SUMO Proteins
SUMO (small ubiquitin-like modifier) proteins form a UBL subfamily with four human paralogs, SUMO1, SUMO2, SUMO3 and SUMO4. Like ubiquitin, they are processed to expose a C-terminal diglycine and conjugated to lysines through a dedicated machinery: the E1 heterodimer SAE1/SAE2, the E2 enzyme UBC9 and various E3 ligases; SUMO2 and SUMO3 can additionally form polymeric chains through an internal consensus site. SUMOylation is reversible, being removed by SENP proteases, and regulates nucleocytoplasmic transport, transcription, DNA repair, chromatin organization, PML nuclear bodies and the stress response. Aberrant SUMO modification is linked to cancer, neurodegeneration and viral infection, making the pathway a growing therapeutic focus.
