Fig. 1

The Sumoylation Process. The small ubiquitin-like modifier (SUMO) pro-peptide is processed by the Sentrin-specific proteases (SENPs), during maturation, to reveal the C-terminal di-glycine motif. The SUMO-activating enzyme (composed of SAE1 and SAE2) adenylates the SUMO di-glycine motif in an ATP- and Mg²⁺-dependent manner. A transient intermediate thioester bond forms between SUMO and SAE2 C173. SAE2 passes SUMO to the ubiquitin-like conjugating enzyme (Ubc9), forming a second transient intermediate thioester bond. Ubc9 recognizes the ΨKxD/E SUMO motif within a target protein and catalyzes the formation of an isopeptide bond with the C-terminal SUMO di-glycine motif and the ε-amino group of the lysine residue within the SUMO motif of the target protein. The end result (sometimes with the assistance of a SUMO E3 ligase) is the mono- or poly-sumoylation of the target protein. The whole process can be reversed by SENPs, which contains a tryptophan tunnel that allows for the accurate positioning of the SUMO di-glycine motif and the cleavage of the SUMO-target protein isopeptide bond