title: Identification of a novel family of ubiquitin-conjugating enzymes with distinct amino-terminal extensions.
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.
authors.affiliation: Zentrum für Molekulare Biologie, Universität Heidelberg, Federal Republic of Germany.
authors.forename: K
authors.initials: K
authors.lastname: Matuschewski
authors.forename: H P
authors.initials: HP
authors.lastname: Hauser
authors.forename: M
authors.initials: M
authors.lastname: Treier
authors.forename: S
authors.initials: S
authors.lastname: Jentsch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D014452:Ubiquitins; D008025:Ligases