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Conserved domains on  [gi|1952684988|ref|XP_038299284|]
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smoothened homolog isoform X1 [Canis lupus familiaris]

Protein Classification

CRD_SMO and 7tmF_SMO_homolog domain-containing protein( domain architecture ID 11575552)

CRD_SMO and 7tmF_SMO_homolog domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
219-549 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: 666.30  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 219 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADG 298
Cdd:cd15030     1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 299 TMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVA 378
Cdd:cd15030    81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 379 QVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLA 458
Cdd:cd15030   161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 459 FGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKKPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTK 538
Cdd:cd15030   241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTIAEQTNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                         330
                  ....*....|.
gi 1952684988 539 ATLLIWRRTWC 549
Cdd:cd15030   321 ATLETWKRFWR 331
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
65-195 3.25e-82

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: 258.45  E-value: 3.25e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  65 RAAPCEPLRYNVCLGSALPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRT 144
Cdd:cd07451     1 RPAKCEPLKNTTCLGSKLPYTYTSLDLVPDSTTQEEVQEKLHLWSGLRNVPKCWAVIQPLLCALYMPKCENGKVELPSQE 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1952684988 145 LCQATRGPCAIVERERGWPDFLRCTPDHFP-EGCPNEVQNIKFNSSGQCEAP 195
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 ...
219-549 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: 666.30  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 219 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADG 298
Cdd:cd15030     1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 299 TMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVA 378
Cdd:cd15030    81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 379 QVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLA 458
Cdd:cd15030   161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 459 FGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKKPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTK 538
Cdd:cd15030   241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTIAEQTNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                         330
                  ....*....|.
gi 1952684988 539 ATLLIWRRTWC 549
Cdd:cd15030   321 ATLETWKRFWR 331
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
220-551 4.37e-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: 4.37e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 220 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWrNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGT 299
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDW-SRFRYPERPIIFLSLCYLLVSLGYLIRFVLG-REDIACRKDGT 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 300 MRLG--EPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTS-FKALGttYQPLSGKTSYFHLLTWSLPFVLTVAILA 376
Cdd:pfam01534  79 GRGSylITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAaGLKWG--SEAIEKKSSYFHLAAWGIPAVLTITVLA 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 377 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgLLSEKAASKINETMLRLGIFGF 456
Cdd:pfam01534 157 LGKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLK-KDGARATDKLEKLMVRIGVFSV 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 457 LAFGFVLITFSCHFYDFFNQAEWERSFRdYVLCQANvtiglptkkpIPDC--EIKNRPSLLVEKINLFAMFGTGIAMSTW 534
Cdd:pfam01534 236 LYTVPALIVIACYFYEYANRDSWELSWQ-YINCRAY----------GIPCldEPESRPSFSVFMLKYFMSLVVGITSGFW 304
                         330
                  ....*....|....*..
gi 1952684988 535 VWTKATLLIWRRTWCRL 551
Cdd:pfam01534 305 VWSGKTLESWRRFFRRL 321
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
65-195 3.25e-82

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: 258.45  E-value: 3.25e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  65 RAAPCEPLRYNVCLGSALPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRT 144
Cdd:cd07451     1 RPAKCEPLKNTTCLGSKLPYTYTSLDLVPDSTTQEEVQEKLHLWSGLRNVPKCWAVIQPLLCALYMPKCENGKVELPSQE 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1952684988 145 LCQATRGPCAIVERERGWPDFLRCTPDHFP-EGCPNEVQNIKFNSSGQCEAP 195
Cdd:cd07451    81 MCQATRGPCKIVENERGWPDFLRCDNDRFPpRGCKNDVRELKFNTSGQCESP 132
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
69-177 4.44e-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: 120.49  E-value: 4.44e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988   69 CEPLRYNVCLGsaLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPrCWAVIQPLLCAVYMPKCEND-RVELPSRTLCQ 147
Cdd:smart00063   1 CEPITIPLCKD--LGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQ-CSPDLRFFLCSVYAPICTEDlRPILPCRSLCE 77
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1952684988  148 ATRGPCAIVERERG--WPDFLRCtpDHFP---EGC 177
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 ...
69-175 2.88e-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: 69.90  E-value: 2.88e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVCLGsaLPYGATSTLLAGDSDSQEEAHGKLVL-----WSGLRNApRCWAVIQPLLCAVYMPKCE----NDRVE 139
Cdd:pfam01392   1 CEPITLPMCLG--LGYNATVFPNLLGHQTQEEAELSLAYlvlseFEPLVDL-SCSPSLRLFLCSLYFPPCTlgpsPKPVC 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1952684988 140 LPSRTLCQATRGPCAIVERERG----WPDFLRCtpDHFPE 175
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 ...
219-549 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: 666.30  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 219 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADG 298
Cdd:cd15030     1 PLFTEDEHRQIHKFIAVFASVCLLCTLFTVLTFFIDWKNSNRYPAVILFYINACFFIGSIGWLAQFLPGAREDIVCRKDG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 299 TMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVA 378
Cdd:cd15030    81 TMRLGEPSAGENLSCVVIFVLVYYFLMAGCVWFVILTYAWHMSFKALGTIQDRLDKKTAYFHLIAWSLPLVLTITIMALG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 379 QVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLA 458
Cdd:cd15030   161 QVDGDSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISSPEILSEKASSKIRETIVRLGIFAFLA 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 459 FGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKKPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTK 538
Cdd:cd15030   241 LGFVLITFACHVYEFFNQAEWEKSFRDYIVCEANVTIAEQTNGDIPECELKSRPSLAMLQLHLLALFGAGIAMSSWVWTR 320
                         330
                  ....*....|.
gi 1952684988 539 ATLLIWRRTWC 549
Cdd:cd15030   321 ATLETWKRFWR 331
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
220-551 4.37e-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: 4.37e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 220 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWrNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGT 299
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDW-SRFRYPERPIIFLSLCYLLVSLGYLIRFVLG-REDIACRKDGT 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 300 MRLG--EPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTS-FKALGttYQPLSGKTSYFHLLTWSLPFVLTVAILA 376
Cdd:pfam01534  79 GRGSylITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAaGLKWG--SEAIEKKSSYFHLAAWGIPAVLTITVLA 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 377 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgLLSEKAASKINETMLRLGIFGF 456
Cdd:pfam01534 157 LGKVDGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLK-KDGARATDKLEKLMVRIGVFSV 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 457 LAFGFVLITFSCHFYDFFNQAEWERSFRdYVLCQANvtiglptkkpIPDC--EIKNRPSLLVEKINLFAMFGTGIAMSTW 534
Cdd:pfam01534 236 LYTVPALIVIACYFYEYANRDSWELSWQ-YINCRAY----------GIPCldEPESRPSFSVFMLKYFMSLVVGITSGFW 304
                         330
                  ....*....|....*..
gi 1952684988 535 VWTKATLLIWRRTWCRL 551
Cdd:pfam01534 305 VWSGKTLESWRRFFRRL 321
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
219-549 1.75e-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: 362.41  E-value: 1.75e-119
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 219 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNsNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADG 298
Cdd:cd13951     1 GLFTSSEKKFAEIWISAWSALCFLLTLFTLLTFLIDPSR-FRYPERPIIFLALCYNFYSLGYLVRLVVG-REGIACGKDE 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 299 TM-RLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTyQPLSGKTSYFHLLTWSLPFVLTVAILAV 377
Cdd:cd13951    79 GKpYLLLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSS-EAIEKKSSYFHLVAWGLPAVLTIAVLVL 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 378 AQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGllSEKAASKINETMLRLGIFGFL 457
Cdd:cd13951   158 RKVDGDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSILSN--DGKKTDKLEKLMLRIGIFAVL 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 458 AFGFVLITFSCHFYDFFNQAEWERSFRDYVLCqanvtiglptkkpIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWT 537
Cdd:cd13951   236 YTLPALIVIACYFYEYANRPDWLRSWEPHSCC-------------SPDCEILSRPSLAVFLLKYFMQLVIGITTGVWVWS 302
                         330
                  ....*....|..
gi 1952684988 538 KATLLIWRRTWC 549
Cdd:cd13951   303 KKTLLSWRRLLR 314
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
65-195 3.25e-82

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: 258.45  E-value: 3.25e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  65 RAAPCEPLRYNVCLGSALPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRT 144
Cdd:cd07451     1 RPAKCEPLKNTTCLGSKLPYTYTSLDLVPDSTTQEEVQEKLHLWSGLRNVPKCWAVIQPLLCALYMPKCENGKVELPSQE 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1952684988 145 LCQATRGPCAIVERERGWPDFLRCTPDHFP-EGCPNEVQNIKFNSSGQCEAP 195
Cdd:cd07451    81 MCQATRGPCKIVENERGWPDFLRCDNDRFPpRGCKNDVRELKFNTSGQCESP 132
7tmF_FZD5_FZD8-like cd15035
class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G ...
219-549 1.42e-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: 195.96  E-value: 1.42e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 219 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADg 298
Cdd:cd15035     1 PFFSEDEKTFATFWIGLWSILCFISTLITVLTFLID-MQRFQYPERPIIFLSFCYFMVSVGYIIRLIVG-HEAVACDGG- 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 299 TMRLGeptSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTYQP--LSGKTSYFHLLTWSLPFVLTVAILA 376
Cdd:cd15035    78 IIRYA---TTGPALCTVVFLLTYFFGMASSIWWVILSLTW---FLAAGLKWGNeaISSYSQYFHLVAWLIPAVQTIAILA 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 377 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS---NHPGllseKAASKINETMLRLGI 453
Cdd:cd15035   152 LSAVDGDPISGICYVGNQNLNNLRGFVLAPLVVYLILGTSFLLAGFVSLFRIRNvikQQGG----DKTDKLEKLMIRIGI 227
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 454 FGFLAFGFVLITFSCHFYDFFNQAEWERSfrdyVLCqanvtiglptkkPIPDCEIKNRPSLLVEKINLFAMFGTGIAMST 533
Cdd:cd15035   228 FSVLYTVPATIVIACYFYEQHYREIWEKS----LNC------------PCSPGSIKSRPEYSIFMLKYFMSLVVGITSGF 291
                         330
                  ....*....|....*.
gi 1952684988 534 WVWTKATLLIWRRTWC 549
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 ...
242-549 4.50e-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: 4.50e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 242 LCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRAD--GTMRLGEPTSNETLsCVIIFVI 319
Cdd:cd15909    24 ASTAFTVLTFLID-TSRFRYPERPIIFLSMCYFIYSLGYLIRLFLG-RERIACDSLnsGVSYLIQEGLESTW-CTIVFLL 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 320 VYYALMAGVVWFVVLTYAWHTSfKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYR 399
Cdd:cd15909   101 LYYFGMASALWWVILTFTWYLA-AGRKWGPEAIEAASSYFHLVAWALPAVKTIVILIMHKVDADELTGLCYVGNHDSDAL 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 400 AGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSN--HPGLlsekAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQA 477
Cdd:cd15909   180 LGFVLVPLAIYLLIGTLFILAGFVSMFRIRRNlkTRGT----DTSKLEKLMVKIGVFSVLYTVPATCVIACYFYEYLNMD 255
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1952684988 478 EWERSFRDyVLCQANVTIGLPTkkpipdCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWRRTWC 549
Cdd:cd15909   256 QWRIAAIE-CKCQSPNAIGSDC------CLQPSIPSVEIYMLKIFMSLVVGITSGMWVWSSKTLQSWQRFIC 320
7tmF_FZD1_2_7-like cd15034
class F frizzled subfamilies 1, 2 and 7; member of 7-transmembrane G protein-coupled receptors; ...
237-546 5.27e-49

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: 175.61  E-value: 5.27e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 237 GAVTGLC---TLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMdgARREIVCR----ADGTMRLGEPTSNE 309
Cdd:cd15034    16 GIWSVLCaasTLFTVLTFLID-MDRFRYPERPIIFLSGCYFMVSIAYIVGFF--LGDKVACNgpfpPGGPKTVTQGTKKE 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 310 tlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSG 387
Cdd:cd15034    93 --GCTILFMMLYFFSMASSIWWVILTLTW---FLAAGLKWghEAIEANSQYFHLAAWAVPAIKTIAILAMGKVDGDVLSG 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 388 ICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGIFGFLAFGFVLIT 465
Cdd:cd15034   168 VCFVGLSDVDALRGFVLAPLFVYLLIGTSFLLAGFVSLFRIRTvmKHDGTKTD----KLEKLMVRIGVFSVLYTVPATIV 243
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 466 FSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPtkkpiPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWR 545
Cdd:cd15034   244 IACYFYEQANRESWEKSWLSQNCKKYEDPCPCP-----PTPHPLDRPDFTVFMIKYLMTLIVGITSGFWIWSGKTLQSWR 318

                  .
gi 1952684988 546 R 546
Cdd:cd15034   319 Q 319
7tmF_FZD1_insect cd15248
class F insect frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
221-551 7.37e-49

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: 175.77  E-value: 7.37e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 221 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGarREIVCRA--DG 298
Cdd:cd15248     3 FPERERTFSRYWIGSWAAVCMASCLFTVLTFLIDSSRF-RYPERPIVFLSVCYLMVAAAYVAGLGAG--DSVSCNEpfPP 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 299 TMRLGEPTSNETL-------SCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFV 369
Cdd:cd15248    80 PVKLGRLQMVSTItqgtkteSCTVLFMVLYFFSMAASIWWVVLTLTW---FLAAGLKWghEAIEAKSHYFHLVAWAVPAL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 370 LTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGllseKAASKINET 447
Cdd:cd15248   157 KTISILAMGKVEGDVLSGVCYVGLWDMHALRGFVLAPLCVYLSLGTIFLLAGFISLFRIRTvmKHDG----TKTDKLEKL 232
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 448 MLRLGIFGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTI--GLPTKKPIPdceiknRPSLLVEKINLFAMF 525
Cdd:cd15248   233 MLRIGIFSFLYTLPALIVLACLFYEQAHFDSWMLQWHRDICKPPSWSIpaCRATGSPEA------RPEFQVFMIKYLMSM 306
                         330       340
                  ....*....|....*....|....*.
gi 1952684988 526 GTGIAMSTWVWTKATLLIWRRTWCRL 551
Cdd:cd15248   307 IVGITSSVWIWSSKTLVSWRNFYERL 332
7tmF_FZD7 cd15246
class F frizzled subfamily 7, member of 7-transmembrane G protein-coupled receptors; This ...
221-558 1.06e-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: 175.21  E-value: 1.06e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 221 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNrYPAVILFYVNACFFVGSIGWLAQFMDGARreIVC----RA 296
Cdd:cd15246     3 FKEEEVRFARLWVGIWSILCCASTLFTVLTYLVDMRRFS-YPERPIIFLSGCYFMVAVAYAAGFLLEDR--VVCverfSD 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 297 DGTMRLGEPTSNEtlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAI 374
Cdd:cd15246    80 DGYRTVAQGTKKE--GCTILFMVLYFFGMASSIWWVILSLTW---FLSAGMKWghEAIEANSQYFHLAAWAVPAVKTITI 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 375 LAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLG 452
Cdd:cd15246   155 LAMGQVDGDLLSGVCYVGIYSVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTimKHDGTKTE----KLEKLMVRIG 230
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 453 IFGFLAFGFVLITFSCHFYDFFNQAEWERSFrdyvLCQANVTIGLPtkkpipdCEIKN----RPSLLVEKINLFAMFGTG 528
Cdd:cd15246   231 VFSVLYTVPATIVLACYFYEQAFRETWEKTW----LLQTCKRYAVP-------CPNNNfapmSPDFTVFMIKYLMTMIVG 299
                         330       340       350
                  ....*....|....*....|....*....|
gi 1952684988 529 IAMSTWVWTKATLLIWRRTWCRLTGQSDDE 558
Cdd:cd15246   300 ITSGFWIWSGKTLQSWRRFYHRLSNGSKGE 329
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
229-534 1.70e-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: 169.53  E-value: 1.70e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 229 MHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARREIvcradgtmrlgepTSN 308
Cdd:cd14964     1 TTIILSLLTCLGLLGNLLVLLSLVRLRKRP-RSTRLLLASLAACDLLASLVVLVLFFLLGLTEA-------------SSR 66
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 309 ETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGT-TYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV-- 385
Cdd:cd14964    67 PQALCYLIYLLWYGANLASIWTTLVLTYHRYFALCGPLKyTRLSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRYNtl 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 386 SGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgllseKAASKINETMLRLGIFGFLAFGFVLIT 465
Cdd:cd14964   147 TGSCYLICTTIYLTWGFLLVSFLLPLVAFLVIFSRIVLRLRRRVRAIR-----SAASLNTDKNLKATKSLLILVITFLLC 221
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1952684988 466 FSCHFYDFFNQAEWErsfrdyvlcqanvtiglptkkpipDCEIKNRPSLLVEKINLFAMFGTGIAMSTW 534
Cdd:cd14964   222 WLPFSIVFILHALVA------------------------AGQGLNLLSILANLLAVLASTLNPFIYCLG 266
7tmF_FZD2 cd15245
class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This ...
220-558 4.53e-47

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


Pssm-ID: 320373  Cd Length: 330  Bit Score: 170.59  E-value: 4.53e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 220 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVCR---- 295
Cdd:cd15245     2 FFSQDEIRFARIWILIWSVLCCASTFFTVTTYLVDMQRF-RYPERPIIFLSGCYTMVSVAYIAGFVLGDK--VVCNerfs 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 296 ADGTMRLGEPTSNEtlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVA 373
Cdd:cd15245    79 EDGYKTVVQGTKKE--GCTILFMMLYFFSMASSIWWVILSLTW---FLAAGMKWghEAIEANSQYFHLAAWAVPAVKTIT 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 374 ILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRL 451
Cdd:cd15245   154 ILAMGQIDGDLLSGVCFVGLNNIDPLRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTimKHDGTKTE----KLERLMVRI 229
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 452 GIFGFLAFGFVLITFSCHFYDFFNQAEWERSFrdyvLCQANVTIGLPTK-KPIPdceiKNRPSLLVEKINLFAMFGTGIA 530
Cdd:cd15245   230 GVFSVLYTVPATIVIACYFYEQAFRQHWERSW----ISQNCKSLAIPCPlQYTP----RMTPDFTVYMIKYLMTLIVGIT 301
                         330       340
                  ....*....|....*....|....*...
gi 1952684988 531 MSTWVWTKATLLIWRRTWCRLTGQSDDE 558
Cdd:cd15245   302 SGFWIWSGKTLHSWRKFYTRLTNSRQGE 329
7tmF_FZD1 cd15247
class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
221-558 5.36e-46

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


Pssm-ID: 320375  Cd Length: 341  Bit Score: 167.91  E-value: 5.36e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 221 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNrYPAVILFYVNACFFVGSIGWLAQFMdgARREIVCR----A 296
Cdd:cd15247    13 FGPEELRFARIWIGIWSVLCCASTLFTVLTYLVDMKRFS-YPERPIIFLSGCYTMVAIAYIAGFL--LEDKVVCNdkfaE 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 297 DGTMRLGEPTSNEtlSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAI 374
Cdd:cd15247    90 DGIKTVAQGTKKE--GCTILFMMLYFFSMASSIWWVILSLTW---FLAAGMKWghEAIEANSQYFHLAAWAVPAIKTITI 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 375 LAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLG 452
Cdd:cd15247   165 LAVGQVDGDVLSGVCFVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTimKHDGTKTE----KLEKLMVRIG 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 453 IFGFLAFGFVLITFSCHFYDFFNQAEWERSFrdyvLCQANVTIGLPTKK-PIPDCEiknrPSLLVEKINLFAMFGTGIAM 531
Cdd:cd15247   241 IFSVLYTVPATIVIACYFYEQAFREQWERSW----ISQSCKTYAIPCPAhSHPPMS----PDFTVFMIKYLMTLIVGITS 312
                         330       340
                  ....*....|....*....|....*..
gi 1952684988 532 STWVWTKATLLIWRRTWCRLTGQSDDE 558
Cdd:cd15247   313 GFWIWSGKTLNSWRKFYTRLTNSKQGE 339
7tmF_FZD5 cd15249
class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This ...
219-546 5.32e-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: 5.32e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 219 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARReIVCRADG 298
Cdd:cd15249     1 PYFSQDERTFATFWIGLWSVLCFISTFTTVATFLIDMERF-RYPERPIIFLSACYLFVSLGYIVRLVVGHES-VACNREH 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 299 TMRLGEPTSNETlsCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILA 376
Cdd:cd15249    79 NHIHYETTGPAL--CTIVFLLIYFFGMASSIWWVILSFTW---FLAAGMKWgnEAIAGYSQYFHLAAWLIPSVKSIAVLA 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 377 VAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGIF 454
Cdd:cd15249   154 LSSVDGDPVAGICYVGNQNLNNLRGFVLAPLVVYLFTGTLFLLAGFVSLFRIRSviKQGGTKTD----KLEKLMIRIGIF 229
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 455 GFLAFGFVLITFSCHFYDFFNQAEWERSfrdyvlcqanvtigLPTKKPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTW 534
Cdd:cd15249   230 TVLYTVPATIVVACYVYEQHYRESWEAA--------------LNCSCPGDDTQPRARPDYAVFMLKYFMCLVVGITSGVW 295
                         330
                  ....*....|..
gi 1952684988 535 VWTKATLLIWRR 546
Cdd:cd15249   296 IWSGKTLESWRR 307
7tmF_FZD4 cd15038
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This ...
220-546 4.84e-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: 158.39  E-value: 4.84e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 220 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGaRREIVCRADGT 299
Cdd:cd15038     2 LFTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRF-KYPERPIIFLSMCYNIYSIAYIVRLLAG-RESISCDLDSQ 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 300 ----MRLGEPTSNetLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSfKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAIL 375
Cdd:cd15038    80 tavsILIQEGLEN--TGCAIVFLLLYFFGMASSIWWVILTLTWFLA-AGLKWGHEAIQMHSSYFHIAAWALPAVKTIVIL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 376 AVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSN--HPGLLSEkaasKINETMLRLGI 453
Cdd:cd15038   157 VMRVVDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQlqRDGTKTD----KLERLMVRIGI 232
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 454 FGFLAFGFVLITFSCHFYDFFNQAEWERSfrdyvlcqanvtiglptkkpipdcEIKNRPSLLVEKINLFAMFGTGIAMST 533
Cdd:cd15038   233 FSVLYTVPATCVIACYFYEYSNRDLWYYG------------------------GSAARPNMEVFMLKIFMSLVVGITSGM 288
                         330
                  ....*....|...
gi 1952684988 534 WVWTKATLLIWRR 546
Cdd:cd15038   289 WIWSAKTLSSWRN 301
7tmF_FZD8 cd15250
class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This ...
219-545 9.52e-43

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


Pssm-ID: 320378  Cd Length: 314  Bit Score: 157.78  E-value: 9.52e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 219 PLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGarREIVCRADG 298
Cdd:cd15250     1 PYFSQEERTFTAFWIGLWSVLCFLSTFATVSTFLIDMERF-KYPERPIIFLSACYLFVSLGYLVRLIAG--HEKVACSRG 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 299 TMRLGEPTSNETLS---CVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVA 373
Cdd:cd15250    78 ALAEVEHIHYETTGpalCTVVFLLIYFFGMASSIWWVILSLTW---FLAAGMKWgnEAIAGYSQYFHLAAWLIPSVKSIA 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 374 ILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSnhpgLLSEKAAS--KINETMLRL 451
Cdd:cd15250   155 VLALSSVDGDPVAGICYVGNQNLDNLRGFVLAPLVIYLFIGTMFLLAGFVSLFRIRS----VIKQGGTKtdKLEKLMIRI 230
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 452 GIFGFLAFGFVLITFSCHFYDFFNQAEWErsfrdyvlcqanVTIGLPTKKPIPDcEIKnRPSLLVEKINLFAMFGTGIAM 531
Cdd:cd15250   231 GIFTVLYTVPATIVVACYFYEQHNRQRWE------------ITHNCNCLRDQPD-QAR-RPDYAVFMLKYFMCLVVGITS 296
                         330
                  ....*....|....
gi 1952684988 532 STWVWTKATLLIWR 545
Cdd:cd15250   297 GVWTWSGKTLESWR 310
7tmF_FZD10 cd15037
class F frizzled subfamily 10, member of 7-transmembrane G protein-coupled receptors; This ...
232-545 2.50e-41

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


Pssm-ID: 320165  Cd Length: 320  Bit Score: 153.99  E-value: 2.50e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 232 YIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARrEIVCRADGTMRLGEPTSNETL 311
Cdd:cd15037    14 WIAIWSILCFFSSAFTVLTFLID-PQRFKYPERPIIFLSMCYCVYSVGYIIRLFAGAE-SIACDRDSGQLYVIQEGLEST 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 312 SCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 389
Cdd:cd15037    92 GCTIVFLILYYFGMASSLWWVILTLTW---FLAAGKKWghEAIEANSSYFHLAAWAIPAVKTIMILVMRRVAGDELTGVC 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 390 FVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPglLSEKAASKINETMLRLGIFGFLAFGFVLITFSCH 469
Cdd:cd15037   169 YVGSMDVNALTGFVLIPLACYLIIGTSFILSGFVALFHIRRVMK--TGGENTDKLEKLMVRIGVFSVLYTVPATCVIACY 246
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1952684988 470 FYDFFNQAEWErsfrdyvLCQANVTIGLPTKKPIPDCEIKNR-PSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWR 545
Cdd:cd15037   247 FYERLNMDYWK-------ILATQQKCKMDNQTKTLDCVMTSSiPAVEIFMVKIFMLLVVGITSGMWIWTSKTLQSWQ 316
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
232-545 1.52e-38

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


Pssm-ID: 320164  Cd Length: 320  Bit Score: 145.87  E-value: 1.52e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 232 YIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARrEIVCRADGtmrlGEP----TS 307
Cdd:cd15036    14 WMAVWSTLCFVSTAFTVLTFLLD-PHRFQYPERPIIFLSMCYNVYSVAFLIRAVAGAE-SIACDREN----GALyiiqEG 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 308 NETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV 385
Cdd:cd15036    88 LESTGCTLVFLILYYFGMASSLWWVVLTLTW---FLAAGKKWghEAIESHGSYFHMAAWGIPALKTIVILTMRKVAGDEL 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 386 SGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGIFGFLAFGFVL 463
Cdd:cd15036   165 TGLCYVGSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVALFHIRKvmKTGGTNTE----KLEKLMVKIGVFSILYTVPAT 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 464 ITFSCHFYDFFNQAEWERSFRDyvlcQANVTigLPTKKPiPDCEIKNR-PSLLVEKINLFAMFGTGIAMSTWVWTKATLL 542
Cdd:cd15036   241 CVIVCYFYERLNMDYWDLRALE----ESCRT--VPGRRR-PDCSLPHSvPTVAVFMLKIFMSLVVGITSGVWVWSSKTLQ 313

                  ...
gi 1952684988 543 IWR 545
Cdd:cd15036   314 TWQ 316
7tmF_FZD3 cd15033
class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This ...
237-544 3.43e-35

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


Pssm-ID: 320161  Cd Length: 321  Bit Score: 136.23  E-value: 3.43e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 237 GAVTGLC---TLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVCRADGTMRLGEPT---SNET 310
Cdd:cd15033    16 GVISIVClsaTLFTFLTFLID-VTRFRYPERPIIFYAVCYMMVSLIFFIGFLLEDR--VACNAASPGQYKASTvtqGSHN 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 311 LSCVIIFVIVYYALMAGVVWFVVLTYAWH-TSFKALGTtyQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 389
Cdd:cd15033    93 KACTMLFMVLYFFTMAGSVWWVILTITWFlAAVPKWGS--EAIEKKALLFHASAWGIPGTLTIILLAMNKIEGDNISGVC 170
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 390 FVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPglLSEKAASKINETMLRLGIFGFLAFGFVLITFSCH 469
Cdd:cd15033   171 FVGLYDVDALRYFVLAPLCLDVVVGVSLLLAGIISLNRVRIEIP--LEKENQDKLVKFMIRIGVFSVLYLVPLLVVIGCY 248
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 470 FYDFFNQAEWERSF-----RDYVLcqanvtiglptkkPIP-DCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLI 543
Cdd:cd15033   249 FYEQAYRGVWETTWvqercREYHI-------------PCPyKVTQTSRPDLILFLMKYLMALVVGIPSVFWVGSKKTCFE 315

                  .
gi 1952684988 544 W 544
Cdd:cd15033   316 W 316
7tmF_FZD3_FZD6-like cd15910
class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G ...
231-544 1.71e-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: 131.51  E-value: 1.71e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 231 SYIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVCR-ADGTMRLGEPT--S 307
Cdd:cd15910    13 YFIGVVSILCLLATLFTFLTFLID-VNRFRYPERPIIFYAVCYFVVSLIFFVGFLLGDD--VACNhAIMDENNGATVveG 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 308 NETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV 385
Cdd:cd15910    90 SRNKACTILFMILYFFTMAGTVWWVILTITW---FLAAGFKWgsEAIEKKALYFHALAWGIPGVLTMVLLATNKIEGDNI 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 386 SGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPglLSEKAASKINETMLRLGIFGFLAFGFVLIT 465
Cdd:cd15910   167 SGVCFVGLYDSDGLRFFVLLPLCLYVLVGMSLLLAGIICLNRVRKSIH--DDETNQEKLAKFMIRIGVFSILYLVPLLTL 244
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 466 FSCHFYDFFNQAEWE-----RSFRDYVLcqanvtiglptkkPIP-DCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKA 539
Cdd:cd15910   245 IGCYAYEQSNRKSWEstwvvRNCRRYHI-------------PCPqLAQGNPRPGLFLFCIKYLMTLIVGIPPVFWVGSKK 311

                  ....*
gi 1952684988 540 TLLIW 544
Cdd:cd15910   312 TCAEW 316
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
69-177 4.44e-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: 120.49  E-value: 4.44e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988   69 CEPLRYNVCLGsaLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPrCWAVIQPLLCAVYMPKCEND-RVELPSRTLCQ 147
Cdd:smart00063   1 CEPITIPLCKD--LGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQ-CSPDLRFFLCSVYAPICTEDlRPILPCRSLCE 77
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1952684988  148 ATRGPCAIVERERG--WPDFLRCtpDHFP---EGC 177
Cdd:smart00063  78 AAREGCEPLMEKFGfpWPEFLRC--DRFPvqeELC 110
7tmF_FZD6 cd15032
class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This ...
221-544 9.01e-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: 126.50  E-value: 9.01e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 221 FTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSnRYPAVILFYVNACFFVGSIGWLAQFMDGARreIVC-RADGT 299
Cdd:cd15032     3 FKSDELDFAKSFIGIVSIFCLCATLFTFLTFLIDVKRF-RYPERPIIYYSVCYSIVSLMYFIGFLLGNS--TACnKADEK 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 300 MRLGEPT--SNETLSCVIIFVIVYYALMAGVVWFVVLTYAWhtsFKALGTTY--QPLSGKTSYFHLLTWSLPFVLTVAIL 375
Cdd:cd15032    80 LELGDTVvlGSQNKACTVLFMLLYFFTMAGTIWWVILTITW---FLAAGRKWscEAIEQKALWFHAVAWGIPGFLTIMLL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 376 AVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKS--NHPGLLSEkaasKINETMLRLGI 453
Cdd:cd15032   157 AMNKVEGDNISGVCFVGLYDLDASRYFVLLPLCLCVFVGLSLLLAGIISLNHVRQviQHDGRNQE----KLKKFMIRIGV 232
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 454 FGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKKPipdceikNRPSLLVEKINLFAMFGTGIAMST 533
Cdd:cd15032   233 FSGLYLVPLVTLLGCYVYEQVYRRTWEITWVSDHCQQYHIPCPYQAKAV-------ARPELALFLIKYLMTLIVGISAVF 305
                         330
                  ....*....|.
gi 1952684988 534 WVWTKATLLIW 544
Cdd:cd15032   306 WVGSKKTCSEW 316
7tmF_FZD3_insect cd15031
class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; ...
220-546 1.09e-17

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: 84.82  E-value: 1.09e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 220 LFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADwRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCR---A 296
Cdd:cd15031     2 FYTTRQKKLVESWMLVLSAVSFILTLFALVTFWAE-PTRFGYPERPVLFMALCYNLISLCYLERGILGTFTNCSARslaI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 297 DGTMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWH-TSFKALGTTyqPLSGKTSYFHLLTWSLPFVLTVAIL 375
Cdd:cd15031    81 DCDDRYLRQDCLLTPQCLASFIITYYLSLSAASWWLIFALCWYlSSAKKWSSE--ALEKKSGLFHVLAWVPPLAPPIAAL 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 376 AVAQVDGDSVSGICfvgYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNhpglLSEKAASKINETMLRLGIFG 455
Cdd:cd15031   159 LLERVSASELTGTC---TASGFVESSISELPALILLLLGLYLTIAALRSLLSLQQQ----LQSRLAHAPQRILARVSIFS 231
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 456 FLAF---GFVLITFSChfydffnqaewERSFRDYVLCQANVTIGLPTKKPIPDCEIknRPSLLveKINLFAMFGTGIAMs 532
Cdd:cd15031   232 LLYLipaAAALICKLC-----------ERWLQPVPECNALQEDCAPPATDNEFLSA--LPALL--RVFFFLIGGTATGL- 295
                         330
                  ....*....|....
gi 1952684988 533 tWVWTKATLLIWRR 546
Cdd:cd15031   296 -WLWSRKSCESWRS 308
CRD_FZ cd07066
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
69-196 1.46e-17

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: 79.09  E-value: 1.46e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVClgSALPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNApRCWAVIQPLLCAVYMPKCEND--RVELPSRTLC 146
Cdd:cd07066     2 CEPIPLPLC--RGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNS-GCHPDLRFFLCSLYFPECTPDgdRPIPPCRSLC 78
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1952684988 147 QATRGPCAIVERERG--WPDFLRCtpDHFPEgcpnevqnikFNSSGQCEAPL 196
Cdd:cd07066    79 EEVRDSCEPLMLAFGfpWPEPLDC--DRFPD----------SNEEGLCISPP 118
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
69-175 2.88e-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: 69.90  E-value: 2.88e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVCLGsaLPYGATSTLLAGDSDSQEEAHGKLVL-----WSGLRNApRCWAVIQPLLCAVYMPKCE----NDRVE 139
Cdd:pfam01392   1 CEPITLPMCLG--LGYNATVFPNLLGHQTQEEAELSLAYlvlseFEPLVDL-SCSPSLRLFLCSLYFPPCTlgpsPKPVC 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1952684988 140 LPSRTLCQATRGPCAIVERERG----WPDFLRCtpDHFPE 175
Cdd:pfam01392  78 PPCRSLCEEVRYGCEPLLEEAKfgfsWPEFLDC--DSLPA 115
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
242-477 3.71e-12

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: 67.24  E-value: 3.71e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 242 LCTLFTLATFVA--DWRNsnrYPAVILFYVNACFFVGSIGWLAqfmdgarreivcradgtmRLGEPTSNETLSCVIIFVI 319
Cdd:cd13952    17 VGLLLTIITYLLfpKLRN---LRGKILINLCLSLLLAQLLFLI------------------GQLLTSSDRPVLCKALAIL 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 320 VYYALMAGVVWFVVLT-YAWHTSFKALGTTYqplSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSV----SGICFVGYK 394
Cdd:cd13952    76 LHYFLLASFFWMLVEAfDLYRTFVKVFGSSE---RRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSpgygGEYCWLSNG 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 395 NYRYraGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgllsekAASKINETMLRLGIFGFLafgFVL--ITFSCHFYD 472
Cdd:cd13952   153 NALL--WAFYGPVLLILLVNLVFFILTVRILLRKLRETP------KQSERKSDRKQLRAYLKL---FPLmgLTWIFGILA 221

                  ....*
gi 1952684988 473 FFNQA 477
Cdd:cd13952   222 PFVGG 226
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
231-470 6.09e-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: 66.44  E-value: 6.09e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 231 SYIAAFG-AVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAqfmdgarreivcradgtmrlGEPTSNE 309
Cdd:cd15040     5 SIITYIGcGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFLF--------------------GINSTDN 64
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 310 TLSCVIIFVIVYYALMAGVVWFVVLtyAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGIC 389
Cdd:cd15040    65 PVLCTAVAALLHYFLLASFMWMLVE--ALLLYLRLVKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYC 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 390 FVGYKNYRYraGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPgllsekaASKINETMLRLG-------------IFGF 456
Cdd:cd15040   143 WLSNGNGLY--YAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRN-------KKKRKKTKAQLRaavslffllgltwIFGI 213
                         250
                  ....*....|....
gi 1952684988 457 LAFGFVLITFSCHF 470
Cdd:cd15040   214 LAIFGARVVFQYLF 227
CRD_FZ3 cd07449
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich ...
69-175 6.56e-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: 54.63  E-value: 6.56e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVCLGsaLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNApRCWAVIQPLLCAVYMPKC-ENDRVELPSRTLCQ 147
Cdd:cd07449     5 CEPITLRMCQD--LPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNL-ECSRDFRPFLCALYAPVCmEYGRVTLPCRRLCQ 81
                          90       100       110
                  ....*....|....*....|....*....|
gi 1952684988 148 ATRGPCAIVERERG--WPDFLRCTpdHFPE 175
Cdd:cd07449    82 RAYSECSKLMEMFGvpWPEDMECS--RFPD 109
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
69-175 4.40e-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: 52.46  E-value: 4.40e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVCLGsaLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNApRCWAVIQPLLCAVYMPKCeNDRVEL---PSRTL 145
Cdd:cd07448     4 CEPIRIEMCQG--LGYNVTRMPNLVGHELQTDAELQLQTFTPLIQY-GCSSQLKFFLCSVYVPMC-TEKVPVpigPCRPL 79
                          90       100       110
                  ....*....|....*....|....*....|..
gi 1952684988 146 CQATRGPCAIVERERG--WPDFLRCtpDHFPE 175
Cdd:cd07448    80 CLSVKKRCLPVLKEFGfpWPEALNC--SKFPP 109
CRD_FZ9 cd07463
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich ...
65-168 2.42e-07

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: 50.41  E-value: 2.42e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  65 RAAPCEPLRYNVCLGsaLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPrCWAVIQPLLCAVYMPKCeNDRVELP--- 141
Cdd:cd07463     1 RAAKCQPVVIPMCRG--IGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYG-CHVHLRFFLCSLYAPMC-TDQVSTSipa 76
                          90       100
                  ....*....|....*....|....*....
gi 1952684988 142 SRTLCQATRGPCA-IVER-ERGWPDFLRC 168
Cdd:cd07463    77 CRPMCEQARQKCSpIMEQfNFGWPESLDC 105
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
306-475 2.43e-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: 2.43e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 306 TSNETLSCVIIFVIVYYALMAGVVWFVVLTY-AWHT-SFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGD 383
Cdd:cd15039    61 SSGDSTLCVALGILLHFFFLAAFFWLNVMSFdIWRTfRGKRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDFSPNT 140
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988 384 SV------SGICFVGYKNYRYRagFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNhpgllSEKAASKINETM------LRL 451
Cdd:cd15039   141 DSlrpgygEGSCWISNPWALLL--YFYGPVALLLLFNIILFILTAIRIRKVKKE-----TAKVQSRLRSDKqrfrlyLKL 213
                         170       180       190
                  ....*....|....*....|....*....|.
gi 1952684988 452 G-------IFGFLAFGFVLITFSCHFYDFFN 475
Cdd:cd15039   214 FvimgvtwILEIISWFVGGSSVLWYIFDILN 244
CRD_SFRP5 cd07444
Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt ...
94-174 2.72e-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: 47.25  E-value: 2.72e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  94 DSDSQEEAHGKLVLWSGLRnAPRCWAVIQPLLCAVYMPKCEnDRVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpD 171
Cdd:cd07444    32 EHESMAEVKQQASSWVPLL-AKRCHADTQVFLCSLFAPVCL-DRPIYPCRSLCEAVRDSCAPVMESYGfpWPEMLHC--H 107

                  ...
gi 1952684988 172 HFP 174
Cdd:cd07444   108 KFP 110
CRD_SFRP1 cd07443
Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt ...
94-176 2.82e-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: 47.20  E-value: 2.82e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  94 DSDSQEEAHGKLVLWSGLRNApRCWAVIQPLLCAVYMPKCEnDRVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpD 171
Cdd:cd07443    32 DHETMAEVKQQASSWVPLLNK-NCHKGTQVFLCSLFAPVCL-DRPVYPCRWLCEAVRDSCEPVMQFFGfyWPEMLKC--D 107

                  ....*
gi 1952684988 172 HFPEG 176
Cdd:cd07443   108 KFPEG 112
CRD_Carboxypeptidase_Z cd07447
Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The ...
116-177 3.39e-06

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: 47.06  E-value: 3.39e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1952684988 116 RCWAVIQPLLCAVYMPKCENDRVELPSRTLCQATRGPC--AIVERERGWPDFLRCtpDHF----PEGC 177
Cdd:cd07447    53 ECNPDIRLLGCSVLAPRCENDKVIKPCRSTCEALRKRCshAFDAIQMAWPYFLDC--DRFfageQEGC 118
CRD_FZ8 cd07461
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich ...
116-179 3.53e-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: 46.90  E-value: 3.53e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1952684988 116 RCWAVIQPLLCAVYMPKCEND--RVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpDHFPE-GCPN 179
Cdd:cd07461    49 QCSPDLKFFLCSMYTPICLEDykKPLPPCRSVCERAKAGCAPLMRQYGfpWPDRMRC--DLLPEqGNPD 115
CRD_FZ5_like cd07456
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich ...
69-176 5.08e-06

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: 46.24  E-value: 5.08e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVCLGsaLPYGATSTLLAGDSDSQEEAhGKLV--LWSGLRnaPRCWAVIQPLLCAVYMPKCEND--RVELPSRT 144
Cdd:cd07456     2 CEEITIPMCKG--IGYNMTYMPNQFNHDTQEEA-GLEVhqFWPLVE--IQCSPDLKFFLCSMYTPICLEDydKPLPPCRS 76
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1952684988 145 LCQATRGPCAIVERERG--WPDFLRCtpDHFPEG 176
Cdd:cd07456    77 VCERARDGCAPIMRQYGfaWPERMSC--DALPEG 108
CRD_SFRP4 cd07442
Cysteine-rich domain of the secreted frizzled-related protein 4 (SFRP4), a Wnt antagonist; The ...
65-168 6.68e-06

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: 46.17  E-value: 6.68e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  65 RAAPCEPLRYNVClgSALPYGATSTLLAGDSDSQEEAHGKLVLWSGLRnAPRCWAVIQPLLCAVYMPKCE----NDRVEl 140
Cdd:cd07442     1 QGAPCEAVRIPMC--RHMPWNITRMPNHLHHSTQENAVLAIEQYEELV-DTGCSPVLPFFLCAMYAPICTleflYDPIK- 76
                          90       100       110
                  ....*....|....*....|....*....|
gi 1952684988 141 PSRTLCQATRGPCAIVER--ERGWPDFLRC 168
Cdd:cd07442    77 PCRSVCQRARDGCEPIMRryNHSWPESLAC 106
CRD_FZ9_like cd07457
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich ...
67-176 7.21e-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: 42.87  E-value: 7.21e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  67 APCEPLRYNVCLGsaLPYGATS--TLLAgdSDSQEEAHGKLVLWSGLRnAPRCWAVIQPLLCAVYMPKCeNDRVELP--- 141
Cdd:cd07457     1 GKCERITIPMCQG--IGYNMTRmpNLLG--HESQSEAAISIHEFAPLV-QYGCAEHLRFFLCSLYAPMC-TEQVSIPipa 74
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1952684988 142 SRTLCQATRGPCA-IVER-ERGWPDFLRCtpDHFPEG 176
Cdd:cd07457    75 CRSMCEQARDKCSpIMEQfSFSWPDSLDC--DRLPRK 109
CRD_FZ1_like cd07458
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 1; The cysteine-rich ...
117-181 2.43e-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: 41.24  E-value: 2.43e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1952684988 117 CWAVIQPLLCAVYMPKCEN-DRVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpDHFPEGCPNEV 181
Cdd:cd07458    48 CSPDLKFFLCSVYAPVCTVlERPIPPCRSLCESARQGCEALMNKFGfqWPESLDC--EKFPVHGAGDL 113
CRD_crescent cd07453
Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential ...
124-175 3.92e-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: 41.08  E-value: 3.92e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1952684988 124 LLCAVYMPKCEnDRVELPSRTLCQATRGPCAIVERERG--WPDFLRCtpDHFPE 175
Cdd:cd07453    57 FLCSLFAPICW-DRPIYPCRSLCEAVRSSCAPLMACYGypWPEILHC--DKFPV 107
CRD_corin_1 cd07445
One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ...
69-169 6.04e-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: 40.69  E-value: 6.04e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVClgSALPYGATSTLLAGDSDSQEEAhgKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVE----LPSRT 144
Cdd:cd07445     5 CMNITHSQC--QMLPYHSTLKPSLLSVKNMEME--KFLKFFSYLHRLSCYQHIMLFGCSLALPECISDGDDrhglLPCRS 80
                          90       100
                  ....*....|....*....|....*..
gi 1952684988 145 LCQATRGPCAIVER--ERGWPDFLRCT 169
Cdd:cd07445    81 FCEAAKEGCEPVLGmvNASWPDFLRCS 107
CRD_SFRP2 cd07446
Cysteine-rich domain of the secreted frizzled-related protein 2 (SFRP2), a regulator of Wnt ...
116-176 6.39e-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: 40.28  E-value: 6.39e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1952684988 116 RCWAVIQPLLCAVYMPKCENDRVEL--PSRTLCQATRGPCAIVERERG--WPDFLRCtpDHFPEG 176
Cdd:cd07446    51 QCHPDTKKFLCSLFAPVCLDDLDEAiqPCRSLCEAVKDGCAPVMSAFGfpWPDMLDC--TRFPLD 113
CRD_SFRP3 cd07441
Cysteine-rich domain of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), a Wnt ...
66-168 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 1952684988  66 AAPCEPLRYNVClgSALPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNApRCWAVIQPLLCAVYMPKC----ENDRVElP 141
Cdd:cd07441     1 AASCEPVRIPMC--KSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGT-QCSPDLLFFLCAMYAPICtidfQHEPIK-P 76
                          90       100
                  ....*....|....*....|....*....
gi 1952684988 142 SRTLCQATRGPC--AIVERERGWPDFLRC 168
Cdd:cd07441    77 CKSVCERARAGCepVLIRYRHTWPESLAC 105
CRD_FZ2 cd07464
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich ...
69-174 2.37e-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: 2.37e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVCLGSALPYGATSTLLAgdSDSQEEAHGKLVLWSGLRNApRCWAVIQPLLCAVYMPKCEN-DRVELPSRTLCQ 147
Cdd:cd07464     5 CQPISIPLCTDIAYNQTIMPNLLG--HTNQEDAGLEVHQFYPLVKV-QCSLELRFFLCSMYAPVCTVlEQAIPPCRSICE 81
                          90       100
                  ....*....|....*....|....*....
gi 1952684988 148 ATRGPCAIVERERG--WPDFLRCtpDHFP 174
Cdd:cd07464    82 RARQGCEALMNKFGfqWPERLRC--ENFP 108
CRD_FZ7 cd07466
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich ...
69-188 6.33e-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: 37.37  E-value: 6.33e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVCLGSALPYGATSTLLAgdSDSQEEAHGKLVLWSGLRNApRCWAVIQPLLCAVYMPKCEN-DRVELPSRTLCQ 147
Cdd:cd07466     5 CQPISIPLCTDIAYNQTIMPNLLG--HTNQEDAGLEVHQFYPLVKV-QCSPELKFFLCSMYAPVCTVlEQAIPPCRSLCE 81
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1952684988 148 ATRGPCAIVERERG--WPDFLRCtpDHFPEGCPNEV---QNIKFNS 188
Cdd:cd07466    82 RARQGCEALMNKFGfqWPERLRC--ENFPVHGAGEIcvgQNTSDAS 125
CRD_FZ1 cd07465
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich ...
69-174 9.84e-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: 36.96  E-value: 9.84e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952684988  69 CEPLRYNVCLGSALPYGATSTLLAgdSDSQEEAHGKLVLWSGLRNApRCWAVIQPLLCAVYMPKCENDRVELPS-RTLCQ 147
Cdd:cd07465     5 CQPISIPLCTDIAYNQTIMPNLLG--HTNQEDAGLEVHQFYPLVKV-QCSAELKFFLCSMYAPVCTVLEQALPPcRSLCE 81
                          90       100
                  ....*....|....*....|....*....
gi 1952684988 148 ATRGPCAIVERERG--WPDFLRCtpDHFP 174
Cdd:cd07465    82 RARQGCEALMNKFGfqWPDTLRC--EKFP 108
 
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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