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Q08464

- FZD2_RAT

UniProt

Q08464 - FZD2_RAT

Protein

Frizzled-2

Gene

Fzd2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      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 Wnt5A stimulates PKC activity via a G-protein-dependent mechanism.

    GO - Molecular functioni

    1. G-protein coupled receptor activity Source: UniProtKB-KW
    2. identical protein binding Source: IntAct
    3. PDZ domain binding Source: RefGenome
    4. protein binding Source: IntAct
    5. protein heterodimerization activity Source: BHF-UCL
    6. Wnt-activated receptor activity Source: RGD
    7. 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. cell activation Source: RGD
    5. cellular response to growth factor stimulus Source: RGD
    6. cellular response to peptide hormone stimulus Source: RGD
    7. cellular response to vitamin D Source: RGD
    8. epithelial cell differentiation Source: RefGenome
    9. gonad development Source: RefGenome
    10. G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Source: RGD
    11. positive regulation of cytosolic calcium ion concentration Source: RGD
    12. vasculature development Source: RefGenome
    13. Wnt signaling pathway, calcium modulating pathway Source: RGD

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Wnt signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_221970. Ca2+ pathway.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled-2
    Short name:
    Fz-2
    Short name:
    rFz2
    Gene namesi
    Name:Fzd2
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi71012. Fzd2.

    Subcellular locationi

    GO - Cellular componenti

    1. apical part of cell Source: RefGenome
    2. cytoplasm Source: RefGenome
    3. integral component of membrane Source: RGD
    4. neuron projection membrane Source: RefGenome
    5. plasma membrane Source: BHF-UCL

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2828Sequence AnalysisAdd
    BLAST
    Chaini29 – 570542Frizzled-2PRO_0000012980Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi44 ↔ 105PROSITE-ProRule annotation
    Disulfide bondi52 ↔ 98PROSITE-ProRule annotation
    Glycosylationi58 – 581N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi89 ↔ 126PROSITE-ProRule annotation
    Disulfide bondi115 ↔ 155PROSITE-ProRule annotation
    Disulfide bondi119 ↔ 143PROSITE-ProRule annotation
    Glycosylationi159 – 1591N-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

    PaxDbiQ08464.

    PTM databases

    PhosphoSiteiQ08464.

    Expressioni

    Tissue specificityi

    Widely expressed. Most abundant in kidney, liver, uterus, ovary and heart. Lower levels seen in brain and intestine. Extremely low in calvaria, mammary glands and testis.

    Developmental stagei

    Expressed predominantly in neonatal tissues, at lower levels in adult.

    Gene expression databases

    GenevestigatoriQ08464.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-7402050,EBI-7402050
    Fzd1Q084636EBI-7402050,EBI-8766455

    Protein-protein interaction databases

    BioGridi249097. 1 interaction.
    IntActiQ08464. 3 interactions.
    MINTiMINT-1780823.
    STRINGi10116.ENSRNOP00000036154.

    Structurei

    3D structure databases

    ProteinModelPortaliQ08464.
    SMRiQ08464. Positions 42-159.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini29 – 252224ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini274 – 28411CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini306 – 33227ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini354 – 37522CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini397 – 41923ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini441 – 46626CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini488 – 52437ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini546 – 57025CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei253 – 27321Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei285 – 30521Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei333 – 35321Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei376 – 39621Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei420 – 44021Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei467 – 48721Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei525 – 54521Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini39 – 158120FZPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi548 – 5536Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
    Motifi568 – 5703PDZ-binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi186 – 1927Poly-Gly

    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

    eggNOGiNOG257258.
    HOGENOMiHOG000233237.
    HOVERGENiHBG006977.
    InParanoidiQ08464.
    KOiK02235.
    PhylomeDBiQ08464.

    Family and domain databases

    Gene3Di1.10.2000.10. 1 hit.
    InterProiIPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026550. FZD2.
    IPR017981. GPCR_2-like.
    [Graphical view]
    PANTHERiPTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF34. PTHR11309:SF34. 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.

    Q08464-1 [UniParc]FASTAAdd to Basket

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    MRARSALPRS ALPRLLLPLL LLPAAGPAQF HGEKGISIPD HGFCQPISIP    50
    LCTDIAYNQT IMPNLLGHTN QEDAGLEVHQ FYPLVKVQCS PELRFFLCSM 100
    YAPVCTVLEQ AIPPCRSICE RARQGCEALM NKFGFQWPER LRCEHFPRHG 150
    AEQICVGQNH SEDGTPALLT TAPPSGLQPG AGGTPGGPGG GGAPPRYATL 200
    EHPFHCPRVL KVPSYLSYKF LGERDCAAPC EPARPDGSMF FSHHHTRFAR 250
    LWILTWSVLC CASTFFTVTT SLVAMQRFRY PERPIIFLSG CYTMVSVAYI 300
    AGFVLQERVV CNERFSEDGY RTVGQGTKKE GCTILFMMLY FFSMASSIWW 350
    VILSLTWFLA AGMKWGHAAI EANSQYFHLA AWAVPAVKTI TILAMGQIDG 400
    DLLSGVCFVG LNRLDPLRGF VLAPLFVYLF IGTSFLLAGF VSLFRIRTIM 450
    KHDGTKTEPL ERLMVRIGVF SVLYTVPATI VIACYFYEQA FREHWERSWV 500
    SQHCKSLAIP CPAHYTPRTS PDFTVYMIKY LMTLIVGITS GFWIWSGKTL 550
    HSWRKFYTRL TNSRHGETTV 570
    Length:570
    Mass (Da):63,885
    Last modified:November 1, 1996 - v1
    Checksum:i4FB895D9BEAFCA4E
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L02530 mRNA. Translation: AAA41172.1.
    RefSeqiNP_742032.1. NM_172035.1.
    UniGeneiRn.92324.

    Genome annotation databases

    GeneIDi64512.
    KEGGirno:64512.
    UCSCiRGD:71012. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L02530 mRNA. Translation: AAA41172.1 .
    RefSeqi NP_742032.1. NM_172035.1.
    UniGenei Rn.92324.

    3D structure databases

    ProteinModelPortali Q08464.
    SMRi Q08464. Positions 42-159.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 249097. 1 interaction.
    IntActi Q08464. 3 interactions.
    MINTi MINT-1780823.
    STRINGi 10116.ENSRNOP00000036154.

    Chemistry

    GuidetoPHARMACOLOGYi 230.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q08464.

    Proteomic databases

    PaxDbi Q08464.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 64512.
    KEGGi rno:64512.
    UCSCi RGD:71012. rat.

    Organism-specific databases

    CTDi 2535.
    RGDi 71012. Fzd2.

    Phylogenomic databases

    eggNOGi NOG257258.
    HOGENOMi HOG000233237.
    HOVERGENi HBG006977.
    InParanoidi Q08464.
    KOi K02235.
    PhylomeDBi Q08464.

    Enzyme and pathway databases

    Reactomei REACT_221970. Ca2+ pathway.

    Miscellaneous databases

    NextBioi 613298.
    PROi Q08464.

    Gene expression databases

    Genevestigatori Q08464.

    Family and domain databases

    Gene3Di 1.10.2000.10. 1 hit.
    InterProi IPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026550. FZD2.
    IPR017981. GPCR_2-like.
    [Graphical view ]
    PANTHERi PTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF34. PTHR11309:SF34. 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. "Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues."
      Chan S.D.H., Karpf D.B., Fowlkes M.E., Hooks M., Bradley M.S., Vuong V., Bambino T., Liu M.Y.C., Arnaud C.D., Strewler G.J., Nissenson R.A.
      J. Biol. Chem. 267:25202-25207(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.
      Tissue: Osteosarcoma.
    2. "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: WNT-MEDIATED PKC ACTIVATION.

    Entry informationi

    Entry nameiFZD2_RAT
    AccessioniPrimary (citable) accession number: Q08464
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 5, 2001
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 119 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    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