Ubiquitin may be a small regulatory protein found in most tissues of eukaryotic organisms, i.e. it occurs ubiquitously. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the 1970s and 1980s. Four genes within the human
genome code for ubiquitin: UBB, UBC, UBA52, and RPS27A. The addition of
ubiquitin to a substrate protein is named ubiquitination (or, less frequently, ubiquitylation or ubiquitinylation). Ubiquitination affects proteins in many ways: it can mark them for degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions. Ubiquitination involves three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating
enzymes (E1s), ubiquitin-conjugating
enzymes (E2s), and
ubiquitin ligases (E3s), respectively. The results of this sequential cascade are to bind
ubiquitin to lysine residues on the protein substrate via an isopeptide bond, cysteine residues through a thioester bond, serine and threonine residues through an ester bond, or the amino of the protein's N-terminus via a peptide linkage.
Relevant Topics in Medical Sciences
