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P27467

- WNT3A_MOUSE

UniProt

P27467 - WNT3A_MOUSE

Protein

Protein Wnt-3a

Gene

Wnt3a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 1 (01 Aug 1992)
      Previous versions | rss
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    Functioni

    Ligand for members of the frizzled family of seven transmembrane receptors. Wnt-3 and Wnt-3a play distinct roles in cell-cell signaling during morphogenesis of the developing neural tube.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei26 – 272Cleavage; by TIKI1 and TIKI2

    GO - Molecular functioni

    1. frizzled-2 binding Source: MGI
    2. frizzled binding Source: MGI
    3. protein binding Source: IntAct
    4. protein domain specific binding Source: UniProtKB
    5. receptor binding Source: MGI
    6. transcription coactivator activity Source: UniProtKB

    GO - Biological processi

    1. anterior/posterior pattern specification Source: MGI
    2. axis elongation involved in somitogenesis Source: MGI
    3. axon guidance Source: MGI
    4. axonogenesis Source: MGI
    5. BMP signaling pathway Source: MGI
    6. canonical Wnt signaling pathway Source: UniProtKB
    7. canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment Source: Ensembl
    8. cardiac muscle cell fate commitment Source: MGI
    9. cell-cell signaling Source: MGI
    10. cell proliferation in forebrain Source: BHF-UCL
    11. cellular protein localization Source: MGI
    12. COP9 signalosome assembly Source: BHF-UCL
    13. determination of left/right symmetry Source: MGI
    14. dorsal/ventral neural tube patterning Source: MGI
    15. extracellular matrix organization Source: MGI
    16. heart looping Source: MGI
    17. hemopoiesis Source: MGI
    18. hippocampus development Source: MGI
    19. inner ear morphogenesis Source: MGI
    20. in utero embryonic development Source: MGI
    21. mammary gland development Source: MGI
    22. mesoderm development Source: MGI
    23. negative regulation of axon extension involved in axon guidance Source: MGI
    24. negative regulation of fat cell differentiation Source: MGI
    25. negative regulation of heart induction by canonical Wnt signaling pathway Source: Ensembl
    26. negative regulation of neurogenesis Source: BHF-UCL
    27. negative regulation of neuron projection development Source: UniProtKB
    28. organ morphogenesis Source: MGI
    29. osteoblast differentiation Source: MGI
    30. palate development Source: Ensembl
    31. paraxial mesodermal cell fate commitment Source: MGI
    32. platelet activation Source: MGI
    33. platelet aggregation Source: MGI
    34. positive regulation of B cell proliferation Source: MGI
    35. positive regulation of canonical Wnt signaling pathway Source: MGI
    36. positive regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation Source: UniProtKB
    37. positive regulation of cardiac muscle cell differentiation Source: Ensembl
    38. positive regulation of catenin import into nucleus Source: Ensembl
    39. positive regulation of cell-cell adhesion mediated by cadherin Source: MGI
    40. positive regulation of cell proliferation Source: UniProtKB
    41. positive regulation of collateral sprouting in absence of injury Source: MGI
    42. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
    43. positive regulation of dermatome development Source: Ensembl
    44. positive regulation of mesodermal cell fate specification Source: Ensembl
    45. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
    46. positive regulation of protein binding Source: Ensembl
    47. positive regulation of protein tyrosine kinase activity Source: MGI
    48. positive regulation of receptor internalization Source: Ensembl
    49. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    50. positive regulation of transcription, DNA-templated Source: UniProtKB
    51. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    52. post-anal tail morphogenesis Source: MGI
    53. regulation of axonogenesis Source: MGI
    54. regulation of cell differentiation Source: MGI
    55. regulation of microtubule cytoskeleton organization Source: MGI
    56. signal transduction Source: MGI
    57. skeletal muscle cell differentiation Source: MGI
    58. somatic stem cell division Source: MGI
    59. somitogenesis Source: MGI
    60. spinal cord association neuron differentiation Source: MGI
    61. Wnt signaling pathway Source: MGI
    62. Wnt signaling pathway involved in forebrain neuroblast division Source: MGI

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Wnt signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_207044. TCF dependent signaling in response to WNT.
    REACT_210612. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
    REACT_213035. regulation of FZD by ubiquitination.
    REACT_213918. WNT ligand biogenesis and trafficking.
    REACT_216784. disassembly of the destruction complex and recruitment of AXIN to the membrane.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein Wnt-3a
    Gene namesi
    Name:Wnt3a
    Synonyms:Wnt-3a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:98956. Wnt3a.

    Subcellular locationi

    GO - Cellular componenti

    1. cell surface Source: BHF-UCL
    2. endoplasmic reticulum lumen Source: Reactome
    3. extracellular space Source: BHF-UCL
    4. proteinaceous extracellular matrix Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi25 – 262SL → DD: Partially resistant to proteolysis by TIKI1 and TIKI2. Completely resistant to proteolysis by TIKI1 and TIKI2; when associated with 33-D-D-34.
    Mutagenesisi33 – 342SS → DD: Completely resistant to proteolysis by TIKI1 and TIKI2; when associated with 25-D-D-26.
    Mutagenesisi77 – 771C → A: Forms oxidized oligomers regardless of TIKI2. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 352334Protein Wnt-3aPRO_0000041419Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi77 ↔ 88By similarity
    Glycosylationi87 – 871N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi128 ↔ 136By similarity
    Disulfide bondi138 ↔ 155By similarity
    Disulfide bondi203 ↔ 217By similarity
    Disulfide bondi205 ↔ 212By similarity
    Lipidationi209 – 2091O-palmitoyl serine; by PORCNBy similarity
    Disulfide bondi297 ↔ 312By similarity
    Glycosylationi298 – 2981N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi327 ↔ 342By similarity
    Disulfide bondi329 ↔ 339By similarity
    Disulfide bondi334 ↔ 335By similarity

    Post-translational modificationi

    Palmitoylation at Ser-209 is required for efficient binding to frizzled receptors. Palmitoylation is required for proper trafficking to cell surface, vacuolar acidification is critical to release palmitoylated WNT3A from WLS in secretory vesicles. A palmitoylation site was proposed at Cys-77, but it was later shown that this cysteine is engaged in a disulfide bond By similarity.By similarity
    Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT3A.1 Publication
    Disulfide bonds have critical and distinct roles in secretion and activity. Loss of each conserved cysteine in WNT3A results in high molecular weight oxidized Wnt oligomers, which are formed through inter-Wnt disulfide bonding By similarity.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

    Proteomic databases

    PRIDEiP27467.

    PTM databases

    PhosphoSiteiP27467.

    Expressioni

    Tissue specificityi

    Dorsal portion of the neural tube (developing roof plate), and mesenchyme tissue surrounding the umbilical veins.

    Gene expression databases

    BgeeiP27467.
    CleanExiMM_WNT3A.
    GenevestigatoriP27467.

    Interactioni

    Subunit structurei

    Homooligomer; disulfide-linked, leading to inactivation. Interacts with APCDD1 and WLS. Component of the Wnt-Fzd-LRP5-LRP6 signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly in the complex with LRP6 By similarity. Interacts with PORCN.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PtproE9Q6122EBI-2899665,EBI-8183885
    TRABD2BA6NFA12EBI-2899665,EBI-6257471From a different organism.
    WIF1Q9Y5W57EBI-2899665,EBI-3922719From a different organism.

    Protein-protein interaction databases

    BioGridi204575. 9 interactions.
    DIPiDIP-55954N.
    IntActiP27467. 5 interactions.
    MINTiMINT-7992042.
    STRINGi10090.ENSMUSP00000010044.

    Structurei

    3D structure databases

    ProteinModelPortaliP27467.
    SMRiP27467. Positions 57-351.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the Wnt family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG284879.
    GeneTreeiENSGT00730000110244.
    HOGENOMiHOG000039529.
    HOVERGENiHBG001595.
    InParanoidiP27467.
    KOiK00312.
    OMAiCTTVNDS.
    OrthoDBiEOG7C8GJ8.
    PhylomeDBiP27467.
    TreeFamiTF105310.

    Family and domain databases

    InterProiIPR005817. Wnt.
    IPR009141. Wnt3.
    IPR018161. Wnt_CS.
    [Graphical view]
    PANTHERiPTHR12027. PTHR12027. 1 hit.
    PfamiPF00110. wnt. 1 hit.
    [Graphical view]
    PRINTSiPR01843. WNT3PROTEIN.
    PR01349. WNTPROTEIN.
    SMARTiSM00097. WNT1. 1 hit.
    [Graphical view]
    PROSITEiPS00246. WNT1. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P27467-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAPLGYLLVL CSLKQALGSY PIWWSLAVGP QYSSLSTQPI LCASIPGLVP    50
    KQLRFCRNYV EIMPSVAEGV KAGIQECQHQ FRGRRWNCTT VSNSLAIFGP 100
    VLDKATRESA FVHAIASAGV AFAVTRSCAE GSAAICGCSS RLQGSPGEGW 150
    KWGGCSEDIE FGGMVSREFA DARENRPDAR SAMNRHNNEA GRQAIASHMH 200
    LKCKCHGLSG SCEVKTCWWS QPDFRTIGDF LKDKYDSASE MVVEKHRESR 250
    GWVETLRPRY TYFKVPTERD LVYYEASPNF CEPNPETGSF GTRDRTCNVS 300
    SHGIDGCDLL CCGRGHNART ERRREKCHCV FHWCCYVSCQ ECTRVYDVHT 350
    CK 352
    Length:352
    Mass (Da):39,258
    Last modified:August 1, 1992 - v1
    Checksum:i7ADFC5B38A8EFF63
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X56842 mRNA. Translation: CAA40173.1.
    CCDSiCCDS24766.1.
    PIRiA39532.
    RefSeqiNP_033548.1. NM_009522.2.
    UniGeneiMm.1367.

    Genome annotation databases

    EnsembliENSMUST00000010044; ENSMUSP00000010044; ENSMUSG00000009900.
    GeneIDi22416.
    KEGGimmu:22416.
    UCSCiuc007jdp.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X56842 mRNA. Translation: CAA40173.1 .
    CCDSi CCDS24766.1.
    PIRi A39532.
    RefSeqi NP_033548.1. NM_009522.2.
    UniGenei Mm.1367.

    3D structure databases

    ProteinModelPortali P27467.
    SMRi P27467. Positions 57-351.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204575. 9 interactions.
    DIPi DIP-55954N.
    IntActi P27467. 5 interactions.
    MINTi MINT-7992042.
    STRINGi 10090.ENSMUSP00000010044.

    Chemistry

    ChEMBLi CHEMBL5617.

    PTM databases

    PhosphoSitei P27467.

    Proteomic databases

    PRIDEi P27467.

    Protocols and materials databases

    DNASUi 22416.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000010044 ; ENSMUSP00000010044 ; ENSMUSG00000009900 .
    GeneIDi 22416.
    KEGGi mmu:22416.
    UCSCi uc007jdp.2. mouse.

    Organism-specific databases

    CTDi 89780.
    MGIi MGI:98956. Wnt3a.

    Phylogenomic databases

    eggNOGi NOG284879.
    GeneTreei ENSGT00730000110244.
    HOGENOMi HOG000039529.
    HOVERGENi HBG001595.
    InParanoidi P27467.
    KOi K00312.
    OMAi CTTVNDS.
    OrthoDBi EOG7C8GJ8.
    PhylomeDBi P27467.
    TreeFami TF105310.

    Enzyme and pathway databases

    Reactomei REACT_207044. TCF dependent signaling in response to WNT.
    REACT_210612. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
    REACT_213035. regulation of FZD by ubiquitination.
    REACT_213918. WNT ligand biogenesis and trafficking.
    REACT_216784. disassembly of the destruction complex and recruitment of AXIN to the membrane.

    Miscellaneous databases

    NextBioi 302833.
    PROi P27467.
    SOURCEi Search...

    Gene expression databases

    Bgeei P27467.
    CleanExi MM_WNT3A.
    Genevestigatori P27467.

    Family and domain databases

    InterProi IPR005817. Wnt.
    IPR009141. Wnt3.
    IPR018161. Wnt_CS.
    [Graphical view ]
    PANTHERi PTHR12027. PTHR12027. 1 hit.
    Pfami PF00110. wnt. 1 hit.
    [Graphical view ]
    PRINTSi PR01843. WNT3PROTEIN.
    PR01349. WNTPROTEIN.
    SMARTi SM00097. WNT1. 1 hit.
    [Graphical view ]
    PROSITEi PS00246. WNT1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Expression of two members of the Wnt family during mouse development -- restricted temporal and spatial patterns in the developing neural tube."
      Roelink H., Nusse R.
      Genes Dev. 5:381-388(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Embryo.
    2. "The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family."
      Tanaka K., Okabayashi H., Asashima M., Perrimon N., Kadowaki T.
      Eur. J. Biochem. 267:4300-4311(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PORCN.
    3. "Wnt proteins are lipid-modified and can act as stem cell growth factors."
      Willert K., Brown J.D., Danenberg E., Duncan A.W., Weissman I.L., Reya T., Yates J.R. III, Nusse R.
      Nature 423:448-452(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PRELIMINARY CYSTEINE PALMITOYLATION.
    4. "Tiki1 is required for head formation via Wnt cleavage-oxidation and inactivation."
      Zhang X., Abreu J.G., Yokota C., Macdonald B.T., Singh S., Coburn K.L., Cheong S.M., Zhang M.M., Ye Q.Z., Hang H.C., Steen H., He X.
      Cell 149:1565-1577(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING BY TIKI1 AND TIKI2, DISULFIDE BONDS, SUBUNIT, MUTAGENESIS OF 25-SER-LEU-26; 33-SER-SER-34 AND CYS-77.

    Entry informationi

    Entry nameiWNT3A_MOUSE
    AccessioniPrimary (citable) accession number: P27467
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: August 1, 1992
    Last modified: October 1, 2014
    This is version 135 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3