The SUMO-specific isopeptidase SENP2 is targeted to intracellular membranes via a predicted N-terminal amphipathic α-helix.

Sumoylation regulates a wide range of essential cellular functions， many of which are associated with activities in the nucleus. Although there is also emerging evidence for the involvement of the small ubiquitin-related modifier (SUMO) at intracellular membranes， the mechanisms by which sumoylation is regulated at membranes is largely unexplored. In this study， we report that the SUMO-specific isopeptidase， SENP2， uniquely associates with intracellular membranes. Using in vivo analyses and in vitro binding assays， we show that SENP2 is targeted to intracellular membranes via a predicted N-terminal amphipathic α-helix that promotes direct membrane binding. Furthermore， we demonstrate that SENP2 binding to intracellular membranes is regulated by interactions with the nuclear import receptor karyopherin-α. Consistent with membrane association， biotin identification (BioID) revealed interactions between SENP2 and endoplasmic reticulum， Golgi， and inner nuclear membrane-associated proteins. Collectively， our findings indicate that SENP2 binds to intracellular membranes where it interacts with membrane-associated proteins and has the potential to regulate their sumoylation and membrane-associated functions.