WWP2: A Key E3 Ubiquitin Ligase in Cellular Regulation and Disease
Comprehensive genomic and functional analysis of WWP2, a HECT-type E3 ubiquitin-protein ligase involved in protein degradation, signaling, and cancer.
Gene Information Card
| Symbol | WWP2 |
|---|---|
| Full Name | WW domain containing E3 ubiquitin protein ligase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 11060 ncbi.nlm.nih.gov/gene/11060 |
| Ensembl ID | ENSG00000133424 |
| UniProt ID | O00308 |
| OMIM ID | 602308 |
| HGNC ID | 12799 |
| Aliases | AIP2, WWp2, NEDD4-like E3 ubiquitin-protein ligase WWP2 |
Description
WWP2 (WW domain containing E3 ubiquitin protein ligase 2) encodes a HECT-type E3 ubiquitin ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It plays critical roles in cellular processes such as protein turnover, signal transduction, cell cycle regulation, and apoptosis. WWP2 is involved in the regulation of transcription factors, including PTEN and SMADs, and has been implicated in cancer progression, fibrosis, and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | WWP2 overexpression promotes degradation of tumor suppressors (e.g., PTEN) and enhances oncogenic signaling. | PMID: 23541922, COSMIC |
| Pulmonary fibrosis | WWP2-mediated ubiquitination of SMAD7 enhances TGF-β signaling, leading to fibrosis. | PMID: 26921320 |
| Neurodevelopmental disorders | Mutations in WWP2 are associated with intellectual disability and developmental delay. | ClinVar, PMID: 31036916 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Placenta | 12.8 | Medium |
| Brain (cerebellum) | 10.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | High expression |
| HeLa | 14.7 | Medium expression |
| A549 | 12.1 | Medium expression |
| MCF7 | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | 0.01% | Loss of ubiquitin ligase activity; associated with developmental delay (ClinVar) |
| c.789_790insA (p.Glu264Argfs*12) | Frameshift | <0.01% | Loss of function; reported in cancer (COSMIC) |
| c.1567G>A (p.Glu523Lys) | Missense | 0.02% | Gain of function; increased PTEN degradation (PMID: 23541922) |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the HECT domain or WW domains impair ubiquitin ligase activity, leading to accumulation of substrates and altered signaling.
Gain of Function (GOF)
Certain missense mutations enhance WWP2 activity, promoting excessive degradation of tumor suppressors like PTEN and driving oncogenesis.
Dominant Negative (DN)
Truncating mutations that retain substrate binding but lack catalytic activity can interfere with wild-type WWP2 function, though not well documented.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• TGF-beta signaling pathway (KEGG: hsa04350)
• PTEN regulation (Reactome: R-HSA-6807070)
Protein Summary
WWP2 is a 870-amino acid HECT-type E3 ubiquitin ligase containing four WW domains and a C-terminal HECT catalytic domain. It ubiquitinates diverse substrates, including PTEN, SMAD7, and p53, targeting them for proteasomal degradation. WWP2 regulates key signaling pathways such as TGF-β, PI3K/AKT, and p53, and its dysregulation is linked to cancer, fibrosis, and neurodevelopmental disorders. The protein is predominantly cytoplasmic but can shuttle to the nucleus.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WWP2 Knockout HEK293 Cell Line | EDJ-KQ7261 | Human | 11060 | Details Get a Quote |
| WWP2 Knockout A-549 Cell Line | EDJ-KQ32274 | Human | 11060 | Details Get a Quote |
| WWP2 Knockout HCT 116 Cell Line | EDJ-KQ32275 | Human | 11060 | Details Get a Quote |
| WWP2 Knockout HeLa Cell Line | EDJ-KQ32276 | Human | 11060 | Details Get a Quote |
