Table 4.

Ubiquitination involves several enzymes: ubiquitin-activating enzyme (E1), ubiquitin-coupling enzyme (E2), ubiquitin-ligase (E3), and deubiquitination enzyme (DUBs).

Ubiquitin-related enzymes	Effect
E1	E1 activates ubiquitin molecules in an ATP-dependent manner by forming E1-ubiquitin thioesters.
E2	E2 dominates the determination of ubiquitination and polyubiquitination and attaches ubiquitin peptides to the substrate.
E3	E3 determines substrate specificity and covalently binds ubiquitin carried by E2 to the target protein, thereby triggering degradation or modification of the target protein.
DUBs	Reversal of the ubiquitination of the substrate, cutting the ubiquitin chain from the substrate protein into a single reusable ubiquitin fragment.