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Q14332

- FZD2_HUMAN

UniProt

Q14332 - FZD2_HUMAN

Protein

Frizzled-2

Gene

FZD2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 132 (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.

    GO - Molecular functioni

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

    GO - Biological processi

    1. axonogenesis Source: RefGenome
    2. brain development Source: RefGenome
    3. canonical Wnt signaling pathway Source: UniProtKB
    4. cell-cell signaling Source: Ensembl
    5. cochlea morphogenesis Source: Ensembl
    6. epithelial cell differentiation Source: RefGenome
    7. gonad development Source: RefGenome
    8. G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Source: RefGenome
    9. hard palate development Source: Ensembl
    10. inner ear receptor cell development Source: Ensembl
    11. membranous septum morphogenesis Source: Ensembl
    12. muscular septum morphogenesis Source: Ensembl
    13. neuron differentiation Source: UniProtKB
    14. outflow tract morphogenesis Source: Ensembl
    15. planar cell polarity pathway involved in neural tube closure Source: Ensembl
    16. positive regulation of cGMP metabolic process Source: BHF-UCL
    17. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    18. positive regulation of transcription, DNA-templated Source: BHF-UCL
    19. sensory perception of smell Source: Ensembl
    20. vasculature development Source: RefGenome
    21. 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

    Enzyme and pathway databases

    ReactomeiREACT_172631. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
    REACT_172761. Ca2+ pathway.
    REACT_18372. Class B/2 (Secretin family receptors).
    REACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
    REACT_200777. TCF dependent signaling in response to WNT.

    Protein family/group databases

    MEROPSiI93.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled-2
    Short name:
    Fz-2
    Short name:
    hFz2
    Alternative name(s):
    FzE2
    Gene namesi
    Name:FZD2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:4040. FZD2.

    Subcellular locationi

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28457.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323Sequence AnalysisAdd
    BLAST
    Chaini24 – 565542Frizzled-2PRO_0000012978Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi39 ↔ 100PROSITE-ProRule annotation
    Disulfide bondi47 ↔ 93PROSITE-ProRule annotation
    Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi84 ↔ 121PROSITE-ProRule annotation
    Disulfide bondi110 ↔ 150PROSITE-ProRule annotation
    Disulfide bondi114 ↔ 138PROSITE-ProRule annotation
    Glycosylationi154 – 1541N-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

    MaxQBiQ14332.
    PaxDbiQ14332.
    PRIDEiQ14332.

    PTM databases

    PhosphoSiteiQ14332.

    Expressioni

    Tissue specificityi

    Widely expressed. In the adult, mainly found in heart, placenta, skeletal muscle, lung, kidney, pancreas, prostate, testis, ovary and colon. In the fetus, expressed in brain, lung and kidney. Low levels in fetal liver.

    Gene expression databases

    ArrayExpressiQ14332.
    BgeeiQ14332.
    CleanExiHS_FZD2.
    GenevestigatoriQ14332.

    Organism-specific databases

    HPAiHPA057667.

    Interactioni

    Protein-protein interaction databases

    BioGridi108811. 4 interactions.
    IntActiQ14332. 1 interaction.
    STRINGi9606.ENSP00000323901.

    Structurei

    3D structure databases

    ProteinModelPortaliQ14332.
    SMRiQ14332. Positions 39-145, 191-556.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini24 – 247224ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini269 – 27911CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini301 – 32727ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini349 – 37022CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini392 – 41423ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini436 – 46126CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini483 – 51937ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini541 – 56525CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei248 – 26821Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei280 – 30021Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei328 – 34821Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei371 – 39121Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei415 – 43521Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei462 – 48221Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei520 – 54021Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini34 – 153120FZPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi543 – 5486Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
    Motifi563 – 5653PDZ-binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi181 – 1877Poly-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.
    HOVERGENiHBG006977.
    InParanoidiQ14332.
    KOiK02235.
    OMAiCENFPRH.
    OrthoDBiEOG7M3J01.
    PhylomeDBiQ14332.
    TreeFamiTF317907.

    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.

    Q14332-1 [UniParc]FASTAAdd to Basket

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    MRPRSALPRL LLPLLLLPAA GPAQFHGEKG ISIPDHGFCQ PISIPLCTDI    50
    AYNQTIMPNL LGHTNQEDAG LEVHQFYPLV KVQCSPELRF FLCSMYAPVC 100
    TVLEQAIPPC RSICERARQG CEALMNKFGF QWPERLRCEH FPRHGAEQIC 150
    VGQNHSEDGA PALLTTAPPP GLQPGAGGTP GGPGGGGAPP RYATLEHPFH 200
    CPRVLKVPSY LSYKFLGERD CAAPCEPARP DGSMFFSQEE TRFARLWILT 250
    WSVLCCASTF FTVTTYLVDM QRFRYPERPI IFLSGCYTMV SVAYIAGFVL 300
    QERVVCNERF SEDGYRTVVQ GTKKEGCTIL FMMLYFFSMA SSIWWVILSL 350
    TWFLAAGMKW GHEAIEANSQ YFHLAAWAVP AVKTITILAM GQIDGDLLSG 400
    VCFVGLNSLD PLRGFVLAPL FVYLFIGTSF LLAGFVSLFR IRTIMKHDGT 450
    KTEKLERLMV RIGVFSVLYT VPATIVIACY FYEQAFREHW ERSWVSQHCK 500
    SLAIPCPAHY TPRMSPDFTV YMIKYLMTLI VGITSGFWIW SGKTLHSWRK 550
    FYTRLTNSRH GETTV 565
    Length:565
    Mass (Da):63,554
    Last modified:November 1, 1996 - v1
    Checksum:iAA387876A1DDE063
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L37882 mRNA. Translation: AAB46397.1.
    AB017364 mRNA. Translation: BAA34667.1.
    BC113402 mRNA. Translation: AAI13403.1.
    BC113404 mRNA. Translation: AAI13405.1.
    CCDSiCCDS11484.1.
    PIRiJE0338.
    RefSeqiNP_001457.1. NM_001466.3.
    UniGeneiHs.142912.
    Hs.732654.

    Genome annotation databases

    EnsembliENST00000315323; ENSP00000323901; ENSG00000180340.
    GeneIDi2535.
    KEGGihsa:2535.
    UCSCiuc002igx.2. human.

    Polymorphism databases

    DMDMi17433019.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L37882 mRNA. Translation: AAB46397.1 .
    AB017364 mRNA. Translation: BAA34667.1 .
    BC113402 mRNA. Translation: AAI13403.1 .
    BC113404 mRNA. Translation: AAI13405.1 .
    CCDSi CCDS11484.1.
    PIRi JE0338.
    RefSeqi NP_001457.1. NM_001466.3.
    UniGenei Hs.142912.
    Hs.732654.

    3D structure databases

    ProteinModelPortali Q14332.
    SMRi Q14332. Positions 39-145, 191-556.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108811. 4 interactions.
    IntActi Q14332. 1 interaction.
    STRINGi 9606.ENSP00000323901.

    Chemistry

    GuidetoPHARMACOLOGYi 230.

    Protein family/group databases

    MEROPSi I93.001.
    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q14332.

    Polymorphism databases

    DMDMi 17433019.

    Proteomic databases

    MaxQBi Q14332.
    PaxDbi Q14332.
    PRIDEi Q14332.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000315323 ; ENSP00000323901 ; ENSG00000180340 .
    GeneIDi 2535.
    KEGGi hsa:2535.
    UCSCi uc002igx.2. human.

    Organism-specific databases

    CTDi 2535.
    GeneCardsi GC17P042645.
    HGNCi HGNC:4040. FZD2.
    HPAi HPA057667.
    MIMi 600667. gene.
    neXtProti NX_Q14332.
    PharmGKBi PA28457.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG257258.
    HOVERGENi HBG006977.
    InParanoidi Q14332.
    KOi K02235.
    OMAi CENFPRH.
    OrthoDBi EOG7M3J01.
    PhylomeDBi Q14332.
    TreeFami TF317907.

    Enzyme and pathway databases

    Reactomei REACT_172631. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
    REACT_172761. Ca2+ pathway.
    REACT_18372. Class B/2 (Secretin family receptors).
    REACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
    REACT_200777. TCF dependent signaling in response to WNT.

    Miscellaneous databases

    ChiTaRSi FZD2. human.
    GeneWikii FZD2.
    GenomeRNAii 2535.
    NextBioi 10005.
    PROi Q14332.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14332.
    Bgeei Q14332.
    CleanExi HS_FZD2.
    Genevestigatori Q14332.

    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. "A human homologue of the Drosophila polarity gene frizzled has been identified and mapped to 17q21.1."
      Zhao Z., Lee C.C., Baldini A., Caskey C.T.
      Genomics 27:370-373(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Ovary.
    2. "Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7."
      Sagara N., Toda G., Hirai M., Terada M., Katoh M.
      Biochem. Biophys. Res. Commun. 252:117-122(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal lung.
    3. "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].
    4. "A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals."
      Tanaka S., Akiyoshi T., Mori M., Wands J.R., Sugimachi K.
      Proc. Natl. Acad. Sci. U.S.A. 95:10164-10169(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 282-343.
      Tissue: Esophageal carcinoma.

    Entry informationi

    Entry nameiFZD2_HUMAN
    AccessioniPrimary (citable) accession number: Q14332
    Secondary accession number(s): Q0VG82
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 5, 2001
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 132 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3