SAE1/SAE2 is the heterodimeric E1 enzyme that conjugates SUMO to protein substrates.The conjugation process is very similar to that of protein ubiquitination. SUMO is conjugated onto the catalytic cysteine residue of SAE2 by formation of a thioester bond in an ATP-dependent reaction.The activated SUMO is then passed on to an E2 (Ubc9) to be finally attached to a substrate.