UniProtKB - P56704 (WNT3A_HUMAN)
Protein Wnt-3a
WNT3A
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 PublicationsCaution
GO - Molecular functioni
- co-receptor binding Source: ParkinsonsUK-UCL
- cytokine activity Source: GO_Central
- 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: Ensembl
GO - Biological processi
- axis elongation involved in somitogenesis Source: Ensembl
- axon guidance Source: Ensembl
- calcium ion transmembrane transport via low voltage-gated calcium channel Source: Ensembl
- canonical Wnt signaling pathway Source: UniProtKB
- canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment Source: BHF-UCL
- cell fate commitment Source: GO_Central
- cell population proliferation Source: UniProtKB
- cell proliferation in forebrain Source: BHF-UCL
- cell proliferation in midbrain Source: ParkinsonsUK-UCL
- cellular protein localization Source: Ensembl
- cellular response to retinoic acid Source: UniProtKB
- COP9 signalosome assembly Source: BHF-UCL
- dorsal/ventral neural tube patterning Source: Ensembl
- extracellular matrix organization Source: Ensembl
- heart looping Source: Ensembl
- hemopoiesis Source: Ensembl
- hippocampus development Source: Ensembl
- inner ear morphogenesis Source: Ensembl
- in utero embryonic development Source: Ensembl
- mammary gland development Source: Ensembl
- modulation of chemical synaptic transmission Source: Ensembl
- negative regulation of axon extension involved in axon guidance Source: Ensembl
- negative regulation of dopaminergic neuron differentiation Source: Ensembl
- negative regulation of fat cell differentiation Source: Ensembl
- negative regulation of heart induction by canonical Wnt signaling pathway Source: BHF-UCL
- negative regulation of neurogenesis Source: BHF-UCL
- negative regulation of neuron death Source: Ensembl
- negative regulation of neuron projection development Source: UniProtKB
- neuron differentiation Source: UniProtKB
- osteoblast differentiation Source: Ensembl
- paraxial mesodermal cell fate commitment Source: Ensembl
- platelet aggregation Source: Ensembl
- positive regulation of B cell proliferation Source: Ensembl
- positive regulation of canonical Wnt signaling pathway Source: BHF-UCL
- positive regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation Source: Ensembl
- positive regulation of cardiac muscle cell differentiation Source: BHF-UCL
- positive regulation of cell-cell adhesion mediated by cadherin Source: Ensembl
- positive regulation of cell population proliferation Source: BHF-UCL
- positive regulation of collateral sprouting in absence of injury Source: Ensembl
- positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
- positive regulation of cytokine production Source: Ensembl
- positive regulation of dermatome development Source: BHF-UCL
- positive regulation of DNA-binding transcription factor activity Source: Ensembl
- positive regulation of gene expression Source: BHF-UCL
- positive regulation of hepatocyte proliferation Source: Ensembl
- positive regulation of mesodermal cell fate specification Source: BHF-UCL
- positive regulation of neural precursor cell proliferation Source: Ensembl
- positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
- positive regulation of protein binding Source: BHF-UCL
- positive regulation of protein localization to plasma membrane Source: Ensembl
- positive regulation of protein phosphorylation Source: BHF-UCL
- positive regulation of protein tyrosine kinase activity Source: Ensembl
- positive regulation of receptor internalization Source: BHF-UCL
- positive regulation of skeletal muscle tissue development Source: Ensembl
- positive regulation of transcription, DNA-templated Source: BHF-UCL
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- post-anal tail morphogenesis Source: Ensembl
- postsynapse to nucleus signaling pathway Source: Ensembl
- presynapse assembly Source: ParkinsonsUK-UCL
- regulation of microtubule cytoskeleton organization Source: Ensembl
- regulation of presynapse assembly Source: SynGO
- regulation of synapse organization Source: SynGO
- secondary palate development Source: BHF-UCL
- skeletal muscle cell differentiation Source: Ensembl
- somatic stem cell division Source: Ensembl
- spinal cord association neuron differentiation Source: Ensembl
- synaptic vesicle recycling Source: ParkinsonsUK-UCL
- Wnt signaling pathway involved in forebrain neuroblast division Source: Ensembl
- Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
Keywordsi
Molecular function | Developmental protein |
Biological process | Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | P56704 |
Reactomei | R-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, Signaling by RNF43 mutants |
SignaLinki | P56704 |
SIGNORi | P56704 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein Wnt-3a |
Gene namesi | Name:WNT3A |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:15983, WNT3A |
MIMi | 606359, gene |
neXtProti | NX_P56704 |
VEuPathDBi | HostDB:ENSG00000154342 |
Subcellular locationi
Extracellular region or secreted
- extracellular matrix By similarity
- Secreted 2 Publications
Endoplasmic reticulum
- endoplasmic reticulum lumen Source: Reactome
Endosome
- early endosome membrane Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: Reactome
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Golgi apparatus
- Golgi lumen Source: Reactome
Plasma Membrane
- plasma membrane Source: Reactome
- Wnt-Frizzled-LRP5/6 complex Source: ParkinsonsUK-UCL
Other locations
- cell surface Source: BHF-UCL
- endocytic vesicle membrane Source: Reactome
- glutamatergic synapse Source: SynGO
- presynapse Source: GOC
Keywords - Cellular componenti
Extracellular matrix, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 87 | N → Q: Strongly reduced ability to stimulate Wnt-responsive reporters; when associated with Q-298. 1 Publication | 1 | |
Mutagenesisi | 209 | S → A: Abrogates WLS binding. 3 Publications | 1 | |
Mutagenesisi | 209 | S → A: Complete loss of palmitoleoylation. 3 Publications | 1 | |
Mutagenesisi | 209 | S → T: No effect on palmitoleoylation and secretion; the threonine can functionally replace the serine. 3 Publications | 1 | |
Mutagenesisi | 298 | N → Q: Strongly reduced ability to stimulate Wnt-responsive reporters; when associated with Q-87. 1 Publication | 1 | |
Mutagenesisi | 334 | C → A: No signaling activity despite the presence of significant amounts of secreted monomeric Wnt3a, exhibits dominant negative properties; when associated with A-335. 1 Publication | 1 | |
Mutagenesisi | 335 | C → A: No signaling activity despite the presence of significant amounts of secreted monomeric Wnt3a, exhibits dominant negative properties; when associated with A-334. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 89780 |
MalaCardsi | WNT3A |
OpenTargetsi | ENSG00000154342 |
Orphaneti | 85193, Idiopathic juvenile osteoporosis |
PharmGKBi | PA38074 |
Miscellaneous databases
Pharosi | P56704, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1255137 |
Genetic variation databases
BioMutai | WNT3A |
DMDMi | 20532424 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | Sequence analysisAdd BLAST | 18 | |
ChainiPRO_0000041418 | 19 – 352 | Protein Wnt-3aAdd BLAST | 334 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 77 ↔ 88 | 1 Publication | ||
Glycosylationi | 87 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 128 ↔ 136 | By similarity | ||
Disulfide bondi | 138 ↔ 155 | By similarity | ||
Disulfide bondi | 203 ↔ 217 | By similarity | ||
Disulfide bondi | 205 ↔ 212 | By similarity | ||
Lipidationi | 209 | O-palmitoleoyl serine; by PORCN4 Publications | 1 | |
Disulfide bondi | 281 ↔ 312 | By similarity | ||
Disulfide bondi | 297 ↔ 307 | By similarity | ||
Glycosylationi | 298 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 311 ↔ 351 | By similarity | ||
Disulfide bondi | 327 ↔ 342 | By similarity | ||
Disulfide bondi | 329 ↔ 339 | By similarity | ||
Disulfide bondi | 334 ↔ 335 | By similarity |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 26 – 27 | Cleavage; by TIKI1 and TIKI2By similarity | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, LipoproteinProteomic databases
MassIVEi | P56704 |
PaxDbi | P56704 |
PeptideAtlasi | P56704 |
PRIDEi | P56704 |
ProteomicsDBi | 56937 [P56704-1] |
PTM databases
GlyGeni | P56704, 2 sites |
iPTMneti | P56704 |
PhosphoSitePlusi | P56704 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000154342, Expressed in placenta and 24 other tissues |
Organism-specific databases
HPAi | ENSG00000154342, Tissue enriched (placenta) |
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).
Interacts with PKD1 (via extracellular domain) (PubMed:27214281).
By similarity1 Publication7 PublicationsBinary interactionsi
P56704
With | #Exp. | IntAct |
---|---|---|
APCDD1 [Q8J025] | 3 | EBI-6173037,EBI-2683489 |
FZD8 [Q9H461] | 2 | EBI-6173037,EBI-6254212 |
LRP6 [O75581] | 2 | EBI-6173037,EBI-910915 |
WLS [Q5T9L3] | 4 | EBI-6173037,EBI-2868748 |
GO - Molecular functioni
- co-receptor binding Source: ParkinsonsUK-UCL
- cytokine activity Source: GO_Central
- frizzled binding Source: GO_Central
- protein domain specific binding Source: Ensembl
- receptor ligand activity Source: BHF-UCL
- signaling receptor binding Source: ParkinsonsUK-UCL
Protein-protein interaction databases
BioGRIDi | 124599, 40 interactors |
DIPi | DIP-58592N |
IntActi | P56704, 20 interactors |
STRINGi | 9606.ENSP00000284523 |
Chemistry databases
BindingDBi | P56704 |
Miscellaneous databases
RNActi | P56704, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P56704 |
SMRi | P56704 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3913, Eukaryota |
GeneTreei | ENSGT00940000160510 |
HOGENOMi | CLU_033039_1_0_1 |
InParanoidi | P56704 |
OMAi | GLTHVMA |
OrthoDBi | 965867at2759 |
PhylomeDBi | P56704 |
TreeFami | TF105310 |
Family and domain databases
Gene3Di | 3.30.2460.20, 1 hit |
InterProi | View protein in InterPro IPR005817, Wnt IPR009141, Wnt3 IPR043158, Wnt_C IPR018161, Wnt_CS |
PANTHERi | PTHR12027, PTHR12027, 1 hit |
Pfami | View protein in Pfam PF00110, wnt, 1 hit |
PRINTSi | PR01843, WNT3PROTEIN PR01349, WNTPROTEIN |
SMARTi | View protein in SMART SM00097, WNT1, 1 hit |
PROSITEi | View protein in PROSITE PS00246, WNT1, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_046558 | 352 | K → KNPGSRAGNSAHQPPHPQPP VRFHPPLRRAGKVP in isoform 2. 1 Publication | 1 |
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 |
CCDSi | CCDS1564.1 [P56704-1] |
RefSeqi | NP_149122.1, NM_033131.3 [P56704-1] |
Genome annotation databases
Ensembli | ENST00000284523.2; ENSP00000284523.1; ENSG00000154342.6 |
GeneIDi | 89780 |
KEGGi | hsa:89780 |
MANE-Selecti | ENST00000284523.2; ENSP00000284523.1; NM_033131.4; NP_149122.1 |
UCSCi | uc001hrq.3, human [P56704-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS1564.1 [P56704-1] |
RefSeqi | NP_149122.1, NM_033131.3 [P56704-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
7DRT | electron microscopy | 2.20 | A | 1-352 | [»] | |
AlphaFoldDBi | P56704 | |||||
SMRi | P56704 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 124599, 40 interactors |
DIPi | DIP-58592N |
IntActi | P56704, 20 interactors |
STRINGi | 9606.ENSP00000284523 |
Chemistry databases
BindingDBi | P56704 |
ChEMBLi | CHEMBL1255137 |
PTM databases
GlyGeni | P56704, 2 sites |
iPTMneti | P56704 |
PhosphoSitePlusi | P56704 |
Genetic variation databases
BioMutai | WNT3A |
DMDMi | 20532424 |
Proteomic databases
MassIVEi | P56704 |
PaxDbi | P56704 |
PeptideAtlasi | P56704 |
PRIDEi | P56704 |
ProteomicsDBi | 56937 [P56704-1] |
Protocols and materials databases
Antibodypediai | 34658, 606 antibodies from 36 providers |
DNASUi | 89780 |
Genome annotation databases
Ensembli | ENST00000284523.2; ENSP00000284523.1; ENSG00000154342.6 |
GeneIDi | 89780 |
KEGGi | hsa:89780 |
MANE-Selecti | ENST00000284523.2; ENSP00000284523.1; NM_033131.4; NP_149122.1 |
UCSCi | uc001hrq.3, human [P56704-1] |
Organism-specific databases
CTDi | 89780 |
DisGeNETi | 89780 |
GeneCardsi | WNT3A |
HGNCi | HGNC:15983, WNT3A |
HPAi | ENSG00000154342, Tissue enriched (placenta) |
MalaCardsi | WNT3A |
MIMi | 606359, gene |
neXtProti | NX_P56704 |
OpenTargetsi | ENSG00000154342 |
Orphaneti | 85193, Idiopathic juvenile osteoporosis |
PharmGKBi | PA38074 |
VEuPathDBi | HostDB:ENSG00000154342 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3913, Eukaryota |
GeneTreei | ENSGT00940000160510 |
HOGENOMi | CLU_033039_1_0_1 |
InParanoidi | P56704 |
OMAi | GLTHVMA |
OrthoDBi | 965867at2759 |
PhylomeDBi | P56704 |
TreeFami | TF105310 |
Enzyme and pathway databases
PathwayCommonsi | P56704 |
Reactomei | R-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, Signaling by RNF43 mutants |
SignaLinki | P56704 |
SIGNORi | P56704 |
Miscellaneous databases
BioGRID-ORCSi | 89780, 14 hits in 1072 CRISPR screens |
ChiTaRSi | WNT3A, human |
GeneWikii | WNT3A |
GenomeRNAii | 89780 |
Pharosi | P56704, Tchem |
PROi | PR:P56704 |
RNActi | P56704, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000154342, Expressed in placenta and 24 other tissues |
Family and domain databases
Gene3Di | 3.30.2460.20, 1 hit |
InterProi | View protein in InterPro IPR005817, Wnt IPR009141, Wnt3 IPR043158, Wnt_C IPR018161, Wnt_CS |
PANTHERi | PTHR12027, PTHR12027, 1 hit |
Pfami | View protein in Pfam PF00110, wnt, 1 hit |
PRINTSi | PR01843, WNT3PROTEIN PR01349, WNTPROTEIN |
SMARTi | View protein in SMART SM00097, WNT1, 1 hit |
PROSITEi | View protein in PROSITE PS00246, WNT1, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | WNT3A_HUMAN | |
Accessioni | P56704Primary (citable) accession number: P56704 Secondary accession number(s): Q3SY79, Q3SY80, Q969P2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | May 10, 2002 | |
Last modified: | May 25, 2022 | |
This is version 191 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families