Background
Ubiquitin (Ub) is a highly conserved 76-amino acid protein that plays a critical role in regulating cellular processes. By covalently attaching to target proteins through a three-step process involving Ub-activating (E1), Ub-conjugating (E2), and Ub-ligating (E3) enzymes, ubiquitination marks the target proteins for proteasomal degradation, modulates membrane protein trafficking, alters protein-protein interactions, and controls the activity of many signal transduction pathways. Ubiquitination occurs through the formation of an isopeptide bond between its C-terminal Gly76 and a lysine residue in the target protein. This process can occur either as a monomer (monoubiquitin) or as a polymer (polyubiquitin chains), where the C-terminus of a chain extending ubiquitin becomes linked to the N-terminus (M1) or one of seven Lys residues (Lys6, Lys11, Lys27, Lys29, Lys33, Lys48, and Lys63) within a substrate-bound ubiquitin molecule, resulting in polyubiquitin chains with different functions. Lys6-linked may be involved in DNA repair; Lys11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys29-linked is involved in lysosomal degradation; Lys33-linked is involved in kinase modification; Lys48-linked is involved in protein degradation via the proteasome; Lys63-linked is involved in endocytosis, and DNA-damage responses.
Cellular location
Nucleus, Cytoplasm
