SENP2

SENP2, also known as SUMO-specific protease 2, is an enzyme in humans encoded by the SENP2 gene. It belongs to the SENP family of SUMO/Sentrin-specific proteases that regulate SUMOylation, a reversible post-translational modification in which small ubiquitin-like modifiers (SUMO) are conjugated to target proteins. SENP2 functions as a cysteine protease that both processes SUMO precursors to generate mature SUMO and removes SUMO from SUMOylated substrates.

Regarding substrate specificity, SENP2 can act on multiple SUMO paralogs, with activity reported for SUMO1 as well as SUMO2 and SUMO3. On many substrates, there is particular emphasis on SENP2’s role in desumoylation of SUMO2/3-conjugated proteins, though efficiency can vary by substrate. Through deconjugation, SENP2 modulates the activity, localization, and stability of a wide range of proteins, influencing processes such as transcriptional regulation, DNA damage response, chromatin organization, and cell cycle progression.

Localization and interactions: SENP2 is predominantly associated with the nuclear envelope and the nuclear pore complex, where it participates in the regulation of nucleocytoplasmic transport and signaling. Its targeting to the nuclear pore is facilitated in part by interactions with RanBP2/Nup358, positioning it to modulate SUMOylation dynamics at a key cellular hub.

Genetic and clinical notes: In model systems, disruption of SENP2 function often leads to developmental defects, underscoring its essential role in cellular homeostasis. Dysregulation of SUMO pathways involving SENP2 has been explored in various disease contexts, including cancer, though outcomes are context-dependent and gene-specific.