Function
Ubiquitin exists in two forms: covalently attached to another protein or free (unanchored). Covalent attachment involves conjugation to target proteins via an isopeptide bond, forming either monoubiquitin (a monomer), polyubiquitin chains (polymers linked via different lysine (Lys) residues of ubiquitin), or linear polyubiquitin chains (polymers linked via the initiator methionine (Met) of ubiquitin). The function of polyubiquitin chains depends on the linked Lys residue: Lys-11 is involved in endoplasmic reticulum-associated degradation (ERAD) and cell-cycle regulation; Lys-29 in lysosomal degradation; Lys-33 in kinase modification; Lys-48 in proteasomal protein degradation; and Lys-63 in endocytosis and DNA damage responses. Linear chains, linked via Met, participate in cell signaling. While ubiquitin typically conjugates to Lys residues of target proteins, rare instances of conjugation to cysteine (Cys) or serine (Ser) residues have been reported. Unanchored polyubiquitin also plays distinct roles, including activation of protein kinases and signaling. Ubiquitin is also a component of the 60S ribosomal subunit.