Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Frizzled-8

Gene

Fzd8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes (By similarity). The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.By similarity4 Publications

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: GO_Central
  2. PDZ domain binding Source: BHF-UCL
  3. receptor binding Source: BHF-UCL
  4. ubiquitin protein ligase binding Source: MGI
  5. Wnt-activated receptor activity Source: MGI
  6. Wnt-protein binding Source: MGI

GO - Biological processi

  1. angiogenesis Source: MGI
  2. canonical Wnt signaling pathway Source: MGI
  3. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  4. non-canonical Wnt signaling pathway Source: GO_Central
  5. positive regulation of JUN kinase activity Source: MGI
  6. positive regulation of protein phosphorylation Source: MGI
  7. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  8. T cell differentiation in thymus Source: MGI
  9. Wnt signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_335449. Class B/2 (Secretin family receptors).

Protein family/group databases

MEROPSiI93.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-8
Short name:
Fz-8
Short name:
mFz8
Gene namesi
Name:Fzd8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:108460. Fzd8.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 272245ExtracellularSequence AnalysisAdd
BLAST
Transmembranei273 – 29321Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini294 – 30916CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei310 – 33021Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini331 – 39464ExtracellularSequence AnalysisAdd
BLAST
Transmembranei395 – 41521Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini416 – 43722CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei438 – 45821Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini459 – 48123ExtracellularSequence AnalysisAdd
BLAST
Transmembranei482 – 50221Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini503 – 53028CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei531 – 55121Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini552 – 58231ExtracellularSequence AnalysisAdd
BLAST
Transmembranei583 – 60321Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini604 – 68582CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. Golgi apparatus Source: UniProtKB-SubCell
  3. integral component of membrane Source: GO_Central
  4. plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi685 – 6851V → A: Reduces interaction with GOPC. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 685658Frizzled-8PRO_0000013001Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 96PROSITE-ProRule annotation1 Publication
Disulfide bondi43 ↔ 89PROSITE-ProRule annotation1 Publication
Glycosylationi49 – 491N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi80 ↔ 118PROSITE-ProRule annotation1 Publication
Disulfide bondi107 ↔ 148PROSITE-ProRule annotation1 Publication
Disulfide bondi111 ↔ 135PROSITE-ProRule annotation1 Publication
Glycosylationi152 – 1521N-linked (GlcNAc...)Sequence Analysis
Glycosylationi473 – 4731N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ61091.

PTM databases

PhosphoSiteiQ61091.

Expressioni

Tissue specificityi

Expressed in chondrocytes.

Gene expression databases

BgeeiQ61091.
CleanExiMM_FZD8.
GenevestigatoriQ61091.

Interactioni

Subunit structurei

Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly with LRP5 or LRP6; the interaction is promoted by Wnt-binding and signaling and inhibited by DKK1 (By similarity). Interacts (via the PDZ-binding motif) with GPOC (via its PDZ domain). Interacts with RSPO1 and RSPO3.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GopcQ8BH603EBI-6171689,EBI-296357
LRP6O755814EBI-6171689,EBI-910915From a different organism.

Protein-protein interaction databases

BioGridi199781. 4 interactions.
DIPiDIP-41258N.
IntActiQ61091. 4 interactions.
MINTiMINT-1782989.
STRINGi10090.ENSMUSP00000039660.

Structurei

Secondary structure

1
685
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi41 – 433Combined sources
Beta strandi49 – 513Combined sources
Helixi62 – 698Combined sources
Helixi70 – 723Combined sources
Helixi73 – 786Combined sources
Helixi84 – 929Combined sources
Helixi108 – 12417Combined sources
Helixi131 – 1333Combined sources
Helixi135 – 1373Combined sources
Beta strandi144 – 1463Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IJYX-ray1.35A/B28-155[»]
4F0AX-ray3.25A28-150[»]
SMRiQ61091. Positions 35-150.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61091.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 151122FZPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni71 – 788Palmitate-binding groove
Regioni95 – 1006Wnt-binding
Regioni147 – 1526Wnt-binding

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi606 – 6116Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
Motifi683 – 6853PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi168 – 1736Poly-Pro
Compositional biasi353 – 3619Poly-Ala
Compositional biasi640 – 65415Poly-GlyAdd
BLAST

Domaini

Lys-Thr-X-X-X-Trp motif interacts with the PDZ doman of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.By similarity
The FZ domain is involved in binding with Wnt ligands.

Sequence similaritiesi

Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ61091.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG7M3J01.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q61091-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEWGYLLEVT SLLAALAVLQ RSSGAAAASA KELACQEITV PLCKGIGYNY
60 70 80 90 100
TYMPNQFNHD TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY
110 120 130 140 150
KKPLPPCRSV CERAKAGCAP LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD
160 170 180 190 200
YNRTDLTTAA PSPPRRLPPP PPPGEQPPSG SGHSRPPGAR PPHRGGSSRG
210 220 230 240 250
SGDAAAAPPS RGGKARPPGG GAAPCEPGCQ CRAPMVSVSS ERHPLYNRVK
260 270 280 290 300
TGQIANCALP CHNPFFSQDE RAFTVFWIGL WSVLCFVSTF ATVSTFLIDM
310 320 330 340 350
ERFKYPERPI IFLSACYLFV SVGYLVRLVA GHEKVACSGG APGAGGAGGA
360 370 380 390 400
GGAAAAGAGA AGAGASSPGA RGEYEELGAV EQHVRYETTG PALCTVVFLL
410 420 430 440 450
VYFFGMASSI WWVILSLTWF LAAGMKWGNE AIAGYSQYFH LAAWLVPSVK
460 470 480 490 500
SIAVLALSSV DGDPVAGICY VGNQSLDNLR GFVLAPLVIY LFIGTMFLLA
510 520 530 540 550
GFVSLFRIRS VIKQQGGPTK THKLEKLMIR LGLFTVLYTV PAAVVVACLF
560 570 580 590 600
YEQHNRPRWE ATHNCPCLRD LQPDQARRPD YAVFMLKYFM CLVVGITSGV
610 620 630 640 650
WVWSGKTLES WRALCTRCCW ASKGAAVGAG AGGSGPGGSG PGPGGGGGHG
660 670 680
GGGGSLYSDV STGLTWRSGT ASSVSYPKQM PLSQV
Length:685
Mass (Da):73,045
Last modified:July 26, 2011 - v2
Checksum:i9DB95F068BC45CD8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti347 – 3471A → R in AAC52433 (PubMed:8626800).Curated
Sequence conflicti363 – 3631A → R in AAC52433 (PubMed:8626800).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43321 Genomic DNA. Translation: AAC52433.1.
CH466592 Genomic DNA. Translation: EDL23012.1.
BC132543 mRNA. Translation: AAI32544.1.
BC138062 mRNA. Translation: AAI38063.1.
CCDSiCCDS29048.1.
RefSeqiNP_032084.2. NM_008058.2.
UniGeneiMm.184289.

Genome annotation databases

EnsembliENSMUST00000041080; ENSMUSP00000039660; ENSMUSG00000036904.
GeneIDi14370.
KEGGimmu:14370.
UCSCiuc008eag.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43321 Genomic DNA. Translation: AAC52433.1.
CH466592 Genomic DNA. Translation: EDL23012.1.
BC132543 mRNA. Translation: AAI32544.1.
BC138062 mRNA. Translation: AAI38063.1.
CCDSiCCDS29048.1.
RefSeqiNP_032084.2. NM_008058.2.
UniGeneiMm.184289.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IJYX-ray1.35A/B28-155[»]
4F0AX-ray3.25A28-150[»]
SMRiQ61091. Positions 35-150.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199781. 4 interactions.
DIPiDIP-41258N.
IntActiQ61091. 4 interactions.
MINTiMINT-1782989.
STRINGi10090.ENSMUSP00000039660.

Protein family/group databases

MEROPSiI93.001.
GPCRDBiSearch...

PTM databases

PhosphoSiteiQ61091.

Proteomic databases

PRIDEiQ61091.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000041080; ENSMUSP00000039660; ENSMUSG00000036904.
GeneIDi14370.
KEGGimmu:14370.
UCSCiuc008eag.2. mouse.

Organism-specific databases

CTDi8325.
MGIiMGI:108460. Fzd8.

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ61091.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG7M3J01.
TreeFamiTF317907.

Enzyme and pathway databases

ReactomeiREACT_335449. Class B/2 (Secretin family receptors).

Miscellaneous databases

EvolutionaryTraceiQ61091.
NextBioi285853.
PROiQ61091.
SOURCEiSearch...

Gene expression databases

BgeeiQ61091.
CleanExiMM_FZD8.
GenevestigatoriQ61091.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled."
    Wang Y., Macke J.P., Abella B.S., Andreasson K., Worley P., Gilbert D.J., Copeland N.G., Jenkins N.A., Nathans J.
    J. Biol. Chem. 271:4468-4476(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  4. "Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner."
    Sheldahl L.C., Park M., Malbon C.C., Moon R.T.
    Curr. Biol. 9:695-698(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BETA-CATENIN SIGNALING.
  5. "Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein."
    Hsieh J.C., Rattner A., Smallwood P.M., Nathans J.
    Proc. Natl. Acad. Sci. U.S.A. 96:3546-3551(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  6. "Identification of a PDZ domain containing Golgi protein, GOPC, as an interaction partner of frizzled."
    Yao R., Maeda T., Takada S., Noda T.
    Biochem. Biophys. Res. Commun. 286:771-778(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GOPC, SUBCELLULAR LOCATION, MUTAGENESIS OF VAL-685.
  7. "Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth."
    Lu W., Yamamoto V., Ortega B., Baltimore D.
    Cell 119:97-108(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression."
    Nam J.-S., Turcotte T.J., Smith P.F., Choi S., Yoon J.K.
    J. Biol. Chem. 281:13247-13257(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RSPO1 AND RSPO3, FUNCTION.
  9. "Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains."
    Dann C.E., Hsieh J.-C., Rattner A., Sharma D., Nathans J., Leahy D.J.
    Nature 412:86-90(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 28-155, DISULFIDE BONDS.
  10. "Structural basis of Wnt recognition by Frizzled."
    Janda C.Y., Waghray D., Levin A.M., Thomas C., Garcia K.C.
    Science 337:59-64(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 28-150 IN COMPLEX WITH XENOPUS WNT8.

Entry informationi

Entry nameiFZD8_MOUSE
AccessioniPrimary (citable) accession number: Q61091
Secondary accession number(s): A2RTK9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 4, 2001
Last sequence update: July 26, 2011
Last modified: March 31, 2015
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.