Ubiquitin-conjugating enzyme E2 I (UBE2I) (UBE2I)

Ubiquitin-conjugating enzyme E2 I (UBE2I), commonly referred to as UBC9, is the unique E2 conjugating enzyme responsible for the SUMOylation pathway. It facilitates the covalent attachment of Small Ubiquitin-like Modifier (SUMO) proteins to a wide array of target substrates, thereby modulating their function, localization, and stability (UniProt: P63279). UBE2I is essential for critical cellular processes such as the cell cycle, DNA damage repair, and nucleocytoplasmic transport. In many human malignancies, UBE2I is overexpressed and correlates with poor prognosis, as it supports oncogenic signaling and helps cancer cells evade apoptosis (PubMed: 28655318). Because it is the sole E2 enzyme for SUMOylation, it represents a bottleneck in the pathway and an attractive target for drug development. Current therapeutic strategies focus on small molecule inhibitors, such as 2-D08 and Ginkgolic acid, that block its catalytic activity or its interaction with E1 or E3 enzymes to treat cancer and certain viral infections (PubMed: 24101535).

Other names

UBC9SUMO-conjugating enzyme UBC9P18Ubiquitin-protein ligase I

Inhibition of the E2 SUMO-conjugating enzyme activity, preventing the transfer of SUMO to target proteins.