OTUD4 (OTU Deubiquitinase 4)
A deubiquitinating enzyme involved in DNA repair, innate immunity, and cellular stress responses.
Gene Information Card
| Symbol | OTUD4 |
|---|---|
| Full Name | OTU deubiquitinase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.21 |
| NCBI Gene ID | 54726 ncbi.nlm.nih.gov/gene/54726 |
| Ensembl ID | ENSG00000164164 |
| UniProt ID | Q01804 |
| OMIM ID | 611744 |
| HGNC ID | 25131 |
| Aliases | DUBA6, HIN1, KIAA1046 |
Description
OTUD4 (OTU deubiquitinase 4) encodes a deubiquitinating enzyme that removes ubiquitin chains from specific substrates, thereby regulating DNA repair pathways (e.g., ALKBH2, ALKBH3), innate immune signaling (e.g., MAVS, TRAF3), and cellular stress responses. The protein contains an ovarian tumor (OTU) domain and is implicated in cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (breast, ovarian, lung) | OTUD4 deubiquitinates and stabilizes DNA repair proteins ALKBH2/ALKBH3, promoting alkylation damage repair and chemoresistance. | PMID: 25775507, PMID: 31073040 |
| Neurodegeneration (Alzheimer's disease) | OTUD4 modulates tau protein turnover and autophagy; dysregulation linked to tau pathology. | PMID: 31511692 |
| Viral infection (innate immunity) | OTUD4 removes K63-linked ubiquitin chains from MAVS and TRAF3, negatively regulating antiviral interferon signaling. | PMID: 23746807 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Breast | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 11.2 | Embryonic kidney |
| HeLa | 9.8 | Cervical cancer |
| MCF7 | 8.5 | Breast cancer |
| A549 | 7.1 | Lung cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | 0.01% (gnomAD) | Unknown functional impact |
| c.1567G>A (p.Glu523Lys) | Missense | 0.005% (gnomAD) | Potential loss of deubiquitinase activity |
| c.2044_2045insA (p.Thr682Asnfs*2) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the OTU domain or C-terminal region are predicted to abolish deubiquitinase activity.
Gain of Function (GOF)
Not well characterized; some missense variants may alter substrate specificity or stability.
Dominant Negative (DN)
Not reported for OTUD4.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type deubiquitinase activity (GO:0004843) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • DNA repair (GO:0006281) | • innate immune response (GO:0045087) |
| • nucleus (GO:0005634) | • cytosol (GO:0005829) |
Pathways
• Alkylation damage repair (ALKBH2/ALKBH3 stabilization)
• RIG-I/MDA5-mediated antiviral signaling (MAVS deubiquitination)
• TRAF3 deubiquitination in TLR signaling
Protein Summary
OTUD4 is a 1114-amino acid deubiquitinating enzyme that cleaves K48- and K63-linked polyubiquitin chains. It localizes to the nucleus and cytoplasm, where it regulates DNA repair by stabilizing ALKBH2/ALKBH3, and negatively regulates antiviral innate immunity by deubiquitinating MAVS and TRAF3. Its dysregulation is linked to cancer chemoresistance and neurodegenerative tauopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OTUD4 Knockout HEK293 Cell Line | EDJ-KQ14645 | Human | 54726 | Details Get a Quote |
| OTUD4 Knockout HeLa Cell Line | EDJ-KQ43704 | Human | 54726 | Details Get a Quote |
| OTUD4 Knockout A-549 Cell Line | EDJ-KQ44927 | Human | 54726 | Details Get a Quote |
| OTUD4 Knockout HCT 116 Cell Line | EDJ-KQ44928 | Human | 54726 | Details Get a Quote |
