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OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2)
- Target
- OTUB2
- Molecular classification
- Enzyme, Deubiquitinase, Cysteine protease, OTU (ovarian tumor) domain-containing protein
01
Overview
OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) is a member of the OTU (ovarian tumor) superfamily of deubiquitinating enzymes and functions as a cysteine protease. It contains a catalytic OTU domain that can cleave multiple types of polyubiquitin chains (Lys-11, Lys-48, and Lys-63 linkages), thus regulating protein stability, turnover, and diverse signaling pathways. OTUB2 is involved in key cellular and physiological processes, including DNA damage repair, regulation of signal transduction, cell proliferation, and immune modulation. In cancer, OTUB2 acts as a negative regulator of antitumor immunity by stabilizing PD-L1 on tumor cells, contributing to immune evasion. OTUB2 is recognized as a potential therapeutic target, especially in oncology, with small-molecule inhibitors (e.g., OTUB2-IN-1, LN5P45) under investigation for cancer immunotherapy and possibly other indications.
- Other names
- Otubain-2OTU domain-containing ubiquitin aldehyde-binding protein 2
02
Mechanism of action
Inhibition of OTUB2's deubiquitinase activity (blocks removal of ubiquitin from substrate proteins, promoting their degradation)
03
Biological functions
Protein deubiquitinationRegulation of protein stability and turnoverCell signaling modulationDNA damage repairImmune response regulation (including modulation of PD-L1)
04
Disease associations
Cancer (oncogenesis, tumor progression, metastasis)Neurodegenerative disease (e.g., potential role in amyotrophic lateral sclerosis)Other (potential involvement in broader cell cycle dysfunction and mitosis)
05
Safety considerations
Potential risks of modulating protein homeostasis widely in cells, with broad impact on proteasomal degradation pathwaysDisruption of normal immune homeostasis
06
Interacting drugs
OTUB2-IN-1
1 more in the full profile.
07
Biomarkers
OTUB2 expression may serve as a biomarker for tumor immunosuppression/cytotoxic T cell evasion (e.g., correlation with PD-L1 levels in cancer)
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