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Ubiquitin is a highly conserved protein that is required for ATP-dependent, nonlysosomal intracellular protein degradation of abnormal proteins and normal proteins with a rapid turnover. Ubiquitin becomes covalently linked to itself and/or other proteins either as a single molecule or as poly-ubiquitin chains. The attachment of ubiquitin to the e-amine of lysine residues of target proteins requires a series of ATP-dependent enzymatic steps by E1 (ubiquitin activating), E2 (ubiquitin conjugating) and E3 (ubiquitin ligating) enzymes. The C-terminal Gly75-Gly76 residues of ubiquitin are the key residues that function in the diverse chemistry of ubiquitin reactions. Ubiquitin can be conjugated to itself via specific lysine (K6, K11, K27, K29, K33, K48 or K63) residues which results in diverse types of chain linkages. These covalent ubiquitin bonds (isopeptide linkages) can be reversed by specific deubiquitinating enzymes which remove ubiquitin conjugates from proteins and disassemble ubiquitin chains.

Ubiquitin+1 has a carboxyl terminal amino acid sequence that differs from normal ubiquitin due to a frame shift mutation in the mRNA. This ubiquitin+1 form has been noticed in patients with Alzheimers and Downs syndrome.