Deubiquitinating enzyme: Difference between revisions
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'''Deubiquitinating enzymes''' (DUBs) are a large group of [[protease]]s<ref>{{cite journal |author=Wilkinson K |title=Regulation of ubiquitin-dependent processes by deubiquitinating enzymes |journal=FASEB J. |volume=11 |issue=14 |pages=1245–56 |year=1997 |pmid=9409543}}</ref> (more than 60 known) that regulate [[ubiquitin]]-dependent metabolic pathways by cleaving ubiquitin-protein bonds. DUBs are also commonly referred to as deubiquitinating peptidases, deubiquitinating isopeptidases, deubiquitinases, ubiquitin proteases, ubiquitin hydrolyases, ubiquitin isopeptidases, or DUbs. The human genome encodes nearly 100 DUBs with specificity for ubiquitin in five gene families.<ref name="Turcu">{{cite journal | author=Reyes Turcu FE, Ventii KH, Wilkinson KD | title=Activity and Cellular Roles of Ubiquitin-Specific Deubiquitinating Enzymes | journal=Annual Review of Biochemistry | year=2009| volume=78 | doi=10.1146/annurev.biochem.78.082307.091526 | pmid=19489724 | pages=363–97 | pmc=2734102}}</ref> Potentially, DUBs may act as negative and positive regulators of the ubiquitin system. In addition to ubiquitin recycling, they are involved in processing of ubiquitin precursors, in proofreading of protein ubiquitination and in disassembly of inhibitory ubiquitin chains. |
'''Deubiquitinating enzymes''' (DUBs) are a large group of [[protease]]s<ref>{{cite journal |author=Wilkinson K |title=Regulation of ubiquitin-dependent processes by deubiquitinating enzymes |journal=FASEB J. |volume=11 |issue=14 |pages=1245–56 |year=1997 |pmid=9409543}}</ref> (more than 60 known) that regulate [[ubiquitin]]-dependent metabolic pathways by cleaving ubiquitin-protein bonds. DUBs are also commonly referred to as deubiquitinating peptidases, deubiquitinating isopeptidases, deubiquitinases, ubiquitin proteases, ubiquitin hydrolyases, ubiquitin isopeptidases, or DUbs. The human genome encodes nearly 100 DUBs with specificity for ubiquitin in five gene families.<ref name="Turcu">{{cite journal | author=Reyes Turcu FE, Ventii KH, Wilkinson KD | title=Activity and Cellular Roles of Ubiquitin-Specific Deubiquitinating Enzymes | journal=Annual Review of Biochemistry | year=2009| volume=78 | doi=10.1146/annurev.biochem.78.082307.091526 | pmid=19489724 | pages=363–97 | pmc=2734102}}</ref> Potentially, DUBs may act as negative and positive regulators of the ubiquitin system. In addition to ubiquitin recycling, they are involved in processing of ubiquitin precursors, in proofreading of protein ubiquitination and in disassembly of inhibitory ubiquitin chains. |
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They may be associated with disease.<ref name="pmid19007433">{{cite journal |author=Singhal S, Taylor MC, Baker RT |title=Deubiquitylating enzymes and disease |journal=BMC Biochem. |volume=9 Suppl 1 |issue= |pages=S3 |year=2008 |pmid=19007433 |pmc=2582804 |doi=10.1186/1471-2091-9-S1-S3 |url=http://www.biomedcentral.com/1471-2091/9%20Suppl%201/S3}}</ref> |
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== Classes == |
== Classes == |
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Revision as of 05:37, 21 December 2010
Deubiquitinating enzymes (DUBs) are a large group of proteases[1] (more than 60 known) that regulate ubiquitin-dependent metabolic pathways by cleaving ubiquitin-protein bonds. DUBs are also commonly referred to as deubiquitinating peptidases, deubiquitinating isopeptidases, deubiquitinases, ubiquitin proteases, ubiquitin hydrolyases, ubiquitin isopeptidases, or DUbs. The human genome encodes nearly 100 DUBs with specificity for ubiquitin in five gene families.[2] Potentially, DUBs may act as negative and positive regulators of the ubiquitin system. In addition to ubiquitin recycling, they are involved in processing of ubiquitin precursors, in proofreading of protein ubiquitination and in disassembly of inhibitory ubiquitin chains.
They may be associated with disease.[3]
Classes
DUBs can be classified into two main classes: cysteine proteases and metalloproteases.
Cysteine proteases
There are four main superfamilies of cysteine protease DUBs:
- the ubiquitin-specific processing protease (USP/UBP) superfamily; (USP1, USP2, USP3, USP4, USP5, USP6, USP7, USP8, USP9X, USP9Y, USP10, USP11, USP12, USP13, USP14, USP15, USP16, USP17, USP17L2, USP17L3, USP17L4, USP17L5, USP17L7, USP17L8, USP18, USP19, USP20, USP21, USP22, USP23, USP24, USP25, USP26, USP27X, USP28, USP29, USP30, USP31, USP32, USP33, USP34, USP35, USP36, USP37, USP38, USP39, USP40, USP41, USP42, USP43, USP44, USP45, USP46)
- the ubiquitin C-terminal hydrolyase (UCH) superfamily; (UCHH2, UCHL1, UCHL3)
- the ovarian tumour (OTU) superfamily; and the Machado-Josephin domain (MJD) superfamily. (OTUB1, OTUB2, ATXN3, ATXN3L)
However, there is also a little known putative group of DUBs called the permutated papain fold peptidases of dsDNA viruses and eukaryote (PPPDEs) superfamily, which, if shown to be bona fide DUBs, would be the fifth in the cysteine protease class.[4]
Metalloproteases
The Jab1/Mov34/Mpr1 Pad1 N-terminal+ (MPN+) (JAMM) domain superfamily proteins bind zinc and hence are metalloproteases.
Role in the ubiquitin pathway
DUBs play several roles in the ubiquitin pathway. First, DUBs carry out activation of the ubiquitin proproteins, probably cotranslationally. Second, DUBs recycle ubiquitin that may have been accidentally trapped by the reaction of small cellular nucleophiles with the thiol ester intermediates involved in the ubiquitination of proteins. Third, DUBs reverse the ubiquitination or ubiquitin-like modification of target proteins. Finally, DUBs are also responsible for the regeneration of monoubiquitin from unanchored polyubiquitin, i.e., free polyubiquitin that is synthesized de novo by the conjugating machinery or that has been released from target proteins by other DUBs.[2]
References
- ^ Wilkinson K (1997). "Regulation of ubiquitin-dependent processes by deubiquitinating enzymes". FASEB J. 11 (14): 1245–56. PMID 9409543.
- ^ a b Reyes Turcu FE, Ventii KH, Wilkinson KD (2009). "Activity 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Singhal S, Taylor MC, Baker RT (2008). "Deubiquitylating enzymes and disease". BMC Biochem. 9 Suppl 1: S3. doi:10.1186/1471-2091-9-S1-S3. PMC 2582804. PMID 19007433.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Iyer LM, Koonin EV, Aravind L (2004). "Novel predicted peptidases with a potential role in the ubiquitin signaling system". Cell Cycle. 3: 1440–50. PMID 15483401.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
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