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Conserved domains on  [gi|1813878|gb|AAB41789|]
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smoothened [Rattus norvegicus]

Protein Classification

frizzled family protein; olfactory receptor( domain architecture ID 11575552)

frizzled family protein similar to the ten frizzleds (Fzd1-10) and smoothened (Smo), which are involved in transmitting the signals of Wnts and hedgehog proteins and are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors; contains an N-terminal extracellular cysteine-rich domain (CRD) associated with their role in binding to Wnt ligands; olfactory receptor plays a central role in olfaction or the sense of smell, similar to human family 6 olfactory receptors; belongs to the class A rhodopsin-like family of G protein-coupled receptors; binding of an odorant to the olfactory receptor induces a conformational change that leads to the activation of the olfactory-specific G protein (Golf)

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 ...
224-554 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: 663.61  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  224 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADG 303
Cdd:cd15030   1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  304 TMRFGEPTSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVA 383
Cdd:cd15030  81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  384 QVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLA 463
Cdd:cd15030 161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  464 FGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKKPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTK 543
Cdd:cd15030 241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTIAEQTNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                       330
                ....*....|.
gi 1813878  544 ATLLIWRRTWC 554
Cdd:cd15030 321 ATLETWKRFWR 331
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
70-200 7.48e-81

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: 254.60  E-value: 7.48e-81
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   70 RAAHCEPLRYNVCLGSALPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRT 149
Cdd:cd07451   1 RPAKCEPLKNTTCLGSKLPYTYTSLDLVPDSTTQEEVQEKLHLWSGLRNVPKCWAVIQPLLCALYMPKCENGKVELPSQE 80
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 1813878  150 LCQATRGPCAIVERERGWPDFLRCTPDHFP-EGCPNEVQNIKFNSSGQCEAP 200
Cdd:cd07451  81 MCQATRGPCKIVENERGWPDFLRCDNDRFPpRGCKNDVRELKFNTSGQCESP 132
 
Name Accession Description Interval E-value
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
224-554 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: 663.61  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  224 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADG 303
Cdd:cd15030   1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  304 TMRFGEPTSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVA 383
Cdd:cd15030  81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  384 QVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLA 463
Cdd:cd15030 161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  464 FGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKKPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTK 543
Cdd:cd15030 241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTIAEQTNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                       330
                ....*....|.
gi 1813878  544 ATLLIWRRTWC 554
Cdd:cd15030 321 ATLETWKRFWR 331
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
225-556 4.54e-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: 385.04  E-value: 4.54e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878    225 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWrNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGT 304
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDW-SRFRYPERPIIFLSLCYLLVSLGYLIRFVLG-REDIACRKDGT 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878    305 MR--FGEPTSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTS-FKALGttYQPLSGKTSYFHLLTWSLPFVLTVAILA 381
Cdd:pfam01534  79 GRgsYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAaGLKWG--SEAIEKKSSYFHLAAWGIPAVLTITVLA 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878    382 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgLLSEKAASKINETMLRLGIFGF 461
Cdd:pfam01534 157 LGKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLK-KDGARATDKLEKLMVRIGVFSV 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878    462 LAFGFVLITFSCHFYDFFNQAEWERSFRdYVLCQANvtiglptkkpIPDC--EIKNRPSLLVEKINLFAMFGTGIAMSTW 539
Cdd:pfam01534 236 LYTVPALIVIACYFYEYANRDSWELSWQ-YINCRAY----------GIPCldEPESRPSFSVFMLKYFMSLVVGITSGFW 304
                         330
                  ....*....|....*..
gi 1813878    540 VWTKATLLIWRRTWCRL 556
Cdd:pfam01534 305 VWSGKTLESWRRFFRRL 321
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
70-200 7.48e-81

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: 254.60  E-value: 7.48e-81
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   70 RAAHCEPLRYNVCLGSALPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRT 149
Cdd:cd07451   1 RPAKCEPLKNTTCLGSKLPYTYTSLDLVPDSTTQEEVQEKLHLWSGLRNVPKCWAVIQPLLCALYMPKCENGKVELPSQE 80
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 1813878  150 LCQATRGPCAIVERERGWPDFLRCTPDHFP-EGCPNEVQNIKFNSSGQCEAP 200
Cdd:cd07451  81 MCQATRGPCKIVENERGWPDFLRCDNDRFPpRGCKNDVRELKFNTSGQCESP 132
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
74-182 6.41e-32

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: 120.11  E-value: 6.41e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878      74 CEPLRYNVCLGsaLPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNAPrCWAVIQPLLCAVYMPKCEND-RVELPSRTLCQ 152
Cdd:smart00063   1 CEPITIPLCKD--LGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQ-CSPDLRFFLCSVYAPICTEDlRPILPCRSLCE 77
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1813878     153 ATRGPCAIVERERG--WPDFLRCtpDHFP---EGC 182
Cdd:smart00063  78 AAREGCEPLMEKFGfpWPEFLRC--DRFPvqeELC 110
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
74-180 1.65e-14

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: 70.29  E-value: 1.65e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878     74 CEPLRYNVCLGsaLPYGATTTLLAGDSDSQEEAHSKLVL-----WSGLRNApRCWAVIQPLLCAVYMPKCE----NDRVE 144
Cdd:pfam01392   1 CEPITLPMCLG--LGYNATVFPNLLGHQTQEEAELSLAYlvlseFEPLVDL-SCSPSLRLFLCSLYFPPCTlgpsPKPVC 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1813878    145 LPSRTLCQATRGPCAIVERERG----WPDFLRCtpDHFPE 180
Cdd:pfam01392  78 PPCRSLCEEVRYGCEPLLEEAKfgfsWPEFLDC--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 ...
224-554 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: 663.61  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  224 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADG 303
Cdd:cd15030   1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  304 TMRFGEPTSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVA 383
Cdd:cd15030  81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  384 QVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLA 463
Cdd:cd15030 161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  464 FGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKKPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTK 543
Cdd:cd15030 241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTIAEQTNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                       330
                ....*....|.
gi 1813878  544 ATLLIWRRTWC 554
Cdd:cd15030 321 ATLETWKRFWR 331
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
225-556 4.54e-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: 385.04  E-value: 4.54e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878    225 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWrNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGT 304
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDW-SRFRYPERPIIFLSLCYLLVSLGYLIRFVLG-REDIACRKDGT 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878    305 MR--FGEPTSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTS-FKALGttYQPLSGKTSYFHLLTWSLPFVLTVAILA 381
Cdd:pfam01534  79 GRgsYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAaGLKWG--SEAIEKKSSYFHLAAWGIPAVLTITVLA 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878    382 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgLLSEKAASKINETMLRLGIFGF 461
Cdd:pfam01534 157 LGKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLK-KDGARATDKLEKLMVRIGVFSV 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878    462 LAFGFVLITFSCHFYDFFNQAEWERSFRdYVLCQANvtiglptkkpIPDC--EIKNRPSLLVEKINLFAMFGTGIAMSTW 539
Cdd:pfam01534 236 LYTVPALIVIACYFYEYANRDSWELSWQ-YINCRAY----------GIPCldEPESRPSFSVFMLKYFMSLVVGITSGFW 304
                         330
                  ....*....|....*..
gi 1813878    540 VWTKATLLIWRRTWCRL 556
Cdd:pfam01534 305 VWSGKTLESWRRFFRRL 321
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
224-554 2.54e-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: 362.02  E-value: 2.54e-119
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  224 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNsNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADG 303
Cdd:cd13951   1 GLFTSSEKKFAEIWISAWSALCFLLTLFTLLTFLIDPSR-FRYPERPIIFLALCYNFYSLGYLVRLVVG-REGIACGKDE 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  304 TM-RFGEPTSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTyQPLSGKTSYFHLLTWSLPFVLTVAILAV 382
Cdd:cd13951  79 GKpYLLLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSS-EAIEKKSSYFHLVAWGLPAVLTIAVLVL 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  383 AQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGllSEKAASKINETMLRLGIFGFL 462
Cdd:cd13951 158 RKVDGDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSILSN--DGKKTDKLEKLMLRIGIFAVL 235
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  463 AFGFVLITFSCHFYDFFNQAEWERSFRDYVLCqanvtiglptkkpIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWT 542
Cdd:cd13951 236 YTLPALIVIACYFYEYANRPDWLRSWEPHSCC-------------SPDCEILSRPSLAVFLLKYFMQLVIGITTGVWVWS 302
                       330
                ....*....|..
gi 1813878  543 KATLLIWRRTWC 554
Cdd:cd13951 303 KKTLLSWRRLLR 314
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
70-200 7.48e-81

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: 254.60  E-value: 7.48e-81
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   70 RAAHCEPLRYNVCLGSALPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRT 149
Cdd:cd07451   1 RPAKCEPLKNTTCLGSKLPYTYTSLDLVPDSTTQEEVQEKLHLWSGLRNVPKCWAVIQPLLCALYMPKCENGKVELPSQE 80
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 1813878  150 LCQATRGPCAIVERERGWPDFLRCTPDHFP-EGCPNEVQNIKFNSSGQCEAP 200
Cdd:cd07451  81 MCQATRGPCKIVENERGWPDFLRCDNDRFPpRGCKNDVRELKFNTSGQCESP 132
7tmF_FZD5_FZD8-like cd15035
class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G ...
224-554 1.12e-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: 196.34  E-value: 1.12e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  224 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADg 303
Cdd:cd15035   1 PFFSEDEKTFATFWIGLWSILCFISTLITVLTFLID-MQRFQYPERPIIFLSFCYFMVSVGYIIRLIVG-HEAVACDGG- 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  304 TMRFGeptSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTYQP--LSGKTSYFHLLTWSLPFVLTVAILA 381
Cdd:cd15035  78 IIRYA---TTGPALCTVVFLLTYFFGMASSIWWVILSLTW---FLAAGLKWGNeaISSYSQYFHLVAWLIPAVQTIAILA 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  382 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS---NHPGllseKAASKINETMLRLGI 458
Cdd:cd15035 152 LSAVDGDPISGICYVGNQNLNNLRGFVLAPLVVYLILGTSFLLAGFVSLFRIRNvikQQGG----DKTDKLEKLMIRIGI 227
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  459 FGFLAFGFVLITFSCHFYDFFNQAEWERSfrdyVLCqanvtiglptkkPIPDCEIKNRPSLLVEKINLFAMFGTGIAMST 538
Cdd:cd15035 228 FSVLYTVPATIVIACYFYEQHYREIWEKS----LNC------------PCSPGSIKSRPEYSIFMLKYFMSLVVGITSGF 291
                       330
                ....*....|....*.
gi 1813878  539 WVWTKATLLIWRRTWC 554
Cdd:cd15035 292 WIWSGKTLDSWKRFCR 307
7tmF_FZD4_9_10-like cd15909
class F frizzled subfamilies 4, 9, 10, and related proteins; member of 7-transmembrane G ...
247-554 3.83e-49

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: 175.96  E-value: 3.83e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  247 LCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGTmrfGEPT----SSETLSCVIIF 322
Cdd:cd15909  24 ASTAFTVLTFLID-TSRFRYPERPIIFLSMCYFIYSLGYLIRLFLG-RERIACDSLNS---GVSYliqeGLESTWCTIVF 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  323 VIVYYALMAGVVWFVVLTYAWHTSfKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYR 402
Cdd:cd15909  99 LLLYYFGMASALWWVILTFTWYLA-AGRKWGPEAIEAASSYFHLVAWALPAVKTIVILIMHKVDADELTGLCYVGNHDSD 177
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  403 YRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSN--HPGLlsekAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFN 480
Cdd:cd15909 178 ALLGFVLVPLAIYLLIGTLFILAGFVSMFRIRRNlkTRGT----DTSKLEKLMVKIGVFSVLYTVPATCVIACYFYEYLN 253
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1813878  481 QAEWERSFRDyVLCQANVTIGLPTkkpipdCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWRRTWC 554
Cdd:cd15909 254 MDQWRIAAIE-CKCQSPNAIGSDC------CLQPSIPSVEIYMLKIFMSLVVGITSGMWVWSSKTLQSWQRFIC 320
7tmF_FZD1_insect cd15248
class F insect frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
226-556 1.31e-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: 175.00  E-value: 1.31e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  226 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGarREIVCRA--DG 303
Cdd:cd15248   3 FPERERTFSRYWIGSWAAVCMASCLFTVLTFLIDSSRF-RYPERPIVFLSVCYLMVAAAYVAGLGAG--DSVSCNEpfPP 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  304 TMRFGEPTSSETL-------SCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFV 374
Cdd:cd15248  80 PVKLGRLQMVSTItqgtkteSCTVLFMVLYFFSMAASIWWVVLTLTW---FLAAGLKWghEAIEAKSHYFHLVAWAVPAL 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  375 LTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGllseKAASKINET 452
Cdd:cd15248 157 KTISILAMGKVEGDVLSGVCYVGLWDMHALRGFVLAPLCVYLSLGTIFLLAGFISLFRIRTvmKHDG----TKTDKLEKL 232
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  453 MLRLGIFGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTI--GLPTKKPIPdceiknRPSLLVEKINLFAMF 530
Cdd:cd15248 233 MLRIGIFSFLYTLPALIVLACLFYEQAHFDSWMLQWHRDICKPPSWSIpaCRATGSPEA------RPEFQVFMIKYLMSM 306
                       330       340
                ....*....|....*....|....*.
gi 1813878  531 GTGIAMSTWVWTKATLLIWRRTWCRL 556
Cdd:cd15248 307 IVGITSSVWIWSSKTLVSWRNFYERL 332
7tmF_FZD7 cd15246
class F frizzled subfamily 7, member of 7-transmembrane G protein-coupled receptors; This ...
226-563 1.68e-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: 174.82  E-value: 1.68e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  226 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNrYPAVILFYVNACFFVGSIGWLAQFMDGARreIVC----RA 301
Cdd:cd15246   3 FKEEEVRFARLWVGIWSILCCASTLFTVLTYLVDMRRFS-YPERPIIFLSGCYFMVAVAYAAGFLLEDR--VVCverfSD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  302 DGTMRFGEPTSSEtlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAI 379
Cdd:cd15246  80 DGYRTVAQGTKKE--GCTILFMVLYFFGMASSIWWVILSLTW---FLSAGMKWghEAIEANSQYFHLAAWAVPAVKTITI 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  380 LAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLG 457
Cdd:cd15246 155 LAMGQVDGDLLSGVCYVGIYSVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTimKHDGTKTE----KLEKLMVRIG 230
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  458 IFGFLAFGFVLITFSCHFYDFFNQAEWERSFrdyvLCQANVTIGLPtkkpipdCEIKN----RPSLLVEKINLFAMFGTG 533
Cdd:cd15246 231 VFSVLYTVPATIVLACYFYEQAFRETWEKTW----LLQTCKRYAVP-------CPNNNfapmSPDFTVFMIKYLMTMIVG 299
                       330       340       350
                ....*....|....*....|....*....|
gi 1813878  534 IAMSTWVWTKATLLIWRRTWCRLTGHSDDE 563
Cdd:cd15246 300 ITSGFWIWSGKTLQSWRRFYHRLSNGSKGE 329
7tmF_FZD1_2_7-like cd15034
class F frizzled subfamilies 1, 2 and 7; member of 7-transmembrane G protein-coupled receptors; ...
242-551 9.48e-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: 172.14  E-value: 9.48e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  242 GAVTGLC---TLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMdgARREIVCR----ADGTMRFGEPTSSE 314
Cdd:cd15034  16 GIWSVLCaasTLFTVLTFLID-MDRFRYPERPIIFLSGCYFMVSIAYIVGFF--LGDKVACNgpfpPGGPKTVTQGTKKE 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  315 tlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSG 392
Cdd:cd15034  93 --GCTILFMMLYFFSMASSIWWVILTLTW---FLAAGLKWghEAIEANSQYFHLAAWAVPAIKTIAILAMGKVDGDVLSG 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  393 ICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGIFGFLAFGFVLIT 470
Cdd:cd15034 168 VCFVGLSDVDALRGFVLAPLFVYLLIGTSFLLAGFVSLFRIRTvmKHDGTKTD----KLEKLMVRIGVFSVLYTVPATIV 243
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  471 FSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPtkkpiPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWR 550
Cdd:cd15034 244 IACYFYEQANRESWEKSWLSQNCKKYEDPCPCP-----PTPHPLDRPDFTVFMIKYLMTLIVGITSGFWIWSGKTLQSWR 318

                .
gi 1813878  551 R 551
Cdd:cd15034 319 Q 319
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
234-539 2.98e-47

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: 169.15  E-value: 2.98e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  234 MHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARREIvcradgtmrfgepTSS 313
Cdd:cd14964   1 TTIILSLLTCLGLLGNLLVLLSLVRLRKRP-RSTRLLLASLAACDLLASLVVLVLFFLLGLTEA-------------SSR 66
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  314 ETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGT-TYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV-- 390
Cdd:cd14964  67 PQALCYLIYLLWYGANLASIWTTLVLTYHRYFALCGPLKyTRLSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRYNtl 146
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  391 SGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgllseKAASKINETMLRLGIFGFLAFGFVLIT 470
Cdd:cd14964 147 TGSCYLICTTIYLTWGFLLVSFLLPLVAFLVIFSRIVLRLRRRVRAIR-----SAASLNTDKNLKATKSLLILVITFLLC 221
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1813878  471 FSCHFYDFFNQAEWErsfrdyvlcqanvtiglptkkpipDCEIKNRPSLLVEKINLFAMFGTGIAMSTW 539
Cdd:cd14964 222 WLPFSIVFILHALVA------------------------AGQGLNLLSILANLLAVLASTLNPFIYCLG 266
7tmF_FZD2 cd15245
class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This ...
225-563 1.04e-46

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: 169.43  E-value: 1.04e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  225 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVCR---- 300
Cdd:cd15245   2 FFSQDEIRFARIWILIWSVLCCASTFFTVTTYLVDMQRF-RYPERPIIFLSGCYTMVSVAYIAGFVLGDK--VVCNerfs 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  301 ADGTMRFGEPTSSEtlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVA 378
Cdd:cd15245  79 EDGYKTVVQGTKKE--GCTILFMMLYFFSMASSIWWVILSLTW---FLAAGMKWghEAIEANSQYFHLAAWAVPAVKTIT 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  379 ILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRL 456
Cdd:cd15245 154 ILAMGQIDGDLLSGVCFVGLNNIDPLRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTimKHDGTKTE----KLERLMVRI 229
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  457 GIFGFLAFGFVLITFSCHFYDFFNQAEWERSFrdyvLCQANVTIGLPTK-KPIPdceiKNRPSLLVEKINLFAMFGTGIA 535
Cdd:cd15245 230 GVFSVLYTVPATIVIACYFYEQAFRQHWERSW----ISQNCKSLAIPCPlQYTP----RMTPDFTVYMIKYLMTLIVGIT 301
                       330       340
                ....*....|....*....|....*...
gi 1813878  536 MSTWVWTKATLLIWRRTWCRLTGHSDDE 563
Cdd:cd15245 302 SGFWIWSGKTLHSWRKFYTRLTNSRQGE 329
7tmF_FZD1 cd15247
class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
226-563 1.10e-45

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: 167.14  E-value: 1.10e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  226 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNrYPAVILFYVNACFFVGSIGWLAQFMdgARREIVCR----A 301
Cdd:cd15247  13 FGPEELRFARIWIGIWSVLCCASTLFTVLTYLVDMKRFS-YPERPIIFLSGCYTMVAIAYIAGFL--LEDKVVCNdkfaE 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  302 DGTMRFGEPTSSEtlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAI 379
Cdd:cd15247  90 DGIKTVAQGTKKE--GCTILFMMLYFFSMASSIWWVILSLTW---FLAAGMKWghEAIEANSQYFHLAAWAVPAIKTITI 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  380 LAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLG 457
Cdd:cd15247 165 LAVGQVDGDVLSGVCFVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTimKHDGTKTE----KLEKLMVRIG 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  458 IFGFLAFGFVLITFSCHFYDFFNQAEWERSFrdyvLCQANVTIGLPTKK-PIPDCEiknrPSLLVEKINLFAMFGTGIAM 536
Cdd:cd15247 241 IFSVLYTVPATIVIACYFYEQAFREQWERSW----ISQSCKTYAIPCPAhSHPPMS----PDFTVFMIKYLMTLIVGITS 312
                       330       340
                ....*....|....*....|....*..
gi 1813878  537 STWVWTKATLLIWRRTWCRLTGHSDDE 563
Cdd:cd15247 313 GFWIWSGKTLNSWRKFYTRLTNSKQGE 339
7tmF_FZD5 cd15249
class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This ...
224-551 6.80e-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: 163.96  E-value: 6.80e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  224 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARReIVCRADG 303
Cdd:cd15249   1 PYFSQDERTFATFWIGLWSVLCFISTFTTVATFLIDMERF-RYPERPIIFLSACYLFVSLGYIVRLVVGHES-VACNREH 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  304 TMRFGEPTSSETlsCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILA 381
Cdd:cd15249  79 NHIHYETTGPAL--CTIVFLLIYFFGMASSIWWVILSFTW---FLAAGMKWgnEAIAGYSQYFHLAAWLIPSVKSIAVLA 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  382 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGIF 459
Cdd:cd15249 154 LSSVDGDPVAGICYVGNQNLNNLRGFVLAPLVVYLFTGTLFLLAGFVSLFRIRSviKQGGTKTD----KLEKLMIRIGIF 229
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  460 GFLAFGFVLITFSCHFYDFFNQAEWERSfrdyvlcqanvtigLPTKKPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTW 539
Cdd:cd15249 230 TVLYTVPATIVVACYVYEQHYRESWEAA--------------LNCSCPGDDTQPRARPDYAVFMLKYFMCLVVGITSGVW 295
                       330
                ....*....|..
gi 1813878  540 VWTKATLLIWRR 551
Cdd:cd15249 296 IWSGKTLESWRR 307
7tmF_FZD4 cd15038
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This ...
225-551 1.74e-43

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: 159.54  E-value: 1.74e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  225 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGT 304
Cdd:cd15038   2 LFTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRF-KYPERPIIFLSMCYNIYSIAYIVRLLAG-RESISCDLDSQ 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  305 --MRFGEPTSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSfKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAV 382
Cdd:cd15038  80 taVSILIQEGLENTGCAIVFLLLYFFGMASSIWWVILTLTWFLA-AGLKWGHEAIQMHSSYFHIAAWALPAVKTIVILVM 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  383 AQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSN--HPGLLSEkaasKINETMLRLGIFG 460
Cdd:cd15038 159 RVVDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQlqRDGTKTD----KLERLMVRIGIFS 234
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  461 FLAFGFVLITFSCHFYDFFNQAEWERSfrdyvlcqanvtiglptkkpipdcEIKNRPSLLVEKINLFAMFGTGIAMSTWV 540
Cdd:cd15038 235 VLYTVPATCVIACYFYEYSNRDLWYYG------------------------GSAARPNMEVFMLKIFMSLVVGITSGMWI 290
                       330
                ....*....|.
gi 1813878  541 WTKATLLIWRR 551
Cdd:cd15038 291 WSAKTLSSWRN 301
7tmF_FZD8 cd15250
class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This ...
224-550 2.01e-42

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: 157.01  E-value: 2.01e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  224 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGarREIVCRADG 303
Cdd:cd15250   1 PYFSQEERTFTAFWIGLWSVLCFLSTFATVSTFLIDMERF-KYPERPIIFLSACYLFVSLGYLVRLIAG--HEKVACSRG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  304 TMRFGEPTSSETLS---CVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVA 378
Cdd:cd15250  78 ALAEVEHIHYETTGpalCTVVFLLIYFFGMASSIWWVILSLTW---FLAAGMKWgnEAIAGYSQYFHLAAWLIPSVKSIA 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  379 ILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSnhpgLLSEKAAS--KINETMLRL 456
Cdd:cd15250 155 VLALSSVDGDPVAGICYVGNQNLDNLRGFVLAPLVIYLFIGTMFLLAGFVSLFRIRS----VIKQGGTKtdKLEKLMIRI 230
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  457 GIFGFLAFGFVLITFSCHFYDFFNQAEWErsfrdyvlcqanVTIGLPTKKPIPDcEIKnRPSLLVEKINLFAMFGTGIAM 536
Cdd:cd15250 231 GIFTVLYTVPATIVVACYFYEQHNRQRWE------------ITHNCNCLRDQPD-QAR-RPDYAVFMLKYFMCLVVGITS 296
                       330
                ....*....|....
gi 1813878  537 STWVWTKATLLIWR 550
Cdd:cd15250 297 GVWTWSGKTLESWR 310
7tmF_FZD10 cd15037
class F frizzled subfamily 10, member of 7-transmembrane G protein-coupled receptors; This ...
237-550 4.49e-42

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: 156.30  E-value: 4.49e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  237 YIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARrEIVCRADGTMRFGEPTSSETL 316
Cdd:cd15037  14 WIAIWSILCFFSSAFTVLTFLID-PQRFKYPERPIIFLSMCYCVYSVGYIIRLFAGAE-SIACDRDSGQLYVIQEGLEST 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  317 SCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 394
Cdd:cd15037  92 GCTIVFLILYYFGMASSLWWVILTLTW---FLAAGKKWghEAIEANSSYFHLAAWAIPAVKTIMILVMRRVAGDELTGVC 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  395 FVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPglLSEKAASKINETMLRLGIFGFLAFGFVLITFSCH 474
Cdd:cd15037 169 YVGSMDVNALTGFVLIPLACYLIIGTSFILSGFVALFHIRRVMK--TGGENTDKLEKLMVRIGVFSVLYTVPATCVIACY 246
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1813878  475 FYDFFNQAEWErsfrdyvLCQANVTIGLPTKKPIPDCEIKNR-PSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWR 550
Cdd:cd15037 247 FYERLNMDYWK-------ILATQQKCKMDNQTKTLDCVMTSSiPAVEIFMVKIFMLLVVGITSGMWIWTSKTLQSWQ 316
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
237-550 4.67e-39

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: 147.41  E-value: 4.67e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  237 YIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARrEIVCRADGTMRFGEPTSSETL 316
Cdd:cd15036  14 WMAVWSTLCFVSTAFTVLTFLLD-PHRFQYPERPIIFLSMCYNVYSVAFLIRAVAGAE-SIACDRENGALYIIQEGLEST 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  317 SCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 394
Cdd:cd15036  92 GCTLVFLILYYFGMASSLWWVVLTLTW---FLAAGKKWghEAIESHGSYFHMAAWGIPALKTIVILTMRKVAGDELTGLC 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  395 FVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGIFGFLAFGFVLITFS 472
Cdd:cd15036 169 YVGSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVALFHIRKvmKTGGTNTE----KLEKLMVKIGVFSILYTVPATCVIV 244
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1813878  473 CHFYDFFNQAEWERSFRDyvlcQANVTigLPTKKPiPDCEIKNR-PSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWR 550
Cdd:cd15036 245 CYFYERLNMDYWDLRALE----ESCRT--VPGRRR-PDCSLPHSvPTVAVFMLKIFMSLVVGITSGVWVWSSKTLQTWQ 316
7tmF_FZD3 cd15033
class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This ...
242-549 1.65e-36

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: 140.08  E-value: 1.65e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  242 GAVTGLC---TLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVCRADGTMRFGEPT---SSET 315
Cdd:cd15033  16 GVISIVClsaTLFTFLTFLID-VTRFRYPERPIIFYAVCYMMVSLIFFIGFLLEDR--VACNAASPGQYKASTvtqGSHN 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  316 LSCVIIFVIVYYALMAGVVWFVVLTYAWH-TSFKALGTtyQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 394
Cdd:cd15033  93 KACTMLFMVLYFFTMAGSVWWVILTITWFlAAVPKWGS--EAIEKKALLFHASAWGIPGTLTIILLAMNKIEGDNISGVC 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  395 FVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPglLSEKAASKINETMLRLGIFGFLAFGFVLITFSCH 474
Cdd:cd15033 171 FVGLYDVDALRYFVLAPLCLDVVVGVSLLLAGIISLNRVRIEIP--LEKENQDKLVKFMIRIGVFSVLYLVPLLVVIGCY 248
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  475 FYDFFNQAEWERSF-----RDYVLcqanvtiglptkkPIP-DCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLI 548
Cdd:cd15033 249 FYEQAYRGVWETTWvqercREYHI-------------PCPyKVTQTSRPDLILFLMKYLMALVVGIPSVFWVGSKKTCFE 315

                .
gi 1813878  549 W 549
Cdd:cd15033 316 W 316
7tmF_FZD3_FZD6-like cd15910
class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G ...
236-549 1.22e-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: 131.90  E-value: 1.22e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  236 SYIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVCR-ADGTMRFGEPT--S 312
Cdd:cd15910  13 YFIGVVSILCLLATLFTFLTFLID-VNRFRYPERPIIFYAVCYFVVSLIFFVGFLLGDD--VACNhAIMDENNGATVveG 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  313 SETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV 390
Cdd:cd15910  90 SRNKACTILFMILYFFTMAGTVWWVILTITW---FLAAGFKWgsEAIEKKALYFHALAWGIPGVLTMVLLATNKIEGDNI 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  391 SGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPglLSEKAASKINETMLRLGIFGFLAFGFVLIT 470
Cdd:cd15910 167 SGVCFVGLYDSDGLRFFVLLPLCLYVLVGMSLLLAGIICLNRVRKSIH--DDETNQEKLAKFMIRIGVFSILYLVPLLTL 244
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  471 FSCHFYDFFNQAEWE-----RSFRDYVLcqanvtiglptkkPIP-DCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKA 544
Cdd:cd15910 245 IGCYAYEQSNRKSWEstwvvRNCRRYHI-------------PCPqLAQGNPRPGLFLFCIKYLMTLIVGIPPVFWVGSKK 311

                ....*
gi 1813878  545 TLLIW 549
Cdd:cd15910 312 TCAEW 316
7tmF_FZD6 cd15032
class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This ...
226-549 4.14e-32

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: 127.27  E-value: 4.14e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  226 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVC-RADGT 304
Cdd:cd15032   3 FKSDELDFAKSFIGIVSIFCLCATLFTFLTFLIDVKRF-RYPERPIIYYSVCYSIVSLMYFIGFLLGNS--TACnKADEK 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  305 MRFGEPT--SSETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAIL 380
Cdd:cd15032  80 LELGDTVvlGSQNKACTVLFMLLYFFTMAGTIWWVILTITW---FLAAGRKWscEAIEQKALWFHAVAWGIPGFLTIMLL 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  381 AVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGI 458
Cdd:cd15032 157 AMNKVEGDNISGVCFVGLYDLDASRYFVLLPLCLCVFVGLSLLLAGIISLNHVRQviQHDGRNQE----KLKKFMIRIGV 232
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  459 FGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKKPipdceikNRPSLLVEKINLFAMFGTGIAMST 538
Cdd:cd15032 233 FSGLYLVPLVTLLGCYVYEQVYRRTWEITWVSDHCQQYHIPCPYQAKAV-------ARPELALFLIKYLMTLIVGISAVF 305
                       330
                ....*....|.
gi 1813878  539 WVWTKATLLIW 549
Cdd:cd15032 306 WVGSKKTCSEW 316
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
74-182 6.41e-32

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: 120.11  E-value: 6.41e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878      74 CEPLRYNVCLGsaLPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNAPrCWAVIQPLLCAVYMPKCEND-RVELPSRTLCQ 152
Cdd:smart00063   1 CEPITIPLCKD--LGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQ-CSPDLRFFLCSVYAPICTEDlRPILPCRSLCE 77
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1813878     153 ATRGPCAIVERERG--WPDFLRCtpDHFP---EGC 182
Cdd:smart00063  78 AAREGCEPLMEKFGfpWPEFLRC--DRFPvqeELC 110
CRD_FZ cd07066
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
73-201 6.34e-18

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: 80.24  E-value: 6.34e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   73 HCEPLRYNVClgSALPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKCEND--RVELPSRTL 150
Cdd:cd07066   1 KCEPIPLPLC--RGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNS-GCHPDLRFFLCSLYFPECTPDgdRPIPPCRSL 77
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 1813878  151 CQATRGPCAIVERERG--WPDFLRCtpDHFPEgcpnevqnikFNSSGQCEAPL 201
Cdd:cd07066  78 CEEVRDSCEPLMLAFGfpWPEPLDC--DRFPD----------SNEEGLCISPP 118
7tmF_FZD3_insect cd15031
class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; ...
225-551 8.33e-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: 85.21  E-value: 8.33e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  225 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCR---A 301
Cdd:cd15031   2 FYTTRQKKLVESWMLVLSAVSFILTLFALVTFWAE-PTRFGYPERPVLFMALCYNLISLCYLERGILGTFTNCSARslaI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  302 DGTMRFGEPTSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWH-TSFKALGTTyqPLSGKTSYFHLLTWSLPFVLTVAIL 380
Cdd:cd15031  81 DCDDRYLRQDCLLTPQCLASFIITYYLSLSAASWWLIFALCWYlSSAKKWSSE--ALEKKSGLFHVLAWVPPLAPPIAAL 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  381 AVAQVDGDSVSGICfvgYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNhpglLSEKAASKINETMLRLGIFG 460
Cdd:cd15031 159 LLERVSASELTGTC---TASGFVESSISELPALILLLLGLYLTIAALRSLLSLQQQ----LQSRLAHAPQRILARVSIFS 231
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  461 FLAF---GFVLITFSChfydffnqaewERSFRDYVLCQANVTIGLPTKKPIPDCEIKnrPSLLveKINLFAMFGTGIAMs 537
Cdd:cd15031 232 LLYLipaAAALICKLC-----------ERWLQPVPECNALQEDCAPPATDNEFLSAL--PALL--RVFFFLIGGTATGL- 295
                       330
                ....*....|....
gi 1813878  538 tWVWTKATLLIWRR 551
Cdd:cd15031 296 -WLWSRKSCESWRS 308
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
74-180 1.65e-14

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: 70.29  E-value: 1.65e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878     74 CEPLRYNVCLGsaLPYGATTTLLAGDSDSQEEAHSKLVL-----WSGLRNApRCWAVIQPLLCAVYMPKCE----NDRVE 144
Cdd:pfam01392   1 CEPITLPMCLG--LGYNATVFPNLLGHQTQEEAELSLAYlvlseFEPLVDL-SCSPSLRLFLCSLYFPPCTlgpsPKPVC 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1813878    145 LPSRTLCQATRGPCAIVERERG----WPDFLRCtpDHFPE 180
Cdd:pfam01392  78 PPCRSLCEEVRYGCEPLLEEAKfgfsWPEFLDC--DSLPA 115
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
236-475 4.07e-12

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: 67.21  E-value: 4.07e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  236 SYIAAFG-AVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLaqfmdgarreivcradgtmrFGEPTSSE 314
Cdd:cd15040   5 SIITYIGcGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFL--------------------FGINSTDN 64
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  315 TLSCVIIFVIVYYALMAGVVWFVVLtyAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 394
Cdd:cd15040  65 PVLCTAVAALLHYFLLASFMWMLVE--ALLLYLRLVKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYC 142
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  395 FVGYKNYRYraGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgllsekaASKINETMLRLG-------------IFGF 461
Cdd:cd15040 143 WLSNGNGLY--YAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRN-------KKKRKKTKAQLRaavslffllgltwIFGI 213
                       250
                ....*....|....
gi 1813878  462 LAFGFVLITFSCHF 475
Cdd:cd15040 214 LAIFGARVVFQYLF 227
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
247-482 1.16e-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: 65.70  E-value: 1.16e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  247 LCTLFTLATFVA--DWRNsnrYPAVILFYVNACFFVGSIGWLAqfmdgarreivcradgtmRFGEPTSSETLSCVIIFVI 324
Cdd:cd13952  17 VGLLLTIITYLLfpKLRN---LRGKILINLCLSLLLAQLLFLI------------------GQLLTSSDRPVLCKALAIL 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  325 VYYALMAGVVWFVVLT-YAWHTSFKALGTTYqplSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV----SGICFVGYK 399
Cdd:cd13952  76 LHYFLLASFFWMLVEAfDLYRTFVKVFGSSE---RRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSpgygGEYCWLSNG 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  400 NYRYraGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgllsekAASKINETMLRLGIFGFLafgFVL--ITFSCHFYD 477
Cdd:cd13952 153 NALL--WAFYGPVLLILLVNLVFFILTVRILLRKLRETP------KQSERKSDRKQLRAYLKL---FPLmgLTWIFGILA 221

                ....*
gi 1813878  478 FFNQA 482
Cdd:cd13952 222 PFVGG 226
CRD_FZ3 cd07449
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich ...
74-180 3.99e-09

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


Pssm-ID: 143558 [Multi-domain]  Cd Length: 127  Bit Score: 55.40  E-value: 3.99e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   74 CEPLRYNVCLGsaLPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKC-ENDRVELPSRTLCQ 152
Cdd:cd07449   5 CEPITLRMCQD--LPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNL-ECSRDFRPFLCALYAPVCmEYGRVTLPCRRLCQ 81
                        90       100       110
                ....*....|....*....|....*....|
gi 1813878  153 ATRGPCAIVERERG--WPDFLRCTpdHFPE 180
Cdd:cd07449  82 RAYSECSKLMEMFGvpWPEDMECS--RFPD 109
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
74-180 3.35e-08

Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 4 (Fz4) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and the Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Frizzled 4 (Fz4) activates the Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C of the Wnt/Ca(2+) signaling pathway during retinal angiogenesis. Mutations in Fz4 lead to familial exudative vitreoretinopathy (FEVR), a hereditary ocular disorder characterized by failure of the peripheral retinal vascularization. In addition, the interplay between Fz4 and norrin as a receptor-ligand pair plays an important role in vascular development in the retina and inner ear in a Wnt-independent manner.


Pssm-ID: 143557  Cd Length: 126  Bit Score: 52.85  E-value: 3.35e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   74 CEPLRYNVCLGsaLPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKCeNDRVEL---PSRTL 150
Cdd:cd07448   4 CEPIRIEMCQG--LGYNVTRMPNLVGHELQTDAELQLQTFTPLIQY-GCSSQLKFFLCSVYVPMC-TEKVPVpigPCRPL 79
                        90       100       110
                ....*....|....*....|....*....|..
gi 1813878  151 CQATRGPCAIVERERG--WPDFLRCtpDHFPE 180
Cdd:cd07448  80 CLSVKKRCLPVLKEFGfpWPEALNC--SKFPP 109
CRD_Carboxypeptidase_Z cd07447
Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The ...
72-182 2.77e-07

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: 50.14  E-value: 2.77e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   72 AHCEPLRYNVClgSALPYGATT--TLLAGDSDSQEEAHSKLVLWSGLRN--APRCWAVIQPLLCAVYMPKCENDRVELPS 147
Cdd:cd07447   2 ATCTDLLLSYC--SDVSYTQTTfpNLLGHRSREVTEAGAEYLLLSVLHGllGGECNPDIRLLGCSVLAPRCENDKVIKPC 79
                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 1813878  148 RTLCQATRGPC--AIVERERGWPDFLRCtpDHF----PEGC 182
Cdd:cd07447  80 RSTCEALRKRCshAFDAIQMAWPYFLDC--DRFfageQEGC 118
CRD_FZ9 cd07463
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich ...
70-173 1.28e-06

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 9 (Fz9) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz9 may play a signaling role in lymphoid development and maturation, particularly at points where B cells undergo self-renewal prior to further differentiation.


Pssm-ID: 143572  Cd Length: 127  Bit Score: 48.10  E-value: 1.28e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   70 RAAHCEPLRYNVCLGsaLPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNAPrCWAVIQPLLCAVYMPKCeNDRVELP--- 146
Cdd:cd07463   1 RAAKCQPVVIPMCRG--IGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYG-CHVHLRFFLCSLYAPMC-TDQVSTSipa 76
                        90       100
                ....*....|....*....|....*....
gi 1813878  147 SRTLCQATRGPCA-IVER-ERGWPDFLRC 173
Cdd:cd07463  77 CRPMCEQARQKCSpIMEQfNFGWPESLDC 105
CRD_SFRP5 cd07444
Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt ...
99-179 1.66e-06

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


Pssm-ID: 143553  Cd Length: 127  Bit Score: 48.02  E-value: 1.66e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   99 DSDSQEEAHSKLVLWSGLRnAPRCWAVIQPLLCAVYMPKCEnDRVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpD 176
Cdd:cd07444  32 EHESMAEVKQQASSWVPLL-AKRCHADTQVFLCSLFAPVCL-DRPIYPCRSLCEAVRDSCAPVMESYGfpWPEMLHC--H 107

                ...
gi 1813878  177 HFP 179
Cdd:cd07444 108 KFP 110
CRD_SFRP1 cd07443
Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt ...
99-181 1.93e-06

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: 47.59  E-value: 1.93e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   99 DSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKCEnDRVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpD 176
Cdd:cd07443  32 DHETMAEVKQQASSWVPLLNK-NCHKGTQVFLCSLFAPVCL-DRPVYPCRWLCEAVRDSCEPVMQFFGfyWPEMLKC--D 107

                ....*
gi 1813878  177 HFPEG 181
Cdd:cd07443 108 KFPEG 112
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
318-480 2.21e-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: 49.92  E-value: 2.21e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  318 CVIIFVIVYYALMAGVVWFVVLTY-AWHT-SFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV----- 390
Cdd:cd15039  68 CVALGILLHFFFLAAFFWLNVMSFdIWRTfRGKRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDFSPNTDSlrpgy 147
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878  391 -SGICFVGYKNYRYRagFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNhpgllSEKAASKINETM------LRLG------ 457
Cdd:cd15039 148 gEGSCWISNPWALLL--YFYGPVALLLLFNIILFILTAIRIRKVKKE-----TAKVQSRLRSDKqrfrlyLKLFvimgvt 220
                       170       180
                ....*....|....*....|....
gi 1813878  458 -IFGFLAFGFVLITFSCHFYDFFN 480
Cdd:cd15039 221 wILEIISWFVGGSSVLWYIFDILN 244
CRD_FZ8 cd07461
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich ...
74-184 2.82e-06

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 8 (Fz8) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Xenopus Fz8 is important in Wnt/beta-catenin signaling pathways controlling the transcriptional activation of target genes Siamois and Xnr3 in the animal caps of late blastula.


Pssm-ID: 143570  Cd Length: 125  Bit Score: 47.28  E-value: 2.82e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   74 CEPLRYNVCLGsaLPYGATTTLLAGDSDSQEEAHSKL-VLWSGLRnaPRCWAVIQPLLCAVYMPKCEND--RVELPSRTL 150
Cdd:cd07461   5 CQEITVPLCKG--IGYNYTYMPNQFNHDTQDEAGLEVhQFWPLVE--IQCSPDLKFFLCSMYTPICLEDykKPLPPCRSV 80
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 1813878  151 CQATRGPCAIVERERG--WPDFLRCtpDHFPE-GCPN 184
Cdd:cd07461  81 CERAKAGCAPLMRQYGfpWPDRMRC--DLLPEqGNPD 115
CRD_FZ5_like cd07456
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich ...
74-181 1.54e-05

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 5 (Fz5) and frizzled 8 (Fz8) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143565  Cd Length: 120  Bit Score: 44.70  E-value: 1.54e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   74 CEPLRYNVCLGsaLPYGATTTLLAGDSDSQEEA-HSKLVLWSGLRnaPRCWAVIQPLLCAVYMPKCEND--RVELPSRTL 150
Cdd:cd07456   2 CEEITIPMCKG--IGYNMTYMPNQFNHDTQEEAgLEVHQFWPLVE--IQCSPDLKFFLCSMYTPICLEDydKPLPPCRSV 77
                        90       100       110
                ....*....|....*....|....*....|...
gi 1813878  151 CQATRGPCAIVERERG--WPDFLRCtpDHFPEG 181
Cdd:cd07456  78 CERARDGCAPIMRQYGfaWPERMSC--DALPEG 108
CRD_FZ9_like cd07457
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich ...
72-181 3.38e-05

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 9 (Fz9) and frizzled 10 (Fz10) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143566  Cd Length: 121  Bit Score: 44.02  E-value: 3.38e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   72 AHCEPLRYNVCLGsaLPYGATT--TLLAgdSDSQEEAHSKLVLWSGLRnAPRCWAVIQPLLCAVYMPKCeNDRVELP--- 146
Cdd:cd07457   1 GKCERITIPMCQG--IGYNMTRmpNLLG--HESQSEAAISIHEFAPLV-QYGCAEHLRFFLCSLYAPMC-TEQVSIPipa 74
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 1813878  147 SRTLCQATRGPCA-IVER-ERGWPDFLRCtpDHFPEG 181
Cdd:cd07457  75 CRSMCEQARDKCSpIMEQfSFSWPDSLDC--DRLPRK 109
CRD_corin_1 cd07445
One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ...
74-174 1.45e-04

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: 42.23  E-value: 1.45e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   74 CEPLRYNVClgSALPYGATTTLLAGDSDSQEeaHSKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVE----LPSRT 149
Cdd:cd07445   5 CMNITHSQC--QMLPYHSTLKPSLLSVKNME--MEKFLKFFSYLHRLSCYQHIMLFGCSLALPECISDGDDrhglLPCRS 80
                        90       100
                ....*....|....*....|....*..
gi 1813878  150 LCQATRGPCAIVER--ERGWPDFLRCT 174
Cdd:cd07445  81 FCEAAKEGCEPVLGmvNASWPDFLRCS 107
CRD_SFRP4 cd07442
Cysteine-rich domain of the secreted frizzled-related protein 4 (SFRP4), a Wnt antagonist; The ...
70-173 1.50e-04

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


Pssm-ID: 143551  Cd Length: 127  Bit Score: 42.32  E-value: 1.50e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   70 RAAHCEPLRYNVClgSALPYGATTTLLAGDSDSQEEAHSKLVLWSGLRnAPRCWAVIQPLLCAVYMPKCE----NDRVEl 145
Cdd:cd07442   1 QGAPCEAVRIPMC--RHMPWNITRMPNHLHHSTQENAVLAIEQYEELV-DTGCSPVLPFFLCAMYAPICTleflYDPIK- 76
                        90       100       110
                ....*....|....*....|....*....|
gi 1813878  146 PSRTLCQATRGPCAIVER--ERGWPDFLRC 173
Cdd:cd07442  77 PCRSVCQRARDGCEPIMRryNHSWPESLAC 106
CRD_FZ1_like cd07458
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 1; The cysteine-rich ...
74-186 1.61e-04

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 1; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 1 (Fz1), frizzled 2 (Fz2), and frizzled 7 (Fz7) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143567  Cd Length: 119  Bit Score: 42.01  E-value: 1.61e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   74 CEPLRYNVCLGsaLPYGATT--TLLAgdSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKCEN-DRVELPSRTL 150
Cdd:cd07458   3 CEPITIPLCTD--IPYNMTIfpNLLG--HTKQEDAGLEVHQFYPLVKV-QCSPDLKFFLCSVYAPVCTVlERPIPPCRSL 77
                        90       100       110
                ....*....|....*....|....*....|....*...
gi 1813878  151 CQATRGPCAIVERERG--WPDFLRCtpDHFPEGCPNEV 186
Cdd:cd07458  78 CESARQGCEALMNKFGfqWPESLDC--EKFPVHGAGDL 113
CRD_crescent cd07453
Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential ...
129-180 3.80e-04

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: 41.46  E-value: 3.80e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 1813878  129 LLCAVYMPKCEnDRVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpDHFPE 180
Cdd:cd07453  57 FLCSLFAPICW-DRPIYPCRSLCEAVRSSCAPLMACYGypWPEILHC--DKFPV 107
CRD_SFRP2 cd07446
Cysteine-rich domain of the secreted frizzled-related protein 2 (SFRP2), a regulator of Wnt ...
70-181 5.79e-04

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


Pssm-ID: 143555  Cd Length: 128  Bit Score: 40.66  E-value: 5.79e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   70 RAAHCEPLRYNVCLGSALPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKCENDRVEL--PS 147
Cdd:cd07446   1 KKSNCKPIPANMLLCHGIEYTNMRLPNLLGHETMKEVLQQAGSWIPLVQK-QCHPDTKKFLCSLFAPVCLDDLDEAiqPC 79
                        90       100       110
                ....*....|....*....|....*....|....*.
gi 1813878  148 RTLCQATRGPCAIVERERG--WPDFLRCtpDHFPEG 181
Cdd:cd07446  80 RSLCEAVKDGCAPVMSAFGfpWPDMLDC--TRFPLD 113
CRD_SFRP3 cd07441
Cysteine-rich domain of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), a Wnt ...
71-173 1.34e-03

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


Pssm-ID: 143550  Cd Length: 126  Bit Score: 39.65  E-value: 1.34e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   71 AAHCEPLRYNVClgSALPYGATTTLLAGDSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKC----ENDRVElP 146
Cdd:cd07441   1 AASCEPVRIPMC--KSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGT-QCSPDLLFFLCAMYAPICtidfQHEPIK-P 76
                        90       100
                ....*....|....*....|....*....
gi 1813878  147 SRTLCQATRGPC--AIVERERGWPDFLRC 173
Cdd:cd07441  77 CKSVCERARAGCepVLIRYRHTWPESLAC 105
CRD_FZ2 cd07464
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich ...
74-179 2.06e-03

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 2 (Fz2) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz2 is involved in the Wnt/beta-catenin signaling pathway and in the activation of protein kinase C and calcium/calmodulin-dependent protein kinase (CaM kinase).


Pssm-ID: 143573  Cd Length: 127  Bit Score: 38.91  E-value: 2.06e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   74 CEPLRYNVCLGSALPYGATTTLLAgdSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKCEN-DRVELPSRTLCQ 152
Cdd:cd07464   5 CQPISIPLCTDIAYNQTIMPNLLG--HTNQEDAGLEVHQFYPLVKV-QCSLELRFFLCSMYAPVCTVlEQAIPPCRSICE 81
                        90       100
                ....*....|....*....|....*....
gi 1813878  153 ATRGPCAIVERERG--WPDFLRCtpDHFP 179
Cdd:cd07464  82 RARQGCEALMNKFGfqWPERLRC--ENFP 108
CRD_FZ1 cd07465
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich ...
72-179 4.51e-03

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 1 (Fz1) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata.


Pssm-ID: 143574  Cd Length: 127  Bit Score: 38.11  E-value: 4.51e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   72 AHCEPLRYNVCLGSALPYGATTTLLAgdSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKCENDRVELPS-RTL 150
Cdd:cd07465   3 GYCQPISIPLCTDIAYNQTIMPNLLG--HTNQEDAGLEVHQFYPLVKV-QCSAELKFFLCSMYAPVCTVLEQALPPcRSL 79
                        90       100       110
                ....*....|....*....|....*....|.
gi 1813878  151 CQATRGPCAIVERERG--WPDFLRCtpDHFP 179
Cdd:cd07465  80 CERARQGCEALMNKFGfqWPDTLRC--EKFP 108
CRD_FZ7 cd07466
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich ...
74-193 5.11e-03

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 7 (Fz7) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Xenopus Fz7 is important in Wnt/beta-catenin signaling pathways controlling the transcriptional activation of target genes Siamois and Xnr3 in the animal caps of late blastula.


Pssm-ID: 143575 [Multi-domain]  Cd Length: 125  Bit Score: 37.76  E-value: 5.11e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1813878   74 CEPLRYNVCLGSALPYGATTTLLAgdSDSQEEAHSKLVLWSGLRNApRCWAVIQPLLCAVYMPKCEN-DRVELPSRTLCQ 152
Cdd:cd07466   5 CQPISIPLCTDIAYNQTIMPNLLG--HTNQEDAGLEVHQFYPLVKV-QCSPELKFFLCSMYAPVCTVlEQAIPPCRSLCE 81
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 1813878  153 ATRGPCAIVERERG--WPDFLRCtpDHFPEGCPNEV---QNIKFNS 193
Cdd:cd07466  82 RARQGCEALMNKFGfqWPERLRC--ENFPVHGAGEIcvgQNTSDAS 125
 
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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