Activated ubiquitin is transferred from E1 to the active site cystine of ubiquitin conjugating enzymes (E2s) via a trans-esterification reaction. E2s catalyze covalent attachment of ubiquitin to target proteins. They all share an active-site ubiquitin-binding cysteine residue and are distinguished by the presence of a ubiquitin-conjugating catalytic (UBC) fold required for binding of distinct ubiquitin ligases or E3s. Once conjugated to ubiquitin, the E2 molecule binds one of several E3s (Glickman et al. 2002).