UBE1, the ubiquitin activating enzyme, is the first enzyme in the pathway for conjugation of ubiquitin to target substrates through a ubiquitin-protein isopeptide bond. The C-terminal glycine of a ubiquitin (G76) is initially adenylated in an ATP dependent manner, followed by activation through transfer to the active site cysteine of UBE1, forming a ubiquitin-UBE1 thiolester. With the help of the other enzymes in the ubiquitin conjugation pathway (E2/E3 enzymes) ubiquitin is then transferred to a specific lysine on a target substrate.
