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Q9QZH0

- FZD4_RAT

UniProt

Q9QZH0 - FZD4_RAT

Protein

Frizzled-4

Gene

Fzd4

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      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 By similarity.By similarity

    GO - Molecular functioni

    1. G-protein coupled receptor activity Source: UniProtKB-KW
    2. PDZ domain binding Source: RefGenome
    3. Wnt-activated receptor activity Source: RefGenome
    4. Wnt-protein binding Source: RGD

    GO - Biological processi

    1. brain development Source: RefGenome
    2. canonical Wnt signaling pathway Source: RefGenome
    3. cerebellum vasculature morphogenesis Source: Ensembl
    4. extracellular matrix-cell signaling Source: Ensembl
    5. locomotion involved in locomotory behavior Source: Ensembl
    6. negative regulation of cell-substrate adhesion Source: Ensembl
    7. positive regulation of JUN kinase activity Source: Ensembl
    8. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
    9. positive regulation of transcription, DNA-templated Source: Ensembl
    10. progesterone secretion Source: RefGenome
    11. regulation of vascular endothelial growth factor receptor signaling pathway Source: RefGenome
    12. retinal blood vessel morphogenesis Source: Ensembl
    13. sensory perception of sound Source: Ensembl
    14. substrate adhesion-dependent cell spreading Source: RefGenome
    15. vasculogenesis Source: RefGenome
    16. 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_194690. Ca2+ pathway.
    REACT_198398. WNT5A-dependent internalization of FZD4.
    REACT_206128. regulation of FZD by ubiquitination.

    Protein family/group databases

    MEROPSiI93.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled-4
    Short name:
    Fz-4
    Short name:
    rFz4
    Alternative name(s):
    CD_antigen: CD344
    Gene namesi
    Name:Fzd4
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 1

    Organism-specific databases

    RGDi71017. Fzd4.

    Subcellular locationi

    GO - Cellular componenti

    1. cell-cell junction Source: Ensembl
    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: RefGenome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3737Sequence AnalysisAdd
    BLAST
    Chaini38 – 538501Frizzled-4PRO_0000012987Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi46 ↔ 107PROSITE-ProRule annotation
    Disulfide bondi54 ↔ 100PROSITE-ProRule annotation
    Glycosylationi60 – 601N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi91 ↔ 129PROSITE-ProRule annotation
    Disulfide bondi118 ↔ 159PROSITE-ProRule annotation
    Disulfide bondi122 ↔ 146PROSITE-ProRule annotation
    Glycosylationi145 – 1451N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi382 – 3821N-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

    PaxDbiQ9QZH0.
    PRIDEiQ9QZH0.

    PTM databases

    PhosphoSiteiQ9QZH0.

    Expressioni

    Gene expression databases

    GenevestigatoriQ9QZH0.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000023205.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9QZH0.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini38 – 223186ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini245 – 25511CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini277 – 30327ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini325 – 34521CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini367 – 39024ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini412 – 43726CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini459 – 47820ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini500 – 53839CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei224 – 24421Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei256 – 27621Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei304 – 32421Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei346 – 36621Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei391 – 41121Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei438 – 45821Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei479 – 49921Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini41 – 162122FZPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi500 – 5056Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
    Motifi536 – 5383PDZ-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.
    InParanoidiQ9QZH0.
    KOiK02354.
    OMAiSMCLSVK.
    OrthoDBiEOG7M3J01.
    PhylomeDBiQ9QZH0.
    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.

    Q9QZH0-1 [UniParc]FASTAAdd to Basket

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    MAWQGTGPSV RGMPGGVRLR LGLLLLQLLL LQRPALGFGD EEERRCDPIR    50
    IAMCQNLGYN VTKMPNLVGH ELQTDAELQL TTFTPLIQYG CSSQLQFFLC 100
    SVYVPMCTEK INIPIGPCGG MCLSVKRRCE PVLKEFGFAW PDSLNCSKFP 150
    PQNDHNHMCM EGPGDEEVPL PHKTPIQPGE ECHSVGTNSD QYIWVKRSLN 200
    CVLKCGYDAG LYSRSAKEFT DIWMAVWASL CFISTTFTVL TFLIDSSRFS 250
    YPERPIIFLS MCYNIYSIAY IVRLTVGRER ISCDFEEAAE PVLIQEGLKN 300
    TGCAIIFLLM YFFGMASSIW WVILTLTWFL AAGLKWGHEA IEMHSSYFHI 350
    AAWAIPAVKT IVILIMRLVD ADELTGLCYV GNQSLDALTG FVVAPLFTYL 400
    VIGTLFIAAG LVALFKIRSN LQKDGTKTDK LERLMVKIGV FSVLYTVPAT 450
    CVIACYFYEI SNWALFRYSA DDSNMAVEML KIFMSLLVGI TSGMWIWSAK 500
    TLHTWQKCSN RLVNSGKVKR EKRGNGWVKP GKGNETVV 538
    Length:538
    Mass (Da):60,355
    Last modified:May 1, 2000 - v1
    Checksum:i07DAAE606B46E005
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF183910 mRNA. Translation: AAF01036.1.
    RefSeqiNP_072145.1. NM_022623.2.
    UniGeneiRn.18388.
    Rn.48736.

    Genome annotation databases

    EnsembliENSRNOT00000023205; ENSRNOP00000023205; ENSRNOG00000016848.
    GeneIDi64558.
    KEGGirno:64558.
    UCSCiRGD:71017. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF183910 mRNA. Translation: AAF01036.1 .
    RefSeqi NP_072145.1. NM_022623.2.
    UniGenei Rn.18388.
    Rn.48736.

    3D structure databases

    ProteinModelPortali Q9QZH0.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000023205.

    Protein family/group databases

    MEROPSi I93.001.
    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q9QZH0.

    Proteomic databases

    PaxDbi Q9QZH0.
    PRIDEi Q9QZH0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000023205 ; ENSRNOP00000023205 ; ENSRNOG00000016848 .
    GeneIDi 64558.
    KEGGi rno:64558.
    UCSCi RGD:71017. rat.

    Organism-specific databases

    CTDi 8322.
    RGDi 71017. Fzd4.

    Phylogenomic databases

    eggNOGi NOG284049.
    GeneTreei ENSGT00750000117488.
    HOGENOMi HOG000233236.
    HOVERGENi HBG006977.
    InParanoidi Q9QZH0.
    KOi K02354.
    OMAi SMCLSVK.
    OrthoDBi EOG7M3J01.
    PhylomeDBi Q9QZH0.
    TreeFami TF317907.

    Enzyme and pathway databases

    Reactomei REACT_194690. Ca2+ pathway.
    REACT_198398. WNT5A-dependent internalization of FZD4.
    REACT_206128. regulation of FZD by ubiquitination.

    Miscellaneous databases

    NextBioi 613472.
    PROi Q9QZH0.

    Gene expression databases

    Genevestigatori Q9QZH0.

    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. "Expression of a putative seven-pass transmembrane frizzled receptor in the Corpus Luteum (CL) of the rat during pregnancy and involution."
      Walther P.R., Lacher M.D., Saurer S., Friis R.R.
      Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Corpus luteum.

    Entry informationi

    Entry nameiFZD4_RAT
    AccessioniPrimary (citable) accession number: Q9QZH0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 5, 2001
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 106 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