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O93274

- FZD8_XENLA

UniProt

O93274 - FZD8_XENLA

Protein

Frizzled-8

Gene

fzd8

Organism
Xenopus laevis (African clawed frog)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 98 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      Previous versions | rss
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    Functioni

    Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which 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. Activation by Wnt8, Wnt5A or Wnt3A induces expression of beta-catenin target genes. Displays an axis-inducing activity.1 Publication

    GO - Molecular functioni

    1. G-protein coupled receptor activity Source: UniProtKB-KW
    2. protein binding Source: IntAct

    GO - Biological processi

    1. canonical Wnt signaling pathway Source: BHF-UCL
    2. multicellular organismal development Source: UniProtKB-KW
    3. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Wnt signaling pathway

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled-8
    Short name:
    Fz-8
    Short name:
    Xfz8
    Gene namesi
    Name:fzd8
    Synonyms:fz8
    OrganismiXenopus laevis (African clawed frog)
    Taxonomic identifieri8355 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiAmphibiaBatrachiaAnuraPipoideaPipidaeXenopodinaeXenopusXenopus

    Organism-specific databases

    XenbaseiXB-GENE-865411. fzd8.

    Subcellular locationi

    Membrane 1 Publication; Multi-pass membrane protein 1 Publication. Cell membrane By similarity; Multi-pass membrane protein By similarity

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323Sequence AnalysisAdd
    BLAST
    Chaini24 – 581558Frizzled-8PRO_0000013002Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi28 ↔ 89PROSITE-ProRule annotation
    Disulfide bondi36 ↔ 82PROSITE-ProRule annotation
    Glycosylationi42 – 421N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi73 ↔ 111PROSITE-ProRule annotation
    Disulfide bondi100 ↔ 141PROSITE-ProRule annotation
    Disulfide bondi104 ↔ 128PROSITE-ProRule annotation
    Glycosylationi146 – 1461N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Expressioni

    Developmental stagei

    First expressed at high levels in the late blastula stages. At early gastrula, expressed in the deep cells of the Spemann organizer prior to involution of the dorsal blastopore lip. Detected in presumptive neurectoderm as gastrulation proceeds. Becomes restricted to the anterior ectoderm by the end of gastrulation. At neurula stages, localized in the most anterior region of the embryo, mainly in the anterior ectoderm including telencephalic and cement gland regions.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FRIEDQ6EHH92EBI-7735236,EBI-7735259

    Protein-protein interaction databases

    IntActiO93274. 1 interaction.
    MINTiMINT-1893946.

    Structurei

    3D structure databases

    ProteinModelPortaliO93274.
    SMRiO93274. Positions 25-144.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini24 – 239216ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini261 – 27111CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini293 – 32028ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini342 – 37736CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini399 – 4079ExtracellularSequence Analysis
    Topological domaini429 – 45426CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini476 – 50530ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini527 – 58155CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei240 – 26021Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei272 – 29221Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei321 – 34121Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei378 – 39821Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei408 – 42821Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei455 – 47521Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei506 – 52621Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini24 – 144121FZPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni64 – 718Palmitate-binding grooveBy similarity
    Regioni88 – 936Wnt-bindingBy similarity
    Regioni140 – 1467Wnt-bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi529 – 5346Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
    Motifi579 – 5813PDZ-binding

    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.By similarity

    Sequence similaritiesi

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

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOVERGENiHBG006977.
    KOiK02375.

    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.

    O93274-1 [UniParc]FASTAAdd to Basket

    « Hide

    MESLSLSLLL LVSWLQGSQC AAAKELSCQE ITVPLCKDIG YNYTYMPNQF    50
    NHDTQDEAGM EVHQFWPLVV IHCSPDLKFF LCSMYTPICL EDYKKPLPPC 100
    RSVCERARAG CAPLMRQYGF AWPDRMRCDR LPEQGNPDTL CMDYYNRTEQ 150
    TTAAPSHPEP PKPPARSVPK GRTRVEPPRS RSRATGCESG CQCRAPMVQV 200
    SNERHPLYNR VRTGQIPNCA MPCHNPFFSP EERTFTEFWI GLWSVLCFAS 250
    TFATVSTFLI DMERFKYPER PIIFLSACYL LVSTGYLIRL IAGHEKVACS 300
    RGELDLEHII HYETTGPALC TLVFLLIYFF GMASSIWWVI LSLTWFLAAG 350
    MKWGNEAIAG YSQYFHLAAW LVPSIKSIAV LALSSVDGDP VAGICFVGNQ 400
    NLDNLRGFVL APLVIYLFIG SMFLLAGFVS LFRIRSVIKQ GGTKTDKLEK 450
    LMIRIGIFSV LYTVPATIVV ACFFYEQHNR QGWEVAHNCN SCQPEMAQPH 500
    RPDYAVFMLK YFMCLVVGIT SGVWIWSGKT LESWRAFCTR CCWGSKATGG 550
    SMYSDVSTGL TWRSGTGSSV SCPKQMPLSQ V 581
    Length:581
    Mass (Da):65,379
    Last modified:November 1, 1998 - v1
    Checksum:i80890C408AB21E23
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti1 – 33MES → MECPY(PubMed:9636083)Curated
    Sequence conflicti7 – 71S → L in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti10 – 101L → V in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti14 – 141W → G in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti20 – 201C → S in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti135 – 1351G → S in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti171 – 1711G → S in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti175 – 1751V → A in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti185 – 1851T → P in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti216 – 2161I → T in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti237 – 2371E → D in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti494 – 4963PEM → SEG in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti500 – 5001H → R in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti547 – 5471A → T in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti565 – 5651G → A in AAC77361. (PubMed:9636083)Curated
    Sequence conflicti572 – 5721C → Y in AAC77361. (PubMed:9636083)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF017177 mRNA. Translation: AAC31121.1.
    AF033110 mRNA. Translation: AAC77361.1.
    RefSeqiNP_001079144.1. NM_001085675.1.
    NP_001084206.1. NM_001090737.1.
    UniGeneiXl.293.
    Xl.412.

    Genome annotation databases

    GeneIDi373690.
    399367.
    KEGGixla:373690.
    xla:399367.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF017177 mRNA. Translation: AAC31121.1 .
    AF033110 mRNA. Translation: AAC77361.1 .
    RefSeqi NP_001079144.1. NM_001085675.1.
    NP_001084206.1. NM_001090737.1.
    UniGenei Xl.293.
    Xl.412.

    3D structure databases

    ProteinModelPortali O93274.
    SMRi O93274. Positions 25-144.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi O93274. 1 interaction.
    MINTi MINT-1893946.

    Protein family/group databases

    GPCRDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 373690.
    399367.
    KEGGi xla:373690.
    xla:399367.

    Organism-specific databases

    CTDi 373690.
    399367.
    Xenbasei XB-GENE-865411. fzd8.

    Phylogenomic databases

    HOVERGENi HBG006977.
    KOi K02375.

    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 role for Xenopus Frizzled 8 in dorsal development."
      Itoh K., Jacob J., Sokol S.Y.
      Mech. Dev. 74:145-157(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], COUPLING TO BETA-CATENIN PATHWAY.
      Tissue: Embryo.
    2. "Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis."
      Deardorff M.A., Tan C., Conrad L.J., Klein P.S.
      Development 125:2687-2700(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Embryo.
    3. "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.

    Entry informationi

    Entry nameiFZD8_XENLA
    AccessioniPrimary (citable) accession number: O93274
    Secondary accession number(s): Q9YI55
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 5, 2001
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 98 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3