WWP1: A Key E3 Ubiquitin Ligase in Cancer and Development
Comprehensive genomic and functional analysis of WW domain-containing E3 ubiquitin protein ligase 1
Gene Information Card
| Symbol | WWP1 |
|---|---|
| Full Name | WW domain containing E3 ubiquitin protein ligase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 8q21.3 |
| NCBI Gene ID | 11059 ncbi.nlm.nih.gov/gene/11059 |
| Ensembl ID | ENSG00000123124 |
| UniProt ID | Q9H0M0 |
| OMIM ID | 602307 |
| HGNC ID | 12756 |
| Aliases | AIP5, hSDRP, Tiul1, WWP1_HUMAN |
Description
WWP1 (WW domain containing E3 ubiquitin protein ligase 1) encodes a member of the NEDD4-like family of HECT domain E3 ubiquitin ligases. The protein contains an N-terminal C2 domain, multiple WW domains, and a C-terminal HECT domain. It ubiquitinates target proteins, regulating their stability, localization, and function. WWP1 is involved in diverse cellular processes including cell growth, apoptosis, and signal transduction, and its dysregulation is implicated in several cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | WWP1 overexpression promotes degradation of tumor suppressors such as PTEN and TGFBR2, enhancing oncogenic signaling. | PMID: 21746835; COSMIC |
| Prostate Cancer | WWP1 amplification and overexpression correlate with poor prognosis; targets PTEN for ubiquitination. | PMID: 21746835; COSMIC |
| Colorectal Cancer | WWP1 upregulation stabilizes β-catenin and promotes Wnt signaling. | PMID: 23431171; COSMIC |
| Gastric Cancer | WWP1 overexpression linked to increased cell proliferation and invasion via EGFR pathway. | PMID: 25636872; COSMIC |
| Developmental Disorders | WWP1 mutations (e.g., p.Arg422Gln) associated with intellectual disability and autism spectrum disorder. | ClinVar; PMID: 27616483 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain | 8.3 | Low |
| Lung | 15.2 | Medium |
| Liver | 10.1 | Medium |
| Kidney | 18.7 | Medium |
| Testis | 22.4 | High |
| Breast | 14.6 | Medium |
| Colon | 11.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.5 | High expression |
| HeLa | 14.2 | Medium expression |
| MCF7 | 16.8 | Medium-high expression |
| HCT116 | 12.3 | Medium expression |
| A549 | 10.9 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1265G>A (p.Arg422Gln) | Missense | Rare | Alters WW domain binding specificity; associated with neurodevelopmental disorders |
| c.2083C>T (p.Arg695Trp) | Missense | Rare | Located in HECT domain; potential loss of ubiquitin ligase activity |
| c.1234_1235insA (p.Thr412Asnfs*5) | Frameshift | Very rare | Truncation; loss of function |
| c.1742A>G (p.Tyr581Cys) | Missense | Rare | Unknown functional effect; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr412Asnfs*5) that truncate the HECT domain lead to loss of E3 ligase activity.
Gain of Function (GOF)
Amplification or overexpression of wild-type WWP1 in cancers (e.g., breast, prostate) results in increased ubiquitination of tumor suppressors, acting as an oncogenic gain of function.
Dominant Negative (DN)
Missense mutations in the WW domains (e.g., p.Arg422Gln) may disrupt substrate binding without affecting dimerization, potentially exerting dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• TGF-beta signaling pathway (KEGG: hsa04350)
• Wnt signaling pathway (KEGG: hsa04310)
• PTEN regulation (Reactome: R-HSA-6807070)
• EGFR signaling (Reactome: R-HSA-177929)
Protein Summary
WWP1 is a 922-amino acid HECT-type E3 ubiquitin ligase. It contains an N-terminal C2 domain (calcium-dependent membrane targeting), four WW domains (protein-protein interaction modules that bind proline-rich motifs), and a C-terminal HECT domain (catalytic ubiquitin transfer). WWP1 ubiquitinates substrates including PTEN, TGFBR2, and SMAD7, targeting them for proteasomal degradation. It is widely expressed and plays roles in cell proliferation, apoptosis, and differentiation. Dysregulation of WWP1 contributes to oncogenesis and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WWP1 Knockout HEK293 Cell Line | EDJ-KQ3164 | Human | 11059 | Details Get a Quote |
| WWP1 Knockout A-549 Cell Line | EDJ-KQ24574 | Human | 11059 | Details Get a Quote |
| WWP1 Knockout HCT 116 Cell Line | EDJ-KQ24575 | Human | 11059 | Details Get a Quote |
| WWP1 Knockout HeLa Cell Line | EDJ-KQ24576 | Human | 11059 | Details Get a Quote |
