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.