Ubiquitylation

Ubiquitylation

Ubiquitylation (also known as ubiquitination or ubiquitinylation) is an enzymatic post-translational modification in which a ubiquitin moiety is attached to a substrate protein. This process most commonly binds the last amino acid of ubiquitin (glycine 76) to a lysine residue on the substrate. An isopeptide bond is formed between the carboxyl group (COO) of the ubiquitin's glycine and the epsilon-amino group (ε-NH
₃) of the substrate's lysine. Trypsin cleavage of a ubiquitin-conjugated substrate leaves a di-glycine "remnant" that is used to identify the site of ubiquitylation. Ubiquitin can also be bound to other sites in a protein which are electron-rich nucleophiles, termed "non-canonical ubiquitylation". This was first observed with the amine group of a protein's N-terminus being used for ubiquitylation, rather than a lysine residue, in the protein MyoD and has been observed since in 22 other proteins in multiple species, including ubiquitin itself. There is also increasing evidence for non-lysine residues as ubiquitylation targets using non-amine groups, such as the sulfhydryl group on cysteine, and the hydroxyl group on threonine and serine. The end result of this process is the addition of one ubiquitin molecule (monoubiquitylation) or a chain of ubiquitin molecules (polyubiquitination) to the substrate protein.