Figure 1.

The cellular ubiquitylation system. Ubiquitin is activated by an ATP consuming Ubiquitin acitvating enzyme (E1), and transferred from E1 to the active site cysteine of the Ubiquitin-conjugating enzyme (E2). E3 enzymes are capable of interacting with both E2 and the substrate and catalyze the transfer of the ubiquitin moeity to a lysine or the n-terminal Methionine of the substrate. Repeated cycles of the ubiquitylation cascade lead to poly-ubiquitylation, where any of the lysines of ubiquitin may be utilized as attachment site.