PROSITE documentation PDOC00163
Ubiquitin-conjugating (UBC) active site signature and core domain profile


Ubiquitin-conjugating enzymes (EC (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.

Expert(s) to contact by email:

Jentsch S.

Last update:

April 2020 / Profile and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

UBC_2, PS50127; Ubiquitin-conjugating (UBC) core domain profile  (MATRIX)

UBC_1, PS00183; Ubiquitin-conjugating (UBC) active site signature  (PATTERN)


1AuthorsJentsch S. Seufert W. Sommer T. Reins H.-A.
TitleUbiquitin-conjugating enzymes: novel regulators of eukaryotic cells.
SourceTrends Biochem. Sci. 15:195-198(1990).
PubMed ID2193438

2AuthorsJentsch S. Seufert W. Hauser H.-P.
TitleGenetic analysis of the ubiquitin system.
SourceBiochim. Biophys. Acta 1089:127-139(1991).
PubMed ID1647207

3AuthorsHershko A.
TitleThe ubiquitin pathway for protein degradation.
SourceTrends Biochem. Sci. 16:265-268(1991).
PubMed ID1656558

4AuthorsJiang F. Basavappa R.
TitleCrystal structure of the cyclin-specific ubiquitin-conjugating enzyme from clam, E2-C, at 2.0 A resolution.
SourceBiochemistry 38:6471-6478(1999).
PubMed ID10350465

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)