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P27467 (WNT3A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein Wnt-3a
Gene names
Name:Wnt3a
Synonyms:Wnt-3a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length352 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.2 Ref.4

Subcellular location

Secretedextracellular spaceextracellular matrix.

Tissue specificity

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

Post-translational modification

Palmitoylation at Ser-209 is required for efficient binding to frizzled receptors. It is also required for subsequent palmitoylation at Cys-77. Palmitoylation is required for proper trafficking to cell surface, vacuolar acidification is critical to release palmitoylated WNT3A from WLS in secretory vesicles By similarity. Ref.3

Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT3A.

Sequence similarities

Belongs to the Wnt family.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentExtracellular matrix
Secreted
   DomainSignal
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from sequence orthology PubMed 19850029. Source: MGI

COP9 signalosome assembly

Inferred from direct assay PubMed 17569865. Source: BHF-UCL

Wnt signaling pathway

Inferred from genetic interaction PubMed 10933391PubMed 11029008PubMed 16115200. Source: MGI

Wnt signaling pathway involved in forebrain neuroblast division

Inferred from mutant phenotype PubMed 10631167. Source: MGI

anterior/posterior pattern specification

Inferred from direct assay PubMed 15148409. Source: MGI

axis elongation involved in somitogenesis

Inferred from genetic interaction PubMed 11029008. Source: MGI

axon guidance

Inferred from direct assay PubMed 18716223. Source: MGI

axonogenesis

Inferred from direct assay PubMed 15454084. Source: MGI

canonical Wnt signaling pathway

Inferred from direct assay PubMed 10557084. Source: UniProtKB

canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment

Inferred from electronic annotation. Source: Ensembl

cardiac muscle cell fate commitment

Inferred from genetic interaction PubMed 21554246. Source: MGI

cell proliferation in forebrain

Inferred from direct assay PubMed 12843296. Source: BHF-UCL

cell-cell signaling

Traceable author statement PubMed 9889131. Source: MGI

cellular protein localization

Inferred from direct assay PubMed 17606995. Source: MGI

determination of left/right symmetry

Inferred from mutant phenotype PubMed 16291790. Source: MGI

dorsal/ventral neural tube patterning

Inferred from mutant phenotype PubMed 8299937. Source: MGI

extracellular matrix organization

Inferred from direct assay PubMed 17943183. Source: MGI

heart looping

Inferred from mutant phenotype PubMed 16291790. Source: MGI

hemopoiesis

Inferred from direct assay PubMed 12717450. Source: MGI

hippocampus development

Inferred from mutant phenotype PubMed 10631167. Source: MGI

in utero embryonic development

Inferred from mutant phenotype PubMed 4819561. Source: MGI

inner ear morphogenesis

Inferred from genetic interaction PubMed 15961523. Source: MGI

mammary gland development

Inferred from direct assay PubMed 15342465. Source: MGI

mesoderm development

Inferred from mutant phenotype PubMed 8299937. Source: MGI

negative regulation of axon extension involved in axon guidance

Inferred from direct assay PubMed 18716223. Source: MGI

negative regulation of fat cell differentiation

Inferred from direct assay PubMed 15796911PubMed 17888405. Source: MGI

negative regulation of heart induction by canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of neurogenesis

Inferred from direct assay PubMed 12843296. Source: BHF-UCL

negative regulation of neuron projection development

Inferred from direct assay PubMed 21539518. Source: UniProtKB

organ morphogenesis

Traceable author statement PubMed 9889131. Source: MGI

osteoblast differentiation

Inferred from genetic interaction PubMed 16581771. Source: MGI

palate development

Inferred from electronic annotation. Source: Ensembl

paraxial mesodermal cell fate commitment

Inferred from mutant phenotype PubMed 9126297. Source: MGI

platelet activation

Inferred from direct assay PubMed 19901330. Source: MGI

platelet aggregation

Inferred from direct assay PubMed 19901330. Source: MGI

positive regulation of B cell proliferation

Inferred from direct assay PubMed 10933391. Source: MGI

positive regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 18155657. Source: MGI

positive regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation

Inferred from direct assay PubMed 17994217. Source: UniProtKB

positive regulation of cardiac muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of catenin import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from direct assay PubMed 17994217. Source: UniProtKB

positive regulation of cell-cell adhesion mediated by cadherin

Inferred from direct assay PubMed 10893270. Source: MGI

positive regulation of collateral sprouting in absence of injury

Inferred from direct assay PubMed 18716223. Source: MGI

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 17251350. Source: MGI

positive regulation of dermatome development

Inferred from electronic annotation. Source: Ensembl

positive regulation of mesodermal cell fate specification

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein tyrosine kinase activity

Inferred from genetic interaction PubMed 19920076. Source: MGI

positive regulation of receptor internalization

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 18929644. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17360443. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 17994217. Source: UniProtKB

post-anal tail morphogenesis

Inferred from mutant phenotype PubMed 8299937. Source: MGI

regulation of axonogenesis

Inferred from genetic interaction PubMed 18716223. Source: MGI

regulation of cell differentiation

Inferred from direct assay PubMed 12717450. Source: MGI

regulation of microtubule cytoskeleton organization

Inferred from genetic interaction PubMed 18716223. Source: MGI

signal transduction

Traceable author statement PubMed 9889131. Source: MGI

skeletal muscle cell differentiation

Inferred from genetic interaction PubMed 19699733. Source: MGI

somatic stem cell division

Inferred from direct assay PubMed 12717450. Source: MGI

somitogenesis

Inferred from mutant phenotype PubMed 12636920PubMed 16291790PubMed 8299937. Source: MGI

spinal cord association neuron differentiation

Inferred from direct assay PubMed 11877374. Source: MGI

   Cellular_componentcell surface

Inferred from direct assay PubMed 8167409. Source: BHF-UCL

endoplasmic reticulum lumen

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 12897152. Source: BHF-UCL

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionfrizzled binding

Inferred from physical interaction PubMed 18606138. Source: MGI

frizzled-2 binding

Inferred from direct assay PubMed 19910923. Source: MGI

protein domain specific binding

Inferred from physical interaction PubMed 15454084. Source: UniProtKB

receptor binding

Traceable author statement PubMed 9889131. Source: MGI

transcription coactivator activity

Inferred from direct assay PubMed 17994217. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PtproE9Q6122EBI-2899665,EBI-8183885
TRABD2BA6NFA12EBI-2899665,EBI-6257471From a different organism.
WIF1Q9Y5W57EBI-2899665,EBI-3922719From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 352334Protein Wnt-3a
PRO_0000041419

Sites

Site26 – 272Cleavage; by TIKI1 and TIKI2

Amino acid modifications

Lipidation771S-palmitoyl cysteine Ref.3
Lipidation2091O-palmitoyl serine; by PORCN By similarity
Glycosylation871N-linked (GlcNAc...) Potential
Glycosylation2981N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis25 – 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.
Mutagenesis33 – 342SS → DD: Completely resistant to proteolysis by TIKI1 and TIKI2; when associated with 25-D-D-26.
Mutagenesis771C → A: Forms oxidized oligomers regardless of TIKI2. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P27467 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 7ADFC5B38A8EFF63

FASTA35239,258
        10         20         30         40         50         60 
MAPLGYLLVL CSLKQALGSY PIWWSLAVGP QYSSLSTQPI LCASIPGLVP KQLRFCRNYV 

        70         80         90        100        110        120 
EIMPSVAEGV KAGIQECQHQ FRGRRWNCTT VSNSLAIFGP VLDKATRESA FVHAIASAGV 

       130        140        150        160        170        180 
AFAVTRSCAE GSAAICGCSS RLQGSPGEGW KWGGCSEDIE FGGMVSREFA DARENRPDAR 

       190        200        210        220        230        240 
SAMNRHNNEA GRQAIASHMH LKCKCHGLSG SCEVKTCWWS QPDFRTIGDF LKDKYDSASE 

       250        260        270        280        290        300 
MVVEKHRESR GWVETLRPRY TYFKVPTERD LVYYEASPNF CEPNPETGSF GTRDRTCNVS 

       310        320        330        340        350 
SHGIDGCDLL CCGRGHNART ERRREKCHCV FHWCCYVSCQ ECTRVYDVHT CK 

« Hide

References

[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: PALMITOYLATION AT CYS-77.
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X56842 mRNA. Translation: CAA40173.1.
PIRA39532.
RefSeqNP_033548.1. NM_009522.2.
UniGeneMm.1367.

3D structure databases

ProteinModelPortalP27467.
SMRP27467. Positions 57-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204575. 9 interactions.
DIPDIP-55954N.
IntActP27467. 4 interactions.
MINTMINT-7992042.
STRING10090.ENSMUSP00000010044.

Chemistry

ChEMBLCHEMBL5617.

PTM databases

PhosphoSiteP27467.

Proteomic databases

PRIDEP27467.

Protocols and materials databases

DNASU22416.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000010044; ENSMUSP00000010044; ENSMUSG00000009900.
GeneID22416.
KEGGmmu:22416.
UCSCuc007jdp.2. mouse.

Organism-specific databases

CTD89780.
MGIMGI:98956. Wnt3a.

Phylogenomic databases

eggNOGNOG284879.
GeneTreeENSGT00730000110244.
HOGENOMHOG000039529.
HOVERGENHBG001595.
InParanoidP27467.
KOK00312.
OMAFLKCKCH.
OrthoDBEOG7C8GJ8.
PhylomeDBP27467.
TreeFamTF105310.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.

Gene expression databases

BgeeP27467.
CleanExMM_WNT3A.
GenevestigatorP27467.

Family and domain databases

InterProIPR005817. Wnt.
IPR009141. Wnt3.
IPR018161. Wnt_CS.
[Graphical view]
PANTHERPTHR12027. PTHR12027. 1 hit.
PTHR12027:SF18. PTHR12027:SF18. 1 hit.
PfamPF00110. wnt. 1 hit.
[Graphical view]
PRINTSPR01843. WNT3PROTEIN.
PR01349. WNTPROTEIN.
SMARTSM00097. WNT1. 1 hit.
[Graphical view]
PROSITEPS00246. WNT1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio302833.
PROP27467.
SOURCESearch...

Entry information

Entry nameWNT3A_MOUSE
AccessionPrimary (citable) accession number: P27467
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: April 16, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot