The reversible sumoylation mechanism. The sumoylation pathway starts with an immature SUMO protein that needs to be protealytically processed by SENPs to reveal its target binding site, an invariant Gly-Gly motif. The mature SUMO protein is then activated by E1 heterodimer in an ATP-dependent reaction. SUMO is then transferred to an E2 enzyme, UBC9, which is responsible for the recognition of target binding sites. After the recognition, the SUMO protein is transferred to a lysine residue in the target binding site. This process is generally assisted by an E3 ligase. Sumoylated sites can also act as substrates for SENPs, so the sumoylation can be reversed. This ensures the dynamic and reversible nature of sumoylation.