InterPro domain: IPR000608

Ubiquitin-conjugating enzymes (UBC or E2 enzymes) ( 2.3.2.23 ) [ 1 , 2 , 3 ]catalyse the covalent attachment of ubiquitin to target proteins. Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1, IPR000011 ), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3, IPR000569 , IPR003613 ), which work sequentially in a cascade [ 4 ]. The E1 enzyme mediates an ATP-dependent transfer of a thioester-linked ubiquitin molecule to a cysteine residue on the E2 enzyme. The E2 enzyme then either transfers the ubiquitin moiety directly to a substrate, or to an E3 ligase, which can also ubiquitinylate a substrate.

There are several different E2 enzymes (over 30 in humans), which are broadly grouped into four classes, all of which have a core catalytic domain (containing the active site cysteine), and some of which have short N- and C-terminal amino acid extensions: class I enzymes consist of just the catalytic core domain (UBC), class II possess a UBC and a C-terminal extension, class III possess a UBC and an N-terminal extension, and class IV possess a UBC and both N- and C-terminal extensions. These extensions appear to be important for some subfamily function, including E2 localisation and protein-protein interactions [ 5 ]. In addition, there are proteins with an E2-like fold that are devoid of catalytic activity (such as protein crossbronx from flies), but which appear to assist in poly-ubiquitin chain formation.

1. Ubiquitin-conjugating enzymes: novel regulators of eukaryotic cells. Trends Biochem. Sci. 15, 195-8
2. Genetic analysis of the ubiquitin system. Biochim. Biophys. Acta 1089, 127-39
3. The ubiquitin pathway for protein degradation. Trends Biochem. Sci. 16, 265-8
4. Getting into position: the catalytic mechanisms of protein ubiquitylation. Biochem. J. 379, 513-25
5. Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import. J. Cell Biol. 167, 649-59