Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein Wnt-3a

Gene

WNT3A

Organism
Homo sapiens (Human)
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:20093360, PubMed:21244856, PubMed:24841207, PubMed:26902720). Required for normal embryonic mesoderm development and formation of caudal somites. Required for normal morphogenesis of the developing neural tube (By similarity). Mediates self-renewal of the stem cells at the bottom on intestinal crypts (in vitro) (PubMed:26902720).By similarityCurated4 Publications

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

GO - Molecular functioni

  • co-receptor binding Source: ParkinsonsUK-UCL
  • frizzled binding Source: GO_Central
  • protein domain specific binding Source: Ensembl
  • receptor ligand activity Source: BHF-UCL
  • signaling receptor binding Source: ParkinsonsUK-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
MIMi606359 gene
neXtProtiNX_P56704

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, exhibits 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, exhibits 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
ProteomicsDBi56937

PTM databases

iPTMnetiP56704
PhosphoSitePlusiP56704

Expressioni

Tissue specificityi

Moderately expressed in placenta and at low levels in adult lung, spleen, and prostate.1 Publication

Gene expression databases

BgeeiENSG00000154342 Expressed in 20 organ(s), highest expression level in placenta
CleanExiHS_WNT3A

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 (By similarity). Interacts with PORCN (PubMed:20826466). Interacts with APCDD1 and WLS (PubMed:16678095, PubMed:20393562). 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 (PubMed:20093360). Interacts with glypican GPC3 (PubMed:16227623).By similarity1 Publication6 Publications

Binary interactionsi

GO - Molecular functioni

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 No translation available.
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB060284 mRNA Translation: BAB61052.1
AK056278 mRNA Translation: BAB71136.1
AL136379 Genomic DNA No translation available.
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

3D structure databases

ProteinModelPortaliP56704
SMRiP56704
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiP56704
ChEMBLiCHEMBL1255137

PTM databases

iPTMnetiP56704
PhosphoSitePlusiP56704

Polymorphism and mutation databases

BioMutaiWNT3A
DMDMi20532424

Proteomic databases

PaxDbiP56704
PeptideAtlasiP56704
PRIDEiP56704
ProteomicsDBi56937

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi89780
DisGeNETi89780
EuPathDBiHostDB:ENSG00000154342.5
GeneCardsiWNT3A
HGNCiHGNC:15983 WNT3A
MalaCardsiWNT3A
MIMi606359 gene
neXtProtiNX_P56704
OpenTargetsiENSG00000154342
Orphaneti85193 Idiopathic juvenile osteoporosis
PharmGKBiPA38074
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3913 Eukaryota
ENOG410XQZ1 LUCA
GeneTreeiENSGT00760000118943
HOGENOMiHOG000039529
HOVERGENiHBG001595
InParanoidiP56704
KOiK00312
OMAiKCRCVFH
OrthoDBiEOG091G0OFF
PhylomeDBiP56704
TreeFamiTF105310

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

Miscellaneous databases

ChiTaRSiWNT3A human
GeneWikiiWNT3A
GenomeRNAii89780
PROiPR:P56704
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000154342 Expressed in 20 organ(s), highest expression level in placenta
CleanExiHS_WNT3A

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
ProtoNetiSearch...

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: October 10, 2018
This is version 170 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again