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Protein

Protein Wnt-3a

Gene

Wnt3a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 domain specific binding Source: UniProtKB
  4. receptor agonist activity Source: MGI
  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: MGI
  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: MGI
  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: MGI
  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: MGI
  38. positive regulation of catenin import into nucleus Source: MGI
  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 cytokine production Source: MGI
  44. positive regulation of dermatome development Source: MGI
  45. positive regulation of mesodermal cell fate specification Source: MGI
  46. positive regulation of neural precursor cell proliferation Source: MGI
  47. positive regulation of peptidyl-serine phosphorylation Source: MGI
  48. positive regulation of protein binding Source: MGI
  49. positive regulation of protein phosphorylation Source: MGI
  50. positive regulation of protein tyrosine kinase activity Source: MGI
  51. positive regulation of receptor internalization Source: MGI
  52. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  53. positive regulation of transcription, DNA-templated Source: UniProtKB
  54. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  55. post-anal tail morphogenesis Source: MGI
  56. regulation of axonogenesis Source: MGI
  57. regulation of cell differentiation Source: MGI
  58. regulation of microtubule cytoskeleton organization Source: MGI
  59. signal transduction Source: MGI
  60. skeletal muscle cell differentiation Source: MGI
  61. somatic stem cell division Source: MGI
  62. somitogenesis Source: MGI
  63. spinal cord association neuron differentiation Source: MGI
  64. Wnt signaling pathway Source: MGI
  65. Wnt signaling pathway involved in forebrain neuroblast division Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_286817. RNF mutants show enhanced WNT signaling and proliferation.
REACT_295052. WNT ligand biogenesis and trafficking.
REACT_305098. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
REACT_317277. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_335449. Class B/2 (Secretin family receptors).
REACT_335672. TCF dependent signaling in response to WNT.
REACT_347741. regulation of FZD by ubiquitination.

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 Componenti: 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 region Source: Reactome
  4. extracellular space Source: BHF-UCL
  5. proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

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. 1 Publication
Mutagenesisi33 – 342SS → DD: Completely resistant to proteolysis by TIKI1 and TIKI2; when associated with 25-D-D-26. 1 Publication
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.
GeneTreeiENSGT00760000118943.
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

        10         20         30         40         50
MAPLGYLLVL CSLKQALGSY PIWWSLAVGP QYSSLSTQPI LCASIPGLVP
60 70 80 90 100
KQLRFCRNYV EIMPSVAEGV KAGIQECQHQ FRGRRWNCTT VSNSLAIFGP
110 120 130 140 150
VLDKATRESA FVHAIASAGV AFAVTRSCAE GSAAICGCSS RLQGSPGEGW
160 170 180 190 200
KWGGCSEDIE FGGMVSREFA DARENRPDAR SAMNRHNNEA GRQAIASHMH
210 220 230 240 250
LKCKCHGLSG SCEVKTCWWS QPDFRTIGDF LKDKYDSASE MVVEKHRESR
260 270 280 290 300
GWVETLRPRY TYFKVPTERD LVYYEASPNF CEPNPETGSF GTRDRTCNVS
310 320 330 340 350
SHGIDGCDLL CCGRGHNART ERRREKCHCV FHWCCYVSCQ ECTRVYDVHT

CK
Length:352
Mass (Da):39,258
Last modified:July 31, 1992 - v1
Checksum:i7ADFC5B38A8EFF63
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
X56842 mRNA. Translation: CAA40173.1.
CCDSiCCDS24766.1.
PIRiA39532.
RefSeqiNP_033548.1. NM_009522.2.
UniGeneiMm.1367.

3D structure databases

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

Protein-protein interaction databases

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

Chemistry

BindingDBiP27467.
ChEMBLiCHEMBL5617.

PTM databases

PhosphoSiteiP27467.

Proteomic databases

PRIDEiP27467.

Protocols and materials databases

DNASUi22416.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi89780.
MGIiMGI:98956. Wnt3a.

Phylogenomic databases

eggNOGiNOG284879.
GeneTreeiENSGT00760000118943.
HOGENOMiHOG000039529.
HOVERGENiHBG001595.
InParanoidiP27467.
KOiK00312.
OMAiCTTVNDS.
OrthoDBiEOG7C8GJ8.
PhylomeDBiP27467.
TreeFamiTF105310.

Enzyme and pathway databases

ReactomeiREACT_286817. RNF mutants show enhanced WNT signaling and proliferation.
REACT_295052. WNT ligand biogenesis and trafficking.
REACT_305098. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
REACT_317277. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_335449. Class B/2 (Secretin family receptors).
REACT_335672. TCF dependent signaling in response to WNT.
REACT_347741. regulation of FZD by ubiquitination.

Miscellaneous databases

NextBioi302833.
PROiP27467.
SOURCEiSearch...

Gene expression databases

BgeeiP27467.
CleanExiMM_WNT3A.
GenevestigatoriP27467.

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]
ProtoNetiSearch...

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(1990) [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(1999) [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(2002) [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(2011) [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: July 31, 1992
Last sequence update: July 31, 1992
Last modified: March 31, 2015
This is version 141 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.