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Q9H461

- FZD8_HUMAN

UniProt

Q9H461 - FZD8_HUMAN

Protein

Frizzled-8

Gene

FZD8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 Mar 2001)
      Previous versions | rss
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    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 signalosomes. 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 WNT1.1 Publication

    GO - Molecular functioni

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

    GO - Biological processi

    1. axonogenesis Source: RefGenome
    2. brain development Source: RefGenome
    3. canonical Wnt signaling pathway Source: RefGenome
    4. gonad development Source: RefGenome
    5. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    6. neuron differentiation Source: UniProtKB
    7. positive regulation of JUN kinase activity Source: Ensembl
    8. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    9. T cell differentiation in thymus Source: RefGenome
    10. 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_18372. Class B/2 (Secretin family receptors).
    REACT_200716. regulation of FZD by ubiquitination.
    SignaLinkiQ9H461.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled-8
    Short name:
    Fz-8
    Short name:
    hFz8
    Gene namesi
    Name:FZD8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:4046. FZD8.

    Subcellular locationi

    Membrane; Multi-pass membrane protein. Golgi apparatus By similarity. Cell membrane By similarity; Multi-pass membrane protein By similarity
    Note: Colocalizes with GOPC at the Golgi apparatus.By similarity

    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
    5. plasma membrane Source: RefGenome

    Keywords - Cellular componenti

    Cell membrane, Golgi apparatus, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28463.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2727Sequence AnalysisAdd
    BLAST
    Chaini28 – 694667Frizzled-8PRO_0000013000Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi35 ↔ 96PROSITE-ProRule annotation
    Disulfide bondi43 ↔ 89PROSITE-ProRule annotation
    Glycosylationi49 – 491N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi80 ↔ 118PROSITE-ProRule annotation
    Disulfide bondi107 ↔ 148PROSITE-ProRule annotation
    Disulfide bondi111 ↔ 135PROSITE-ProRule annotation
    Glycosylationi152 – 1521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi475 – 4751N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ9H461.
    PRIDEiQ9H461.

    PTM databases

    PhosphoSiteiQ9H461.

    Expressioni

    Tissue specificityi

    Most abundant in fetal kidney, followed by brain and lung. In adult tissues, expressed in kidney, heart, pancreas and skeletal muscle.

    Gene expression databases

    BgeeiQ9H461.
    CleanExiHS_FZD8.
    GenevestigatoriQ9H461.

    Organism-specific databases

    HPAiHPA045025.

    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. Interacts with GPOC, RSPO1 and RSPO3 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    C1qaP980863EBI-6254212,EBI-299840From a different organism.
    WNT3AP567042EBI-6254212,EBI-6173037

    Protein-protein interaction databases

    BioGridi113921. 4 interactions.
    IntActiQ9H461. 3 interactions.
    STRINGi9606.ENSP00000363826.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9H461.
    SMRiQ9H461. Positions 35-150, 233-619.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini28 – 275248ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini297 – 31216CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini334 – 39663ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini418 – 43922CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini461 – 48323ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini505 – 53228CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini554 – 58431ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini606 – 69489CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei276 – 29621Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei313 – 33321Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei397 – 41721Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei440 – 46021Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei484 – 50421Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei533 – 55321Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei585 – 60521Helical; 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 grooveBy similarity
    Regioni95 – 1006Wnt-bindingBy similarity
    Regioni147 – 1526Wnt-bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi608 – 6136Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
    Motifi692 – 6943PDZ-binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi168 – 1725Poly-Pro
    Compositional biasi194 – 2029Poly-Gly
    Compositional biasi211 – 2166Poly-Gly
    Compositional biasi639 – 66325Poly-GlyAdd
    BLAST

    Domaini

    The PDZ-binding motif mediates interaction with GOPC.By similarity
    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.By similarity

    Sequence similaritiesi

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

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG257258.
    HOGENOMiHOG000233236.
    HOVERGENiHBG006977.
    InParanoidiQ9H461.
    KOiK02375.
    OMAiHEKVACN.
    OrthoDBiEOG7M3J01.
    PhylomeDBiQ9H461.
    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.

    Q9H461-1 [UniParc]FASTAAdd to Basket

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    MEWGYLLEVT SLLAALALLQ RSSGAAAASA KELACQEITV PLCKGIGYNY    50
    TYMPNQFNHD TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY 100
    KKPLPPCRSV CERAKAGCAP LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD 150
    YNRTDLTTAA PSPPRRLPPP PPGEQPPSGS GHGRPPGARP PHRGGGRGGG 200
    GGDAAAPPAR GGGGGGKARP PGGGAAPCEP GCQCRAPMVS VSSERHPLYN 250
    RVKTGQIANC ALPCHNPFFS QDERAFTVFW IGLWSVLCFV STFATVSTFL 300
    IDMERFKYPE RPIIFLSACY LFVSVGYLVR LVAGHEKVAC SGGAPGAGGA 350
    GGAGGAAAGA GAAGAGAGGP GGRGEYEELG AVEQHVRYET TGPALCTVVF 400
    LLVYFFGMAS SIWWVILSLT WFLAAGMKWG NEAIAGYSQY FHLAAWLVPS 450
    VKSIAVLALS SVDGDPVAGI CYVGNQSLDN LRGFVLAPLV IYLFIGTMFL 500
    LAGFVSLFRI RSVIKQQDGP TKTHKLEKLM IRLGLFTVLY TVPAAVVVAC 550
    LFYEQHNRPR WEATHNCPCL RDLQPDQARR PDYAVFMLKY FMCLVVGITS 600
    GVWVWSGKTL ESWRSLCTRC CWASKGAAVG GGAGATAAGG GGGPGGGGGG 650
    GPGGGGGPGG GGGSLYSDVS TGLTWRSGTA SSVSYPKQMP LSQV 694
    Length:694
    Mass (Da):73,300
    Last modified:March 1, 2001 - v1
    Checksum:iE740CBFDA2A233EF
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB043703 mRNA. Translation: BAB41064.1.
    AL121749 Genomic DNA. Translation: CAC10185.1.
    CCDSiCCDS7192.1.
    RefSeqiNP_114072.1. NM_031866.2.
    UniGeneiHs.302634.

    Genome annotation databases

    EnsembliENST00000374694; ENSP00000363826; ENSG00000177283.
    GeneIDi8325.
    KEGGihsa:8325.
    UCSCiuc001iyz.1. human.

    Polymorphism databases

    DMDMi17433053.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB043703 mRNA. Translation: BAB41064.1 .
    AL121749 Genomic DNA. Translation: CAC10185.1 .
    CCDSi CCDS7192.1.
    RefSeqi NP_114072.1. NM_031866.2.
    UniGenei Hs.302634.

    3D structure databases

    ProteinModelPortali Q9H461.
    SMRi Q9H461. Positions 35-150, 233-619.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113921. 4 interactions.
    IntActi Q9H461. 3 interactions.
    STRINGi 9606.ENSP00000363826.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q9H461.

    Polymorphism databases

    DMDMi 17433053.

    Proteomic databases

    PaxDbi Q9H461.
    PRIDEi Q9H461.

    Protocols and materials databases

    DNASUi 8325.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000374694 ; ENSP00000363826 ; ENSG00000177283 .
    GeneIDi 8325.
    KEGGi hsa:8325.
    UCSCi uc001iyz.1. human.

    Organism-specific databases

    CTDi 8325.
    GeneCardsi GC10M035927.
    HGNCi HGNC:4046. FZD8.
    HPAi HPA045025.
    MIMi 606146. gene.
    neXtProti NX_Q9H461.
    PharmGKBi PA28463.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG257258.
    HOGENOMi HOG000233236.
    HOVERGENi HBG006977.
    InParanoidi Q9H461.
    KOi K02375.
    OMAi HEKVACN.
    OrthoDBi EOG7M3J01.
    PhylomeDBi Q9H461.
    TreeFami TF317907.

    Enzyme and pathway databases

    Reactomei REACT_18372. Class B/2 (Secretin family receptors).
    REACT_200716. regulation of FZD by ubiquitination.
    SignaLinki Q9H461.

    Miscellaneous databases

    GeneWikii FZD8.
    GenomeRNAii 8325.
    NextBioi 31175.
    PROi Q9H461.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9H461.
    CleanExi HS_FZD8.
    Genevestigatori Q9H461.

    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. "Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2."
      Saitoh T., Hirai M., Katoh M.
      Int. J. Oncol. 18:991-996(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "The DNA sequence and comparative analysis of human chromosome 10."
      Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
      , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
      Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6."
      Semenov M.V., Tamai K., Brott B.K., Kuhl M., Sokol S., He X.
      Curr. Biol. 11:951-961(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LRP5 AND LRP6 IN THE WNT-FZD-LRP5-LRP6 COMPLEX, FUNCTION.
    4. "Solution structure of GOPC PDZ domain and its interaction with the C-terminal motif of neuroligin."
      Li X., Zhang J., Cao Z., Wu J., Shi Y.
      Protein Sci. 15:2149-2158(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GOPC.
    5. Cited for: UBIQUITINATION BY ZNRF3.

    Entry informationi

    Entry nameiFZD8_HUMAN
    AccessioniPrimary (citable) accession number: Q9H461
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 5, 2001
    Last sequence update: March 1, 2001
    Last modified: October 1, 2014
    This is version 124 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3