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SUMO specific peptidase 5 (SENP5)
- Target
- SENP5
- Molecular classification
- Enzyme, Specifically, SUMO-specific cysteine protease (Ulp/SENP family)
01
Overview
SUMO specific peptidase 5 (SENP5) is a nucleolar-localized cysteine protease of the Ulp/SENP family that preferentially cleaves SUMO2 and SUMO3 from modified substrates and processes full-length SUMO3 to its mature form. SENP5 plays a crucial, nonredundant role in cell division, specifically mitosis and cytokinesis, and regulates nuclear processes such as transcription and DNA repair by modulating the SUMOylation state of target proteins. Its substrate specificity and unique nucleolar localization distinguish SENP5 from other family members, and its dysregulation is associated with cancer, neurodegenerative, and cardiovascular diseases. The recently resolved structural details of SENP5-SUMO complexes highlight key determinants for isoform specificity and enable the rational design of selective inhibitors, opening an avenue for targeted therapies with reduced off-target risks.
- Other names
- Sentrin-specific protease 5FKSG45MGC27076Sentrin/SUMO-specific protease SENP5SUMO1/sentrin specific peptidase 5SUMO1/sentrin specific protease 5
02
Mechanism of action
Enzyme inhibition: Blocking the protease activity to prevent SUMO2/3 deconjugation from substrate proteins, thereby modifying SUMOylation homeostasis in disease contexts
03
Biological functions
SUMO precursor processing (SUMO3 maturation)Deconjugation (de-SUMOylation) of SUMO2/3 from target proteinsRegulation of cell division (mitosis and cytokinesis)Modulation of chromosome segregationRegulation of transcription, DNA repair, and nucleocytoplasmic traffickingMaintenance of nuclear architecture
04
Disease associations
CancerNeurodegenerative diseaseCardiovascular diseaseOther roles: General cellular dysregulation via SUMO pathway imbalance
05
Safety considerations
Potential for disrupted cell proliferation and defects in mitosis/cytokinesis if SENP5 function is alteredRisk of nuclear morphology abnormalities and chromosome segregation defects
06
Biomarkers
Levels of SUMO-conjugates (SUMO-1 and SUMO-2/3 conjugates) in cells may reflect SENP5 function or inhibitionNuclear morphology abnormalities (e.g., binucleate cells, aberrant nuclear structures) as a result of SENP5 deficiency
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