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Protein

Protein Wnt-3a

Gene

WNT3A

Organism
Homo sapiens (Human)
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: ParkinsonsUK-UCL
  • frizzled-2 binding Source: Ensembl
  • frizzled binding Source: GO_Central
  • protein domain specific binding Source: Ensembl
  • receptor binding Source: ParkinsonsUK-UCL
  • receptor ligand activity Source: BHF-UCL
  • transcription coactivator activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-3238698. WNT ligand biogenesis and trafficking.
R-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-HSA-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.
R-HSA-4641263. Regulation of FZD by ubiquitination.
R-HSA-5340588. RNF mutants show enhanced WNT signaling and proliferation.
SignaLinkiP56704.
SIGNORiP56704.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein Wnt-3a
Gene namesi
Name:WNT3A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000154342.5.
HGNCiHGNC:15983. 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
Mutagenesisi87N → Q: Strongly reduced ability to stimulate Wnt-responsive reporters; when associated with Q-298. 1 Publication1
Mutagenesisi209S → A: Abrogates WLS binding. 3 Publications1
Mutagenesisi209S → A: Complete loss of palmitoleoylation. 3 Publications1
Mutagenesisi209S → T: No effect on palmitoleoylation and secretion; the threonine can functionally replace the serine. 3 Publications1
Mutagenesisi298N → Q: Strongly reduced ability to stimulate Wnt-responsive reporters; when associated with Q-87. 1 Publication1
Mutagenesisi334C → A: No signaling activity despite the presence of significant amounts of secreted monomeric Wnt3a exhibit dominant negative properties; when associated with A-335. 1 Publication1
Mutagenesisi335C → A: No signaling activity despite the presence of significant amounts of secreted monomeric Wnt3a, exhibit dominant negative properties; when associated with A-334. 1 Publication1

Organism-specific databases

DisGeNETi89780.
MalaCardsiWNT3A.
OpenTargetsiENSG00000154342.
Orphaneti85193. Idiopathic juvenile osteoporosis.
PharmGKBiPA38074.

Chemistry databases

ChEMBLiCHEMBL1255137.

Polymorphism and mutation databases

BioMutaiWNT3A.
DMDMi20532424.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000004141819 – 352Protein Wnt-3aAdd BLAST334

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi77 ↔ 881 Publication
Glycosylationi87N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi128 ↔ 136By similarity
Disulfide bondi138 ↔ 155By similarity
Disulfide bondi203 ↔ 217By similarity
Disulfide bondi205 ↔ 212By similarity
Lipidationi209O-palmitoleoyl serine; by PORCN4 Publications1
Disulfide bondi297 ↔ 312By similarity
Glycosylationi298N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi327 ↔ 342By similarity
Disulfide bondi329 ↔ 339By similarity
Disulfide bondi334 ↔ 335By similarity

Post-translational modificationi

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:20826466, PubMed:21244856, PubMed:24292069). Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway, possibly by promoting disulfide bond formation and oligomerization (PubMed:25731175).4 Publications
Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT3A.By similarity
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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei26 – 27Cleavage; by TIKI1 and TIKI2By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein

Proteomic databases

PaxDbiP56704.
PeptideAtlasiP56704.
PRIDEiP56704.

PTM databases

iPTMnetiP56704.
PhosphoSitePlusiP56704.

Expressioni

Tissue specificityi

Moderately expressed in placenta and at low levels in adult lung, spleen, and prostate.

Gene expression databases

BgeeiENSG00000154342.
CleanExiHS_WNT3A.

Organism-specific databases

HPAiHPA066281.

Interactioni

Subunit structurei

Homooligomer; disulfide-linked, leading to inactivation (By similarity). Interacts with PORCN. 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 similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • co-receptor binding Source: ParkinsonsUK-UCL
  • frizzled-2 binding Source: Ensembl
  • frizzled binding Source: GO_Central
  • protein domain specific binding Source: Ensembl
  • receptor binding Source: ParkinsonsUK-UCL
  • receptor ligand activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi124599. 16 interactors.
DIPiDIP-58592N.
IntActiP56704. 5 interactors.
STRINGi9606.ENSP00000284523.

Chemistry databases

BindingDBiP56704.

Structurei

3D structure databases

ProteinModelPortaliP56704.
SMRiP56704.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Wnt family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3913. Eukaryota.
ENOG410XQZ1. LUCA.
GeneTreeiENSGT00760000118943.
HOGENOMiHOG000039529.
HOVERGENiHBG001595.
InParanoidiP56704.
KOiK00312.
OMAiKCRCVFH.
OrthoDBiEOG091G0OFF.
PhylomeDBiP56704.
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.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P56704-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAPLGYFLLL CSLKQALGSY PIWWSLAVGP QYSSLGSQPI LCASIPGLVP
60 70 80 90 100
KQLRFCRNYV EIMPSVAEGI KIGIQECQHQ FRGRRWNCTT VHDSLAIFGP
110 120 130 140 150
VLDKATRESA FVHAIASAGV AFAVTRSCAE GTAAICGCSS RHQGSPGKGW
160 170 180 190 200
KWGGCSEDIE FGGMVSREFA DARENRPDAR SAMNRHNNEA GRQAIASHMH
210 220 230 240 250
LKCKCHGLSG SCEVKTCWWS QPDFRAIGDF LKDKYDSASE MVVEKHRESR
260 270 280 290 300
GWVETLRPRY TYFKVPTERD LVYYEASPNF CEPNPETGSF GTRDRTCNVS
310 320 330 340 350
SHGIDGCDLL CCGRGHNARA ERRREKCRCV FHWCCYVSCQ ECTRVYDVHT

CK
Length:352
Mass (Da):39,365
Last modified:May 10, 2002 - v2
Checksum:iA317BD6D4A73920B
GO
Isoform 2 (identifier: P56704-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     352-352: K → KNPGSRAGNSAHQPPHPQPPVRFHPPLRRAGKVP

Show »
Length:385
Mass (Da):42,905
Checksum:iB2BBBFD1C7CA7E56
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046558352K → KNPGSRAGNSAHQPPHPQPP VRFHPPLRRAGKVP in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB060284 mRNA. Translation: BAB61052.1.
AK056278 mRNA. Translation: BAB71136.1.
AL136379 Genomic DNA. Translation: CAI23122.1.
BC103921 mRNA. Translation: AAI03922.1.
BC103922 mRNA. Translation: AAI03923.1.
BC103923 mRNA. Translation: AAI03924.1.
CCDSiCCDS1564.1. [P56704-1]
RefSeqiNP_149122.1. NM_033131.3. [P56704-1]
UniGeneiHs.336930.

Genome annotation databases

EnsembliENST00000284523; ENSP00000284523; ENSG00000154342. [P56704-1]
GeneIDi89780.
KEGGihsa:89780.
UCSCiuc001hrq.3. human. [P56704-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiWNT3A_HUMAN
AccessioniPrimary (citable) accession number: P56704
Secondary accession number(s): Q3SY79, Q3SY80, Q969P2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 10, 2002
Last modified: November 22, 2017
This is version 162 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

A palmitoylation site was proposed at Cys-77, but it was later shown that this cysteine is engaged in a disulfide bond (PubMed:24292069).1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families