2l80

Structural highlights

Function

UBP13_HUMAN Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy and endoplasmic reticulum-associated degradation (ERAD). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Has a weak deubiquitinase activity in vitro and preferentially cleaves 'Lys-63'-linked polyubiquitin chains. In contrast to USP5, it is not able to mediate unanchored polyubiquitin disassembly. Able to cleave ISG15 in vitro; however, additional experiments are required to confirm such data.^{[1] [2] [3] [4] [5] [6]}

See Also

• Thioesterase 3D structures

References

1. ↑ Catic A, Fiebiger E, Korbel GA, Blom D, Galardy PJ, Ploegh HL. Screen for ISG15-crossreactive deubiquitinases. PLoS One. 2007 Jul 25;2(7):e679. PMID:17653289 doi:http://dx.doi.org/10.1371/journal.pone.0000679
2. ↑ Liu J, Xia H, Kim M, Xu L, Li Y, Zhang L, Cai Y, Norberg HV, Zhang T, Furuya T, Jin M, Zhu Z, Wang H, Yu J, Li Y, Hao Y, Choi A, Ke H, Ma D, Yuan J. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell. 2011 Sep 30;147(1):223-34. doi: 10.1016/j.cell.2011.08.037. PMID:21962518 doi:http://dx.doi.org/10.1016/j.cell.2011.08.037
3. ↑ Scortegagna M, Subtil T, Qi J, Kim H, Zhao W, Gu W, Kluger H, Ronai ZA. USP13 enzyme regulates Siah2 ligase stability and activity via noncatalytic ubiquitin-binding domains. J Biol Chem. 2011 Aug 5;286(31):27333-41. doi: 10.1074/jbc.M111.218214. Epub 2011, Jun 9. PMID:21659512 doi:http://dx.doi.org/10.1074/jbc.M111.218214
4. ↑ Zhao X, Fiske B, Kawakami A, Li J, Fisher DE. Regulation of MITF stability by the USP13 deubiquitinase. Nat Commun. 2011 Aug 2;2:414. doi: 10.1038/ncomms1421. PMID:21811243 doi:http://dx.doi.org/10.1038/ncomms1421
5. ↑ Chen M, Gutierrez GJ, Ronai ZA. Ubiquitin-recognition protein Ufd1 couples the endoplasmic reticulum (ER) stress response to cell cycle control. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9119-24. doi:, 10.1073/pnas.1100028108. Epub 2011 May 13. PMID:21571647 doi:http://dx.doi.org/10.1073/pnas.1100028108
6. ↑ Zhang YH, Zhou CJ, Zhou ZR, Song AX, Hu HY. Domain analysis reveals that a deubiquitinating enzyme USP13 performs non-activating catalysis for Lys63-linked polyubiquitin. PLoS One. 2011;6(12):e29362. Epub 2011 Dec 28. PMID:22216260 doi:10.1371/journal.pone.0029362