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Q61088

- FZD4_MOUSE

UniProt

Q61088 - FZD4_MOUSE

Protein

Frizzled-4

Gene

Fzd4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 129 (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 (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. 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.2 Publications

    GO - Molecular functioni

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

    GO - Biological processi

    1. blood vessel development Source: MGI
    2. canonical Wnt signaling pathway Source: BHF-UCL
    3. cerebellum vasculature morphogenesis Source: BHF-UCL
    4. extracellular matrix-cell signaling Source: BHF-UCL
    5. locomotion involved in locomotory behavior Source: MGI
    6. luteinization Source: MGI
    7. negative regulation of cell-substrate adhesion Source: BHF-UCL
    8. positive regulation of JUN kinase activity Source: MGI
    9. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    10. positive regulation of transcription, DNA-templated Source: BHF-UCL
    11. progesterone secretion Source: MGI
    12. regulation of transcription from RNA polymerase II promoter Source: RefGenome
    13. regulation of vascular endothelial growth factor receptor signaling pathway Source: MGI
    14. retinal blood vessel morphogenesis Source: BHF-UCL
    15. retina vasculature morphogenesis in camera-type eye Source: MGI
    16. sensory perception of sound Source: MGI
    17. substrate adhesion-dependent cell spreading Source: MGI
    18. vasculogenesis Source: MGI
    19. Wnt signaling pathway, calcium modulating pathway Source: Ensembl

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Wnt signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_213035. regulation of FZD by ubiquitination.
    REACT_221970. Ca2+ pathway.
    REACT_222404. WNT5A-dependent internalization of FZD4.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled-4
    Short name:
    Fz-4
    Short name:
    mFz4
    Alternative name(s):
    CD_antigen: CD344
    Gene namesi
    Name:Fzd4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:108520. Fzd4.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cell-cell junction Source: MGI
    2. cell projection Source: RefGenome
    3. cell surface Source: Ensembl
    4. cytoplasm Source: RefGenome
    5. integral component of membrane Source: UniProtKB-KW
    6. plasma membrane Source: BHF-UCL

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Defects in retinal vascularization.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3636Sequence AnalysisAdd
    BLAST
    Chaini37 – 537501Frizzled-4PRO_0000012986Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi45 ↔ 106PROSITE-ProRule annotation
    Disulfide bondi53 ↔ 99PROSITE-ProRule annotation
    Glycosylationi59 – 591N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi90 ↔ 128PROSITE-ProRule annotation
    Disulfide bondi117 ↔ 158PROSITE-ProRule annotation
    Disulfide bondi121 ↔ 145PROSITE-ProRule annotation
    Glycosylationi144 – 1441N-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

    PaxDbiQ61088.
    PRIDEiQ61088.

    PTM databases

    PhosphoSiteiQ61088.

    Expressioni

    Tissue specificityi

    Expressed in chondrocytes.

    Gene expression databases

    ArrayExpressiQ61088.
    BgeeiQ61088.
    CleanExiMM_FZD4.
    GenevestigatoriQ61088.

    Interactioni

    Subunit structurei

    Interacts with MAGI3 and NDP. Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP).3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    UBCP0CG483EBI-7987880,EBI-3390054From a different organism.

    Protein-protein interaction databases

    BioGridi199777. 3 interactions.
    DIPiDIP-41623N.
    IntActiQ61088. 7 interactions.
    MINTiMINT-1779328.

    Structurei

    3D structure databases

    ProteinModelPortaliQ61088.
    SMRiQ61088. Positions 45-161, 193-511.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini37 – 222186ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini244 – 25411CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini276 – 30227ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini324 – 34421CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini366 – 38924ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini411 – 43626CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini458 – 47720ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini499 – 53739CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei223 – 24321Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei255 – 27521Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei303 – 32321Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei345 – 36521Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei390 – 41021Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei437 – 45721Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei478 – 49821Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini40 – 161122FZPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi499 – 5046Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
    Motifi535 – 5373PDZ-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

    eggNOGiNOG284049.
    GeneTreeiENSGT00750000117488.
    HOGENOMiHOG000233236.
    HOVERGENiHBG006977.
    InParanoidiQ61088.
    KOiK02354.
    OMAiSMCLSVK.
    OrthoDBiEOG7M3J01.
    PhylomeDBiQ61088.
    TreeFamiTF317907.

    Family and domain databases

    Gene3Di1.10.2000.10. 1 hit.
    InterProiIPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026551. FZD4.
    IPR017981. GPCR_2-like.
    [Graphical view]
    PANTHERiPTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF23. PTHR11309:SF23. 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.

    Q61088-1 [UniParc]FASTAAdd to Basket

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    MAWPGTGPSS RGAPGGVGLR LGLLLQFLLL LRPTLGFGDE EERRCDPIRI    50
    AMCQNLGYNV TKMPNLVGHE LQTDAELQLT TFTPLIQYGC SSQLQFFLCS 100
    VYVPMCTEKI NIPIGPCGGM CLSVKRRCEP VLREFGFAWP DTLNCSKFPP 150
    QNDHNHMCME GPGDEEVPLP HKTPIQPGEE CHSVGSNSDQ YIWVKRSLNC 200
    VLKCGYDAGL YSRSAKEFTD IWMAVWASLC FISTTFTVLT FLIDSSRFSY 250
    PERPIIFLSM CYNIYSIAYI VRLTVGRERI SCDFEEAAEP VLIQEGLKNT 300
    GCAIIFLLMY FFGMASSIWW VILTLTWFLA AGLKWGHEAI EMHSSYFHIA 350
    AWAIPAVKTI VILIMRLVDA DELTGLCYVG NQNLDALTGF VVAPLFTYLV 400
    IGTLFIAAGL VALFKIRSNL QKDGTKTDKL ERLMVKIGVF SVLYTVPATC 450
    VIACYFYEIS NWALFRYSAD DSNMAVEMLK IFMSLLVGIT SGMWIWSAKT 500
    LHTWQKCSNR LVNSGKVKRE KRGNGWVKPG KGNETVV 537
    Length:537
    Mass (Da):60,143
    Last modified:November 1, 1996 - v1
    Checksum:i6641996E6960BCD8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti27 – 271F → L in AAH15256. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U43317 mRNA. Translation: AAC52430.1.
    BC015256 mRNA. Translation: AAH15256.1.
    CCDSiCCDS21441.1.
    RefSeqiNP_032081.3. NM_008055.4.
    UniGeneiMm.86755.

    Genome annotation databases

    EnsembliENSMUST00000058755; ENSMUSP00000049852; ENSMUSG00000049791.
    GeneIDi14366.
    KEGGimmu:14366.
    UCSCiuc009ifx.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U43317 mRNA. Translation: AAC52430.1 .
    BC015256 mRNA. Translation: AAH15256.1 .
    CCDSi CCDS21441.1.
    RefSeqi NP_032081.3. NM_008055.4.
    UniGenei Mm.86755.

    3D structure databases

    ProteinModelPortali Q61088.
    SMRi Q61088. Positions 45-161, 193-511.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199777. 3 interactions.
    DIPi DIP-41623N.
    IntActi Q61088. 7 interactions.
    MINTi MINT-1779328.

    Chemistry

    GuidetoPHARMACOLOGYi 232.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q61088.

    Proteomic databases

    PaxDbi Q61088.
    PRIDEi Q61088.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000058755 ; ENSMUSP00000049852 ; ENSMUSG00000049791 .
    GeneIDi 14366.
    KEGGi mmu:14366.
    UCSCi uc009ifx.2. mouse.

    Organism-specific databases

    CTDi 8322.
    MGIi MGI:108520. Fzd4.

    Phylogenomic databases

    eggNOGi NOG284049.
    GeneTreei ENSGT00750000117488.
    HOGENOMi HOG000233236.
    HOVERGENi HBG006977.
    InParanoidi Q61088.
    KOi K02354.
    OMAi SMCLSVK.
    OrthoDBi EOG7M3J01.
    PhylomeDBi Q61088.
    TreeFami TF317907.

    Enzyme and pathway databases

    Reactomei REACT_213035. regulation of FZD by ubiquitination.
    REACT_221970. Ca2+ pathway.
    REACT_222404. WNT5A-dependent internalization of FZD4.

    Miscellaneous databases

    NextBioi 285835.
    PROi Q61088.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q61088.
    Bgeei Q61088.
    CleanExi MM_FZD4.
    Genevestigatori Q61088.

    Family and domain databases

    Gene3Di 1.10.2000.10. 1 hit.
    InterProi IPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026551. FZD4.
    IPR017981. GPCR_2-like.
    [Graphical view ]
    PANTHERi PTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF23. PTHR11309:SF23. 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 [MRNA].
    2. "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: Kidney.
    3. "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.
    4. "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.
    5. "Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair."
      Xu Q., Wang Y., Dabdoub A., Smallwood P.M., Williams J., Woods C., Kelley M.W., Jiang L., Tasman W., Zhang K., Nathans J.
      Cell 116:883-895(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NDP, DISRUPTION PHENOTYPE.
    6. "MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap."
      Yao R., Natsume Y., Noda T.
      Oncogene 23:6023-6030(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAGI3.
    7. "TSPAN12 regulates retinal vascular development by promoting Norrin-but not Wnt-induced FZD4/beta-catenin signaling."
      Junge H.J., Yang S., Burton J.B., Paes K., Shu X., French D.M., Costa M., Rice D.S., Ye W.
      Cell 139:299-311(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH NDP AND TSPAN12.

    Entry informationi

    Entry nameiFZD4_MOUSE
    AccessioniPrimary (citable) accession number: Q61088
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 5, 2001
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 129 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3