SUMO-activating enzyme subunit 2 (SAE2)

SUMO-activating enzyme subunit 2 (SAE2), also known as UBA2, is an enzyme in humans encoded by the UBA2 gene[1]. SAE2 forms a heterodimer with SAE1 to constitute the E1 activating enzyme for sumoylation, a modification process where small ubiquitin-like modifier (SUMO) proteins are covalently attached to target proteins[1][3]. This enzymatic complex initiates the SUMO conjugation cascade by activating SUMO proteins in an ATP-dependent manner, forming a thioester bond with SUMO and transferring it to the E2 conjugating enzyme, Ubc9. Sumoylation influences protein stability, subcellular localization, activity, and interactions, impacting processes such as DNA repair, cell cycle progression, signal transduction (including regulation of transcription factors like NF-kB and p53), and stress responses[1][2]. Dysregulation of this pathway is implicated in cancer and other diseases[2]. SAE2 is a rational target for drug discovery efforts due to its central role in regulating protein function via SUMOylation, but specific clinical agents targeting SAE2 remain under development.

Other names

Ubiquitin-like 1-activating enzyme E1BUBA2SUMO E1 subunit 2

Inhibition: Blocking SAE2 activity suppresses SUMOylation, affecting target protein stability, localization, and function. Activation: Experimental activators can enhance SAE2 activity, increasing global SUMOylation levels