E3 Ubiquitin Ligases
An ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2
ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a
protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the
E2 to the protein substrate. The ubiquitin protein is linked to lysine from target
protein by ISO peptide bond. E3 ligase interacts with target protein and E2 enzyme,
thus giving E2 substrate specificity.
Usually, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin,
targeting substrates to be destroyed by proteasomes. However, many other types of
connections are possible and change the activity, interaction, or localization of
proteins. The ubiquitination of E3 ligase regulates many regions, such as cell
transport, DNA repair, and signal transduction, and is important in cell biology. E3
ligase is also a key participant in cell cycle control, mediating the degradation of
cyclin and cyclin-dependent kinase inhibitor protein. The human genome encodes
more than 600 putative E3 ligase, which makes the substrate have enormous
diversity.