Fig. 1.

The SUMO conjugation pathway. After they are translated, SUMO proteins must first be processed by a SUMO protease such as Ulp1, which removes four C-terminal residues so that the mature form ends with a glycine. These SUMO proteases are also responsible for removing SUMO groups from proteins. This mature form is then activated in an ATP-dependent manner by forming a thioester bond with a cysteine residue in the SAE2 subunit of the heterodimeric E1 activating enzyme. Following this activation step, the SUMO moiety is transferred to the E2 conjugating enzyme ubc9. In the final step SUMO is transferred in a ligation reaction from ubc9 to substrate proteins, forming an isopeptide bond between the terminal glycine on SUMO and the ε-amino group of a lysine in the target protein. The efficiency of sumoylation of some proteins is enhanced by SUMO ligase E3 proteins, via their ability to bind both ubc9 and the target protein, thereby increasing the kinetics of the SUMO transfer.