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P18537

- FRIZ_DROME

UniProt

P18537 - FRIZ_DROME

Protein

Frizzled

Gene

fz

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 162 (01 Oct 2014)
      Sequence version 1 (01 Nov 1990)
      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. Required to coordinate the cytoskeletons of epidermal cells to produce a parallel array of cuticular hairs and bristles.

    GO - Molecular functioni

    1. G-protein coupled receptor activity Source: UniProtKB-KW
    2. PDZ domain binding Source: RefGenome
    3. protein binding Source: IntAct
    4. transmembrane signaling receptor activity Source: FlyBase
    5. Wnt-activated receptor activity Source: FlyBase
    6. Wnt-protein binding Source: FlyBase

    GO - Biological processi

    1. asymmetric cell division Source: FlyBase
    2. asymmetric protein localization Source: FlyBase
    3. axon extension Source: FlyBase
    4. border follicle cell migration Source: FlyBase
    5. brain development Source: RefGenome
    6. canonical Wnt signaling pathway Source: FlyBase
    7. compound eye morphogenesis Source: FlyBase
    8. establishment of cell polarity Source: FlyBase
    9. establishment of epithelial cell apical/basal polarity Source: FlyBase
    10. establishment of imaginal disc-derived wing hair orientation Source: FlyBase
    11. establishment of ommatidial planar polarity Source: FlyBase
    12. establishment of planar polarity Source: FlyBase
    13. establishment of tissue polarity Source: FlyBase
    14. establishment or maintenance of cell polarity Source: UniProtKB
    15. gonad development Source: RefGenome
    16. G-protein coupled receptor signaling pathway Source: FlyBase
    17. heart development Source: FlyBase
    18. homophilic cell adhesion Source: FlyBase
    19. imaginal disc-derived wing hair organization Source: FlyBase
    20. imaginal disc-derived wing hair site selection Source: FlyBase
    21. imaginal disc-derived wing morphogenesis Source: FlyBase
    22. morphogenesis of a polarized epithelium Source: FlyBase
    23. negative regulation of Notch signaling pathway Source: FlyBase
    24. ommatidial rotation Source: FlyBase
    25. protein localization Source: FlyBase
    26. R3/R4 cell fate commitment Source: FlyBase
    27. regulation of actin filament bundle assembly Source: FlyBase
    28. regulation of hemocyte proliferation Source: FlyBase
    29. regulation of tube length, open tracheal system Source: FlyBase
    30. salivary gland morphogenesis Source: FlyBase
    31. sensory organ precursor cell fate determination Source: FlyBase
    32. signal transduction Source: FlyBase
    33. vasculature development Source: RefGenome
    34. Wnt signaling pathway Source: FlyBase

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Wnt signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_184329. PCP/CE pathway.
    REACT_207070. TCF dependent signaling in response to WNT.
    REACT_218761. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
    SignaLinkiP18537.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled
    Alternative name(s):
    Frizzled-1
    Short name:
    dFz1
    Gene namesi
    Name:fz
    ORF Names:CG17697
    OrganismiDrosophila melanogaster (Fruit fly)
    Taxonomic identifieri7227 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
    ProteomesiUP000000803: Chromosome 3L

    Organism-specific databases

    FlyBaseiFBgn0001085. fz.

    Subcellular locationi

    GO - Cellular componenti

    1. cell cortex Source: FlyBase
    2. integral component of membrane Source: UniProtKB
    3. integral component of plasma membrane Source: FlyBase
    4. neuron projection membrane Source: RefGenome
    5. plasma membrane Source: FlyBase

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 581563FrizzledPRO_0000013010Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi53 ↔ 114PROSITE-ProRule annotation
    Disulfide bondi61 ↔ 107PROSITE-ProRule annotation
    Glycosylationi67 – 671N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi98 ↔ 134PROSITE-ProRule annotation
    Disulfide bondi124 ↔ 163PROSITE-ProRule annotation
    Disulfide bondi128 ↔ 151PROSITE-ProRule annotation
    Glycosylationi167 – 1671N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP18537.
    PRIDEiP18537.

    Expressioni

    Gene expression databases

    BgeeiP18537.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    stanQ9V5N83EBI-251576,EBI-119250

    Protein-protein interaction databases

    BioGridi69580. 25 interactions.
    DIPiDIP-22727N.
    IntActiP18537. 3 interactions.
    MINTiMINT-1663972.

    Structurei

    3D structure databases

    ProteinModelPortaliP18537.
    SMRiP18537. Positions 53-164, 208-562.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini19 – 247229Extracellular1 PublicationAdd
    BLAST
    Topological domaini271 – 28010Cytoplasmic1 Publication
    Topological domaini304 – 34340Extracellular1 PublicationAdd
    BLAST
    Topological domaini365 – 38016Cytoplasmic1 PublicationAdd
    BLAST
    Topological domaini402 – 42120Extracellular1 PublicationAdd
    BLAST
    Topological domaini440 – 47132Cytoplasmic1 PublicationAdd
    BLAST
    Topological domaini493 – 52937Extracellular1 PublicationAdd
    BLAST
    Topological domaini554 – 58128Cytoplasmic1 PublicationAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei248 – 27023Helical; Name=1CuratedAdd
    BLAST
    Transmembranei281 – 30323Helical; Name=2CuratedAdd
    BLAST
    Transmembranei344 – 36421Helical; Name=3CuratedAdd
    BLAST
    Transmembranei381 – 40121Helical; Name=4CuratedAdd
    BLAST
    Transmembranei422 – 43918Helical; Name=5CuratedAdd
    BLAST
    Transmembranei472 – 49221Helical; Name=6CuratedAdd
    BLAST
    Transmembranei530 – 55324Helical; Name=7CuratedAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini48 – 166119FZPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi556 – 5616Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
    Motifi579 – 5813PDZ-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

    eggNOGiNOG257258.
    GeneTreeiENSGT00740000114899.
    InParanoidiP18537.
    KOiK02432.
    OrthoDBiEOG7M3J01.
    PhylomeDBiP18537.

    Family and domain databases

    Gene3Di1.10.2000.10. 1 hit.
    InterProiIPR026561. dFz1.
    IPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR017981. GPCR_2-like.
    [Graphical view]
    PANTHERiPTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF47. PTHR11309:SF47. 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]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform I (identifier: P18537-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MWRQILFILP TLIQGVQRYD QSPLDASPYY RSGGGLMASS GTELDGLPHH    50
    NRCEPITISI CKNIPYNMTI MPNLIGHTKQ EEAGLEVHQF APLVKIGCSD 100
    DLQLFLCSLY VPVCTILERP IPPCRSLCES ARVCEKLMKT YNFNWPENLE 150
    CSKFPVHGGE DLCVAENTTS SASTAATPTR SVAKVTTRKH QTGVESPHRN 200
    IGFVCPVQLK TPLGMGYELK VGGKDLHDCG APCHAMFFPE RERTVLRYWV 250
    GSWAAVCVAS CLFTVLTFLI DSSRFRYPER AIVFLAVCYL VVGCAYVAGL 300
    GAGDSVSCRE PFPPPVKLGR LQMMSTITQG HRQTTSCTVL FMALYFCCMA 350
    AFAWWSCLAF AWFLAAGLKW GHEAIENKSH LFHLVAWAVP ALQTISVLAL 400
    AKVEGDILSG VCFVGQLDTH SLGAFLILPL CIYLSIGALF LLAGFISLFR 450
    IRTVMKTDGK RTDKLERLML RIGFFSGLFI LPAVGLLGCL FYEYYNFDEW 500
    MIQWHRDICK PFSIPCPAAR APGSPEARPI FQIFMVKYLC SMLVGVTSSV 550
    WLYSSKTMVS WRNFVERLQG KEPRTRAQAY V 581
    Length:581
    Mass (Da):64,847
    Last modified:November 1, 1990 - v1
    Checksum:i486721D84DA0D0A1
    GO
    Isoform II (identifier: P18537-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         406-415: DILSGVCFVG → MYLWQFHTIN
         416-581: Missing.

    Show »
    Length:415
    Mass (Da):46,118
    Checksum:iF0A0A5AA080BAAE7
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei406 – 41510DILSGVCFVG → MYLWQFHTIN in isoform II. 1 PublicationVSP_002013
    Alternative sequencei416 – 581166Missing in isoform II. 1 PublicationVSP_002014Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X54648
    , X54649, X54650, X54651 Genomic DNA. Translation: CAA38460.1.
    X54648
    , X54649, X54650, X54652 Genomic DNA. Translation: CAA38461.1.
    X54646 mRNA. Translation: CAA38458.1.
    X54647 mRNA. Translation: CAA38459.1. Sequence problems.
    AE014296 Genomic DNA. Translation: AAF49746.3.
    AE014296 Genomic DNA. Translation: AAN11810.1.
    AY051808 mRNA. Translation: AAK93232.1.
    PIRiS03540.
    RefSeqiNP_524812.1. NM_080073.3. [P18537-1]
    NP_729970.1. NM_168587.2. [P18537-2]
    UniGeneiDm.1456.

    Genome annotation databases

    EnsemblMetazoaiFBtr0075743; FBpp0075485; FBgn0001085. [P18537-1]
    GeneIDi45307.
    KEGGidme:Dmel_CG17697.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X54648
    , X54649 , X54650 , X54651 Genomic DNA. Translation: CAA38460.1 .
    X54648
    , X54649 , X54650 , X54652 Genomic DNA. Translation: CAA38461.1 .
    X54646 mRNA. Translation: CAA38458.1 .
    X54647 mRNA. Translation: CAA38459.1 . Sequence problems.
    AE014296 Genomic DNA. Translation: AAF49746.3 .
    AE014296 Genomic DNA. Translation: AAN11810.1 .
    AY051808 mRNA. Translation: AAK93232.1 .
    PIRi S03540.
    RefSeqi NP_524812.1. NM_080073.3. [P18537-1 ]
    NP_729970.1. NM_168587.2. [P18537-2 ]
    UniGenei Dm.1456.

    3D structure databases

    ProteinModelPortali P18537.
    SMRi P18537. Positions 53-164, 208-562.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 69580. 25 interactions.
    DIPi DIP-22727N.
    IntActi P18537. 3 interactions.
    MINTi MINT-1663972.

    Protein family/group databases

    GPCRDBi Search...

    Proteomic databases

    PaxDbi P18537.
    PRIDEi P18537.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblMetazoai FBtr0075743 ; FBpp0075485 ; FBgn0001085 . [P18537-1 ]
    GeneIDi 45307.
    KEGGi dme:Dmel_CG17697.

    Organism-specific databases

    CTDi 45307.
    FlyBasei FBgn0001085. fz.

    Phylogenomic databases

    eggNOGi NOG257258.
    GeneTreei ENSGT00740000114899.
    InParanoidi P18537.
    KOi K02432.
    OrthoDBi EOG7M3J01.
    PhylomeDBi P18537.

    Enzyme and pathway databases

    Reactomei REACT_184329. PCP/CE pathway.
    REACT_207070. TCF dependent signaling in response to WNT.
    REACT_218761. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
    SignaLinki P18537.

    Miscellaneous databases

    GenomeRNAii 45307.
    NextBioi 837994.

    Gene expression databases

    Bgeei P18537.

    Family and domain databases

    Gene3Di 1.10.2000.10. 1 hit.
    InterProi IPR026561. dFz1.
    IPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR017981. GPCR_2-like.
    [Graphical view ]
    PANTHERi PTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF47. PTHR11309:SF47. 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 Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains."
      Vinson C.R., Conover S., Adler P.N.
      Nature 338:263-264(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORM I).
    2. "Molecular structure of frizzled, a Drosophila tissue polarity gene."
      Adler P.N., Vinson C., Park W.J., Conover S., Klein L.
      Genetics 126:401-416(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS I AND II).
      Strain: Canton-S.
      Tissue: Embryo.
    3. "The genome sequence of Drosophila melanogaster."
      Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D.
      , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.
      Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Berkeley.
    4. Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
      Strain: Berkeley.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I).
      Strain: Berkeley.
      Tissue: Embryo.
    6. "Frizzled-suc2 fusion gene studies in Saccharomyces cerevisiae."
      Goo J.H., Ahn Y., Park W.J.
      DNA Cell Biol. 18:429-434(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY.

    Entry informationi

    Entry nameiFRIZ_DROME
    AccessioniPrimary (citable) accession number: P18537
    Secondary accession number(s): Q9VUE0, Q9VUE2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1990
    Last sequence update: November 1, 1990
    Last modified: October 1, 2014
    This is version 162 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programDrosophila annotation project

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Drosophila
      Drosophila: entries, gene names and cross-references to FlyBase
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3