OTUD3 (OTU Deubiquitinase 3)
A deubiquitinating enzyme involved in protein stability, cell cycle regulation, and tumor suppression.
Gene Information Card
| Symbol | OTUD3 |
|---|---|
| Full Name | OTU deubiquitinase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 23252 ncbi.nlm.nih.gov/gene/23252 |
| Ensembl ID | ENSG00000162521 |
| UniProt ID | Q5T2D3 |
| OMIM ID | 612027 |
| HGNC ID | 26124 |
| Aliases | DUBA5, OTU3 |
Description
OTUD3 (OTU deubiquitinase 3) encodes a member of the ovarian tumor (OTU) domain-containing deubiquitinating enzyme family. The protein removes ubiquitin chains from specific substrates, thereby regulating protein stability, cell cycle progression, and signal transduction. OTUD3 has been implicated as a tumor suppressor in several cancers, particularly through its interaction with PTEN and regulation of the PI3K/AKT pathway.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | OTUD3 deubiquitinates and stabilizes PTEN, suppressing PI3K/AKT signaling; loss of OTUD3 promotes tumorigenesis. | PMID: 25986432 |
| Lung cancer | Reduced OTUD3 expression correlates with poor prognosis; OTUD3 inhibits cell proliferation and invasion. | PMID: 31570782 |
| Hepatocellular carcinoma | OTUD3 overexpression suppresses tumor growth; downregulation associated with metastasis. | PMID: 32415263 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Breast | 8.1 | Medium |
| Lung | 6.7 | Medium |
| Liver | 4.9 | Low |
| Kidney | 7.3 | Medium |
| Testis | 12.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 9.5 | Moderate expression |
| A549 (lung cancer) | 7.8 | Moderate expression |
| HepG2 (liver cancer) | 5.1 | Low expression |
| HEK293 (embryonic kidney) | 11.2 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.511C>T (p.Arg171Trp) | Missense | <0.01% | Unknown functional impact |
| c.763_764del (p.Leu255fs) | Frameshift | <0.01% | Predicted loss of function |
| c.1012G>A (p.Gly338Arg) | Missense | <0.01% | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations are predicted to cause loss of deubiquitinase activity, potentially impairing PTEN stabilization.
Gain of Function (GOF)
No gain-of-function mutations have been reported.
Dominant Negative (DN)
No dominant-negative mutations have been described.
View complete mutation data：
Gene Ontology (GO)
| • thiol-dependent deubiquitinase (GO:0004843) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • nucleus (GO:0005634) | • cytosol (GO:0005829) |
| • protein deubiquitination (GO:0016579) | • proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) |
Pathways
• PI3K/AKT signaling (via PTEN stabilization)
• Ubiquitin-proteasome system
Protein Summary
OTUD3 is a 521-amino acid deubiquitinase containing an OTU domain. It cleaves ubiquitin chains from substrates such as PTEN, thereby preventing their proteasomal degradation. Through PTEN stabilization, OTUD3 negatively regulates the PI3K/AKT pathway, suppressing cell proliferation and survival. The protein is predominantly cytoplasmic and nuclear, and its expression is frequently downregulated in cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OTUD3 Knockout HEK293 Cell Line | EDJ-KQ7921 | Human | 23252 | Details Get a Quote |
| OTUD3 Knockout A-549 Cell Line | EDJ-KQ33554 | Human | 23252 | Details Get a Quote |
| OTUD3 Knockout HCT 116 Cell Line | EDJ-KQ33555 | Human | 23252 | Details Get a Quote |
| OTUD3 Knockout HeLa Cell Line | EDJ-KQ33556 | Human | 23252 | Details Get a Quote |
