SAE2
Encoded by the UBA2 gene, SAE2 (Uba2) is the catalytic subunit of the heterodimeric SUMO E1, pairing with the scaffolding subunit SAE1 (Aos1). SAE2 carries both the adenylation domain, which forms the SUMO-adenylate intermediate, and the catalytic cysteine domain, where the activated modifier is held as a thioester before transfer to the E2 enzyme UBE2I. In contrast to ubiquitin, which uses several E1s, SUMO1, SUMO2, and SUMO3 all depend on this single SAE1/SAE2 complex, giving it gatekeeper status over nuclear and cytoplasmic SUMOylation. The enzyme is broadly expressed and concentrated in the nucleus, and it is targeted by investigational inhibitors that block SUMO conjugation in cancer models.
