Deubiquitinating enzyme

USP21 (blue) covalently linked to linear diubiquitin aldehyde (green). The C-terminus of the ubiquitin protrudes through the active site of USP21 (lower right).
Ubiquitin-AMC,a fluorogenic substrate for a wide range of DUBs

Deubiquitinating enzymes (DUBs), also known as deubiquitinating peptidases, deubiquitinating isopeptidases, deubiquitinases, ubiquitin proteases, ubiquitin hydrolases, or ubiquitin isopeptidases, are a large group of proteases[1] that cleave ubiquitin from proteins.[2] Ubiquitin is attached to proteins in order to regulate the degradation of proteins via the proteasome and lysosome; coordinate the cellular localisation of proteins; activate and inactivate proteins; and modulate protein-protein interactions.[3][4][5] DUBs can reverse these effects by cleaving the peptide or isopeptide bond between ubiquitin and its substrate protein. In humans there are nearly 100 DUB genes, which can be classified into two main classes: cysteine proteases and metalloproteases. The cysteine proteases comprise ubiquitin-specific proteases (USPs), ubiquitin C-terminal hydrolases (UCHs), Machado-Josephin domain proteases (MJDs) and ovarian tumour proteases (OTU). The metalloprotease group contains only the Jab1/Mov34/Mpr1 Pad1 N-terminal+ (MPN+) (JAMM) domain proteases.[2]

  1. ^ Wilkinson KD (December 1997). "Regulation of ubiquitin-dependent processes by deubiquitinating enzymes". FASEB Journal. 11 (14): 1245–56. doi:10.1096/fasebj.11.14.9409543. PMID 9409543. S2CID 11788220.
  2. ^ a b Reyes-Turcu FE, Ventii KH, Wilkinson KD (2009). "Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes". Annual Review of Biochemistry. 78: 363–97. doi:10.1146/annurev.biochem.78.082307.091526. PMC 2734102. PMID 19489724.
  3. ^ Glickman MH, Ciechanover A (April 2002). "The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction". Physiological Reviews. 82 (2): 373–428. doi:10.1152/physrev.00027.2001. PMID 11917093.
  4. ^ Mukhopadhyay D, Riezman H (January 2007). "Proteasome-independent functions of ubiquitin in endocytosis and signaling". Science. 315 (5809): 201–5. Bibcode:2007Sci...315..201M. doi:10.1126/science.1127085. PMID 17218518. S2CID 35434448.
  5. ^ Schnell JD, Hicke L (September 2003). "Non-traditional functions of ubiquitin and ubiquitin-binding proteins". The Journal of Biological Chemistry. 278 (38): 35857–60. doi:10.1074/jbc.R300018200. PMID 12860974.