Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q61091

- FZD8_MOUSE

UniProt

Q61091 - FZD8_MOUSE

Protein

Frizzled-8

Gene

Fzd8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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: UniProtKB-KW
    2. PDZ domain binding Source: BHF-UCL
    3. protein binding Source: UniProtKB
    4. receptor binding Source: BHF-UCL
    5. Wnt-activated receptor activity Source: MGI
    6. Wnt-protein binding Source: MGI

    GO - Biological processi

    1. axonogenesis Source: RefGenome
    2. brain development Source: RefGenome
    3. canonical Wnt signaling pathway Source: MGI
    4. gonad development Source: RefGenome
    5. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    6. positive regulation of JUN kinase activity Source: MGI
    7. positive regulation of protein phosphorylation Source: MGI
    8. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    9. regulation of transcription from RNA polymerase II promoter Source: RefGenome
    10. T cell differentiation in thymus Source: MGI
    11. vasculature development Source: RefGenome

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Wnt signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_214043. PCP/CE pathway.

    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: Chromosome 18

    Organism-specific databases

    MGIiMGI:108460. Fzd8.

    Subcellular locationi

    GO - Cellular componenti

    1. cell projection Source: RefGenome
    2. cytoplasm Source: RefGenome
    3. Golgi apparatus Source: UniProtKB-SubCell
    4. integral component of membrane Source: UniProtKB-KW
    5. plasma membrane Source: BHF-UCL

    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 ↔ 961 PublicationPROSITE-ProRule annotation
    Disulfide bondi43 ↔ 891 PublicationPROSITE-ProRule annotation
    Glycosylationi49 – 491N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi80 ↔ 1181 PublicationPROSITE-ProRule annotation
    Disulfide bondi107 ↔ 1481 PublicationPROSITE-ProRule annotation
    Disulfide bondi111 ↔ 1351 PublicationPROSITE-ProRule annotation
    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 – 433
    Beta strandi49 – 513
    Helixi62 – 698
    Helixi70 – 723
    Helixi73 – 786
    Helixi84 – 929
    Helixi108 – 12417
    Helixi131 – 1333
    Helixi135 – 1373
    Beta strandi144 – 1463

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IJYX-ray1.35A/B28-155[»]
    4F0AX-ray3.25A28-150[»]
    ProteinModelPortaliQ61091.
    SMRiQ61091. Positions 35-150, 230-612.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ61091.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini28 – 272245ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini294 – 30916CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini331 – 39464ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini416 – 43722CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini459 – 48123ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini503 – 53028CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini552 – 58231ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini604 – 68582CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei273 – 29321Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei310 – 33021Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei395 – 41521Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei438 – 45821Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei482 – 50221Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei531 – 55121Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei583 – 60321Helical; Name=7Sequence AnalysisAdd
    BLAST

    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.
    GeneTreeiENSGT00750000117488.
    HOGENOMiHOG000233236.
    HOVERGENiHBG006977.
    InParanoidiA2RTK9.
    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

    MEWGYLLEVT SLLAALAVLQ RSSGAAAASA KELACQEITV PLCKGIGYNY    50
    TYMPNQFNHD TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY 100
    KKPLPPCRSV CERAKAGCAP LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD 150
    YNRTDLTTAA PSPPRRLPPP PPPGEQPPSG SGHSRPPGAR PPHRGGSSRG 200
    SGDAAAAPPS RGGKARPPGG GAAPCEPGCQ CRAPMVSVSS ERHPLYNRVK 250
    TGQIANCALP CHNPFFSQDE RAFTVFWIGL WSVLCFVSTF ATVSTFLIDM 300
    ERFKYPERPI IFLSACYLFV SVGYLVRLVA GHEKVACSGG APGAGGAGGA 350
    GGAAAAGAGA AGAGASSPGA RGEYEELGAV EQHVRYETTG PALCTVVFLL 400
    VYFFGMASSI WWVILSLTWF LAAGMKWGNE AIAGYSQYFH LAAWLVPSVK 450
    SIAVLALSSV DGDPVAGICY VGNQSLDNLR GFVLAPLVIY LFIGTMFLLA 500
    GFVSLFRIRS VIKQQGGPTK THKLEKLMIR LGLFTVLYTV PAAVVVACLF 550
    YEQHNRPRWE ATHNCPCLRD LQPDQARRPD YAVFMLKYFM CLVVGITSGV 600
    WVWSGKTLES WRALCTRCCW ASKGAAVGAG AGGSGPGGSG PGPGGGGGHG 650
    GGGGSLYSDV STGLTWRSGT ASSVSYPKQM PLSQV 685
    Length:685
    Mass (Da):73,045
    Last modified:July 27, 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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U43321 Genomic DNA. Translation: AAC52433.1 .
    CH466592 Genomic DNA. Translation: EDL23012.1 .
    BC132543 mRNA. Translation: AAI32544.1 .
    BC138062 mRNA. Translation: AAI38063.1 .
    CCDSi CCDS29048.1.
    RefSeqi NP_032084.2. NM_008058.2.
    UniGenei Mm.184289.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1IJY X-ray 1.35 A/B 28-155 [» ]
    4F0A X-ray 3.25 A 28-150 [» ]
    ProteinModelPortali Q61091.
    SMRi Q61091. Positions 35-150, 230-612.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199781. 4 interactions.
    DIPi DIP-41258N.
    IntActi Q61091. 4 interactions.
    MINTi MINT-1782989.
    STRINGi 10090.ENSMUSP00000039660.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q61091.

    Proteomic databases

    PRIDEi Q61091.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000041080 ; ENSMUSP00000039660 ; ENSMUSG00000036904 .
    GeneIDi 14370.
    KEGGi mmu:14370.
    UCSCi uc008eag.2. mouse.

    Organism-specific databases

    CTDi 8325.
    MGIi MGI:108460. Fzd8.

    Phylogenomic databases

    eggNOGi NOG257258.
    GeneTreei ENSGT00750000117488.
    HOGENOMi HOG000233236.
    HOVERGENi HBG006977.
    InParanoidi A2RTK9.
    KOi K02375.
    OMAi HEKVACN.
    OrthoDBi EOG7M3J01.
    TreeFami TF317907.

    Enzyme and pathway databases

    Reactomei REACT_214043. PCP/CE pathway.

    Miscellaneous databases

    EvolutionaryTracei Q61091.
    NextBioi 285853.
    PROi Q61091.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q61091.
    CleanExi MM_FZD8.
    Genevestigatori Q61091.

    Family and domain databases

    Gene3Di 1.10.2000.10. 1 hit.
    InterProi IPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR017981. GPCR_2-like.
    [Graphical view ]
    PANTHERi PTHR11309. PTHR11309. 1 hit.
    Pfami PF01534. Frizzled. 1 hit.
    PF01392. Fz. 1 hit.
    [Graphical view ]
    PRINTSi PR00489. FRIZZLED.
    SMARTi SM00063. FRI. 1 hit.
    [Graphical view ]
    SUPFAMi SSF63501. SSF63501. 1 hit.
    PROSITEi PS50038. FZ. 1 hit.
    PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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(1996) [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 (SEP-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(2004) [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(1999) [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(1999) [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(2001) [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(2004) [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(2006) [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(2001) [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(2012) [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 5, 2001
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 132 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