Recombinant Human GST-Ubiquitin E1 Enzyme (UBE1L2/UBA6), CF

Ubiquitin-activating Enzyme 1-like 2 (UBE1L2), also known as Ubiquitin-like Modifier Activating Enzyme 6 (UBA6), is a 1052 amino acid (aa) member of the Ubiquitin-activating (E1) enzyme family with a predicted molecular weight of 118 kDa. The mouse and rat UBE1L2/UBA6 orthologs share 88% aa sequence identity with the human protein. UBE1L2/UBA6 is expressed in vertebrate cells where four isoforms have been identified (1). UBE1L2/UBA6 is an activating enzyme for both Ubiquitin and FAT10 via a similar molecular mechanism but has a higher affinity for FAT10 than for Ubiquitin (2-4). UBE1L2/UBA6 contains an ATP-binding motif and an active site cysteine residue, Cys625 in humans, common to E1 enzymes. It shares 40% aa sequence identity with the related family member Ubiquitin Activating Enzyme/UBE1 (1). Similar to UBE1, UBE1L2/UBA6 can transfer activated Ubiquitin to Ubiquitin-conjugating (E2) enzymes including the UbcH5 isoforms and UbcH7 (5). Unlike UBE1, which can transfer Ubiquitin to the cell cycle-associated E2 enzyme, UbcH3, UBE1L2/UBA6 can transfer Ubiquitin to Use1/UBE2Z, an E2 enzyme that cannot be charged with Ubiquitin by UBE1 (1,5). UBE1L2/UBA6-initiated covalent linkage of FAT10 to protein targets results in proteasomal degradation (2). UBE1L2/UBA6 is essential for embryonic development (3). One isoform, nUBE1L, is highly expressed in human testis and may play a role in spermatogenesis and male fertility (6).