Gene Symbol: Sirt2
Description: sirtuin 2
Alias: NAD-dependent protein deacetylase sirtuin-2, 5E5 antigen, NAD-dependent deacetylase sirtuin-2, SIR2-like protein 2, regulatory protein SIR2 homolog 2
Species: rat
Products:     Sirt2

Top Publications

  1. Dryden S, Nahhas F, Nowak J, Goustin A, Tainsky M. Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. Mol Cell Biol. 2003;23:3173-85 pubmed
    ..Our functional studies of human SIRT2, a homolog of the product of the yeast SIR2 gene, indicate that it plays a role in mitosis...
  2. North B, Marshall B, Borra M, Denu J, Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003;11:437-44 pubmed
    ..Here, we report that a human ortholog of Sir2p, sirtuin type 2 (SIRT2), is a predominantly cytoplasmic protein that colocalizes with microtubules...
  3. Bae N, Swanson M, Vassilev A, Howard B. Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10. J Biochem. 2004;135:695-700 pubmed
    ..Currently, there is no report on the interacting protein partner of a human Sir2 homolog, SIRT2. Here we show for the first time that SIRT2 interacts with the homeobox transcription factor, HOXA10, which was ..
  4. Yang Y, Chen Y, Zhang C, Nimmakayalu M, Ward D, Weissman S. Cloning and characterization of two mouse genes with homology to the yeast Sir2 gene. Genomics. 2000;69:355-69 pubmed
    ..The two mouse genes have completely different genomic structures but were mapped on the same chromosome. It seems that the two mouse proteins, though they have Sir2 conserved domains, may function differently than yeast Sir2p. ..
  5. Wang Y, Mu Y, Zhou X, Ji H, Gao X, Cai W, et al. SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering FasL-induced cell apoptosis during renal ischemia reperfusion. Apoptosis. 2017;22:519-530 pubmed publisher
    ..Results demonstrated that when SIRT2 was activated by renal ischemia/reperfusion, activated SIRT2 could bind to and deacetylate FOXO3a, promoting ..
  6. Yang W, Guo X, Thein S, Xu F, Sugii S, Baas P, et al. Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of ?-tubulin. Biochem J. 2013;449:605-12 pubmed publisher
    ..Moreover, acetylation of ?-tubulin is under the control of the acetyltransferase MEC-17 and deacetylases SIRT2 (Sirtuin 2) and HDAC6 (histone deacetylase 6)...
  7. Fulco M, Schiltz R, Iezzi S, King M, Zhao P, Kashiwaya Y, et al. Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. Mol Cell. 2003;12:51-62 pubmed
    ..In response to exercise, food intake, and starvation, Sir2 may sense modifications of the redox state and promptly modulate gene expression. ..
  8. Beirowski B, Gustin J, Armour S, Yamamoto H, Viader A, North B, et al. Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. Proc Natl Acad Sci U S A. 2011;108:E952-61 pubmed publisher examine peripheral nerve myelination and identified the NAD(+)-dependent deacetylase Sir-two-homolog 2 (Sirt2) as a protein likely to be involved in myelination...
  9. van der Horst A, Tertoolen L, de Vries Smits L, Frye R, Medema R, Burgering B. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J Biol Chem. 2004;279:28873-9 pubmed
    ..These data demonstrate that acetylation functions in a second pathway of negative control for FOXO factors and provides a novel mechanism whereby hSir2(SIRT1) can promote cellular survival and increase lifespan. ..

More Information


  1. Orpinell M, Fournier M, Riss A, Nagy Z, Krebs A, Frontini M, et al. The ATAC acetyl transferase complex controls mitotic progression by targeting non-histone substrates. EMBO J. 2010;29:2381-94 pubmed publisher
    ..mitotic function: ATAC/Gcn5-mediated acetylation targets Cyclin A for degradation, which in turn regulates the SIRT2 deacetylase activity...
  2. Yin T, Wang P, Li J, Zheng R, Zheng B, Cheng D, et al. Ultrasound-sensitive siRNA-loaded nanobubbles formed by hetero-assembly of polymeric micelles and liposomes and their therapeutic effect in gliomas. Biomaterials. 2013;34:4532-43 pubmed publisher
    ..achieved in a nude mouse glioma model, using siRNA-NBs bearing siRNA to target the anti-apoptosis gene sirtuin 2 (SIRT2)...
  3. Ma B, Shi J, Jia L, Yuan W, Wu J, Fu Z, et al. Over-expression of PUMA correlates with the apoptosis of spinal cord cells in rat neuropathic intermittent claudication model. PLoS ONE. 2013;8:e56580 pubmed publisher
    ..were upregulated significantly in spinal cord under compression, while the expression of p53 inhibitor MDM2 and SirT2 decreased in the same region...
  4. Pizarro J, Folch J, Esparza J, Jordan J, Pallas M, Camins A. A molecular study of pathways involved in the inhibition of cell proliferation in neuroblastoma B65 cells by the GSK-3 inhibitors lithium and SB-415286. J Cell Mol Med. 2009;13:3906-17 pubmed publisher
    ..On the other hand, SB-415286 increased the expression of SIRT2, involved in the regulation of proliferation...
  5. Yamaguchi Y, Miyagi Y, Baba H. Two-dimensional electrophoresis with cationic detergents: a powerful tool for the proteomic analysis of myelin proteins. Part 2: analytical aspects. J Neurosci Res. 2008;86:766-75 pubmed
  6. North B, Verdin E. Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis. PLoS ONE. 2007;2:e784 pubmed
    The human NAD+-dependent protein deacetylase SIRT2 resides predominantly in the cytoplasm where it functions as a tubulin deacetylase...
  7. Jing E, Gesta S, Kahn C. SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab. 2007;6:105-14 pubmed
    The family of mammalian Sirtuin proteins comprises seven members homologous to yeast Sir2. Here we show that SIRT2, a cytoplasmic sirtuin, is the most abundant sirtuin in adipocytes...
  8. Wang F, Nguyen M, Qin F, Tong Q. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell. 2007;6:505-14 pubmed
    ..The mammalian ortholog of Hst2, SIRT2, was shown to co-localize with microtubules and functions as alpha-tubulin deacetylase...
  9. North B, Verdin E. Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent phosphorylation. J Biol Chem. 2007;282:19546-55 pubmed
    ..Here, we demonstrate that SIRT2 is phosphorylated both in vitro and in vivo on serine 368 by the cell-cycle regulator, cyclin-dependent kinase 1, ..
  10. Qin B, Panickar K, Anderson R. Cinnamon polyphenols regulate S100?, sirtuins, and neuroactive proteins in rat C6 glioma cells. Nutrition. 2014;30:210-7 pubmed publisher
  11. Yu W, Zhou H, Lin R, Fu Y, Wang W. Short?term calorie restriction activates SIRT1?4 and ?7 in cardiomyocytes in vivo and in vitro. Mol Med Rep. 2014;9:1218-24 pubmed publisher
    ..This was in contrast with SIRT2, which was detected exclusively in the cytoplasm in rat cardiac tissues, but was found predominantly in the ..
  12. Lin R, Tao R, Gao X, Li T, Zhou X, Guan K, et al. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell. 2013;51:506-518 pubmed publisher
    ..Conversely, the protein deacetylase sirtuin 2 (SIRT2) deacetylates and destabilizes ACLY...
  13. Eskandarian H, Impens F, Nahori M, Soubigou G, Coppee J, Cossart P, et al. A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science. 2013;341:1238858 pubmed publisher
    ..We found that during infection with the bacterium Listeria monocytogenes, the host deacetylase sirtuin 2 (SIRT2) translocates to the nucleus, in a manner dependent on the bacterial factor InlB...
  14. Finnin M, Donigian J, Pavletich N. Structure of the histone deacetylase SIRT2. Nat Struct Biol. 2001;8:621-5 pubmed
    ..The 1.7 A crystal structure of the 323 amino acid catalytic core of human SIRT2, a homolog of yeast Sir2, reveals an NAD-binding domain, which is a variant of the Rossmann fold, and a smaller ..
  15. Binker M, Richards D, Gaisano H, Cosen Binker L. ER stress-associated CTRC mutants decrease stimulated pancreatic zymogen secretion through SIRT2-mediated microtubule dysregulation. Biochem Biophys Res Commun. 2015;463:329-35 pubmed publisher
    ..also reduces the levels of acetylated tubulin by increasing both the levels and phosphorylation of the deacetylase SIRT2. Remarkably, inhibition of SIRT2 not only greatly recovers tubulin acetylation, but also amylase secretion in ..
  16. Yuan Q, Zhan L, Zhou Q, Zhang L, Chen X, Hu X, et al. SIRT2 regulates microtubule stabilization in diabetic cardiomyopathy. Eur J Pharmacol. 2015;764:554-61 pubmed publisher
    ..The present study investigated whether SIRT2, a deacetylase, regulates MT stability through α-tubulin deacetylation in DCM and whether the receptor of ..
  17. Gurd B, Holloway G, Yoshida Y, Bonen A. In mammalian muscle, SIRT3 is present in mitochondria and not in the nucleus; and SIRT3 is upregulated by chronic muscle contraction in an adenosine monophosphate-activated protein kinase-independent manner. Metabolism. 2012;61:733-41 pubmed publisher
  18. Wang F, Chan C, Chen K, Guan X, Lin H, Tong Q. Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. Oncogene. 2012;31:1546-57 pubmed publisher
    ..SIRT1 and SIRT2 deacetylate FOXO factors to regulate FOXO function...
  19. Lynn E, McLeod C, Gordon J, Bao J, Sack M. SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via regulation of 14-3-3 zeta and BAD in H9c2 cells. FEBS Lett. 2008;582:2857-62 pubmed publisher
    Knockdown or inhibition of SIRT2 enhances biological stress-tolerance. We extend this phenotype showing that SIRT2 knockdown reduces anoxia-reoxygenation injury in H9c2 cells...
  20. Shimazu T, Horinouchi S, Yoshida M. Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing. J Biol Chem. 2007;282:4470-8 pubmed
    ..Whereas CBP acetylated these proteins, HDAC1, HDAC3, HDAC10, SIRT1, and SIRT2 were involved in in vivo deacetylation...
  21. Suzuki E, Kojima N, Yoshimura K, Uyemura K, Obata K, Akagawa K. Cloning and sequence analysis of cDNA for a possible DNA-binding protein 5E5 in the nervous system. J Biochem. 1995;118:122-8 pubmed
    ..Transfection studies indicated that 5E5 protein expressed in COS-1 is localized in cell nuclei. These results suggest that 5E5 protein is a possible DNA-binding protein which is expressed especially in neurons. ..
  22. Cao W, Hong Y, Chen H, Wu F, Wei X, Ying W. SIRT2 mediates NADH-induced increases in Nrf2, GCL, and glutathione by modulating Akt phosphorylation in PC12 cells. FEBS Lett. 2016;590:2241-55 pubmed publisher
    b>SIRT2 plays important roles in multiple biological processes. It is unclear whether SIRT2 affects antioxidant capacity by modulating Nrf2, a key transcription factor for multiple antioxidant genes...
  23. Michishita E, Park J, Burneskis J, Barrett J, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005;16:4623-35 pubmed
  24. Wang X, Guan Q, Wang M, Yang L, Bai J, Yan Z, et al. Aging-related rotenone-induced neurochemical and behavioral deficits: role of SIRT2 and redox imbalance, and neuroprotection by AK-7. Drug Des Devel Ther. 2015;9:2553-63 pubmed publisher
    Aging is one of the strongest risk factors for Parkinson's disease (PD). SIRT2 has been implicated in the aging process...
  25. Vaquero A, Scher M, Lee D, Sutton A, Cheng H, Alt F, et al. SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev. 2006;20:1256-61 pubmed
    The mammalian cytoplasmic protein SirT2 is a member of the Sir2 family of NAD+-dependent protein deacetylases involved in caloric restriction-dependent life span extension...
  26. Seo K, Park J, Heo J, Jing K, Han J, Min K, et al. SIRT2 regulates tumour hypoxia response by promoting HIF-1? hydroxylation. Oncogene. 2015;34:1354-62 pubmed publisher
    ..In this study, it is shown that SIRT2-mediated deacetylation of HIF-1? regulates its stability in tumour cells...
  27. Zhang L, Hou X, Ma R, Moley K, Schedl T, Wang Q. Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. FASEB J. 2014;28:1435-45 pubmed publisher
    ..Here, by confocal scanning and quantitative analysis, we show that specific depletion of Sirt2 in mouse oocytes results in spindle defects and chromosome disorganization (35.5±8.7 vs. 9.6±3...
  28. Rack J, Vanlinden M, Lutter T, Aasland R, Ziegler M. Constitutive nuclear localization of an alternatively spliced sirtuin-2 isoform. J Mol Biol. 2014;426:1677-91 pubmed publisher
    Sirtuin-2 (SIRT2), the cytoplasmic member of the sirtuin family, has been implicated in the deacetylation of nuclear proteins...
  29. Nagai T, Ikeda M, Chiba S, Kanno S, Mizuno K. Furry promotes acetylation of microtubules in the mitotic spindle by inhibition of SIRT2 tubulin deacetylase. J Cell Sci. 2013;126:4369-80 pubmed publisher
    ..We also found that Fry binds to the tubulin deacetylase SIRT2, preferentially in mitotic cells...
  30. Han Y, Jin Y, Kim Y, Kang B, Choi H, Kim D, et al. Acetylation of Sirt2 by p300 attenuates its deacetylase activity. Biochem Biophys Res Commun. 2008;375:576-80 pubmed publisher
    ..Here, we report that p300 interacts with Sirt2, a member of the Sir2 family, and triggers the acetylation and subsequent down-regulation of the deacetylation ..
  31. Li W, Zhang B, Tang J, Cao Q, Wu Y, Wu C, et al. Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating alpha-tubulin. J Neurosci. 2007;27:2606-16 pubmed
    ..Here, we show that sirtuin 2 (SIRT2), a mammalian SIR2 homolog, is an oligodendroglial cytoplasmic protein and localized to the outer and juxtanodal ..
  32. Southwood C, Peppi M, Dryden S, Tainsky M, Gow A. Microtubule deacetylases, SirT2 and HDAC6, in the nervous system. Neurochem Res. 2007;32:187-95 pubmed
    ..Herein, we analyze two microtubule regulatory alpha-tubulin deacetylases, histone deacetylase-6 (HDAC6) and SirT2. HDAC6 is expressed by most neurons but is abundant in cerebellar Purkinje cells...
  33. Liu R, Dang W, Du Y, Zhou Q, Jiao K, Liu Z. SIRT2 is involved in the modulation of depressive behaviors. Sci Rep. 2015;5:8415 pubmed publisher
    Exposure to chronic stress produces negative effects on mood and hippocampus-dependent memory formation. SIRT2 alteration has been reported in mood disorders; however, the role of SIRT2 in depression remains unclear...
  34. Wang F, Tong Q. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. Mol Biol Cell. 2009;20:801-8 pubmed publisher
    ..have previously reported that caloric restriction increases the expression of one of the seven mammalian sirtuins, SIRT2, in tissues such as white adipose tissue...
  35. Misawa T, Takahama M, Kozaki T, Lee H, Zou J, Saitoh T, et al. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat Immunol. 2013;14:454-60 pubmed publisher
    ..Therefore, in addition to direct activation of NLRP3, the creation of optimal sites for signal transduction by microtubules is required for activation of the entire NLRP3 inflammasome. ..
  36. Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015;350:1208-13 pubmed publisher
    ..Here we review factors that regulate NAD(+) and discuss how supplementation with NAD(+) precursors may represent a new therapeutic opportunity for aging and its associated disorders, particularly neurodegenerative diseases. ..
  37. Zhao Y, Yang J, Liao W, Liu X, Zhang H, Wang S, et al. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol. 2010;12:665-75 pubmed publisher
    ..In response to stress, FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2), a NAD(+)-dependent histone deacetylase, and the acetylated FoxO1 bound to Atg7, an E1-like protein, to influence ..
  38. Valdecantos M, Perez Matute P, Gonzalez Muniesa P, Prieto Hontoria P, Moreno Aliaga M, Martinez J. Lipoic acid improves mitochondrial function in nonalcoholic steatosis through the stimulation of sirtuin 1 and sirtuin 3. Obesity (Silver Spring). 2012;20:1974-83 pubmed publisher