Ubiquitin-Proteasome Pathway: Polyubiquitination of substrates targets them for degradation by the 26S proteasome. Ubiquitin is an evolutionarily highly conserved 76 amino acid polypeptide that is abundant in all eukaryotic cells. The consecutive addition of ubiquitin moieties to a substrate generates a polyubiquitin chain. The nomenclature of E1, E2, and E3 came from the identification of ubiquitin enzymes in eluates from ubiquitin affinity columns.