A 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.

E3 ligases are critical for modulating cellular homeostasis owning to their efficient regulation and substrate specificity during the cascade of ubiquitination.

The E3 ligases of the HECT (homologous to the E6AP carboxyl terminus) domain family catalyze ubiquitin transfer to the substrate protein through a two-step reaction: ubiquitin is first transferred to a catalytic cysteine on the E3 and then from the E3 to the substrate.

2021年7月30日 · E3 ubiquitin ligases are a large family of enzymes that join in a three-enzyme ubiquitination cascade together with ubiquitin activating enzyme E1 and ubiquitin conjugating enzyme E2.

2017年6月20日 · Ubiquitin E3 ligases control every aspect of eukaryotic biology by promoting protein ubiquitination and degradation. At the end of a three-enzyme cascade, ubiquitin ligases mediate the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to …

2023年11月23日 · We show that BioE3 identifies both known and new targets of two RING-type E3 ligases: RNF4 (DNA damage response, PML bodies), and MIB1 (endocytosis, autophagy, centrosome dynamics). Versatile...

2014年4月4日 · Three distinct classes of E3 ligases have been identified that stimulate transfer of ubiquitin and ubiquitin-like proteins through either a direct or an indirect mechanism. Only...

2016年8月3日 · Ubiquitin ligases (E3s) recruit ubiquitin-conjugating enzyme (E2) ∼ ubiquitin (∼ denotes a thioester linkage; here, the linkage is between the catalytic cysteine of E2 and the carboxyl terminus...

The selectivity of the ubiquitin-26 S proteasome system (UPS) for a particular substrate protein relies on the interaction between a ubiquitin-conjugating enzyme (E2, of which a cell contains relatively few) and a ubiquitin-protein ligase (E3, of which there are possibly hundreds).

E3 ligases show diverse molecular sizes and domain architecture. Both the small RING domain and large CRLs complex catalyze the ubiquitination reaction. This structural diversity is responsible for various ubiquitination signals in the cell. Moreover, multidomain and/or oligomerization of E3 ligases appear to be key.