssm-ID: 143553  Cd Length: 127  Bit Score: 99.64  E-value: 1.18e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETI--RIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKaPVHaigPCRSL 122
Cdd:cd07444   6 QCVDIpaDLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDR-PIY---PCRSL 81
                        90       100       110
                ....*....|....*....|....*....|...
gi 45551429 123 CESVRIRCHPVLQGFGFPWPPALDCDKFPRENN 155
Cdd:cd07444  82 CEAVRDSCAPVMESYGFPWPEMLHCHKFPLDND 114
CRD_SFRP4 cd07442
Cysteine-rich domain of the secreted frizzled-related protein 4 (SFRP4), a Wnt antagonist; The ...
46-151 1.25e-24

Cysteine-rich domain of the secreted frizzled-related protein 4 (SFRP4), a Wnt antagonist; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related Protein 4 (SFRP4), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to the CRDs domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs.


Pssm-ID: 143551  Cd Length: 127  Bit Score: 99.72  E-value: 1.25e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVHAIGPCRSLCES 125
Cdd:cd07442   5 CEAVRIPMCRHMPWNITRMPNHLHHSTQENAVLAIEQYEELVDTGCSPVLPFFLCAMYAPICTLEFLYDPIKPCRSVCQR 84
                        90       100
                ....*....|....*....|....*.
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFP 151
Cdd:cd07442  85 ARDGCEPIMRRYNHSWPESLACDDLP 110
CRD_SFRP1 cd07443
Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt ...
45-153 1.69e-24

Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related protein 1 (SFRP1), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to the CRDs domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs. SFRP1 is expressed in many tissues and is involved in the regulation of Wnt signaling in osteoblasts, leading to enhanced trabecular bone formation in adults; it has also been shown to control the growth of retinal ganglion cell axons and the elongation of the antero-posterior axis.


Pssm-ID: 143552  Cd Length: 124  Bit Score: 99.20  E-value: 1.69e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETIRIEM--CRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKaPVHaigPCRSL 122
Cdd:cd07443   6 QCVDIPADLrlCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDR-PVY---PCRWL 81
                        90       100       110
                ....*....|....*....|....*....|.
gi 45551429 123 CESVRIRCHPVLQGFGFPWPPALDCDKFPRE 153
Cdd:cd07443  82 CEAVRDSCEPVMQFFGFYWPEMLKCDKFPEG 112
7tmF_FZD5 cd15249
class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This ...
224-544 3.05e-24

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: 103.87  E-value: 3.05e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 224 FTPAEKHLAEIWVSTWAYAALgLALVATVCLLASDGSRLASAKwsrllSPLIW---CHNMVTLGWAVRFMVGRTGTACGT 300
Cdd:cd15249   3 FSQDERTFATFWIGLWSVLCF-ISTFTTVATFLIDMERFRYPE-----RPIIFlsaCYLFVSLGYIVRLVVGHESVACNR 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 301 DPQApneslLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWhrdirrhspdskghvvipsnFGGSPAKRNSAKTAq 380
Cdd:cd15249  77 EHNH-----IHYETTGPALCTIVFLLIYFFGMASSIWWVILSFTW--------------------FLAAGMKWGNEAIA- 130
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 381 qdlTQNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRTKE 460
Cdd:cd15249 131 ---GYSQYFHLAAWLIPSVKSIAVLALSSVDGDPVAGICYVGNQNLNNLRGFVLAPLVVYLFTGTLFLLAGFVSLFRIRS 207
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 461 ILRNSNALSVQQQLQQLSahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWLGSGDTNTP-----------LWPFLLR 529
Cdd:cd15249 208 VIKQGGTKTDKLEKLMIR------IGIFTVLYTVPATIVVACYVYEQHYRESWEAALNCSCPgddtqprarpdYAVFMLK 281
                       330
                ....*....|....*
gi 45551429 530 AFMELMLGICCFAWV 544
Cdd:cd15249 282 YFMCLVVGITSGVWI 296
CRD_SFRP3 cd07441
Cysteine-rich domain of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), a Wnt ...
46-151 7.25e-24

Cysteine-rich domain of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), a Wnt antagonist; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), which plays important roles in embryogenesis and postnatal development as an antagonist of Wnt proteins, key players in a number of fundamental cellular processes. SFRPs antagonize the activation of Wnt signaling by binding to the CRD domains of frizzled proteins (Fz), thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs. SFRP3 regulates Wnt signaling activity in bone development and homeostasis. It is also involved in the control of planar cell polarity.


Pssm-ID: 143550  Cd Length: 126  Bit Score: 97.43  E-value: 7.25e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVHAIGPCRSLCES 125
Cdd:cd07441   4 CEPVRIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTIDFQHEPIKPCKSVCER 83
                        90       100
                ....*....|....*....|....*.
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFP 151
Cdd:cd07441  84 ARAGCEPVLIRYRHTWPESLACEELP 109
CRD_FZ6 cd07450
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 6 (Fz6) receptor; The cysteine-rich ...
46-151 1.28e-23

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 6 (Fz6) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 6 (Fz6) 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. Frizzled 6 (Fz6) is expressed in the skin and hair follicles and controls hair patterning in mammals using a Fz-dependent tissue polarity system, which is similar to the one that patterns the Drosophila cuticle.


Pssm-ID: 143559 [Multi-domain]  Cd Length: 127  Bit Score: 96.76  E-value: 1.28e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  46 CETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTpkAPVHAIGPCRSLCES 125
Cdd:cd07450   5 CEPITVPRCLKMPYNMTFFPNLMGHYDQDIAAVEMEPFLPLANLRCSPNVHTFLCQAFVPTCT--EQIHVVRPCRELCEK 82
                        90       100
                ....*....|....*....|....*.
gi 45551429 126 VRIRCHPVLQGFGFPWPPALDCDKFP 151
Cdd:cd07450  83 VYSDCKKLIDTFGISWPEELECDRLQ 108
7tmF_FZD8 cd15250
class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This ...
224-544 2.35e-23

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: 101.54  E-value: 2.35e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 224 FTPAEKHLAEIWVSTWAYAALgLALVATVCLLASDGSRLASAKwsRLLSPLIWCHNMVTLGWAVRFMVGRTGTACGTDPQ 303
Cdd:cd15250   3 FSQEERTFTAFWIGLWSVLCF-LSTFATVSTFLIDMERFKYPE--RPIIFLSACYLFVSLGYLVRLIAGHEKVACSRGAL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 304 ApNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWhrdirrhspdskghvvipsnFGGSPAKRNSAKTAQQdl 383
Cdd:cd15250  80 A-EVEHIHYETTGPALCTVVFLLIYFFGMASSIWWVILSLTW--------------------FLAAGMKWGNEAIAGY-- 136
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 384 tqNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRTKEILR 463
Cdd:cd15250 137 --SQYFHLAAWLIPSVKSIAVLALSSVDGDPVAGICYVGNQNLDNLRGFVLAPLVIYLFIGTMFLLAGFVSLFRIRSVIK 214
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 464 NSNALSVQQQLQQLSahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWLGSGDTNT-------PLWP----FLLRAFM 532
Cdd:cd15250 215 QGGTKTDKLEKLMIR------IGIFTVLYTVPATIVVACYFYEQHNRQRWEITHNCNClrdqpdqARRPdyavFMLKYFM 288
                       330
                ....*....|..
gi 45551429 533 ELMLGICCFAWV 544
Cdd:cd15250 289 CLVVGITSGVWT 300
CRD_crescent cd07453
Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential ...
53-161 9.29e-23

Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential part of the crescent protein, a member of the secreted frizzled-related protein (SFRP) family, which regulates convergent extension movements (CEMs) during gastrulation and neurulation. Xenopus laevis crescent efficiently forms inhibitory complexes with Wnt5a and Wnt11, but this effect is cancelled in the presence of another member of the SFRP family, Frzb1. A potential role for Crescent in head formation is to regulate a non-canonical Wnt pathway positively in the adjacent posterior mesoderm, and negatively in the overlying anterior neuroectoderm.


Pssm-ID: 143562 [Multi-domain]  Cd Length: 135  Bit Score: 94.62  E-value: 9.29e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  53 MCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKApvhaIGPCRSLCESVRIRCHP 132
Cdd:cd07453  12 LCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRP----IYPCRSLCEAVRSSCAP 87
                        90       100
                ....*....|....*....|....*....
gi 45551429 133 VLQGFGFPWPPALDCDKFPRENNhetMCM 161
Cdd:cd07453  88 LMACYGYPWPEILHCDKFPVDHD---LCI 113
CRD_LIN_17 cd07454
Cysteine-rich domain (CRD) of LIN_17; A cysteine-rich domain (CRD) is an essential component ...
45-162 6.85e-22

Cysteine-rich domain (CRD) of LIN_17; A cysteine-rich domain (CRD) 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 protein lin-17 is involved in cell type specification during Caenorhabditis elegans vulval development.


Pssm-ID: 143563  Cd Length: 124  Bit Score: 91.77  E-value: 6.85e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPvHAIGPCRSLCE 124
Cdd:cd07454   4 KCIPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMCPIGMP-QAVTSCKSVCE 82
                        90       100       110
                ....*....|....*....|....*....|....*...
gi 45551429 125 SVRIRCHPVLQGFGFPWPPALDCDKFPRENNhetMCME 162
Cdd:cd07454  83 QVKADCFSILEEFGIGWPEPLNCAQFPDPPE---LCMK 117
7tmF_FZD1_insect cd15248
class F insect frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
222-514 1.64e-20

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: 93.34  E-value: 1.64e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 222 ILFTPAEKHLAEIWVSTWAYAALGLALVaTVCLLASDGSRLASAKwsRLLSPLIWCHNMVTLGWAVRFMVGRTgTACGT- 300
Cdd:cd15248   1 MFFPERERTFSRYWIGSWAAVCMASCLF-TVLTFLIDSSRFRYPE--RPIVFLSVCYLMVAAAYVAGLGAGDS-VSCNEp 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 301 -DP-----QAPNESLLTvDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRdirrHSPDSKGHVVIPSNfggspakrn 374
Cdd:cd15248  77 fPPpvklgRLQMVSTIT-QGTKTESCTVLFMVLYFFSMAASIWWVVLTLTWFL----AAGLKWGHEAIEAK--------- 142
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 375 saktaqqdltqNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLV 454
Cdd:cd15248 143 -----------SHYFHLVAWAVPALKTISILAMGKVEGDVLSGVCYVGLWDMHALRGFVLAPLCVYLSLGTIFLLAGFIS 211
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 455 HCRTKEILRNSNALSVQQQLQQLSahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWL 514
Cdd:cd15248 212 LFRIRTVMKHDGTKTDKLEKLMLR------IGIFSFLYTLPALIVLACLFYEQAHFDSWM 265
7tmF_FZD1 cd15247
class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
224-544 4.30e-20

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: 92.41  E-value: 4.30e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 224 FTPAEKHLAEIWVSTWAYAALGLALVATVCLLAsDGSRLASAKwsRLLSPLIWCHNMVTLGWAVRFMVgRTGTACgTDPQ 303
Cdd:cd15247  13 FGPEELRFARIWIGIWSVLCCASTLFTVLTYLV-DMKRFSYPE--RPIIFLSGCYTMVAIAYIAGFLL-EDKVVC-NDKF 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 304 APNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRdirrHSPDSKGHVVIPSNfggspakrnsaktaqqdl 383
Cdd:cd15247  88 AEDGIKTVAQGTKKEGCTILFMMLYFFSMASSIWWVILSLTWFL----AAGMKWGHEAIEAN------------------ 145
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 384 tqNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRTKEILR 463
Cdd:cd15247 146 --SQYFHLAAWAVPAIKTITILAVGQVDGDVLSGVCFVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMK 223
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 464 NSNALSVQQQLQQLSahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWLGSGDTNT--------------PLWP---- 525
Cdd:cd15247 224 HDGTKTEKLEKLMVR------IGIFSVLYTVPATIVIACYFYEQAFREQWERSWISQScktyaipcpahshpPMSPdftv 297
                       330
                ....*....|....*....
gi 45551429 526 FLLRAFMELMLGICCFAWV 544
Cdd:cd15247 298 FMIKYLMTLIVGITSGFWI 316
CRD_sizzled cd07452
Cysteine-rich domain of the sizzled protein; The cysteine-rich domain (CRD) is an essential ...
45-161 3.16e-19

Cysteine-rich domain of the sizzled protein; The cysteine-rich domain (CRD) is an essential part of the sizzled protein, which regulates bone morphogenetic protein (Bmp) signaling by stabilizing chordin, and plays a critical role in the patterning of vertebrate and invertebrate embryos. Sizzled also functions in the ventral region as a Wnt inhibitor and modulates canonical Wnt signaling. Sizzled proteins belong to the secreted frizzled-related protein family (SFRP), and have be identified in the genomes of birds, fishes and frogs, but not mammals.


Pssm-ID: 143561  Cd Length: 141  Bit Score: 84.55  E-value: 3.16e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETIRIEM--CRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKApvhaIGPCRSL 122
Cdd:cd07452   8 KCVPIPPEMsmCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVCLDTF----IQPCRSM 83
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 45551429 123 CESVRIRCHPVLQGFGFPWPPALDCDKFPREnnhETMCM 161
Cdd:cd07452  84 CVAVRDSCAPVLACHGHSWPESLDCDRFPAG---EDMCL 119
7tmF_FZD7 cd15246
class F frizzled subfamily 7, member of 7-transmembrane G protein-coupled receptors; This ...
224-544 3.63e-19

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: 89.31  E-value: 3.63e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 224 FTPAEKHLAEIWVSTWAYAALGLALVATVCLLAsDGSRLASAKwsrllSPLIW---CHNMVTLGWAVRFMVGRTGTACgt 300
Cdd:cd15246   3 FKEEEVRFARLWVGIWSILCCASTLFTVLTYLV-DMRRFSYPE-----RPIIFlsgCYFMVAVAYAAGFLLEDRVVCV-- 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 301 dPQAPNESLLTV-DGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRdirrhSPDSK-GHVVIPSNfggspakrnsakt 378
Cdd:cd15246  75 -ERFSDDGYRTVaQGTKKEGCTILFMVLYFFGMASSIWWVILSLTWFL-----SAGMKwGHEAIEAN------------- 135
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 379 aqqdltqNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRT 458
Cdd:cd15246 136 -------SQYFHLAAWAVPAVKTITILAMGQVDGDLLSGVCYVGIYSVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRI 208
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 459 KEILRNSNALSVQQQLQQLSahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWLGSGDTNT--------------PLW 524
Cdd:cd15246 209 RTIMKHDGTKTEKLEKLMVR------IGVFSVLYTVPATIVLACYFYEQAFRETWEKTWLLQTckryavpcpnnnfaPMS 282
                       330       340
                ....*....|....*....|....
gi 45551429 525 P----FLLRAFMELMLGICCFAWV 544
Cdd:cd15246 283 PdftvFMIKYLMTMIVGITSGFWI 306
7tmF_FZD2 cd15245
class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This ...
222-544 1.50e-17

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: 84.30  E-value: 1.50e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 222 ILFTPAEKHLAEIWVSTWAYAALGLALVaTVCLLASDGSRLASAKwsrllSPLIW---CHNMVTLGWAVRFMVGRTgTAC 298
Cdd:cd15245   1 MFFSQDEIRFARIWILIWSVLCCASTFF-TVTTYLVDMQRFRYPE-----RPIIFlsgCYTMVSVAYIAGFVLGDK-VVC 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 299 GTDPQaPNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHRdirrHSPDSKGHVVIPSNfggspakrnsakt 378
Cdd:cd15245  74 NERFS-EDGYKTVVQGTKKEGCTILFMMLYFFSMASSIWWVILSLTWFL----AAGMKWGHEAIEAN------------- 135
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 379 aqqdltqNNFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRT 458
Cdd:cd15245 136 -------SQYFHLAAWAVPAVKTITILAMGQIDGDLLSGVCFVGLNNIDPLRGFVLAPLFVYLFIGTSFLLAGFVSLFRI 208
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 459 KEILRNSNALSVQQQLQQLSahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWLGSGDTNT--------PLWP----- 525
Cdd:cd15245 209 RTIMKHDGTKTEKLERLMVR------IGVFSVLYTVPATIVIACYFYEQAFRQHWERSWISQNckslaipcPLQYtprmt 282
                       330       340
                ....*....|....*....|....
gi 45551429 526 -----FLLRAFMELMLGICCFAWV 544
Cdd:cd15245 283 pdftvYMIKYLMTLIVGITSGFWI 306
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
277-516 7.91e-17

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: 82.34  E-value: 7.91e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 277 CHNMVTLGWAVRFMVG--------RTGTACGTDPQApNESLltvdglsnaSCASVFLMRYYFGMAACAWWAVLCLGWHRD 348
Cdd:cd15030  54 CFFIGSIGWLAQFLPGaredivcrKDGTMRLGEPSA-GENL---------SCVVIFVLVYYFLMAGCVWFVILTYAWHMS 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 349 IRRHspdskghvvipsnfgGSPAKRNSAKTAqqdltqnnFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKA 428
Cdd:cd15030 124 FKAL---------------GTIQDRLDKKTA--------YFHLIAWSLPLVLTITIMALGQVDGDSVSGICFVGYKNHMY 180
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 429 LQILVATPVFCYWIFGSMNLISGYLVHCRTKeilRNSNALsvqqqlqqLSAHSSSGI-------GIFLFIYGLACAMLLL 501
Cdd:cd15030 181 RAGFVLAPVGLVLVIGGYFLVRGLYTLIKLK---ISSPEI--------LSEKASSKIretivrlGIFAFLALGFVLITFA 249
                       250
                ....*....|....*
gi 45551429 502 AVIYEFANIDVWLGS 516
Cdd:cd15030 250 CHVYEFFNQAEWEKS 264
CRD_Carboxypeptidase_Z cd07447
Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The ...
45-150 3.47e-15

Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The cysteine-rich-domain (CRD) is an essential part of carboxypeptidase Z, a member of the carboxypeptidase E family of metallocarboxypeptidases. This is a group of Zn-dependent enzymes implicated in the intra- and extracellular processing of proteins. Carboxypeptidase Z removes C-terminal basic amino acid residues from its substrates, particularly arginine. The CRD acts as a ligand-binding domain for Wnts involved in developmental processes. CPZ binds and may process Wnt-4, CPZ has also been found to enhance the induction of the homeobox gene Cdx1. During vertebrate embryogenesis, the CRD of CPZ upregulates Pax3, a Wnt reporter gene essential for patterning of somites and limb development.


Pssm-ID: 143556  Cd Length: 128  Bit Score: 72.48  E-value: 3.47e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETIRIEMCRKIGYNETSMPNLVGNEMQTDVEYT-----LQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKApvhAIGPC 119
Cdd:cd07447   3 TCTDLLLSYCSDVSYTQTTFPNLLGHRSREVTEAGaeyllLSVLHGLLGGECNPDIRLLGCSVLAPRCENDK---VIKPC 79
                        90       100       110
                ....*....|....*....|....*....|.
gi 45551429 120 RSLCESVRIRCHPVLQGFGFPWPPALDCDKF 150
Cdd:cd07447  80 RSTCEALRKRCSHAFDAIQMAWPYFLDCDRF 110
7tmF_FZD3_FZD6-like cd15910
class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G ...
273-544 1.65e-14

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: 75.28  E-value: 1.65e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 273 PLIW---CHNMVTLGWAVRFMVGrTGTACGTDPQAPNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWhrdi 349
Cdd:cd15910  46 PIIFyavCYFVVSLIFFVGFLLG-DDVACNHAIMDENNGATVVEGSRNKACTILFMILYFFTMAGTVWWVILTITW---- 120
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 350 rrhspdskghvvipsnFGGSPAKRNSAKTAQQDLTQNNfvcfVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKAL 429
Cdd:cd15910 121 ----------------FLAAGFKWGSEAIEKKALYFHA----LAWGIPGVLTMVLLATNKIEGDNISGVCFVGLYDSDGL 180
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 430 QILVATPVFCYWIFGSMNLISGYLVHCRTKEIL----RNSNALsvqqqlqqlsAHSSSGIGIFLFIYGLACAMLLLAVIY 505
Cdd:cd15910 181 RFFVLLPLCLYVLVGMSLLLAGIICLNRVRKSIhddeTNQEKL----------AKFMIRIGVFSILYLVPLLTLIGCYAY 250
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 45551429 506 EFANIDVW------------------LGSGDTNTPLWPFLLRAFMELMLGICCFAWV 544
Cdd:cd15910 251 EQSNRKSWestwvvrncrryhipcpqLAQGNPRPGLFLFCIKYLMTLIVGIPPVFWV 307
7tmF_FZD3 cd15033
class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This ...
241-544 1.60e-12

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: 69.21  E-value: 1.60e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 241 YAALGLALVATVCLLASDGSRLA----SAKWSRLLSPLIW---CHNMVTLGWAVRFMVgRTGTACGTDPQAPNESLLTVD 313
Cdd:cd15033  10 FARYFIGVISIVCLSATLFTFLTflidVTRFRYPERPIIFyavCYMMVSLIFFIGFLL-EDRVACNAASPGQYKASTVTQ 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 314 GLSNASCASVFLMRYYFGMAACAWWAVLCLGWhrdirrhspdskghvvipsnFGGSPAKRNSAKTAQQDLTQNNfvcfVA 393
Cdd:cd15033  89 GSHNKACTMLFMVLYFFTMAGSVWWVILTITW--------------------FLAAVPKWGSEAIEKKALLFHA----SA 144
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 394 WGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVFCYWIFGSMNLISGYLVHCRTK-EI-LRNSNALSVQ 471
Cdd:cd15033 145 WGIPGTLTIILLAMNKIEGDNISGVCFVGLYDVDALRYFVLAPLCLDVVVGVSLLLAGIISLNRVRiEIpLEKENQDKLV 224
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 472 QQLQQlsahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWLGS-----------------GDTNTP-LWPFLLRAFME 533
Cdd:cd15033 225 KFMIR--------IGVFSVLYLVPLLVVIGCYFYEQAYRGVWETTwvqercreyhipcpykvTQTSRPdLILFLMKYLMA 296
                       330
                ....*....|.
gi 45551429 534 LMLGICCFAWV 544
Cdd:cd15033 297 LVVGIPSVFWV 307
7tmF_FZD6 cd15032
class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This ...
224-544 1.19e-11

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: 66.41  E-value: 1.19e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 224 FTPAEKHLAEIWVSTWAYAALGLALVATVCLLAsDGSRLASAKwsrllSPLIW---CHNMVTLGWAVRFMVGRTgTACGT 300
Cdd:cd15032   3 FKSDELDFAKSFIGIVSIFCLCATLFTFLTFLI-DVKRFRYPE-----RPIIYysvCYSIVSLMYFIGFLLGNS-TACNK 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 301 DPQAPNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWhrdirrhspdskghvvipsnFGGSPAKRNSAKTAQ 380
Cdd:cd15032  76 ADEKLELGDTVVLGSQNKACTVLFMLLYFFTMAGTIWWVILTITW--------------------FLAAGRKWSCEAIEQ 135
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 381 QDLtqnnFVCFVAWGLPAFQTSAVIVARFVDADELLGACFVGNQSDKALQILVATPVfCYWIF-GSMNLISGYLVHCRTK 459
Cdd:cd15032 136 KAL----WFHAVAWGIPGFLTIMLLAMNKVEGDNISGVCFVGLYDLDASRYFVLLPL-CLCVFvGLSLLLAGIISLNHVR 210
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 460 EIL----RNSNALSVQQQLqqlsahsssgIGIFLFIYGLACAMLLLAVIYEFANIDVWLGS------------------G 517
Cdd:cd15032 211 QVIqhdgRNQEKLKKFMIR----------IGVFSGLYLVPLVTLLGCYVYEQVYRRTWEITwvsdhcqqyhipcpyqakA 280
                       330       340
                ....*....|....*....|....*..
gi 45551429 518 DTNTPLWPFLLRAFMELMLGICCFAWV 544
Cdd:cd15032 281 VARPELALFLIKYLMTLIVGISAVFWV 307
CRD_corin_1 cd07445
One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ...
45-174 2.03e-10

One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ; The cysteine-rich domain (CRD) is an essential component of corin, a type II transmembrane serine protease which functions as the convertase of the pro-atrial natriuretic peptide (pro-ANP) in the heart. Corin contains two CRDs in its extracellular region, which play an important role in recognition of the physiological substrate, pro-ANP. This model characterizes the first (N-terminal) CRD.


Pssm-ID: 143554  Cd Length: 130  Bit Score: 59.18  E-value: 2.03e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  45 QCETIRIEMCRKIGYNETSMPnLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMC-TPKAPVHAIGPCRSLC 123
Cdd:cd07445   4 ACMNITHSQCQMLPYHSTLKP-SLLSVKNMEMEKFLKFFSYLHRLSCYQHIMLFGCSLALPECiSDGDDRHGLLPCRSFC 82
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 45551429 124 ESVRIRCHPVLQGFGFPWPPALDCDKFpreNNHETMCMEGPGELHQPQQEQ 174
Cdd:cd07445  83 EAAKEGCEPVLGMVNASWPDFLRCSQF---RNNTETAVENRALCFSPQQER 130
CRD_Collagen_XVIII cd07455
Cysteine-rich domain of the variant 3 of collagen XVIII (V3C18 ); The cysteine-rich domain ...
53-154 5.55e-08

Cysteine-rich domain of the variant 3 of collagen XVIII (V3C18 ); The cysteine-rich domain (CRD) is an essential part of the variant 3 of collagen XVIII (V3C18), which regulates major cellular functions such as the differential epithelial morphogenesis of early lung and kidney development. V3C18 is a 170 kD protein, which is proteolotically processed into the CRD-containing 50 kD glucoprotein precursor that binds Wnt3a through its CRD domain and suppresses the Wnt3a-induced stabilization of beta catenin. Full-length V3C18 is unable to inhibit Wnt signaling.


Pssm-ID: 143564  Cd Length: 123  Bit Score: 51.74  E-value: 5.55e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429  53 MCRKIGYNETSMPNLVGNEMQTDVEYTLQTFAPLIEYDCSSQLKLFLCAAYVPMCTPKAPVhAIGPCRSLCESVRIRCHP 132
Cdd:cd07455  14 FCSRLGIRSFWLPNFLNHTSVEEVRAVLAEWAWLLESGCHPSLEWFFCLLLVPSCGGGPPP-PPPPCRQFCEVLQDSCWN 92
                        90       100
                ....*....|....*....|..
gi 45551429 133 VLQGFGFPwppaLDCDKFPREN 154
Cdd:cd07455  93 LLEGGRLP----VACASLPEQE 110
7tmF_FZD3_insect cd15031
class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; ...
223-555 6.92e-05

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: 45.53  E-value: 6.92e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 223 LFTPAEKHLAEIWVSTWAYAALGLALVATVCLLAsDGSRLASAKwsrllSPLIW---CHNMVTLGWAVRFMVGrTGTACG 299
Cdd:cd15031   2 FYTTRQKKLVESWMLVLSAVSFILTLFALVTFWA-EPTRFGYPE-----RPVLFmalCYNLISLCYLERGILG-TFTNCS 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 300 TDPQA--PNESLLTVDGLSNASCASVFLMRYYFGMAACAWWAVLCLGWHrdirrhspdskghvvipsnfggspakRNSAK 377
Cdd:cd15031  75 ARSLAidCDDRYLRQDCLLTPQCLASFIITYYLSLSAASWWLIFALCWY--------------------------LSSAK 128
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 378 TAQQDLTQNNFVCF--VAWGLP-AFQTSAVIVARfVDADELLGACfvgNQSDKALQILVATPVfcywifGSMNLISGYLV 454
Cdd:cd15031 129 KWSSEALEKKSGLFhvLAWVPPlAPPIAALLLER-VSASELTGTC---TASGFVESSISELPA------LILLLLGLYLT 198
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551429 455 HCRTKEILRNSNAL-SVQQQLQQLSAHSSSGIGIFLFIygLACAMLLLAVIYEFANID----------VWLGSGDTNTPL 523
Cdd:cd15031 199 IAALRSLLSLQQQLqSRLAHAPQRILARVSIFSLLYLI--PAAAALICKLCERWLQPVpecnalqedcAPPATDNEFLSA 276
                       330       340       350
                ....*....|....*....|....*....|..
gi 45551429 524 WPFLLRAFMELMLGICCFAWVLGPSISTLYKR 555
Cdd:cd15031 277 LPALLRVFFFLIGGTATGLWLWSRKSCESWRS 308
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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