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Ubiquitin is a small (8.5 kDa) regulatory protein that has been found in almost all tissues (''ubiquitously'') of eukaryotic organisms. It was discovered in 1975〔 by Gideon Goldstein and further characterized throughout the 1970s and 1980s. There are four genes in the human genome that produce ubiquitin: UBB, UBC, UBA52 and RPS27A.〔 The addition of ubiquitin to a substrate protein is called ubiquitination or ubiquitylation. Ubiquitination can affect proteins in many ways: it can signal for their degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions.〔〔〔 Ubiquitination is carried out in three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s), respectively. The result of this sequential cascade binds ubiquitin to lysine residues on the protein substrate via an isopeptide bond or to the amino group of the protein's N-terminus via a peptide bond.〔〔 The protein modifications can be either a single ubiquitin protein (monoubiquitination) or a chain of ubiquitin (polyubiquitination). The ubiquitination bonds are always formed with one of the seven lysine residues from the ubiquitin molecule. These 'linking' lysines are represented by a "K" (which is the one-letter amino acid notation of lysine) and a number, referring to its position in the ubiquitin molecule. First, a ubiquitin molecule is bonded by its C-terminus to a specific lysine residue (e.g. K48, K29, K63,...) on the target protein. Poly-ubiquitination occurs when the C-terminus of another ubiquitin, will be linked again to a lysine residue (for example again K48 or K29) on the previously added ubiquitin molecule, forming a chain. This process repeats several times, leading to the addition of several ubiquitins. Only poly-ubiquitination on defined lysines, mostly on K48 and K29, is related to degradation with the proteasome (referred to as the "molecular kiss of death"), while other polyubiquitinations (e.g. on K63, K11, K6) and monoubiquitinations may regulate processes such as endocytic trafficking, inflammation, translation and DNA repair.〔 Lysine 48-linked chains have been much-studied. They are the forms of chains that signal proteins to the proteasome, which destroys and recycles proteins.〔 This discovery won the Nobel Prize for chemistry in 2004.〔(【引用サイトリンク】 The Nobel Prize in Chemistry 2004 )〕〔(【引用サイトリンク】 The Nobel Prize in Chemistry 2004: Popular Information )〕 ==Identification== Ubiquitin (originally, ubiquitous immunopoietic polypeptide) was first identified in 1975 as an 8.5 kDa protein of unknown function expressed in all eukaryotic cells. The basic functions of ubiquitin and the components of the ubiquitination pathway were elucidated in the early 1980s at the Technion by Aaron Ciechanover, Avram Hershko, and Irwin Rose for which the Nobel Prize in Chemistry was awarded in 2004.〔 The ubiquitination system was initially characterised as an ATP-dependent proteolytic system present in cellular extracts. A heat-stable polypeptide present in these extracts, ATP-dependent proteolysis factor 1 (APF-1), was found to become covalently attached to the model protein substrate lysozyme in an ATP- and Mg2+-dependent process. Multiple APF-1 molecules were linked to a single substrate molecule by an isopeptide linkage, and conjugates were found to be rapidly degraded with the release of free APF-1. Soon after APF-1-protein conjugation was characterised, APF-1 was identified as ubiquitin. The carboxyl group of the C-terminal glycine residue of ubiquitin (Gly76) was identified as the moiety conjugated to substrate lysine residues. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Ubiquitin」の詳細全文を読む スポンサード リンク
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