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Protein

Protein Wnt-3a

Gene

Wnt3a

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

Functioni

Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (PubMed:26902720). Required for normal embryonic mesoderm development and formation of caudal somites (PubMed:8299937). Required for normal morphogenesis of the developing neural tube (PubMed:8299937). Mediates self-renewal of the stem cells at the bottom on intestinal crypts (in vitro) (PubMed:26902720).Curated2 Publications

Miscellaneous

Gene targeting that leads to the production of a truncated mRNA causes full embryonic lethality at 10.5 to 12.5 dpc.1 Publication

Caution

The formation of disulfide-linked oligomers may be an artifact that occurs upon heterologous expression in vitro (PubMed:25771893, PubMed:26902720). Formation of disulfide-linked oligomers is not observed when the protein is coexpressed with AFM (PubMed:26902720).2 Publications
A palmitoylation site was proposed at Cys-77, but it was later shown that this cysteine is engaged in a disulfide bond.

GO - Molecular functioni

  • co-receptor binding Source: MGI
  • frizzled binding Source: MGI
  • protein domain specific binding Source: UniProtKB
  • receptor ligand activity Source: ParkinsonsUK-UCL
  • signaling 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 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 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 death Source: ARUK-UCL
  • negative regulation of neuron projection development Source: UniProtKB
  • neurogenesis Source: ParkinsonsUK-UCL
  • osteoblast differentiation 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 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 core promoter binding Source: BHF-UCL
  • 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 DNA binding transcription factor activity Source: BHF-UCL
  • 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 skeletal muscle tissue development Source: CACAO
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: ParkinsonsUK-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
  • regulation of RNA biosynthetic process Source: MGI
  • roof of mouth development Source: MGI
  • secondary palate development Source: Ensembl
  • 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

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-3238698 WNT ligand biogenesis and trafficking
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:98956 Wnt3a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 palmitoleoylation. 2 Publications1
Mutagenesisi209S → A: Abolishes palmitoleoylation, promoting formation of disulfide bonds and oligomerization. 2 Publications1
Mutagenesisi211S → A: Does not affect palmitoleoylation. 1 Publication1
Mutagenesisi216T → A: Does not affect palmitoleoylation. 1 Publication1
Mutagenesisi277S → A: Does not affect palmitoleoylation. 1 Publication1
Mutagenesisi292T → A: Does not affect palmitoleoylation. 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...) asparagineSequence analysis1
Disulfide bondi128 ↔ 136By similarity
Disulfide bondi138 ↔ 155By similarity
Disulfide bondi203 ↔ 217By similarity
Disulfide bondi205 ↔ 212By similarity
Lipidationi209O-palmitoleoyl serine; by PORCN3 Publications1
Disulfide bondi297 ↔ 312By similarity
Glycosylationi298N-linked (GlcNAc...) asparagineSequence 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
Palmitoleoylation by PORCN is required for efficient binding to frizzled receptors. Palmitoleoylation is required for proper trafficking to cell surface, vacuolar acidification is critical to release palmitoleoylated WNT3A from WLS in secretory vesicles (PubMed:17141155, PubMed:24798332). Depalmitoleoylated 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.1 Publication

Developmental stagei

Detected in the dorsal primitive streak region at 8.5 dpc. Detected in the tailbud region and in the developing central nervous system (CNS) at 9.5 dpc.1 Publication

Gene expression databases

BgeeiENSMUSG00000009900
CleanExiMM_WNT3A
GenevisibleiP27467 MM

Interactioni

Subunit structurei

Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity (PubMed:26902720). The complex with AFM may represent the physiological form in body fluids (PubMed:26902720). 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 (PubMed:10866835).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi204575, 9 interactors
CORUMiP27467
DIPiDIP-55954N
ELMiP27467
IntActiP27467, 8 interactors
MINTiP27467
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
OMAiKCRCVFH
OrthoDBiEOG091G0OFF
PhylomeDBiP27467
TreeFamiTF105310

Family and domain databases

InterProiView protein in InterPro
IPR005817 Wnt
IPR009141 Wnt3
IPR018161 Wnt_CS
PANTHERiPTHR12027 PTHR12027, 1 hit
PfamiView protein in Pfam
PF00110 wnt, 1 hit
PRINTSiPR01843 WNT3PROTEIN
PR01349 WNTPROTEIN
SMARTiView protein in SMART
SM00097 WNT1, 1 hit
PROSITEiView protein in PROSITE
PS00246 WNT1, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiWNT3A_MOUSE
AccessioniPrimary (citable) accession number: P27467
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: May 23, 2018
This is version 174 of the entry and version 1 of the sequence. See 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

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