Ubiquitination is an important mechanism through which three classes of enzymes act in concert to target short-lived or abnormal proteins for destruction. The three classes of enzymes involved in ubiquitination are the ubiquitin-activating enzymes (E1s), the ubiquitin-conjugating enzymes (E2s) and the ubiquitin-protein ligases (E3s). The first step in the ubiquitination process requires the ATP-dependent activation of the ubiquitin C-terminus and the assembly of multi-ubiquitin chains by the E1 enzyme. The ubiquitin chain is then conjugated to the E2 enzyme to generate an intermediate ubiquitin-E2 complex. The E3 enzyme then catalyzes the transfer of ubiquitin from E2 to the appropriate protein substrate, thereby targeting that substrate for degradation. A wide range of enzymes facilitate this proteolytic ubiquitin pathway, one of which is UBE2E2 (also known as UBCH8 in human), which functions as an E2 enzyme and catalyzes the ATP-dependent covalent attachment of ubiquitin to target proteins, thereby playing an important role in protein degradation.