6gf2

Structural highlights

Function

[UBD_HUMAN] Ubiquitin-like protein modifier which can be covalently attached to target protein and subsequently leads to their degradation by the 26S proteasome, in a NUB1L-dependent manner. Probably functions as a survival factor. Conjugation ability activated by UBA6. Promotes the expression of the proteasome subunit beta type-9 (PSMB9/LMP2). Regulates TNF-alpha-induced and LPS-mediated activation of the central mediator of innate immunity NF-kappa-B by promoting TNF-alpha-mediated proteasomal degradation of ubiquitinated-I-kappa-B-alpha. Required for TNF-alpha-induced p65 nuclear translocation in renal tubular epithelial cells (RTECs). May be involved in dendritic cell (DC) maturation, the process by which immature dendritic cells differentiate into fully competent antigen-presenting cells that initiate T-cell responses. Mediates mitotic non-disjunction and chromosome instability, in long-term in vitro culture and cancers, by abbreviating mitotic phase and impairing the kinetochore localization of MAD2L1 during the prometaphase stage of the cell cycle. May be involved in the formation of aggresomes when proteasome is saturated or impaired. Mediates apoptosis in a caspase-dependent manner, especially in renal epithelium and tubular cells during renal diseases such as polycystic kidney disease and Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

References

1. ↑ Hipp MS, Kalveram B, Raasi S, Groettrup M, Schmidtke G. FAT10, a ubiquitin-independent signal for proteasomal degradation. Mol Cell Biol. 2005 May;25(9):3483-91. PMID:15831455 doi:http://dx.doi.org/10.1128/MCB.25.9.3483-3491.2005
2. ↑ Ross MJ, Wosnitzer MS, Ross MD, Granelli B, Gusella GL, Husain M, Kaufman L, Vasievich M, D'Agati VD, Wilson PD, Klotman ME, Klotman PE. Role of ubiquitin-like protein FAT10 in epithelial apoptosis in renal disease. J Am Soc Nephrol. 2006 Apr;17(4):996-1004. Epub 2006 Feb 22. PMID:16495380 doi:http://dx.doi.org/10.1681/ASN.2005070692
3. ↑ Ren J, Kan A, Leong SH, Ooi LL, Jeang KT, Chong SS, Kon OL, Lee CG. FAT10 plays a role in the regulation of chromosomal stability. J Biol Chem. 2006 Apr 21;281(16):11413-21. Epub 2006 Feb 22. PMID:16495226 doi:http://dx.doi.org/10.1074/jbc.M507218200
4. ↑ Chiu YH, Sun Q, Chen ZJ. E1-L2 activates both ubiquitin and FAT10. Mol Cell. 2007 Sep 21;27(6):1014-23. PMID:17889673 doi:http://dx.doi.org/10.1016/j.molcel.2007.08.020
5. ↑ Kalveram B, Schmidtke G, Groettrup M. The ubiquitin-like modifier FAT10 interacts with HDAC6 and localizes to aggresomes under proteasome inhibition. J Cell Sci. 2008 Dec 15;121(Pt 24):4079-88. doi: 10.1242/jcs.035006. Epub 2008, Nov 25. PMID:19033385 doi:http://dx.doi.org/10.1242/jcs.035006
6. ↑ Lukasiak S, Schiller C, Oehlschlaeger P, Schmidtke G, Krause P, Legler DF, Autschbach F, Schirmacher P, Breuhahn K, Groettrup M. Proinflammatory cytokines cause FAT10 upregulation in cancers of liver and colon. Oncogene. 2008 Oct 9;27(46):6068-74. doi: 10.1038/onc.2008.201. Epub 2008 Jun 23. PMID:18574467 doi:http://dx.doi.org/10.1038/onc.2008.201
7. ↑ Schmidtke G, Kalveram B, Groettrup M. Degradation of FAT10 by the 26S proteasome is independent of ubiquitylation but relies on NUB1L. FEBS Lett. 2009 Feb 4;583(3):591-4. doi: 10.1016/j.febslet.2009.01.006. Epub 2009, Jan 21. PMID:19166848 doi:http://dx.doi.org/10.1016/j.febslet.2009.01.006
8. ↑ Ebstein F, Lange N, Urban S, Seifert U, Kruger E, Kloetzel PM. Maturation of human dendritic cells is accompanied by functional remodelling of the ubiquitin-proteasome system. Int J Biochem Cell Biol. 2009 May;41(5):1205-15. doi:, 10.1016/j.biocel.2008.10.023. Epub 2008 Nov 5. PMID:19028597 doi:http://dx.doi.org/10.1016/j.biocel.2008.10.023
9. ↑ Snyder A, Alsauskas Z, Gong P, Rosenstiel PE, Klotman ME, Klotman PE, Ross MJ. FAT10: a novel mediator of Vpr-induced apoptosis in human immunodeficiency virus-associated nephropathy. J Virol. 2009 Nov;83(22):11983-8. doi: 10.1128/JVI.00034-09. Epub 2009 Sep 2. PMID:19726511 doi:http://dx.doi.org/10.1128/JVI.00034-09
10. ↑ Gong P, Canaan A, Wang B, Leventhal J, Snyder A, Nair V, Cohen CD, Kretzler M, D'Agati V, Weissman S, Ross MJ. The ubiquitin-like protein FAT10 mediates NF-kappaB activation. J Am Soc Nephrol. 2010 Feb;21(2):316-26. doi: 10.1681/ASN.2009050479. Epub 2009, Dec 3. PMID:19959714 doi:http://dx.doi.org/10.1681/ASN.2009050479