NAD-dependent protein deacetylase sirtuin-2

NameNAD-dependent protein deacetylase sirtuin-2
Synonyms
  • 3.5.1.-
  • Regulatory protein SIR2 homolog 2
  • SIR2-like protein 2
  • SIR2L
  • SIR2L2
Gene NameSIRT2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009282|NAD-dependent protein deacetylase sirtuin-2
MAEPDPSHPLETQAGKVQEAQDSDSDSEGGAAGGEADMDFLRNLFSQTLSLGSQKERLLD
ELTLEGVARYMQSERCRRVICLVGAGISTSAGIPDFRSPSTGLYDNLEKYHLPYPEAIFE
ISYFKKHPEPFFALAKELYPGQFKPTICHYFMRLLKDKGLLLRCYTQNIDTLERIAGLEQ
EDLVEAHGTFYTSHCVSASCRHEYPLSWMKEKIFSEVTPKCEDCQSLVKPDIVFFGESLP
ARFFSCMQSDFLKVDLLLVMGTSLQVQPFASLISKAPLSTPRLLINKEKAGQSDPFLGMI
MGLGGGMDFDSKKAYRDVAWLGECDQGCLALAELLGWKKELEDLVRREHASIDAQSGAGV
PNPSTSASPKKSPPPAKDEARTTEREKPQ
Number of residues389
Molecular Weight43181.7
Theoretical pINot Available
GO Classification
Functions
  • histone deacetylase activity
  • NAD-dependent protein deacetylase activity
  • tubulin deacetylase activity
  • ubiquitin binding
  • zinc ion binding
  • NAD+ binding
  • histone deacetylase binding
  • protein deacetylase activity
  • histone acetyltransferase binding
  • chromatin binding
  • transcription factor binding
  • NAD-dependent histone deacetylase activity
  • NAD-dependent histone deacetylase activity (H4-K16 specific)
Processes
  • positive regulation of execution phase of apoptosis
  • protein kinase B signaling
  • histone deacetylation
  • hepatocyte growth factor receptor signaling pathway
  • positive regulation of meiotic nuclear division
  • gene silencing
  • negative regulation of autophagy
  • protein ADP-ribosylation
  • positive regulation of oocyte maturation
  • regulation of myelination
  • cellular lipid catabolic process
  • chromatin silencing
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia
  • cellular response to hypoxia
  • cellular response to caloric restriction
  • cellular response to molecule of bacterial origin
  • meiotic cell cycle
  • regulation of exit from mitosis
  • transcription, DNA-templated
  • chromatin silencing at telomere
  • chromatin silencing at rDNA
  • ripoptosome assembly involved in necroptotic process
  • positive regulation of cell division
  • myelination in peripheral nervous system
  • cellular response to hepatocyte growth factor stimulus
  • tubulin deacetylation
  • negative regulation of defense response to bacterium
  • regulation of phosphorylation
  • cellular response to epinephrine stimulus
  • response to redox state
  • negative regulation of NLRP3 inflammasome complex assembly
  • autophagy
  • negative regulation of fat cell differentiation
  • positive regulation of DNA binding
  • negative regulation of oligodendrocyte progenitor proliferation
  • cellular response to oxidative stress
  • negative regulation of transcription, DNA-templated
  • negative regulation of peptidyl-threonine phosphorylation
  • innate immune response
  • substantia nigra development
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  • negative regulation of reactive oxygen species metabolic process
  • mitotic nuclear division
  • histone H3 deacetylation
  • negative regulation of protein catabolic process
  • negative regulation of striated muscle tissue development
  • negative regulation of cell proliferation
  • histone H4 deacetylation
  • regulation of cell cycle
  • proteasome-mediated ubiquitin-dependent protein catabolic process
  • negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
  • positive regulation of transcription from RNA polymerase II promoter
  • peptidyl-lysine deacetylation
  • cell division
  • phosphatidylinositol 3-kinase signaling
  • protein deacetylation
  • positive regulation of attachment of spindle microtubules to kinetochore
  • negative regulation of transcription from RNA polymerase II promoter
Components
  • centrosome
  • spindle
  • centriole
  • growth cone
  • juxtaparanode region of axon
  • chromatin silencing complex
  • mitotic spindle
  • cytosol
  • midbody
  • myelin sheath
  • nuclear heterochromatin
  • perinuclear region of cytoplasm
  • cytoplasm
  • Schmidt-Lanterman incisure
  • microtubule
  • glial cell projection
  • nucleus
  • meiotic spindle
  • chromosome
  • paranodal junction
  • plasma membrane
  • paranode region of axon
  • lateral loop
  • perikaryon
General FunctionZinc ion binding
Specific FunctionNAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by SETD8 leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates SETD8 modulating SETD8 chromatin localization during the mitotic stress response. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy. Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation. Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Deacetylates also EIF5A. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor.Isoform 1: Deacetylates EP300, alpha-tubulin and histone H3 and H4.Isoform 2: Deacetylates EP300, alpha-tubulin and histone H3 and H4.Isoform 5: Lacks deacetylation activity.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ8IXJ6
UniProtKB Entry NameSIR2_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0013716|NAD-dependent protein deacetylase sirtuin-2 (SIRT2)
ATGGACTTCCTGCGGAACTTATTCTCCCAGACGCTCAGCCTGGGCAGCCAGAAGGAGCGT
CTGCTGGACGAGCTGACCTTGGAAGGGGTGGCCCGGTACATGCAGAGCGAACGCTGTCGC
AGAGTCATCTGTTTGGTGGGAGCTGGAATCTCCACATCCGCAGGCATCCCCGACTTTCGC
TCTCCATCCACCGGCCTCTATGACAACCTAGAGAAGTACCATCTTCCCTACCCAGAGGCC
ATCTTTGAGATCAGCTATTTCAAGAAACATCCGGAACCCTTCTTCGCCCTCGCCAAGGAA
CTCTATCCTGGGCAGTTCAAGCCAACCATCTGTCACTACTTCATGCGCCTGCTGAAGGAC
AAGGGGCTACTCCTGCGCTGCTACACGCAGAACATAGATACCCTGGAGCGAATAGCCGGG
CTGGAACAGGAGGACTTGGTGGAGGCGCACGGCACCTTCTACACATCACACTGCGTCAGC
GCCAGCTGCCGGCACGAATACCCGCTAAGCTGGATGAAAGAGAAGATCTTCTCTGAGGTG
ACGCCCAAGTGTGAAGACTGTCAGAGCCTGGTGAAGCCTGATATCGTCTTTTTTGGTGAG
AGCCTCCCAGCGCGTTTCTTCTCCTGTATGCAGTCAGACTTCCTGAAGGTGGACCTCCTC
CTGGTCATGGGTACCTCCTTGCAGGGACGTGGCCTGGCTGGGTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:10886
Chromosome Location19
LocusNot Available
References
  1. Frye RA: Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun. 1999 Jun 24;260(1):273-9. 10381378
  2. Afshar G, Murnane JP: Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2. Gene. 1999 Jun 24;234(1):161-8. 10393250
  3. De Smet C, Nishimori H, Furnari FB, Bogler O, Huang HJ, Cavenee WK: A novel seven transmembrane receptor induced during the early steps of astrocyte differentiation identified by differential expression. J Neurochem. 2002 May;81(3):575-88. 12065666
  4. Rack JG, VanLinden MR, Lutter T, Aasland R, Ziegler M: Constitutive nuclear localization of an alternatively spliced sirtuin-2 isoform. J Mol Biol. 2014 Apr 17;426(8):1677-91. doi: 10.1016/j.jmb.2013.10.027. Epub 2013 Oct 29. 24177535
  5. Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL: Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9543-8. 10931946
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Perrod S, Cockell MM, Laroche T, Renauld H, Ducrest AL, Bonnard C, Gasser SM: A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast. EMBO J. 2001 Jan 15;20(1-2):197-209. 11226170
  9. Grozinger CM, Chao ED, Blackwell HE, Moazed D, Schreiber SL: Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening. J Biol Chem. 2001 Oct 19;276(42):38837-43. Epub 2001 Aug 1. 11483616
  10. Borra MT, O'Neill FJ, Jackson MD, Marshall B, Verdin E, Foltz KR, Denu JM: Conserved enzymatic production and biological effect of O-acetyl-ADP-ribose by silent information regulator 2-like NAD+-dependent deacetylases. J Biol Chem. 2002 Apr 12;277(15):12632-41. Epub 2002 Jan 25. 11812793
  11. North BJ, Marshall BL, Borra MT, Denu JM, Verdin E: The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003 Feb;11(2):437-44. 12620231
  12. Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA: Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. Mol Cell Biol. 2003 May;23(9):3173-85. 12697818
  13. Hiratsuka M, Inoue T, Toda T, Kimura N, Shirayoshi Y, Kamitani H, Watanabe T, Ohama E, Tahimic CG, Kurimasa A, Oshimura M: Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene. Biochem Biophys Res Commun. 2003 Sep 26;309(3):558-66. 12963026
  14. Bae NS, Swanson MJ, Vassilev A, Howard BH: Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10. J Biochem. 2004 Jun;135(6):695-700. 15213244
  15. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I: Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005 Oct;16(10):4623-35. Epub 2005 Aug 3. 16079181
  16. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  17. Vaquero A, Scher MB, Lee DH, Sutton A, Cheng HL, Alt FW, Serrano L, Sternglanz R, Reinberg D: SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev. 2006 May 15;20(10):1256-61. Epub 2006 Apr 28. 16648462
  18. North BJ, Verdin E: Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent phosphorylation. J Biol Chem. 2007 Jul 6;282(27):19546-55. Epub 2007 May 8. 17488717
  19. Nahhas F, Dryden SC, Abrams J, Tainsky MA: Mutations in SIRT2 deacetylase which regulate enzymatic activity but not its interaction with HDAC6 and tubulin. Mol Cell Biochem. 2007 Sep;303(1-2):221-30. Epub 2007 May 22. 17516032
  20. Suzuki K, Koike T: Mammalian Sir2-related protein (SIRT) 2-mediated modulation of resistance to axonal degeneration in slow Wallerian degeneration mice: a crucial role of tubulin deacetylation. Neuroscience. 2007 Jul 13;147(3):599-612. Epub 2007 Jun 15. 17574768
  21. Inoue T, Hiratsuka M, Osaki M, Yamada H, Kishimoto I, Yamaguchi S, Nakano S, Katoh M, Ito H, Oshimura M: SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress. Oncogene. 2007 Feb 15;26(7):945-57. Epub 2006 Aug 14. 16909107
  22. North BJ, Verdin E: Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis. PLoS One. 2007 Aug 29;2(8):e784. 17726514
  23. Jin YH, Kim YJ, Kim DW, Baek KH, Kang BY, Yeo CY, Lee KY: Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53. Biochem Biophys Res Commun. 2008 Apr 11;368(3):690-5. doi: 10.1016/j.bbrc.2008.01.114. Epub 2008 Feb 4. 18249187
  24. Han Y, Jin YH, Kim YJ, Kang BY, Choi HJ, Kim DW, Yeo CY, Lee KY: Acetylation of Sirt2 by p300 attenuates its deacetylase activity. Biochem Biophys Res Commun. 2008 Oct 31;375(4):576-80. doi: 10.1016/j.bbrc.2008.08.042. Epub 2008 Aug 21. 18722353
  25. Lynn EG, McLeod CJ, Gordon JP, Bao J, Sack MN: SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via regulation of 14-3-3 zeta and BAD in H9c2 cells. FEBS Lett. 2008 Aug 20;582(19):2857-62. doi: 10.1016/j.febslet.2008.07.016. Epub 2008 Jul 18. 18640115
  26. Pandithage R, Lilischkis R, Harting K, Wolf A, Jedamzik B, Luscher-Firzlaff J, Vervoorts J, Lasonder E, Kremmer E, Knoll B, Luscher B: The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility. J Cell Biol. 2008 Mar 10;180(5):915-29. doi: 10.1083/jcb.200707126. 18332217
  27. Black JC, Mosley A, Kitada T, Washburn M, Carey M: The SIRT2 deacetylase regulates autoacetylation of p300. Mol Cell. 2008 Nov 7;32(3):449-55. doi: 10.1016/j.molcel.2008.09.018. 18995842
  28. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  29. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  30. Inoue T, Nakayama Y, Yamada H, Li YC, Yamaguchi S, Osaki M, Kurimasa A, Hiratsuka M, Katoh M, Oshimura M: SIRT2 downregulation confers resistance to microtubule inhibitors by prolonging chronic mitotic arrest. Cell Cycle. 2009 Apr 15;8(8):1279-91. Epub 2009 Apr 19. 19282667
  31. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  32. Vempati RK, Jayani RS, Notani D, Sengupta A, Galande S, Haldar D: p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals. J Biol Chem. 2010 Sep 10;285(37):28553-64. doi: 10.1074/jbc.M110.149393. Epub 2010 Jun 29. 20587414
  33. Rothgiesser KM, Erener S, Waibel S, Luscher B, Hottiger MO: SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310. J Cell Sci. 2010 Dec 15;123(Pt 24):4251-8. doi: 10.1242/jcs.073783. Epub 2010 Nov 16. 21081649
  34. Zhao Y, Yang J, Liao W, Liu X, Zhang H, Wang S, Wang D, Feng J, Yu L, Zhu WG: Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol. 2010 Jul;12(7):665-75. doi: 10.1038/ncb2069. Epub 2010 Jun 13. 20543840
  35. Kim HS, Vassilopoulos A, Wang RH, Lahusen T, Xiao Z, Xu X, Li C, Veenstra TD, Li B, Yu H, Ji J, Wang XW, Park SH, Cha YI, Gius D, Deng CX: SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell. 2011 Oct 18;20(4):487-99. doi: 10.1016/j.ccr.2011.09.004. 22014574
  36. Maxwell MM, Tomkinson EM, Nobles J, Wizeman JW, Amore AM, Quinti L, Chopra V, Hersch SM, Kazantsev AG: The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein that accumulates in the aging CNS. Hum Mol Genet. 2011 Oct 15;20(20):3986-96. doi: 10.1093/hmg/ddr326. Epub 2011 Jul 26. 21791548
  37. Jiang W, Wang S, Xiao M, Lin Y, Zhou L, Lei Q, Xiong Y, Guan KL, Zhao S: Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol Cell. 2011 Jul 8;43(1):33-44. doi: 10.1016/j.molcel.2011.04.028. 21726808
  38. Beirowski B, Gustin J, Armour SM, Yamamoto H, Viader A, North BJ, Michan S, Baloh RH, Golden JP, Schmidt RE, Sinclair DA, Auwerx J, Milbrandt J: 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 Oct 25;108(43):E952-61. doi: 10.1073/pnas.1104969108. Epub 2011 Sep 26. 21949390
  39. Ishfaq M, Maeta K, Maeda S, Natsume T, Ito A, Yoshida M: Acetylation regulates subcellular localization of eukaryotic translation initiation factor 5A (eIF5A). FEBS Lett. 2012 Sep 21;586(19):3236-41. doi: 10.1016/j.febslet.2012.06.042. Epub 2012 Jul 4. 22771473
  40. Gal J, Bang Y, Choi HJ: SIRT2 interferes with autophagy-mediated degradation of protein aggregates in neuronal cells under proteasome inhibition. Neurochem Int. 2012 Dec;61(7):992-1000. doi: 10.1016/j.neuint.2012.07.010. Epub 2012 Jul 20. 22819792
  41. Park SH, Zhu Y, Ozden O, Kim HS, Jiang H, Deng CX, Gius D, Vassilopoulos A: SIRT2 is a tumor suppressor that connects aging, acetylome, cell cycle signaling, and carcinogenesis. Transl Cancer Res. 2012 Jun 1;1(1):15-21. Epub 2012 May 22. 22943040
  42. Choi YH, Kim H, Lee SH, Jin YH, Lee KY: ERK1/2 regulates SIRT2 deacetylase activity. Biochem Biophys Res Commun. 2013 Jul 26;437(2):245-9. doi: 10.1016/j.bbrc.2013.06.053. Epub 2013 Jun 24. 23806683
  43. Serrano L, Martinez-Redondo P, Marazuela-Duque A, Vazquez BN, Dooley SJ, Voigt P, Beck DB, Kane-Goldsmith N, Tong Q, Rabanal RM, Fondevila D, Munoz P, Kruger M, Tischfield JA, Vaquero A: The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation. Genes Dev. 2013 Mar 15;27(6):639-53. doi: 10.1101/gad.211342.112. Epub 2013 Mar 6. 23468428
  44. Lin R, Tao R, Gao X, Li T, Zhou X, Guan KL, Xiong Y, Lei QY: Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell. 2013 Aug 22;51(4):506-18. doi: 10.1016/j.molcel.2013.07.002. Epub 2013 Aug 8. 23932781
  45. Eskandarian HA, Impens F, Nahori MA, Soubigou G, Coppee JY, Cossart P, Hamon MA: A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science. 2013 Aug 2;341(6145):1238858. doi: 10.1126/science.1238858. 23908241
  46. Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, Ling ZQ, Hu FJ, Sun YP, Zhang JY, Yang C, Yang Y, Xiong Y, Guan KL, Ye D: Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. EMBO J. 2014 Jun 17;33(12):1304-20. doi: 10.1002/embj.201387224. Epub 2014 Apr 25. 24769394
  47. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  48. Seo KS, Park JH, Heo JY, Jing K, Han J, Min KN, Kim C, Koh GY, Lim K, Kang GY, Uee Lee J, Yim YH, Shong M, Kwak TH, Kweon GR: SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha hydroxylation. Oncogene. 2015 Mar 12;34(11):1354-62. doi: 10.1038/onc.2014.76. Epub 2014 Mar 31. 24681946
  49. Finnin MS, Donigian JR, Pavletich NP: Structure of the histone deacetylase SIRT2. Nat Struct Biol. 2001 Jul;8(7):621-5. 11427894
  50. Moniot S, Schutkowski M, Steegborn C: Crystal structure analysis of human Sirt2 and its ADP-ribose complex. J Struct Biol. 2013 May;182(2):136-43. doi: 10.1016/j.jsb.2013.02.012. Epub 2013 Feb 26. 23454361
  51. Yamagata K, Goto Y, Nishimasu H, Morimoto J, Ishitani R, Dohmae N, Takeda N, Nagai R, Komuro I, Suga H, Nureki O: Structural basis for potent inhibition of SIRT2 deacetylase by a macrocyclic peptide inducing dynamic structural change. Structure. 2014 Feb 4;22(2):345-52. doi: 10.1016/j.str.2013.12.001. Epub 2014 Jan 2. 24389023