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Q08463

- FZD1_RAT

UniProt

Q08463 - FZD1_RAT

Protein

Frizzled-1

Gene

Fzd1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 118 (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 Wnt8 induces expression of beta-catenin target genes.

    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. protein homodimerization activity Source: BHF-UCL
    7. Wnt-activated receptor activity Source: RefGenome
    8. Wnt-protein binding Source: RefGenome

    GO - Biological processi

    1. axonogenesis Source: RefGenome
    2. brain development Source: RefGenome
    3. canonical Wnt signaling pathway Source: BHF-UCL
    4. cellular response to growth factor stimulus Source: RGD
    5. cellular response to peptide hormone stimulus Source: RGD
    6. cellular response to vitamin D Source: RGD
    7. epithelial cell differentiation Source: RefGenome
    8. gonad development Source: RefGenome
    9. G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Source: RefGenome
    10. lung alveolus development Source: RGD
    11. negative regulation of BMP signaling pathway Source: RefGenome
    12. negative regulation of canonical Wnt signaling pathway Source: RefGenome
    13. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    14. regulation of osteoblast differentiation Source: RGD
    15. vasculature development Source: RefGenome
    16. Wnt signaling pathway Source: RGD
    17. Wnt signaling pathway, calcium modulating pathway Source: RefGenome

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Wnt signaling pathway

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled-1
    Short name:
    Fz-1
    Short name:
    rFz1
    Gene namesi
    Name:Fzd1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi61916. Fzd1.

    Subcellular locationi

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 6868Sequence AnalysisAdd
    BLAST
    Chaini69 – 641573Frizzled-1PRO_0000012975Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi111 ↔ 172PROSITE-ProRule annotation
    Disulfide bondi119 ↔ 165PROSITE-ProRule annotation
    Glycosylationi125 – 1251N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi156 ↔ 192PROSITE-ProRule annotation
    Disulfide bondi182 ↔ 221PROSITE-ProRule annotation
    Disulfide bondi186 ↔ 209PROSITE-ProRule annotation
    Glycosylationi225 – 2251N-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

    PaxDbiQ08463.
    PRIDEiQ08463.

    PTM databases

    PhosphoSiteiQ08463.

    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

    GenevestigatoriQ08463.

    Interactioni

    Subunit structurei

    Interacts with MYOC.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself4EBI-8766455,EBI-8766455
    Fzd2Q084646EBI-8766455,EBI-7402050

    Protein-protein interaction databases

    IntActiQ08463. 1 interaction.
    STRINGi10116.ENSRNOP00000021979.

    Structurei

    3D structure databases

    ProteinModelPortaliQ08463.
    SMRiQ08463. Positions 109-225.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini69 – 316248ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini338 – 34811CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini370 – 39627ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini418 – 43922CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini461 – 48323ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini505 – 53026CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini552 – 59544ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini617 – 64125CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei317 – 33721Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei349 – 36921Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei397 – 41721Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei440 – 46021Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei484 – 50421Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei531 – 55121Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei596 – 61621Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini106 – 224119FZPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi619 – 6246Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
    Motifi639 – 6413PDZ-binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi85 – 906Poly-Pro

    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.
    HOGENOMiHOG000233236.
    HOVERGENiHBG006977.
    InParanoidiQ08463.
    PhylomeDBiQ08463.

    Family and domain databases

    Gene3Di1.10.2000.10. 1 hit.
    InterProiIPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026548. FZD1.
    IPR017981. GPCR_2-like.
    [Graphical view]
    PANTHERiPTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF81. PTHR11309:SF81. 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.

    Q08463-1 [UniParc]FASTAAdd to Basket

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    MAEEAVPSES RAAGRPSLEL CAVALPGRRE EVGHQDTAGH RRPRAHSRCW    50
    ARGLLLLLWL LEAPLLLGVR AQPAGQVSGP GQQRPPPPQP QQGGQQYNGE 100
    RGISIPDHGY CQPISIPLCT DIAYNQTIMP NLLGHTNQED AGLEVHQFYP 150
    LVKVQCSAEL KFFLCSMYAP VCTVLEQALP PCRSLCERAQ GCEALMNKFG 200
    FQWPDTLKCE KFPVHGAGEL CVGQNTSDKG TPTPSLLPEF WTSNPQHGGG 250
    GYRGGYPGGA GPVERGKFSC PRALRVPSYL NYHFLGEKDC GAPCEPTKVY 300
    GLMYFGPEEL RFSRTWIGIW SVLCCASTLF TVLTYLVDMR RFSYPERPII 350
    FLSGCYTAVA VAYIAGFLLE DRVVCNDKFA EDGARTVAQG TKKEGCTILF 400
    MMLYFFSMAS SIWWVILSLT WFLAAGMKWG HEAIEANSQY FHLAAWAVPA 450
    IKTITILALG QVDGDVLSGV CFVGLNNVDA LRGFVLAPLF VYLFIGTSFL 500
    LAGFVSLFRI RTIMKHDGTK TEKLEKLMVR IGVFSVLYTV PATIVIACYF 550
    YEQAFRDQWE RSWVAQSCKS YAIPCPHLQG GGGVPPHPPM SPDFTVFMIK 600
    YLMTLIVGIT SGFWIWSGKT LNSWRKFYTR LTNSKQGETT V 641
    Length:641
    Mass (Da):71,027
    Last modified:November 1, 1996 - v1
    Checksum:iD82E2C113E81B8B6
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L02529 mRNA. Translation: AAA41173.1.
    PIRiA45054.
    UniGeneiRn.6575.

    Genome annotation databases

    UCSCiRGD:61916. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L02529 mRNA. Translation: AAA41173.1 .
    PIRi A45054.
    UniGenei Rn.6575.

    3D structure databases

    ProteinModelPortali Q08463.
    SMRi Q08463. Positions 109-225.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q08463. 1 interaction.
    STRINGi 10116.ENSRNOP00000021979.

    Chemistry

    GuidetoPHARMACOLOGYi 229.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q08463.

    Proteomic databases

    PaxDbi Q08463.
    PRIDEi Q08463.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    UCSCi RGD:61916. rat.

    Organism-specific databases

    RGDi 61916. Fzd1.

    Phylogenomic databases

    eggNOGi NOG257258.
    HOGENOMi HOG000233236.
    HOVERGENi HBG006977.
    InParanoidi Q08463.
    PhylomeDBi Q08463.

    Miscellaneous databases

    PROi Q08463.

    Gene expression databases

    Genevestigatori Q08463.

    Family and domain databases

    Gene3Di 1.10.2000.10. 1 hit.
    InterProi IPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026548. FZD1.
    IPR017981. GPCR_2-like.
    [Graphical view ]
    PANTHERi PTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF81. PTHR11309:SF81. 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: COUPLING TO BETA-CATENIN PATHWAY.

    Entry informationi

    Entry nameiFZD1_RAT
    AccessioniPrimary (citable) accession number: Q08463
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 5, 2001
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 118 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