Proteolytic degradation by the ubiquitin (Ub) system is essential for normal cell cycle progression, cellular differentiation and stress responses. Proteins conjugated to Ub are marked for progressive degradation by the 26S Proteasome. AOS-1, also designated SUMO-1-activating enzyme or ubiquitin-like 1-activating enzyme E1A, belongs to the ubiquitin-activating E1 family of proteins and plays an important role in the first step of the UBL1 conjugation pathway. AOS-1, which is a dimeric enzyme, functions as a UBLI E1 ligase, mediating the ATP-dependent activation of UBL1. AOS-1 can bind with UBLE1A and UBLE1B to form a heterodimer which can bind UBL1.