5lru

Structural highlights

Function

[OTU7B_HUMAN] Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Negatively regulates mucosal immunity against infections. Mediates deubiquitination of EGFR. Has deubiquitinating activity toward 'Lys-11', 'Lys-48' or 'Lys-63'-linked polyubiquitin chains. In vitro, has preference for 'Lys-11'-linked polyubiquitin chains; however such data are unsure in vivo. Hydrolyzes both linear and branched forms of polyubiquitin.^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Evans PC, Taylor ER, Coadwell J, Heyninck K, Beyaert R, Kilshaw PJ. Isolation and characterization of two novel A20-like proteins. Biochem J. 2001 Aug 1;357(Pt 3):617-23. PMID:11463333
2. ↑ Evans PC, Smith TS, Lai MJ, Williams MG, Burke DF, Heyninck K, Kreike MM, Beyaert R, Blundell TL, Kilshaw PJ. A novel type of deubiquitinating enzyme. J Biol Chem. 2003 Jun 20;278(25):23180-6. Epub 2003 Apr 7. PMID:12682062 doi:http://dx.doi.org/10.1074/jbc.M301863200
3. ↑ Enesa K, Zakkar M, Chaudhury H, Luong le A, Rawlinson L, Mason JC, Haskard DO, Dean JL, Evans PC. NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling. J Biol Chem. 2008 Mar 14;283(11):7036-45. doi: 10.1074/jbc.M708690200. Epub 2008 , Jan 4. PMID:18178551 doi:http://dx.doi.org/10.1074/jbc.M708690200
4. ↑ Bremm A, Freund SM, Komander D. Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne. Nat Struct Mol Biol. 2010 Aug;17(8):939-47. Epub 2010 Jul 11. PMID:20622874 doi:10.1038/nsmb.1873
5. ↑ Pareja F, Ferraro DA, Rubin C, Cohen-Dvashi H, Zhang F, Aulmann S, Ben-Chetrit N, Pines G, Navon R, Crosetto N, Kostler W, Carvalho S, Lavi S, Schmitt F, Dikic I, Yakhini Z, Sinn P, Mills GB, Yarden Y. Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. Oncogene. 2012 Oct 25;31(43):4599-608. doi: 10.1038/onc.2011.587. Epub 2011 Dec, 19. PMID:22179831 doi:http://dx.doi.org/10.1038/onc.2011.587
6. ↑ Mevissen TE, Hospenthal MK, Geurink PP, Elliott PR, Akutsu M, Arnaudo N, Ekkebus R, Kulathu Y, Wauer T, El Oualid F, Freund SM, Ovaa H, Komander D. OTU Deubiquitinases Reveal Mechanisms of Linkage Specificity and Enable Ubiquitin Chain Restriction Analysis. Cell. 2013 Jul 3;154(1):169-84. doi: 10.1016/j.cell.2013.05.046. PMID:23827681 doi:10.1016/j.cell.2013.05.046