monoubiquitine

Monoubiquitin refers to the attachment of a single ubiquitin molecule to a substrate protein, typically on a lysine residue or, less commonly, on the N-terminus. Ubiquitin is a small, highly conserved 76‑amino‑acid protein that can be covalently linked to target proteins. Monoubiquitination is distinct from polyubiquitination, in which ubiquitin molecules form chains on a substrate; however, a substrate can also undergo multi-monoubiquitination, where several single ubiquitins are attached at different sites.

The conjugation of ubiquitin to substrates follows the ubiquitin‑proteasome system: an E1 activating enzyme, an E2 conjugating enzyme, and an E3 ligase that provides substrate specificity. Deubiquitinating enzymes (DUBs) can remove ubiquitin. Monoubiquitination is often nondegradative and serves to regulate protein activity, interactions, localization, or stability. It frequently plays roles in membrane trafficking, endocytosis, and sorting of surface receptors, as well as in chromatin biology, where histone H2A and H2B monoubiquitination influences chromatin structure and gene expression. It also participates in DNA damage responses and various signaling pathways.

In some cases, monoubiquitination acts as a primer that enables subsequent polyubiquitination or other forms of ubiquitin signaling. The reversibility of monoubiquitination, mediated by DUBs, allows dynamic regulation in response to cellular conditions. Dysregulation of ubiquitination processes has been linked to multiple diseases, including cancer and neurodegenerative disorders, underscoring the importance of precise control of monoubiquitination in cell biology.