Abstract
The ubiquitin/proteasome system is the main eukaryotic nonlysosomal protein degradation system. Substrate selectivity of this pathway is thought to be mediated in part by members of a large family of ubiquitin-conjugating (E2) enzymes, which catalyze the covalent attachment of ubiquitin to proteolytic substrates. E2 enzymes have a conserved approximately 150-residue so-called UBC domain, which harbors the cysteine residue required for enzyme-ubiquitin thioester formation. Some E2 enzymes possess additional carboxyl-terminal extensions that are involved in substrate specificity and intracellular localization of the enzyme. Here we describe a novel family of E2 enzymes from higher eukaryotes (Drosophila, mouse, and man) that have amino-terminal extensions but lack carboxyl-terminal extensions. We have identified four different variants of these enzymes that have virtually identical UBC domains (94% identity) but differ in their amino-terminal extensions. In yeast, these enzymes can partially complement mutants deficient in the UBC4 E2 enzyme. This indicates that members of this novel E2 family may operate in UBC4-related proteolytic pathways.
