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Conserved domains on  [gi|2217368268|ref|XP_047276715|]
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protein smoothened isoform X1 [Homo sapiens]

Protein Classification

CRD_FZ and 7tmF_SMO_homolog domain-containing protein( domain architecture ID 11635468)

CRD_FZ and 7tmF_SMO_homolog domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
90-420 0e+00

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


:

Pssm-ID: 320158  Cd Length: 331  Bit Score: 657.45  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  90 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADG 169
Cdd:cd15030     1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 170 TMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVA 249
Cdd:cd15030    81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 250 QVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLA 329
Cdd:cd15030   161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 330 FGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTK 409
Cdd:cd15030   241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTIAEQTNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                         330
                  ....*....|.
gi 2217368268 410 ATLLIWRRTWC 420
Cdd:cd15030   321 ATLETWKRFWR 331
CRD_FZ super family cl02447
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
1-66 3.91e-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.


The actual alignment was detected with superfamily member cd07451:

Pssm-ID: 470581  Cd Length: 132  Bit Score: 134.80  E-value: 3.91e-37
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217368268   1 MPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFP-EGCTNEVQNIKFNSSGQCEVP 66
Cdd:cd07451    66 MPKCENGKVELPSQEMCQATRGPCKIVENERGWPDFLRCDNDRFPpRGCKNDVRELKFNTSGQCESP 132
 
Name Accession Description Interval E-value
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
90-420 0e+00

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


Pssm-ID: 320158  Cd Length: 331  Bit Score: 657.45  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  90 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADG 169
Cdd:cd15030     1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 170 TMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVA 249
Cdd:cd15030    81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 250 QVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLA 329
Cdd:cd15030   161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 330 FGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTK 409
Cdd:cd15030   241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTIAEQTNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                         330
                  ....*....|.
gi 2217368268 410 ATLLIWRRTWC 420
Cdd:cd15030   321 ATLETWKRFWR 331
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
91-422 6.78e-128

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: 380.42  E-value: 6.78e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  91 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWrNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGT 170
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDW-SRFRYPERPIIFLSLCYLLVSLGYLIRFVLG-REDIACRKDGT 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 171 MRLG--EPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTS-FKALGttYQPLSGKTSYFHLLTWSLPFVLTVAILA 247
Cdd:pfam01534  79 GRGSylITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAaGLKWG--SEAIEKKSSYFHLAAWGIPAVLTITVLA 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 248 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgLLSEKAASKINETMLRLGIFGF 327
Cdd:pfam01534 157 LGKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLK-KDGARATDKLEKLMVRIGVFSV 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 328 LAFGFVLITFSCHFYDFFNQAEWERSFRdYVLCQANvtiglptkqpIPDC--EIKNRPSLLVEKINLFAMFGTGIAMSTW 405
Cdd:pfam01534 236 LYTVPALIVIACYFYEYANRDSWELSWQ-YINCRAY----------GIPCldEPESRPSFSVFMLKYFMSLVVGITSGFW 304
                         330
                  ....*....|....*..
gi 2217368268 406 VWTKATLLIWRRTWCRL 422
Cdd:pfam01534 305 VWSGKTLESWRRFFRRL 321
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
1-66 3.91e-37

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


Pssm-ID: 143560  Cd Length: 132  Bit Score: 134.80  E-value: 3.91e-37
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217368268   1 MPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFP-EGCTNEVQNIKFNSSGQCEVP 66
Cdd:cd07451    66 MPKCENGKVELPSQEMCQATRGPCKIVENERGWPDFLRCDNDRFPpRGCKNDVRELKFNTSGQCESP 132
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
1-51 1.19e-11

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: 61.94  E-value: 1.19e-11
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2217368268    1 MPKCEND-RVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpDRFP---EGCTNE 51
Cdd:smart00063  59 APICTEDlRPILPCRSLCEAAREGCEPLMEKFGfpWPEFLRC--DRFPvqeELCMDP 113
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
2-46 5.01e-04

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: 40.24  E-value: 5.01e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217368268   2 PKCE----NDRVELPSRTLCQATRGPCAIVERERG----WPDFLRCtpDRFPE 46
Cdd:pfam01392  65 PPCTlgpsPKPVCPPCRSLCEEVRYGCEPLLEEAKfgfsWPEFLDC--DSLPA 115
 
Name Accession Description Interval E-value
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
90-420 0e+00

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


Pssm-ID: 320158  Cd Length: 331  Bit Score: 657.45  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  90 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADG 169
Cdd:cd15030     1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 170 TMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVA 249
Cdd:cd15030    81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 250 QVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLA 329
Cdd:cd15030   161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 330 FGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTK 409
Cdd:cd15030   241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTIAEQTNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                         330
                  ....*....|.
gi 2217368268 410 ATLLIWRRTWC 420
Cdd:cd15030   321 ATLETWKRFWR 331
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
91-422 6.78e-128

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: 380.42  E-value: 6.78e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  91 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWrNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGT 170
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDW-SRFRYPERPIIFLSLCYLLVSLGYLIRFVLG-REDIACRKDGT 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 171 MRLG--EPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTS-FKALGttYQPLSGKTSYFHLLTWSLPFVLTVAILA 247
Cdd:pfam01534  79 GRGSylITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAaGLKWG--SEAIEKKSSYFHLAAWGIPAVLTITVLA 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 248 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgLLSEKAASKINETMLRLGIFGF 327
Cdd:pfam01534 157 LGKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLK-KDGARATDKLEKLMVRIGVFSV 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 328 LAFGFVLITFSCHFYDFFNQAEWERSFRdYVLCQANvtiglptkqpIPDC--EIKNRPSLLVEKINLFAMFGTGIAMSTW 405
Cdd:pfam01534 236 LYTVPALIVIACYFYEYANRDSWELSWQ-YINCRAY----------GIPCldEPESRPSFSVFMLKYFMSLVVGITSGFW 304
                         330
                  ....*....|....*..
gi 2217368268 406 VWTKATLLIWRRTWCRL 422
Cdd:pfam01534 305 VWSGKTLESWRRFFRRL 321
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
90-420 1.64e-119

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: 358.55  E-value: 1.64e-119
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  90 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNsNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADG 169
Cdd:cd13951     1 GLFTSSEKKFAEIWISAWSALCFLLTLFTLLTFLIDPSR-FRYPERPIIFLALCYNFYSLGYLVRLVVG-REGIACGKDE 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 170 TM-RLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTyQPLSGKTSYFHLLTWSLPFVLTVAILAV 248
Cdd:cd13951    79 GKpYLLLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSS-EAIEKKSSYFHLVAWGLPAVLTIAVLVL 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 249 AQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGllSEKAASKINETMLRLGIFGFL 328
Cdd:cd13951   158 RKVDGDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSILSN--DGKKTDKLEKLMLRIGIFAVL 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 329 AFGFVLITFSCHFYDFFNQAEWERSFRDYVLCqanvtiglptkqpIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWT 408
Cdd:cd13951   236 YTLPALIVIACYFYEYANRPDWLRSWEPHSCC-------------SPDCEILSRPSLAVFLLKYFMQLVIGITTGVWVWS 302
                         330
                  ....*....|..
gi 2217368268 409 KATLLIWRRTWC 420
Cdd:cd13951   303 KKTLLSWRRLLR 314
7tmF_FZD5_FZD8-like cd15035
class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G ...
90-420 2.63e-56

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: 193.26  E-value: 2.63e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  90 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADg 169
Cdd:cd15035     1 PFFSEDEKTFATFWIGLWSILCFISTLITVLTFLID-MQRFQYPERPIIFLSFCYFMVSVGYIIRLIVG-HEAVACDGG- 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 170 TMRLGeptSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTYQP--LSGKTSYFHLLTWSLPFVLTVAILA 247
Cdd:cd15035    78 IIRYA---TTGPALCTVVFLLTYFFGMASSIWWVILSLTW---FLAAGLKWGNeaISSYSQYFHLVAWLIPAVQTIAILA 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 248 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKsNHPGLLSEKAASKINETMLRLGIFGF 327
Cdd:cd15035   152 LSAVDGDPISGICYVGNQNLNNLRGFVLAPLVVYLILGTSFLLAGFVSLFRIR-NVIKQQGGDKTDKLEKLMIRIGIFSV 230
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 328 LAFGFVLITFSCHFYDFFNQAEWERSfrdyVLCqanvtiglptkqPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVW 407
Cdd:cd15035   231 LYTVPATIVIACYFYEQHYREIWEKS----LNC------------PCSPGSIKSRPEYSIFMLKYFMSLVVGITSGFWIW 294
                         330
                  ....*....|...
gi 2217368268 408 TKATLLIWRRTWC 420
Cdd:cd15035   295 SGKTLDSWKRFCR 307
7tmF_FZD1_insect cd15248
class F insect frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
92-422 1.07e-48

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: 173.46  E-value: 1.07e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  92 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGarREIVCRA--DG 169
Cdd:cd15248     3 FPERERTFSRYWIGSWAAVCMASCLFTVLTFLIDSSRF-RYPERPIVFLSVCYLMVAAAYVAGLGAG--DSVSCNEpfPP 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 170 TMRLGEPTSNETL-------SCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFV 240
Cdd:cd15248    80 PVKLGRLQMVSTItqgtkteSCTVLFMVLYFFSMAASIWWVVLTLTW---FLAAGLKWghEAIEAKSHYFHLVAWAVPAL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 241 LTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGllseKAASKINET 318
Cdd:cd15248   157 KTISILAMGKVEGDVLSGVCYVGLWDMHALRGFVLAPLCVYLSLGTIFLLAGFISLFRIRTvmKHDG----TKTDKLEKL 232
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 319 MLRLGIFGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTI--GLPTKQPIPdceiknRPSLLVEKINLFAMF 396
Cdd:cd15248   233 MLRIGIFSFLYTLPALIVLACLFYEQAHFDSWMLQWHRDICKPPSWSIpaCRATGSPEA------RPEFQVFMIKYLMSM 306
                         330       340
                  ....*....|....*....|....*.
gi 2217368268 397 GTGIAMSTWVWTKATLLIWRRTWCRL 422
Cdd:cd15248   307 IVGITSSVWIWSSKTLVSWRNFYERL 332
7tmF_FZD4_9_10-like cd15909
class F frizzled subfamilies 4, 9, 10, and related proteins; member of 7-transmembrane G ...
113-420 1.18e-48

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: 172.87  E-value: 1.18e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 113 LCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRAD--GTMRLGEPTSNETLsCVIIFVI 190
Cdd:cd15909    24 ASTAFTVLTFLID-TSRFRYPERPIIFLSMCYFIYSLGYLIRLFLG-RERIACDSLnsGVSYLIQEGLESTW-CTIVFLL 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 191 VYYALMAGVVWFVVLTYAWHTSfKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYR 270
Cdd:cd15909   101 LYYFGMASALWWVILTFTWYLA-AGRKWGPEAIEAASSYFHLVAWALPAVKTIVILIMHKVDADELTGLCYVGNHDSDAL 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 271 AGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSN--HPGLlsekAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQA 348
Cdd:cd15909   180 LGFVLVPLAIYLLIGTLFILAGFVSMFRIRRNlkTRGT----DTSKLEKLMVKIGVFSVLYTVPATCVIACYFYEYLNMD 255
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217368268 349 EWERSFRDyVLCQANVTIGLPTkqpipdCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWRRTWC 420
Cdd:cd15909   256 QWRIAAIE-CKCQSPNAIGSDC------CLQPSIPSVEIYMLKIFMSLVVGITSGMWVWSSKTLQSWQRFIC 320
7tmF_FZD1_2_7-like cd15034
class F frizzled subfamilies 1, 2 and 7; member of 7-transmembrane G protein-coupled receptors; ...
108-417 1.87e-48

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: 172.52  E-value: 1.87e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 108 GAVTGLC---TLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMdgARREIVCR----ADGTMRLGEPTSNE 180
Cdd:cd15034    16 GIWSVLCaasTLFTVLTFLID-MDRFRYPERPIIFLSGCYFMVSIAYIVGFF--LGDKVACNgpfpPGGPKTVTQGTKKE 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 181 tlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSG 258
Cdd:cd15034    93 --GCTILFMMLYFFSMASSIWWVILTLTW---FLAAGLKWghEAIEANSQYFHLAAWAVPAIKTIAILAMGKVDGDVLSG 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 259 ICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGIFGFLAFGFVLIT 336
Cdd:cd15034   168 VCFVGLSDVDALRGFVLAPLFVYLLIGTSFLLAGFVSLFRIRTvmKHDGTKTD----KLEKLMVRIGVFSVLYTVPATIV 243
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 337 FSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPtkqpiPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWR 416
Cdd:cd15034   244 IACYFYEQANRESWEKSWLSQNCKKYEDPCPCP-----PTPHPLDRPDFTVFMIKYLMTLIVGITSGFWIWSGKTLQSWR 318

                  .
gi 2217368268 417 R 417
Cdd:cd15034   319 Q 319
7tmF_FZD7 cd15246
class F frizzled subfamily 7, member of 7-transmembrane G protein-coupled receptors; This ...
92-429 2.38e-48

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: 172.51  E-value: 2.38e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  92 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNrYPAVILFYVNACFFVGSIGWLAQFMDGARreIVC----RA 167
Cdd:cd15246     3 FKEEEVRFARLWVGIWSILCCASTLFTVLTYLVDMRRFS-YPERPIIFLSGCYFMVAVAYAAGFLLEDR--VVCverfSD 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 168 DGTMRLGEPTSNEtlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAI 245
Cdd:cd15246    80 DGYRTVAQGTKKE--GCTILFMVLYFFGMASSIWWVILSLTW---FLSAGMKWghEAIEANSQYFHLAAWAVPAVKTITI 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 246 LAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLG 323
Cdd:cd15246   155 LAMGQVDGDLLSGVCYVGIYSVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTimKHDGTKTE----KLEKLMVRIG 230
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 324 IFGFLAFGFVLITFSCHFYDFFNQAEWERSFrdyvLCQANVTIGLPtkqpipdCEIKN----RPSLLVEKINLFAMFGTG 399
Cdd:cd15246   231 VFSVLYTVPATIVLACYFYEQAFRETWEKTW----LLQTCKRYAVP-------CPNNNfapmSPDFTVFMIKYLMTMIVG 299
                         330       340       350
                  ....*....|....*....|....*....|
gi 2217368268 400 IAMSTWVWTKATLLIWRRTWCRLTGQSDDE 429
Cdd:cd15246   300 ITSGFWIWSGKTLQSWRRFYHRLSNGSKGE 329
7tmF_FZD2 cd15245
class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This ...
91-429 4.49e-47

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: 169.05  E-value: 4.49e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  91 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVCRA--- 167
Cdd:cd15245     2 FFSQDEIRFARIWILIWSVLCCASTFFTVTTYLVDMQRF-RYPERPIIFLSGCYTMVSVAYIAGFVLGDK--VVCNErfs 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 168 -DGTMRLGEPTSNEtlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVA 244
Cdd:cd15245    79 eDGYKTVVQGTKKE--GCTILFMMLYFFSMASSIWWVILSLTW---FLAAGMKWghEAIEANSQYFHLAAWAVPAVKTIT 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 245 ILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRL 322
Cdd:cd15245   154 ILAMGQIDGDLLSGVCFVGLNNIDPLRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTimKHDGTKTE----KLERLMVRI 229
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 323 GIFGFLAFGFVLITFSCHFYDFFNQAEWERSFrdyvLCQANVTIGLPTK-QPIPdceiKNRPSLLVEKINLFAMFGTGIA 401
Cdd:cd15245   230 GVFSVLYTVPATIVIACYFYEQAFRQHWERSW----ISQNCKSLAIPCPlQYTP----RMTPDFTVYMIKYLMTLIVGIT 301
                         330       340
                  ....*....|....*....|....*...
gi 2217368268 402 MSTWVWTKATLLIWRRTWCRLTGQSDDE 429
Cdd:cd15245   302 SGFWIWSGKTLHSWRKFYTRLTNSRQGE 329
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
100-405 1.86e-46

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


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 165.29  E-value: 1.86e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 100 MHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARREIvcradgtmrlgepTSN 179
Cdd:cd14964     1 TTIILSLLTCLGLLGNLLVLLSLVRLRKRP-RSTRLLLASLAACDLLASLVVLVLFFLLGLTEA-------------SSR 66
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 180 ETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGT-TYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV-- 256
Cdd:cd14964    67 PQALCYLIYLLWYGANLASIWTTLVLTYHRYFALCGPLKyTRLSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRYNtl 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 257 SGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgllseKAASKINETMLRLGIFGFLAFGFVLIT 336
Cdd:cd14964   147 TGSCYLICTTIYLTWGFLLVSFLLPLVAFLVIFSRIVLRLRRRVRAIR-----SAASLNTDKNLKATKSLLILVITFLLC 221
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2217368268 337 FSCHFYDFFNQAEWErsfrdyvlcqanvtiglptkqpipDCEIKNRPSLLVEKINLFAMFGTGIAMSTW 405
Cdd:cd14964   222 WLPFSIVFILHALVA------------------------AGQGLNLLSILANLLAVLASTLNPFIYCLG 266
7tmF_FZD1 cd15247
class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
92-429 6.83e-46

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: 166.37  E-value: 6.83e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  92 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNrYPAVILFYVNACFFVGSIGWLAQFMdgARREIVCR----A 167
Cdd:cd15247    13 FGPEELRFARIWIGIWSVLCCASTLFTVLTYLVDMKRFS-YPERPIIFLSGCYTMVAIAYIAGFL--LEDKVVCNdkfaE 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 168 DGTMRLGEPTSNEtlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAI 245
Cdd:cd15247    90 DGIKTVAQGTKKE--GCTILFMMLYFFSMASSIWWVILSLTW---FLAAGMKWghEAIEANSQYFHLAAWAVPAIKTITI 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 246 LAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLG 323
Cdd:cd15247   165 LAVGQVDGDVLSGVCFVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTimKHDGTKTE----KLEKLMVRIG 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 324 IFGFLAFGFVLITFSCHFYDFFNQAEWERSFrdyvLCQANVTIGLPT-KQPIPDCEiknrPSLLVEKINLFAMFGTGIAM 402
Cdd:cd15247   241 IFSVLYTVPATIVIACYFYEQAFREQWERSW----ISQSCKTYAIPCpAHSHPPMS----PDFTVFMIKYLMTLIVGITS 312
                         330       340
                  ....*....|....*....|....*..
gi 2217368268 403 STWVWTKATLLIWRRTWCRLTGQSDDE 429
Cdd:cd15247   313 GFWIWSGKTLNSWRKFYTRLTNSKQGE 339
7tmF_FZD5 cd15249
class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This ...
90-417 4.57e-45

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: 162.81  E-value: 4.57e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  90 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARReIVCRADG 169
Cdd:cd15249     1 PYFSQDERTFATFWIGLWSVLCFISTFTTVATFLIDMERF-RYPERPIIFLSACYLFVSLGYIVRLVVGHES-VACNREH 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 170 TMRLGEPTSNETlsCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILA 247
Cdd:cd15249    79 NHIHYETTGPAL--CTIVFLLIYFFGMASSIWWVILSFTW---FLAAGMKWgnEAIAGYSQYFHLAAWLIPSVKSIAVLA 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 248 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGIF 325
Cdd:cd15249   154 LSSVDGDPVAGICYVGNQNLNNLRGFVLAPLVVYLFTGTLFLLAGFVSLFRIRSviKQGGTKTD----KLEKLMIRIGIF 229
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 326 GFLAFGFVLITFSCHFYDFFNQAEWERSfrdyvlcqanvtigLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTW 405
Cdd:cd15249   230 TVLYTVPATIVVACYVYEQHYRESWEAA--------------LNCSCPGDDTQPRARPDYAVFMLKYFMCLVVGITSGVW 295
                         330
                  ....*....|..
gi 2217368268 406 VWTKATLLIWRR 417
Cdd:cd15249   296 IWSGKTLESWRR 307
7tmF_FZD8 cd15250
class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This ...
90-416 5.67e-43

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: 157.40  E-value: 5.67e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  90 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGarREIVCRADG 169
Cdd:cd15250     1 PYFSQEERTFTAFWIGLWSVLCFLSTFATVSTFLIDMERF-KYPERPIIFLSACYLFVSLGYLVRLIAG--HEKVACSRG 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 170 TMRLGEPTSNETLS---CVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVA 244
Cdd:cd15250    78 ALAEVEHIHYETTGpalCTVVFLLIYFFGMASSIWWVILSLTW---FLAAGMKWgnEAIAGYSQYFHLAAWLIPSVKSIA 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 245 ILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSnhpgLLSEKAAS--KINETMLRL 322
Cdd:cd15250   155 VLALSSVDGDPVAGICYVGNQNLDNLRGFVLAPLVIYLFIGTMFLLAGFVSLFRIRS----VIKQGGTKtdKLEKLMIRI 230
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 323 GIFGFLAFGFVLITFSCHFYDFFNQAEWErsfrdyvlcqanVTIGLPTKQPIPDcEIKnRPSLLVEKINLFAMFGTGIAM 402
Cdd:cd15250   231 GIFTVLYTVPATIVVACYFYEQHNRQRWE------------ITHNCNCLRDQPD-QAR-RPDYAVFMLKYFMCLVVGITS 296
                         330
                  ....*....|....
gi 2217368268 403 STWVWTKATLLIWR 416
Cdd:cd15250   297 GVWTWSGKTLESWR 310
7tmF_FZD4 cd15038
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This ...
91-417 1.73e-42

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: 155.69  E-value: 1.73e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  91 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGT 170
Cdd:cd15038     2 LFTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRF-KYPERPIIFLSMCYNIYSIAYIVRLLAG-RESISCDLDSQ 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 171 ----MRLGEPTSNetLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSfKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAIL 246
Cdd:cd15038    80 tavsILIQEGLEN--TGCAIVFLLLYFFGMASSIWWVILTLTWFLA-AGLKWGHEAIQMHSSYFHIAAWALPAVKTIVIL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 247 AVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSN--HPGLLSEkaasKINETMLRLGI 324
Cdd:cd15038   157 VMRVVDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQlqRDGTKTD----KLERLMVRIGI 232
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 325 FGFLAFGFVLITFSCHFYDFFNQAEWERSfrdyvlcqanvtiglptkqpipdcEIKNRPSLLVEKINLFAMFGTGIAMST 404
Cdd:cd15038   233 FSVLYTVPATCVIACYFYEYSNRDLWYYG------------------------GSAARPNMEVFMLKIFMSLVVGITSGM 288
                         330
                  ....*....|...
gi 2217368268 405 WVWTKATLLIWRR 417
Cdd:cd15038   289 WIWSAKTLSSWRN 301
7tmF_FZD10 cd15037
class F frizzled subfamily 10, member of 7-transmembrane G protein-coupled receptors; This ...
103-416 8.21e-41

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: 151.67  E-value: 8.21e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 103 YIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARrEIVCRADGTMRLGEPTSNETL 182
Cdd:cd15037    14 WIAIWSILCFFSSAFTVLTFLID-PQRFKYPERPIIFLSMCYCVYSVGYIIRLFAGAE-SIACDRDSGQLYVIQEGLEST 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 183 SCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 260
Cdd:cd15037    92 GCTIVFLILYYFGMASSLWWVILTLTW---FLAAGKKWghEAIEANSSYFHLAAWAIPAVKTIMILVMRRVAGDELTGVC 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 261 FVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPglLSEKAASKINETMLRLGIFGFLAFGFVLITFSCH 340
Cdd:cd15037   169 YVGSMDVNALTGFVLIPLACYLIIGTSFILSGFVALFHIRRVMK--TGGENTDKLEKLMVRIGVFSVLYTVPATCVIACY 246
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217368268 341 FYDFFNQAEWErsfrdyvLCQANVTIGLPTKQPIPDCEIKNR-PSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWR 416
Cdd:cd15037   247 FYERLNMDYWK-------ILATQQKCKMDNQTKTLDCVMTSSiPAVEIFMVKIFMLLVVGITSGMWIWTSKTLQSWQ 316
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
103-416 1.86e-38

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: 144.72  E-value: 1.86e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 103 YIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARrEIVCRADGtmrlGEP----TS 178
Cdd:cd15036    14 WMAVWSTLCFVSTAFTVLTFLLD-PHRFQYPERPIIFLSMCYNVYSVAFLIRAVAGAE-SIACDREN----GALyiiqEG 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 179 NETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV 256
Cdd:cd15036    88 LESTGCTLVFLILYYFGMASSLWWVVLTLTW---FLAAGKKWghEAIESHGSYFHMAAWGIPALKTIVILTMRKVAGDEL 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 257 SGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGIFGFLAFGFVL 334
Cdd:cd15036   165 TGLCYVGSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVALFHIRKvmKTGGTNTE----KLEKLMVKIGVFSILYTVPAT 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 335 ITFSCHFYDFFNQAEWERSFRDyvlcQANVTigLPTKQPiPDCEIKNR-PSLLVEKINLFAMFGTGIAMSTWVWTKATLL 413
Cdd:cd15036   241 CVIVCYFYERLNMDYWDLRALE----ESCRT--VPGRRR-PDCSLPHSvPTVAVFMLKIFMSLVVGITSGVWVWSSKTLQ 313

                  ...
gi 2217368268 414 IWR 416
Cdd:cd15036   314 TWQ 316
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
1-66 3.91e-37

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


Pssm-ID: 143560  Cd Length: 132  Bit Score: 134.80  E-value: 3.91e-37
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217368268   1 MPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFP-EGCTNEVQNIKFNSSGQCEVP 66
Cdd:cd07451    66 MPKCENGKVELPSQEMCQATRGPCKIVENERGWPDFLRCDNDRFPpRGCKNDVRELKFNTSGQCESP 132
7tmF_FZD3 cd15033
class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This ...
108-415 6.76e-35

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: 134.69  E-value: 6.76e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 108 GAVTGLC---TLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVCRADGTMRLGEPT---SNET 181
Cdd:cd15033    16 GVISIVClsaTLFTFLTFLID-VTRFRYPERPIIFYAVCYMMVSLIFFIGFLLEDR--VACNAASPGQYKASTvtqGSHN 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 182 LSCVIIFVIVYYALMAGVVWFVVLTYAWH-TSFKALGTtyQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 260
Cdd:cd15033    93 KACTMLFMVLYFFTMAGSVWWVILTITWFlAAVPKWGS--EAIEKKALLFHASAWGIPGTLTIILLAMNKIEGDNISGVC 170
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 261 FVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPglLSEKAASKINETMLRLGIFGFLAFGFVLITFSCH 340
Cdd:cd15033   171 FVGLYDVDALRYFVLAPLCLDVVVGVSLLLAGIISLNRVRIEIP--LEKENQDKLVKFMIRIGVFSVLYLVPLLVVIGCY 248
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 341 FYDFFNQAEWERSF-----RDYVLcqanvtiglptkqPIP-DCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLI 414
Cdd:cd15033   249 FYEQAYRGVWETTWvqercREYHI-------------PCPyKVTQTSRPDLILFLMKYLMALVVGIPSVFWVGSKKTCFE 315

                  .
gi 2217368268 415 W 415
Cdd:cd15033   316 W 316
7tmF_FZD3_FZD6-like cd15910
class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G ...
102-415 1.36e-33

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: 131.13  E-value: 1.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 102 SYIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVCR-ADGTMRLGEPT--S 178
Cdd:cd15910    13 YFIGVVSILCLLATLFTFLTFLID-VNRFRYPERPIIFYAVCYFVVSLIFFVGFLLGDD--VACNhAIMDENNGATVveG 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 179 NETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV 256
Cdd:cd15910    90 SRNKACTILFMILYFFTMAGTVWWVILTITW---FLAAGFKWgsEAIEKKALYFHALAWGIPGVLTMVLLATNKIEGDNI 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 257 SGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPglLSEKAASKINETMLRLGIFGFLAFGFVLIT 336
Cdd:cd15910   167 SGVCFVGLYDSDGLRFFVLLPLCLYVLVGMSLLLAGIICLNRVRKSIH--DDETNQEKLAKFMIRIGVFSILYLVPLLTL 244
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 337 FSCHFYDFFNQAEWE-----RSFRDYvlcqanvtiGLPTKQPIpdcEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKAT 411
Cdd:cd15910   245 IGCYAYEQSNRKSWEstwvvRNCRRY---------HIPCPQLA---QGNPRPGLFLFCIKYLMTLIVGIPPVFWVGSKKT 312

                  ....
gi 2217368268 412 LLIW 415
Cdd:cd15910   313 CAEW 316
7tmF_FZD6 cd15032
class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This ...
92-415 1.57e-31

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: 125.34  E-value: 1.57e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  92 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVC-RADGT 170
Cdd:cd15032     3 FKSDELDFAKSFIGIVSIFCLCATLFTFLTFLIDVKRF-RYPERPIIYYSVCYSIVSLMYFIGFLLGNS--TACnKADEK 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 171 MRLGEPT--SNETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAIL 246
Cdd:cd15032    80 LELGDTVvlGSQNKACTVLFMLLYFFTMAGTIWWVILTITW---FLAAGRKWscEAIEQKALWFHAVAWGIPGFLTIMLL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 247 AVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGI 324
Cdd:cd15032   157 AMNKVEGDNISGVCFVGLYDLDASRYFVLLPLCLCVFVGLSLLLAGIISLNHVRQviQHDGRNQE----KLKKFMIRIGV 232
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 325 FGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKQPipdceikNRPSLLVEKINLFAMFGTGIAMST 404
Cdd:cd15032   233 FSGLYLVPLVTLLGCYVYEQVYRRTWEITWVSDHCQQYHIPCPYQAKAV-------ARPELALFLIKYLMTLIVGISAVF 305
                         330
                  ....*....|.
gi 2217368268 405 WVWTKATLLIW 415
Cdd:cd15032   306 WVGSKKTCSEW 316
7tmF_FZD3_insect cd15031
class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; ...
91-417 4.22e-18

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: 85.59  E-value: 4.22e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268  91 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCR---A 167
Cdd:cd15031     2 FYTTRQKKLVESWMLVLSAVSFILTLFALVTFWAE-PTRFGYPERPVLFMALCYNLISLCYLERGILGTFTNCSARslaI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 168 DGTMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWH-TSFKALGTTyqPLSGKTSYFHLLTWSLPFVLTVAIL 246
Cdd:cd15031    81 DCDDRYLRQDCLLTPQCLASFIITYYLSLSAASWWLIFALCWYlSSAKKWSSE--ALEKKSGLFHVLAWVPPLAPPIAAL 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 247 AVAQVDGDSVSGICfvgYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNhpglLSEKAASKINETMLRLGIFG 326
Cdd:cd15031   159 LLERVSASELTGTC---TASGFVESSISELPALILLLLGLYLTIAALRSLLSLQQQ----LQSRLAHAPQRILARVSIFS 231
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 327 FLAF---GFVLITFSChfydffnqaewERSFRDYVLCQANVTIGLPTKQPIPDCEIKnrPSLLveKINLFAMFGTGIAMs 403
Cdd:cd15031   232 LLYLipaAAALICKLC-----------ERWLQPVPECNALQEDCAPPATDNEFLSAL--PALL--RVFFFLIGGTATGL- 295
                         330
                  ....*....|....
gi 2217368268 404 tWVWTKATLLIWRR 417
Cdd:cd15031   296 -WLWSRKSCESWRS 308
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
1-51 1.19e-11

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: 61.94  E-value: 1.19e-11
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2217368268    1 MPKCEND-RVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpDRFP---EGCTNE 51
Cdd:smart00063  59 APICTEDlRPILPCRSLCEAAREGCEPLMEKFGfpWPEFLRC--DRFPvqeELCMDP 113
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
102-341 2.14e-11

adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G protein-coupled receptors; The B2 subfamily of class B GPCRs consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320168 [Multi-domain]  Cd Length: 253  Bit Score: 64.52  E-value: 2.14e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 102 SYIAAFG-AVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAqfmdgarreivcradgtmrlGEPTSNE 180
Cdd:cd15040     5 SIITYIGcGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFLF--------------------GINSTDN 64
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 181 TLSCVIIFVIVYYALMAGVVWFVVLtyAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 260
Cdd:cd15040    65 PVLCTAVAALLHYFLLASFMWMLVE--ALLLYLRLVKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYC 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 261 FVGYKNYRYraGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgllsekaASKINETMLRLG-------------IFGF 327
Cdd:cd15040   143 WLSNGNGLY--YAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRN-------KKKRKKTKAQLRaavslffllgltwIFGI 213
                         250
                  ....*....|....
gi 2217368268 328 LAFGFVLITFSCHF 341
Cdd:cd15040   214 LAIFGARVVFQYLF 227
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
113-348 2.69e-11

class B family of seven-transmembrane G protein-coupled receptors; The class B of seven-transmembrane GPCRs is classified into three major subfamilies: subfamily B1 (secretin-like receptor family), B2 (adhesion family), and B3 (Methuselah-like family). The class B receptors have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi or prokaryotes. The B1 subfamily comprises receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the subfamily B1 receptors preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The subfamily B2 consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Furthermore, the subfamily B3 includes Methuselah (Mth) protein, which was originally identified in Drosophila as a GPCR affecting stress resistance and aging, and its closely related proteins.


Pssm-ID: 410627 [Multi-domain]  Cd Length: 260  Bit Score: 64.54  E-value: 2.69e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 113 LCTLFTLATFVA--DWRNsnrYPAVILFYVNACFFVGSIGWLAqfmdgarreivcradgtmRLGEPTSNETLSCVIIFVI 190
Cdd:cd13952    17 VGLLLTIITYLLfpKLRN---LRGKILINLCLSLLLAQLLFLI------------------GQLLTSSDRPVLCKALAIL 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 191 VYYALMAGVVWFVVLT-YAWHTSFKALGTTYqplSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV----SGICFVGYK 265
Cdd:cd13952    76 LHYFLLASFFWMLVEAfDLYRTFVKVFGSSE---RRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSpgygGEYCWLSNG 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 266 NYRYraGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgllsekAASKINETMLRLGIFGFLafgFVL--ITFSCHFYD 343
Cdd:cd13952   153 NALL--WAFYGPVLLILLVNLVFFILTVRILLRKLRETP------KQSERKSDRKQLRAYLKL---FPLmgLTWIFGILA 221

                  ....*
gi 2217368268 344 FFNQA 348
Cdd:cd13952   222 PFVGG 226
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
177-346 7.15e-06

Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G protein-coupled receptors; The subfamily B3 of class B GPCRs consists of Methuselah (Mth) and its closely related proteins found in bilateria. Mth was originally identified in Drosophila as a GPCR affecting stress resistance and aging. In addition to the seven transmembrane helices, Mth contains an N-terminal extracellular domain involved in ligand binding, and a third intracellular loop (IC3) required for the specificity of G-protein coupling. Drosophila Mth mutants showed an increase in average lifespan by 35% and greater resistance to a variety of stress factors, including starvation, high temperature, and paraquat-induced oxidative toxicity. Moreover, mutations in two endogenous peptide ligands of Methuselah, Stunted A and B, showed an increased in lifespan and resistance to oxidative stress induced by dietary paraquat. These results strongly suggest that the Stunted-Methuselah system plays important roles in stress response and aging.


Pssm-ID: 410632 [Multi-domain]  Cd Length: 270  Bit Score: 47.99  E-value: 7.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 177 TSNETLSCVIIFVIVYYALMAGVVWFVVLTY-AWHT-SFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGD 254
Cdd:cd15039    61 SSGDSTLCVALGILLHFFFLAAFFWLNVMSFdIWRTfRGKRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDFSPNT 140
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368268 255 SV------SGICFVGYKNYRYRagFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNhpgllSEKAASKINETM------LRL 322
Cdd:cd15039   141 DSlrpgygEGSCWISNPWALLL--YFYGPVALLLLFNIILFILTAIRIRKVKKE-----TAKVQSRLRSDKqrfrlyLKL 213
                         170       180       190
                  ....*....|....*....|....*....|.
gi 2217368268 323 G-------IFGFLAFGFVLITFSCHFYDFFN 346
Cdd:cd15039   214 FvimgvtwILEIISWFVGGSSVLWYIFDILN 244
CRD_Carboxypeptidase_Z cd07447
Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The ...
2-48 7.02e-05

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: 42.82  E-value: 7.02e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217368268   2 PKCENDRVELPSRTLCQATRGPC--AIVERERGWPDFLRCtpDRF----PEGC 48
Cdd:cd07447    68 PRCENDKVIKPCRSTCEALRKRCshAFDAIQMAWPYFLDC--DRFfageQEGC 118
CRD_FZ cd07066
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
1-51 1.44e-04

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


Pssm-ID: 143549  Cd Length: 119  Bit Score: 41.72  E-value: 1.44e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2217368268   1 MPKCEND--RVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpDRFPEGCTNE 51
Cdd:cd07066    60 FPECTPDgdRPIPPCRSLCEEVRDSCEPLMLAFGfpWPEPLDC--DRFPDSNEEG 112
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
2-46 5.01e-04

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: 40.24  E-value: 5.01e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217368268   2 PKCE----NDRVELPSRTLCQATRGPCAIVERERG----WPDFLRCtpDRFPE 46
Cdd:pfam01392  65 PPCTlgpsPKPVCPPCRSLCEEVRYGCEPLLEEAKfgfsWPEFLDC--DSLPA 115
CRD_SFRP1 cd07443
Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt ...
7-47 2.59e-03

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: 38.34  E-value: 2.59e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2217368268   7 DRVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpDRFPEG 47
Cdd:cd07443    72 DRPVYPCRWLCEAVRDSCEPVMQFFGfyWPEMLKC--DKFPEG 112
CRD_crescent cd07453
Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential ...
7-46 6.22e-03

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: 37.61  E-value: 6.22e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2217368268   7 DRVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpDRFPE 46
Cdd:cd07453    68 DRPIYPCRSLCEAVRSSCAPLMACYGypWPEILHC--DKFPV 107
CRD_corin_1 cd07445
One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ...
1-57 9.21e-03

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: 36.83  E-value: 9.21e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217368268   1 MPKCENDRVE----LPSRTLCQATRGPCAIVER--ERGWPDFLRCTPDRFPEGCTNEVQNIKF 57
Cdd:cd07445    62 LPECISDGDDrhglLPCRSFCEAAKEGCEPVLGmvNASWPDFLRCSQFRNNTETAVENRALCF 124
 
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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