WNT5A (wingless-type MMTV integration site family, member 5A)

2008-06-01   Masaru Katoh  

Genetics, Cell Biology Section, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

Identity

HGNC
LOCATION
3p14.3
LOCUSID
ALIAS
hWNT5A
FUSION GENES

DNA/RNA

Note

WNT5A gene at chromosome 3p14.3 and WNT5B gene at chromosome 12p13.33 are paralogs within the human genome.
Atlas Image
Schematic representation of WNT5A gene.
Atlas Image
Alignment of mammalian WNT5A and WNT5B orthologs. N-terminal signal peptide (double over-line), conserved Cys residues (+), and Asn-linked glycosylation sites are shown.

Description

WNT5A gene consists of 5 exons. First methionine is located in exon 1, while stop codon in exon 5. dbSNP rs655731, located within exon 5 of the human WNT5A gene, is a synonymous SNP corresponding to codon 263.

Transcription

WNT5A is preferentially upregulated in gastric cancer, and melanoma, but downregulated in breast cancer, colorectal cancer, and acute lymphocytic leukemia.
Wnt5a is upregulated by IL6 family cytokines through gp130 in cultured cardiomyocytes, by TGFbeta in mammary epithelial cells, and by TNFalpha in gastric cancer cells. WNT5A upregulation in primary tumor is in part due to stromal expression based on tumor-stromal interaction, while WNT5A downregulation in primary tumor is in part due to epigenetic silencing induced by promoter CpG hypermethylation.

Proteins

Description

Mature WNT5A protein with conserved Cys residues is a secreted-type glycoprotein.

Expression

WNT5A mRNA is relatively abundantly expressed in salivary gland, bladder, uterus, placenta, and fetal kidney.

Localisation

Naive WNT5A protein is synthesized in the endoplasmic reticulum. Mature WNT5A protein with lipid modifications and glycosylations enters the trans-Golgi network for secretion from the cell surface.

Function

WNT5A signals are transduced to the canonical and non-canonical WNT signaling cascades. WNT5A signaling through Frizzled-4 ( FZD4 ) or FZD5 receptor and LRP5 or LRP6 co-receptor leads to the stabilization and nuclear accumulation of beta-catenin for the transcriptional activation of target genes, such as MYC, CCND1, and FGF20. On the other hand, WNT5A signaling through Frizzled family receptor or ROR1 or ROR2 co-receptor leads to the activation of the non-canonical WNT signaling cascades, such as DAG - PKC, IP3 - NFAT, or IP3 - NLK signaling cascades. WNT5A-PKC signaling promotes invasion and metastasis of tumors through SNAI1 (Snail)-mediated epithelial-to-mesenchymal transition (EMT), while WNT5A-NLK signaling suppresses carcinogenesis through inhibition of the canonical WNT signaling cascade. Expression of WNT5A is associated with metastatic or aggressive phenotype in gastric cancer, melanoma, and osteosarcoma, but is associated with non-aggressive or better prognostic phenotype in breast cancer, colorectal cancer, and acute lymphocytic leukemia. Together these facts indicate that WNT5A induces oncogenic as well as tumor suppressive functions in a context-dependent manner.

Homology

Human WNT5A shows 98.7% total amino-acid identity with rodent Wnt5a, indicating that mammalian WNT5A orthologs are highly conserved. Among 19 WNT family members, WNT5A is most homologous to WNT5B.

Mutations

Note

WNT5A gene is located at human chromosome 3p14.3 around the susceptible locus of Zimmermann-Laband Syndrome; however, mutation of WNT5A gene has not been detected.

Germinal

Wnt5a knockout mice show smaller somites and shortened presomitic mesoderm, abnormalities in the lungs with the foreshortened trachea, dysplasia of genitals, and ventricular septal defects.

Implicated in

Entity name
Melanoma
Prognosis
Poor prognosis
Entity name
Gastric cancer
Prognosis
Poor prognosis
Entity name
Prognosis
Poor prognosis
Entity name
Breast cancer
Prognosis
Better prognosis
Entity name
Colorectal cancer
Prognosis
Better prognosis
Prognosis
Better prognosis

Article Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 7474
MIM: 164975
HGNC: 12784
Ensembl: ENSG00000114251

Variants:

dbSNP: 7474
ClinVar: 7474
TCGA: ENSG00000114251
COSMIC: WNT5A

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000114251ENST00000264634P41221
ENSG00000114251ENST00000264634A0A384N611
ENSG00000114251ENST00000474267P41221
ENSG00000114251ENST00000474267A0A384N611
ENSG00000114251ENST00000482079C9J8I8
ENSG00000114251ENST00000497027P41221
ENSG00000114251ENST00000497027A0A024R316

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
mTOR signaling pathwayKEGGko04150
Wnt signaling pathwayKEGGko04310
Axon guidanceKEGGko04360
MelanogenesisKEGGko04916
Basal cell carcinomaKEGGko05217
mTOR signaling pathwayKEGGhsa04150
Wnt signaling pathwayKEGGhsa04310
Axon guidanceKEGGhsa04360
MelanogenesisKEGGhsa04916
Pathways in cancerKEGGhsa05200
Basal cell carcinomaKEGGhsa05217
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Hippo signaling pathwayKEGGhsa04390
Hippo signaling pathwayKEGGko04390
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Wnt signalingKEGGhsa_M00677
Wnt signalingKEGGM00677
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR ligand bindingREACTOMER-HSA-500792
Class B/2 (Secretin family receptors)REACTOMER-HSA-373080
Signaling by WntREACTOMER-HSA-195721
WNT ligand biogenesis and traffickingREACTOMER-HSA-3238698
TCF dependent signaling in response to WNTREACTOMER-HSA-201681
Negative regulation of TCF-dependent signaling by WNT ligand antagonistsREACTOMER-HSA-3772470
Beta-catenin independent WNT signalingREACTOMER-HSA-3858494
PCP/CE pathwayREACTOMER-HSA-4086400
Asymmetric localization of PCP proteinsREACTOMER-HSA-4608870
WNT5A-dependent internalization of FZD4REACTOMER-HSA-5099900
WNT5A-dependent internalization of FZD2, FZD5 and ROR2REACTOMER-HSA-5140745
Ca2+ pathwayREACTOMER-HSA-4086398
Vesicle-mediated transportREACTOMER-HSA-5653656
Membrane TraffickingREACTOMER-HSA-199991
Clathrin-mediated endocytosisREACTOMER-HSA-8856828
Cargo recognition for clathrin-mediated endocytosisREACTOMER-HSA-8856825
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

References

Pubmed IDYearTitleCitations
378141832024Expression of Wnt5a and ROR2, Components of the Noncanonical Wnt-Signaling Pathway, is Associated with Tumor Differentiation in Hepatocellular Carcinoma.0
383592662024Exploring the role of the WNT5A rs566926 polymorphism and its interactions in non-syndromic orofacial cleft: a multicenter study in Brazil.1
383671912024WNT5A regulates the proliferation, apoptosis and stemness of human stem Leydig cells via the β-catenin signaling pathway.0
384456622024Differential expression of WNT5A long and short isoforms in non-muscle-invasive bladder urothelial carcinoma.0
386043452024Upregulated miR-374a-5p drives psoriasis pathogenesis through WIF1 downregulation and Wnt5a/NF-κB activation.0
388984762024Wnt5a-mediated autophagy contributes to the epithelial-mesenchymal transition of human bronchial epithelial cells during asthma.0
378141832024Expression of Wnt5a and ROR2, Components of the Noncanonical Wnt-Signaling Pathway, is Associated with Tumor Differentiation in Hepatocellular Carcinoma.0
383592662024Exploring the role of the WNT5A rs566926 polymorphism and its interactions in non-syndromic orofacial cleft: a multicenter study in Brazil.1
383671912024WNT5A regulates the proliferation, apoptosis and stemness of human stem Leydig cells via the β-catenin signaling pathway.0
384456622024Differential expression of WNT5A long and short isoforms in non-muscle-invasive bladder urothelial carcinoma.0
386043452024Upregulated miR-374a-5p drives psoriasis pathogenesis through WIF1 downregulation and Wnt5a/NF-κB activation.0
388984762024Wnt5a-mediated autophagy contributes to the epithelial-mesenchymal transition of human bronchial epithelial cells during asthma.0
365243562023WNT5A, β‑catenin and SUFU expression patterns, and the significance of microRNA deregulation in placentas with intrauterine growth restriction.1
365395752023WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma.0
366310102023[PDS5B inhibits the proliferation of A549 human lung cancer cells via downregulation of Wnt5a].0

Citation

Masaru Katoh

WNT5A (wingless-type MMTV integration site family, member 5A)

Atlas Genet Cytogenet Oncol Haematol. 2008-06-01

Online version: http://atlasgeneticsoncology.org/gene/42825/js/lib/favicon/welcome