Figure 2.

The canonical pathway of protein ubiquitination for degradation in the 26S proteasome. 1: ATP-dependent activation of the ubiquitin (Ub) by ubiquitin-activating enzyme (Uba). 2: Transfer of the activated ubiquitin to ubiquitin-conjugating enzyme (Ubc). 3: Binding of ubiquitin–protein ligase (ubiquitin-recognizing factor, Ubr), containing the homologous to E6AP carboxyl terminus (HECT) domain, to the ubiquitin and target protein. 4: Covalent attachment of the ubiquitin molecule to the target protein. 5: Building of the ubiquitin chain with the formation of isopeptide bonds Lys48-Gly76. 6: Completion of the labeling of the target protein with a structure of four (or more) ubiquitin molecules recognized by the 26S proteasome.