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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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OTUB1
OTU deubiquitinase, ubiquitin aldehyde binding 1
Chromosome 11 · 11q13.1
NCBI Gene: 55611Ensembl: ENSG00000167770.14HGNC: HGNC:23077UniProt: B3KUV5
213PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairProtease
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cysteine-type deubiquitinase activityprotein bindingprotein deubiquitinationprotein K48-linked deubiquitinationneurodegenerative diseaseneoplasmcolorectal carcinomaovarian cancer
✦AI Summary

OTUB1 (OTU deubiquitinase, ubiquitin aldehyde binding 1) is a deubiquitinating enzyme that plays critical roles in cellular protection, immune regulation, and cancer progression. The protein functions primarily through both catalytic and non-catalytic mechanisms to regulate protein stability and cellular responses. OTUB1 stabilizes key proteins involved in ferroptosis resistance, particularly SLC7A11, the essential component of the cystine-glutamate antiporter 1. Through direct interaction and deubiquitination, OTUB1 prevents SLC7A11 degradation, thereby protecting cancer cells from ferroptosis-induced cell death 1. In immune regulation, OTUB1 promotes cancer immune evasion by stabilizing PD-L1 through removal of K48-linked ubiquitin chains, preventing its degradation via the ER-associated degradation pathway 2. This mechanism reduces tumor cell sensitivity to immune-mediated cytotoxicity and decreases CD8+ T cell infiltration 2. OTUB1 also regulates the stability of other proteins including NCOA4, where it maintains protein levels through deubiquitination, affecting ferritinophagy-dependent ferroptosis in myocardial ischemia-reperfusion injury 3. The enzyme's expression correlates with disease severity in various conditions, including lupus nephritis where reduced OTUB1 levels are associated with podocyte injury 4. These diverse functions establish OTUB1 as a potential therapeutic target for cancer immunotherapy and ferroptosis-related diseases.

Sources cited
1
OTUB1 directly interacts with and stabilizes SLC7A11, preventing ferroptosis in cancer cells
PMID: 30709928
2
OTUB1 stabilizes PD-L1 by removing K48-linked ubiquitin chains and preventing ER-associated degradation
PMID: 33328570
3
OTUB1 deubiquitinates NCOA4 to maintain protein stability and regulate ferritinophagy-dependent ferroptosis
PMID: 40366738
4
Reduced OTUB1 expression correlates with disease severity in lupus nephritis and podocyte injury
PMID: 39500879
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
neoplasmOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.10Suggestive
ovarian cancerOpen Targets
0.10Suggestive
gastric cancerOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.10Suggestive
prostate cancerOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
gliomaOpen Targets
0.09Suggestive
Miyoshi myopathyOpen Targets
0.08Suggestive
urinary bladder carcinomaOpen Targets
0.08Suggestive
renal cell carcinomaOpen Targets
0.08Suggestive
bladder transitional cell carcinomaOpen Targets
0.08Suggestive
head and neck squamous cell carcinomaOpen Targets
0.07Suggestive
papillary thyroid carcinomaOpen Targets
0.07Suggestive
endometriosisOpen Targets
0.07Suggestive
posterior cortical atrophyOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
acute lung injuryOpen Targets
0.06Suggestive
lung adenocarcinomaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RNF128Protein interaction98%UBE2D3Protein interaction98%UBE2E2Protein interaction98%UBE2L3Protein interaction98%UBE2NProtein interaction98%STAMBPProtein interaction98%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
81%
Heart
69%
Lung
66%
Ovary
58%
Liver
54%
Gene Interaction Network
Click a node to explore
OTUB1RNF128UBE2D3UBE2E2UBE2L3UBE2NSTAMBP
PROTEIN STRUCTURE
Preparing viewer…
PDB2ZFY · 1.69 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.55Moderately Constrained
pLIⓘ
0.92Intolerant
Observed/Expected LoF0.32 [0.20–0.55]
RankingsWhere OTUB1 stands among ~20K protein-coding genes
  • #1,950of 20,598
    Most Researched213 · top 10%
  • #3,528of 17,882
    Most Constrained (LOEUF)0.55 · top quartile
Genes detectedOTUB1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
The Deubiquitylase OTUB1 Mediates Ferroptosis via Stabilization of SLC7A11.
PMID: 30709928
Cancer Res · 2019
1.00
2
Deubiquitinase-targeting chimeras for targeted protein stabilization.
PMID: 35210618
Nat Chem Biol · 2022
0.90
3
OTUB1 accelerates hepatocellular carcinoma by stabilizing RACK1 via its non-canonical ubiquitination.
PMID: 38315284
Cell Oncol (Dordr) · 2024
0.84
4
USP28-Based Deubiquitinase-Targeting Chimeras for Cancer Treatment.
PMID: 40214647
J Am Chem Soc · 2025
0.80
5
Deletion of ASPP1 in myofibroblasts alleviates myocardial fibrosis by reducing p53 degradation.
PMID: 39341821
Nat Commun · 2024
0.80