The ubiquitin activating enzyme E1 (UBE1) catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation. UBE1 activates ubiquitin by first adenylating (with ATP) its carboxy-terminal glycine residue and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and a free AMP. UBE1 is an example of an X-Y homologous gene, which is X-linked with a distinct Y-linked gene in many mammals. UBE1L (Ubiquitin-activating enzyme E1 homolog), also known as UBA7 (Ubiquitin-like modifier-activating enzyme 7) or UBE2, is a 1011 amino acid homolog of UBE1. Like UBE1, UBE1L functions in the activation of ubiquitin through ATP-dependent adenylation. UBE1L is expressed in tumor cells and is a retinoid target that, through conjugation with ISG15 (Interferon-induced 15 kDa protein), triggers degradation and apoptosis in acute promyelocytic leukemia.
