Ubiquitin is a small regulatory protein found in most tissues of eukaryotic organisms,i.e.,it is found ubiquitously. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin:UBB,UBC,UBA52 and RPS27A.
Deubiquitinating enzymes (DUBs),also known as deubiquitinating peptidases,deubiquitinating isopeptidases,deubiquitinases,ubiquitin proteases,ubiquitin hydrolases,or ubiquitin isopeptidases,are a large group of proteases that cleave ubiquitin from proteins. 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. 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.
NEDD8 is a protein that in humans is encoded by the NEDD8 gene. This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins,in a process called NEDDylation similar to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases,which are active only when NEDDylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex,thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation.
Polyubiquitin-C is a protein encoded by the UBC gene in humans. Polyubiquitin-C is one of the sources of ubiquitin,along with UBB,UBA52,and RPS27A.
Ubiquitin-specific-processing protease 7 (USP7),also known as ubiquitin carboxyl-terminal hydrolase 7 or herpesvirus-associated ubiquitin-specific protease (HAUSP),is an enzyme that in humans is encoded by the USP7 gene.
Ubiquitin specific peptidase 5 is an enzyme that in humans is encoded by the USP5 gene.
Probable ubiquitin carboxyl-terminal hydrolase FAF-X is an enzyme that in humans is encoded by the USP9X gene.
Ubiquitin carboxyl-terminal hydrolase 8 is an enzyme that in humans is encoded by the USP8 gene.
Ubiquitin carboxyl-terminal hydrolase 6 (USB6),also termed TRE17 and Tre-2,is a deubiquitinating enzyme that in humans is encoded by the hominid USP6 gene located at band 13.2 on the short arm of chromosome 17. Deubiquitinating enzymes (DUBs) are enzymes that act within cells to remove ubiquitins from various functionally important proteins. Ubiquitin enzymes add ubiquitin to these proteins and thereby regulate their cellular location,alter their activity,and/or promote their degradation. By deubiquitinating these proteins,DUBs counter the effects of the ubiquinating enzymes and contribute to regulating the actions of the targeted proteins. In normal adult tissues,USP6 is highly expressed in testicle tissue,modestly expressed in ovarian tissue,and absent or minimally expressed in other tissues. It is also highly expressed in fetal brain tissue. The specific functions of USP6 are poorly defined primarily because its presence is restricted to primates:there are no available animal models to determine the effects of its deletion,although some studies suggest that UPSP6 contributes to normal brain development. In all events,USP6 has gained wide interest because of its abnormally increased expression by the neoplastic cells in various tumors derived from mesenchymal tissue.
Ubiquitin specific peptidase 10,also known as USP10,is an enzyme which in humans is encoded by the USP10 gene.
Proteasomal ubiquitin receptor ADRM1 is a protein that in humans is encoded by the ADRM1 gene. Recent evidences on proteasome complex structure confirmed that the protein encoded by gene ADRM1,also known in yeast as 26S Proteasome regulatory subunit Rpn13,is a subunit of 19S proteasome complex.
Ubiquitin carboxyl-terminal hydrolase or Ubiquitin specific protease 11 is an enzyme that in humans is encoded by the USP11 gene. USP11 belongs to the Ubiquitin specific proteases family (USPs) which is a sub-family of the Deubiquitinating enzymes (DUBs).USPs are multiple domain proteases and belong to the C19 cysteine proteases sub‒family. Depending on their domain architecture and position there is different homology between the various members. Generally the largest domain is the catalytic domain which harbours the three residue catalytic triad that is included inside conserved motifs. The catalytic domain also contains sequences that are not related with the catalysis function and their role is mostly not clearly understood at present,the length of these sequences varies for each USP and therefore the length of the whole catalytic domain can range from approximately 295 to 850 amino acids. Particular sequences inside the catalytic domain or at the N‒terminus of some USPs have been characterised as UBL and DUSP domains respectively. In some cases,regarding the UBL domains,it has been reported to have a catalysis enhancing function as in the case of USP7. In addition,a so‒called DU domain module is the combination of a DUSP domain followed by a UBL domain separated by a linker and is found in USP11 as well as in USP15 and USP4.
Ubiquitin thioesterase OTUB1 also known as otubain-1 is an enzyme that in humans is encoded by the OTUB1 gene. Alternative splicing results in multiple transcript variants.
Ubiquitin-specific protease 36 is an enzyme that in humans is encoded by the USP36 gene.
BRCA1 associated protein-1 is a deubiquitinating enzyme that in humans is encoded by the BAP1 gene. BAP1 encodes an 80.4 kDa nuclear-localizing protein with a ubiquitin carboxy-terminal hydrolase (UCH) domain that gives BAP1 its deubiquitinase activity. Recent studies have shown that BAP1 and its fruit fly homolog,Calypso,are members of the polycomb-group proteins (PcG) of highly conserved transcriptional repressors required for long-term silencing of genes that regulate cell fate determination,stem cell pluripotency,and other developmental processes.
Ubiquitin carboxyl-terminal hydrolase 2 is an enzyme that in humans is encoded by the USP2 gene.
Ubiquitin-specific protease 14 is an enzyme that in humans is encoded by the USP14 gene.
Ubiquitin carboxyl-terminal hydrolase 20 is an enzyme that in humans is encoded by the USP20 gene.
OTU domain containing 6B is a protein that in humans is encoded by the OTUD6B gene.
The ubiquitin carboxyl-terminal hydrolase 27,also known as deubiquitinating enzyme 27,ubiquitin thioesterase 27 and USP27X,is a deubiquitinating enzyme which is mainly characterized for cleaving ubiquitin (Ub) from proteins and other molecules. Ubiquitin binds to proteins so as to regulate the degradation of them via the proteasome and lysosome among many other functions.
