monoubiquitination

Monoubiquitination is a post-translational modification in which a single ubiquitin molecule is covalently attached to a substrate protein. This attachment most commonly occurs on the ε-amino group of a lysine residue, though in rare cases ubiquitin can be linked to the N-terminus of a protein. It is distinct from polyubiquitination, where ubiquitin molecules form chains, and from multi-monoubiquitination, where single ubiquitins are attached to multiple lysines on the same substrate.

The modification is mediated by a cascade of enzymes: an E1 ubiquitin-activating enzyme activates ubiquitin in an ATP-dependent step, an E2 ubiquitin-conjugating enzyme carries the activated ubiquitin, and an E3 ubiquitin ligase transfers ubiquitin from the E2 to the substrate. E3 ligases confer substrate specificity and exist in several families, including RING, HECT, and RBR types. Deubiquitinating enzymes (DUBs) can remove ubiquitin and reverse the modification.

Monoubiquitination often serves regulatory roles rather than serving as a degradation signal. It can alter substrate activity, interaction partners, localization, or stability, and it frequently regulates trafficking and signaling pathways. Notable examples include PCNA monoubiquitination at lysine 164, which promotes translesion synthesis in DNA damage response, and histone H2B monoubiquitination, which participates in transcriptional regulation and chromatin dynamics. In membrane trafficking, monoubiquitination can mark receptors and transporters for endocytosis and endosomal sorting.

In summary, monoubiquitination is a versatile, reversible tag that modulates diverse cellular processes by signaling protein function and localization through the attachment of a single ubiquitin molecule.