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Structural highlights

Function

UCHL3_HUMAN Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders.^{[1] [2] [3] [4] [5]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Thioesterase 3D structures

References

1. ↑ Wilkinson KD, Lee KM, Deshpande S, Duerksen-Hughes P, Boss JM, Pohl J. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science. 1989 Nov 3;246(4930):670-3. PMID:2530630
2. ↑ Wada H, Kito K, Caskey LS, Yeh ET, Kamitani T. Cleavage of the C-terminus of NEDD8 by UCH-L3. Biochem Biophys Res Commun. 1998 Oct 29;251(3):688-92. PMID:9790970 doi:S0006-291X(98)99532-8
3. ↑ Setsuie R, Sakurai M, Sakaguchi Y, Wada K. Ubiquitin dimers control the hydrolase activity of UCH-L3. Neurochem Int. 2009 May-Jun;54(5-6):314-21. doi: 10.1016/j.neuint.2008.12.013., Epub 2008 Dec 25. PMID:19154770 doi:http://dx.doi.org/10.1016/j.neuint.2008.12.013
4. ↑ Dennissen FJ, Kholod N, Hermes DJ, Kemmerling N, Steinbusch HW, Dantuma NP, van Leeuwen FW. Mutant ubiquitin (UBB+1) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3). FEBS Lett. 2011 Aug 19;585(16):2568-74. doi: 10.1016/j.febslet.2011.06.037. Epub , 2011 Jul 6. PMID:21762696 doi:http://dx.doi.org/10.1016/j.febslet.2011.06.037
5. ↑ Iphofer A, Kummer A, Nimtz M, Ritter A, Arnold T, Frank R, van den Heuvel J, Kessler BM, Jansch L, Franke R. Profiling ubiquitin linkage specificities of deubiquitinating enzymes with branched ubiquitin isopeptide probes. Chembiochem. 2012 Jul 9;13(10):1416-20. doi: 10.1002/cbic.201200261. Epub 2012, Jun 11. PMID:22689415 doi:10.1002/cbic.201200261