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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.

GO - Molecular functioni

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

GO - Biological processi

  • animal organ morphogenesis Source: MGI
  • 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
  • calcium ion transmembrane transport via low voltage-gated calcium channel Source: ParkinsonsUK-UCL
  • 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
  • cell proliferation in midbrain Source: ParkinsonsUK-UCL
  • cellular protein localization Source: MGI
  • COP9 signalosome assembly Source: BHF-UCL
  • determination of left/right symmetry Source: MGI
  • dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • 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
  • midbrain development Source: ParkinsonsUK-UCL
  • negative regulation of axon extension involved in axon guidance Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: Reactome
  • negative regulation of dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • 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
  • neurogenesis Source: ParkinsonsUK-UCL
  • 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 calcium ion transmembrane transport Source: Ensembl
  • 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 gene expression Source: MGI
  • positive regulation of hepatocyte proliferation 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 kinase activity Source: ParkinsonsUK-UCL
  • positive regulation of protein localization to plasma membrane Source: ParkinsonsUK-UCL
  • positive regulation of protein phosphorylation Source: ParkinsonsUK-UCL
  • 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: ParkinsonsUK-UCL
  • positive regulation of transcription regulatory region DNA binding Source: BHF-UCL
  • 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

ReactomeiR-MMU-3238698. WNT ligand biogenesis and trafficking.
R-MMU-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-MMU-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.
R-MMU-4641263. 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
Proteomesi
  • UP000000589 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
  • Wnt-Frizzled-LRP5/6 complex Source: MGI
  • Wnt signalosome Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25 – 26SL → 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 Publication2
Mutagenesisi33 – 34SS → DD: Completely resistant to proteolysis by TIKI1 and TIKI2; when associated with 25-D-D-26. 1 Publication2
Mutagenesisi77C → A: Forms oxidized oligomers regardless of TIKI2. Does not affect palmitoleylation. 2 Publications1
Mutagenesisi209S → A: Abolishes palmitoleylation, promoting formation of disulfide bonds and oligomerization. 2 Publications1
Mutagenesisi211S → A: Does not affect palmitoleylation. 1 Publication1
Mutagenesisi216T → A: Does not affect palmitoleylation. 1 Publication1
Mutagenesisi277S → A: Does not affect palmitoleylation. 1 Publication1
Mutagenesisi292T → A: Does not affect palmitoleylation. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5617.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000004141919 – 352Protein Wnt-3aAdd BLAST334

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi77 ↔ 88By similarity
Glycosylationi87N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi128 ↔ 136By similarity
Disulfide bondi138 ↔ 155By similarity
Disulfide bondi203 ↔ 217By similarity
Disulfide bondi205 ↔ 212By similarity
Lipidationi209O-palmitoleyl serine; by PORCN3 Publications1
Disulfide bondi297 ↔ 312By similarity
Glycosylationi298N-linked (GlcNAc...)Sequence analysis1
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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei26 – 27Cleavage; by TIKI1 and TIKI21 Publication2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein

Proteomic databases

MaxQBiP27467.
PaxDbiP27467.
PeptideAtlasiP27467.
PRIDEiP27467.

PTM databases

PhosphoSitePlusiP27467.
SwissPalmiP27467.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000009900.
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.

GO - Molecular functioni

  • co-receptor binding Source: MGI
  • frizzled-2 binding Source: MGI
  • frizzled binding Source: MGI
  • protein domain specific binding Source: UniProtKB
  • receptor agonist activity Source: ParkinsonsUK-UCL
  • receptor binding Source: MGI

Protein-protein interaction databases

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

Chemistry databases

BindingDBiP27467.

Structurei

3D structure databases

ProteinModelPortaliP27467.
SMRiP27467.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Wnt family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3913. Eukaryota.
ENOG410XQZ1. LUCA.
GeneTreeiENSGT00760000118943.
HOGENOMiHOG000039529.
HOVERGENiHBG001595.
InParanoidiP27467.
KOiK00312.
OMAiFLKCKCH.
OrthoDBiEOG091G0OFF.
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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiP27467.
ChEMBLiCHEMBL5617.

PTM databases

PhosphoSitePlusiP27467.
SwissPalmiP27467.

Proteomic databases

MaxQBiP27467.
PaxDbiP27467.
PeptideAtlasiP27467.
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

eggNOGiKOG3913. Eukaryota.
ENOG410XQZ1. LUCA.
GeneTreeiENSGT00760000118943.
HOGENOMiHOG000039529.
HOVERGENiHBG001595.
InParanoidiP27467.
KOiK00312.
OMAiFLKCKCH.
OrthoDBiEOG091G0OFF.
PhylomeDBiP27467.
TreeFamiTF105310.

Enzyme and pathway databases

ReactomeiR-MMU-3238698. WNT ligand biogenesis and trafficking.
R-MMU-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-MMU-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.
R-MMU-4641263. Regulation of FZD by ubiquitination.

Miscellaneous databases

PROiP27467.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000009900.
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...

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: November 30, 2016
This is version 158 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

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 one 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.