Figure 2.

The SUMO pathway

(A) The precursor form of SUMO is processed by a SUMO-specific protease, creating a C-terminal Gly-Gly (GG) motif. In the presence of ATP, mature SUMO is activated by the heterodimeric E1 SUMO-activating enzymes, SAE1 and SAE2, through the cysteine (C) residue of SAE2. Subsequently, SUMO transferred to the cysteine residue of the E2 SUMO-conjugating enzyme (Ubc9) is finally conjugated to the lysine (K) residues of substrate proteins by aid of an E3 SUMO ligase. The SUMO protease deconjugates SUMO from proteins or edits SUMO chains, and then SUMO is recycled through the conjugation system.(B) SUMO is covalently linked to a single lysine residue of a protein (monosumoylation) or multiple lysine residues of a single protein (multisumoylation). Repeated sumoylation cycles build SUMO chain(s) attached on a substrate (polysumoylation).