Ubiquitin-conjugating enzymes (EC 2.3.2.23) (UBC or E2 enzymes) [1,2,3,4] catalyze the covalent attachment of ubiquitin to target proteins. Ubiquitin is conjugated to the target protein through the coordinated action of three enzyme activities designated E1, E2, and E3. The E1 or ubiquitin-activating enzyme (see <PDOC00463>) forms, in an ATP-dependent manner, a thioester linkage between its active site cysteine and the carboxy terminus of ubiquitin. The activated ubiquitin moiety is then transferred from E1 to the active site cysteine in E2 through a trans-thiol esterification reaction. The UBC enzyme later ligates ubiquitin directly to substrate proteins with or without the assistance of 'N-end' recognizing proteins (E3).

In most species there are many forms of UBC (at least 9 in yeast) which are implicated in diverse cellular functions.

The UBC core is an α/β domain containing one four-stranded antiparallel β-sheet and four α-helices (see <PDB:2E2C>). Three of these helices flank two opposite edges of the sheet, and one helix lays diagonally across one broad face of the sheet. The other face of the sheet is exposed to solvent. One turn of a 3(10)-helix is located between the fourth strand of the sheet and the second α-helix. The active site cysteine is situated in a segment between the fourth strand of the sheet and the 3(10)-helix [4].

We have used the region around the active site cysteine as a signature pattern. We also developed a profile that spans the complete catalytic core domain.