SUMO2

SUMO2, short for small ubiquitin-like modifier 2, is a member of the SUMO family of ubiquitin-like proteins that regulate protein function through covalent attachment to lysine residues, a process known as SUMOylation. In humans, SUMO2 is encoded by the SUMO2 gene and is expressed ubiquitously. Like other SUMO proteins, SUMO2 is synthesized as a precursor that is processed by SUMO proteases to reveal a C-terminal diglycine motif required for conjugation. The mature SUMO2 is attached to substrates via an enzymatic cascade involving a heterodimeric E1 activating enzyme (SAE1/SAE2), the E2 conjugating enzyme Ubc9, and often an E3 ligase that provides substrate specificity. SUMO2 can also form polySUMO chains, a feature that is especially prominent under cellular stress.

SUMO2 modified substrates include transcription factors, chromatin regulators, DNA repair proteins, and signaling molecules. SUMOylation can alter substrate stability, localization, activity, or interaction networks, thereby influencing processes such as transcription, chromatin structure, DNA repair, cell cycle control, and stress responses. A distinguishing feature of SUMO2 and SUMO3 is their robust response to cellular stress; SUMO2/3 conjugates rapidly accumulate in conditions such as heat shock, oxidative stress, or proteasome inhibition, and these chains can be recognized by SUMO-targeted ubiquitin ligases, linking SUMOylation to ubiquitin-mediated degradation.

The SUMO2/3 pathway is tightly reversible; SUMO-specific proteases of the SENP family remove SUMO2 from substrates, enabling dynamic regulation. Dysregulation of SUMO2 signaling has been associated with various diseases, including cancer and neurodegenerative disorders, reflecting its broad role in maintaining cellular homeostasis.