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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 TIKI21 Publication

GO - Molecular functioni

  • frizzled-2 binding Source: MGI
  • frizzled binding Source: MGI
  • protein domain specific binding Source: UniProtKB
  • receptor agonist activity Source: MGI
  • receptor binding Source: MGI
  • transcription coactivator activity Source: UniProtKB

GO - Biological processi

  • anterior/posterior pattern specification Source: MGI
  • axis elongation involved in somitogenesis Source: MGI
  • axon guidance Source: MGI
  • axonogenesis Source: MGI
  • BMP signaling pathway Source: MGI
  • canonical Wnt signaling pathway Source: UniProtKB
  • canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment Source: MGI
  • cardiac muscle cell fate commitment Source: MGI
  • cell-cell signaling Source: MGI
  • cell proliferation in forebrain Source: BHF-UCL
  • cellular protein localization Source: MGI
  • COP9 signalosome assembly Source: BHF-UCL
  • determination of left/right symmetry Source: MGI
  • dorsal/ventral neural tube patterning Source: MGI
  • extracellular matrix organization Source: MGI
  • heart looping Source: MGI
  • hemopoiesis Source: MGI
  • hippocampus development Source: MGI
  • inner ear morphogenesis Source: MGI
  • in utero embryonic development Source: MGI
  • mammary gland development Source: MGI
  • mesoderm development Source: MGI
  • negative regulation of axon extension involved in axon guidance Source: MGI
  • negative regulation of fat cell differentiation Source: MGI
  • negative regulation of heart induction by canonical Wnt signaling pathway Source: MGI
  • negative regulation of neurogenesis Source: BHF-UCL
  • negative regulation of neuron projection development Source: UniProtKB
  • organ morphogenesis Source: MGI
  • osteoblast differentiation Source: MGI
  • palate development Source: MGI
  • paraxial mesodermal cell fate commitment Source: MGI
  • platelet activation Source: MGI
  • platelet aggregation Source: MGI
  • positive regulation of B cell proliferation Source: MGI
  • positive regulation of canonical Wnt signaling pathway Source: MGI
  • positive regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation Source: UniProtKB
  • positive regulation of cardiac muscle cell differentiation Source: MGI
  • positive regulation of catenin import into nucleus Source: MGI
  • positive regulation of cell-cell adhesion mediated by cadherin Source: MGI
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of collateral sprouting in absence of injury Source: MGI
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • positive regulation of cytokine production Source: MGI
  • positive regulation of dermatome development Source: MGI
  • positive regulation of mesodermal cell fate specification Source: MGI
  • positive regulation of neural precursor cell proliferation Source: MGI
  • positive regulation of peptidyl-serine phosphorylation Source: MGI
  • positive regulation of protein binding Source: MGI
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of protein tyrosine kinase activity Source: MGI
  • positive regulation of receptor internalization Source: MGI
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • positive regulation of skeletal muscle tissue development Source: CACAO
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • post-anal tail morphogenesis Source: MGI
  • regulation of axonogenesis Source: MGI
  • regulation of cell differentiation Source: MGI
  • regulation of microtubule cytoskeleton organization Source: MGI
  • signal transduction Source: MGI
  • skeletal muscle cell differentiation Source: MGI
  • somatic stem cell division Source: MGI
  • somitogenesis Source: MGI
  • spinal cord association neuron differentiation Source: MGI
  • Wnt signaling pathway Source: MGI
  • 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_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

  • cell surface Source: BHF-UCL
  • endoplasmic reticulum lumen Source: Reactome
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • 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. Does not affect palmitoleylation. 2 Publications
Mutagenesisi209 – 2091S → A: Abolishes palmitoleylation, promoting formation of disulfide bonds and oligomerization. 2 Publications
Mutagenesisi211 – 2111S → A: Does not affect palmitoleylation. 1 Publication
Mutagenesisi216 – 2161T → A: Does not affect palmitoleylation. 1 Publication
Mutagenesisi277 – 2771S → A: Does not affect palmitoleylation. 1 Publication
Mutagenesisi292 – 2921T → A: Does not affect palmitoleylation. 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-palmitoleyl serine; by PORCN3 Publications
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

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.1 Publication
Palmitoleylation by PORCN is required for efficient binding to frizzled receptors. Palmitoleylation is required for proper trafficking to cell surface, vacuolar acidification is critical to release palmitoleylated WNT3A from WLS in secretory vesicles (PubMed:17141155, PubMed:24798332). Depalmitoleylated by NOTUM, leading to inhibit Wnt signaling pathway, possibly by promoting disulfide bond formation and oligomerization (PubMed:25771893).By similarity3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein

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.
GenevisibleiP27467. MM.

Interactioni

Subunit structurei

Homooligomer; disulfide-linked, leading to inactivation (PubMed:25771893). 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 similarity3 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.
OMAiFLKCKCH.
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:August 1, 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.
OMAiFLKCKCH.
OrthoDBiEOG7C8GJ8.
PhylomeDBiP27467.
TreeFamiTF105310.

Enzyme and pathway databases

ReactomeiREACT_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.
GenevisibleiP27467. MM.

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(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.
  5. "Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion."
    Takada R., Satomi Y., Kurata T., Ueno N., Norioka S., Kondoh H., Takao T., Takada S.
    Dev. Cell 11:791-801(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOLEYLATION AT SER-209, MUTAGENESIS OF CYS-77; SER-209; SER-211; THR-216; SER-277 AND THR-292, GLYCOSYLATION.
  6. "Identification of key residues and regions important for porcupine-mediated Wnt acylation."
    Rios-Esteves J., Haugen B., Resh M.D.
    J. Biol. Chem. 289:17009-17019(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOLEYLATION AT SER-209.
  7. "Notum is required for neural and head induction via Wnt deacylation, oxidation, and inactivation."
    Zhang X., Cheong S.M., Amado N.G., Reis A.H., MacDonald B.T., Zebisch M., Jones E.Y., Abreu J.G., He X.
    Dev. Cell 32:719-730(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, PALMITOLEYLATION AT SER-209, DEPALMITOLEYLATION AT SER-209, MUTAGENESIS OF SER-209.

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: July 22, 2015
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

A palmitoylation site was proposed at Cys-77, but it was later shown that this cysteine is engaged in a disulfide bond.

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.