Ubiquitin-activating Enzyme 6

UBE1L2 is a novel human ubiquitin-activating enzyme that initiates the activation and conjugation of ubiquitin-like proteins. It functions as an E1 enzyme with the ability to transfer the activated ubiquitin to the broad spectrum E2 enzyme, UbcH5b, and support the autopolyubiquitylation of two E3 enzymes, HectH9 and E6-AP, and Mdm2-mediated ubiquitylation of p53. The protein also activates ubiquitin-like protein FAT10 by forming a thioester bond between the active-site cysteine of E1-L2 and the C-terminal diglycine motif of FAT10. The protein contains an ATP-binding domain and an active site cysteine conserved among E1 family proteins. The UBE1L2 mRNA is most abundantly expressed in the testis, suggesting an organ-specific regulation of ubiquitin activation. Deletion of the protein in mice caused embryonic lethality, suggesting that UBE1L2 plays an important role in embryogenesis. In humans, the UBE1L2 gene is mapped to chromosome 4q13.2.