Ubiquitin (Ub) was first identified in 1975 as a 76 amino acid protein that is highly conserved in all eukaryotic cells. Ubiquitin requires three-types of enzyme to conjugate to other proteins: Ub-activating enzyme (E1), Ub-conjugating enzymes (E2), and Ub-ligases (E3). Ubiquitin can be covalently attached to lysine (Lys) residues of target proteins either as a monomer (monoubiquitin), a polymer (polyubiquitin chains) or a linear polymer (linear polyubiquitin chains). All seven Lys residues (Lys6, Lys11, Lys27, Lys29, Lys33, Lys48, and Lys63) can be ubiquitinated.