SIRT2

Sirtuin 2
PDB rendering based on 1j8f.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1J8F​, 3ZGO​, 3ZGV​, 4L3O​, 4R8M​, 4RMG​, 4RMH​, 4RMI​, 4RMJ​
Identifiers
Symbols	SIRT2 ; SIR2; SIR2L; SIR2L2
External IDs	OMIM: 604480 MGI: 1927664 HomoloGene: 40823 ChEMBL: 4462 GeneCards: SIRT2 Gene
EC number	3.5.1.-
Gene ontology Molecular function • chromatin binding • NAD+ ADP-ribosyltransferase activity • histone deacetylase activity • protein binding • transcription factor binding • zinc ion binding • NAD-dependent histone deacetylase activity • protein deacetylase activity • NAD-dependent protein deacetylase activity • histone acetyltransferase binding • histone deacetylase binding • tubulin deacetylase activity • ubiquitin binding • NAD-dependent histone deacetylase activity (H4-K16 specific) • beta-tubulin binding • NAD+ binding Cellular component • nucleus • chromatin silencing complex • chromosome • nuclear heterochromatin • cytoplasm • centrosome • centriole • spindle • cytosol • microtubule • plasma membrane • growth cone • midbody • paranodal junction • paranode region of axon • perikaryon • myelin sheath • lateral loop • Schmidt-Lanterman incisure • juxtaparanode region of axon • perinuclear region of cytoplasm • mitotic spindle • meiotic spindle • glial cell projection Biological process • negative regulation of transcription from RNA polymerase II promoter • chromatin silencing at rDNA • chromatin silencing • chromatin silencing at telomere • transcription, DNA-templated • protein ADP-ribosylation • protein deacetylation • autophagy • mitotic nuclear division • regulation of exit from mitosis • negative regulation of cell proliferation • negative regulation of autophagy • negative regulation of peptidyl-threonine phosphorylation • phosphatidylinositol 3-kinase signaling • gene silencing • histone deacetylation • substantia nigra development • myelination in peripheral nervous system • regulation of myelination • positive regulation of proteasomal ubiquitin-dependent protein catabolic process • cellular response to oxidative stress • peptidyl-lysine deacetylation • cellular response to hepatocyte growth factor stimulus • negative regulation of protein catabolic process • regulation of phosphorylation • proteasome-mediated ubiquitin-dependent protein catabolic process • positive regulation of DNA binding • protein kinase B signaling • cellular lipid catabolic process • innate immune response • negative regulation of fat cell differentiation • positive regulation of meiotic nuclear division • negative regulation of striated muscle tissue development • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • hepatocyte growth factor receptor signaling pathway • cell division • meiotic cell cycle • regulation of cell cycle • response to redox state • positive regulation of cell division • positive regulation of attachment of spindle microtubules to kinetochore • negative regulation of transcription from RNA polymerase II promoter in response to hypoxia • cellular response to caloric restriction • negative regulation of oligodendrocyte progenitor proliferation • histone H3 deacetylation • histone H4 deacetylation • cellular response to molecule of bacterial origin • cellular response to hypoxia • cellular response to epinephrine stimulus • tubulin deacetylation • positive regulation of execution phase of apoptosis • positive regulation of oocyte maturation • negative regulation of NLRP3 inflammasome complex assembly • negative regulation of defense response to bacterium • ripoptosome assembly involved in necroptotic process • negative regulation of reactive oxygen species metabolic process • positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	22933	64383
Ensembl	ENSG00000068903	ENSMUSG00000015149
UniProt	Q8IXJ6	Q8VDQ8
RefSeq (mRNA)	NM_001193286	NM_001122765
RefSeq (protein)	NP_001180215	NP_001116237
Location (UCSC)	Chr 19: 38.88 – 38.9 Mb	Chr 7: 28.77 – 28.79 Mb
PubMed search

NAD-dependent deacetylase sirtuin-2 is an enzyme that in humans is encoded by the SIRT2 gene.^[1][2][3] SIRT2 is an NAD+ (nicotinamide adenine dinucleotide)-dependent deacetylase. Studies of this protein have often been divergent, highlighting the dependence of pleiotropic effects of SIRT2 on cellular context. The natural polyphenol resveratrol is known to exert opposite actions on neural cells according to their normal or cancerous status.^[4] Similar to other sirtuin family members, SIRT2 displays a ubiquitous distribution. SIRT2 is expressed in a wide range of tissues and organs and has been detected particularly in metabolically relevant tissues, including the brain, muscle, liver, testes, pancreas, kidney, and adipose tissue of mice. Of note, SIRT2 expression is much higher in the brain than all other organs studied, particularly in the cortex, striatum, hippocampus, and spinal cord.^[5]

Function

Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity.^[3] Cytosolic functions of SIRT2 include the regulation of microtubule acetylation, control of myelination in the central and peripheral nervous system and gluconeogenesis.^[6] There is growing evidence for additional functions of SIRT2 in the nucleus. During the G2/M transition, nuclear SIRT2 is responsible for global deacetylation of H4K16, facilitating H4K20 methylation and subsequent chromatin compaction.^[7] In response to DNA damage, SIRT2 was also found to deacetylate H3K56 in vivo.^[8] Finally, SIRT2 negatively regulates the acetyltransferase activity of the transcriptional co-activator p300 via deacetylation of an automodification loop within its catalytic domain.^[9]

Structure

Gene

Human SIRT2 gene has 18 exons resides on chromosome 19 at q13.^[3] For SIRT2, four different human splice variants are deposited in the GenBank sequence database.^[10]

Protein

SIRT2 gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The protein encoded by this gene is included in class I of the sirtuin family. Several transcript variants are resulted from alternative splicing of this gene.^[3] Only transcript variants 1 and 2 have confirmed protein products of physiological relevance. A leucine-rich nuclear export signal (NES) within the N-terminal region of these two isoforms is identified.^[10] Since deletion of the NES led to nucleocytoplasmic distribution, it is suggested to mediate their cytosolic localization.^[11]

Selective ligands

Inhibitors

• Benzamide compound # 64^[12]
• (S)-2-Pentyl-6-chloro,8-bromo-chroman-4-one: IC₅₀ of 1.5 μM, highly selective over SIRT2 and SIRT3^[13]
• 3′-Phenethyloxy-2-anilinobenzamide (33i): IC₅₀ of 0.57 μM^[14]

Model organisms

The functions of human sirtuins have not yet been determined; however, model organisms have been used in the study of SIRT2 function. Yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA.

Sirt2 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Eye Histopathology	Normal
All tests and analysis from[15]

A conditional knockout mouse line, called Sirt2^{tm1a(EUCOMM)Wtsi[16][17]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.^[18][19][20] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[15][21] Twenty five tests were carried out on homozygous mutant adult mice, however no significant abnormalities were observed.^[15]

Clinical significance

Metabolic actions

Several SIRT2 deacetylation targets play important roles in metabolic homeostasis.

SIRT2 inhibits adipogenesis by deacetylating FOXO1 and thus may protect against insulin resistance.

SIRT2 sensitizes cells to the action of insulin by physically interacting with and activating Akt and downstream targets.

SIRT2 mediates mitochondrial biogenesis by deacetylating PGC-1α, upregulates antioxidant enzyme expression by deacetylating FOXO3a, and thereby reduces ROS levels.

SIRT2 suppresses inflammatory responses in mice through p65 deacetylation and inhibition of NF-κB activity.^[22]

Cell cycle regulation

Although preferentially cytosolic, SIRT2 transiently shuttles to the nucleus during the G2/M transition of the cell cycle, where it has a strong preference for histone H4 lysine 16 (H4K16Ac),^[23] thereby regulating chromosomal condensation during mitosis.^[24] During the cell cycle, SIRT2 associates with several mitotic structures including the centrosome, mitotic spindle, and midbody, presumably to ensure normal cell division.^[11] Finally, cells with SIRT2 overexpression exhibit marked prolongation of the cell cycle.^[25]

Tumorigenesis

Mounting evidence implies a role for SIRT2 in tumorigenesis. SIRT2 has been proposed to act as a tumor suppressor by preventing chromosomal instability during mitosis.^[26] Further studies will be required to determine the therapeutic potential of targeting SIRT2 in cancer.

Neurodegeneration

Several studies in cell and invertebrate models of Parkinson's disease (PD) and Huntington's disease (HD) suggested potential neuroprotective effects of SIRT2 inhibition, in striking contrast with other sirtuin family members.^[27][28] In addition, recent evidence shows that inhibition of SIRT2 protects against MPTP-induced neuronal loss in vivo.^[29]

Interactions

SIRT2 has been shown to interact with:

• α-tubulin,^[30]
• TUG,^[31]
• β-catenin,^[32]
• PGAM2,^[33]
• TIAM1,^[34]
• ApoE4,^[35]
• p53,^[36]
• PEPCK,^[37]
• FOXO1,^[38]
• p300,^[39]
• 14-3-3 protein,^[40] and
• CBP.^[41]

References

1. Afshar G, Murnane JP (Jun 1999). "Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2". Gene 234 (1): 161–8. doi:10.1016/S0378-1119(99)00162-6. PMID 10393250.
2. Frye RA (Jun 1999). "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". Biochemical and Biophysical Research Communications 260 (1): 273–9. doi:10.1006/bbrc.1999.0897. PMID 10381378.
3. "Entrez Gene: SIRT2 sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae)".
4. Sayd S, Junier MP, Chneiweiss H (May 2014). "[SIRT2, a multi-talented deacetylase]". Médecine Sciences 30 (5): 532–6. doi:10.1051/medsci/20143005016. PMID 24939540.
5. Maxwell MM, Tomkinson EM, Nobles J, Wizeman JW, Amore AM, Quinti L, Chopra V, Hersch SM, Kazantsev AG (Oct 2011). "The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein that accumulates in the aging CNS". Human Molecular Genetics 20 (20): 3986–96. doi:10.1093/hmg/ddr326. PMID 21791548.
6. North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (Feb 2003). "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase". Molecular Cell 11 (2): 437–44. PMID 12620231.
7. Serrano L, Martínez-Redondo P, Marazuela-Duque A, Vazquez BN, Dooley SJ, Voigt P, Beck DB, Kane-Goldsmith N, Tong Q, Rabanal RM, Fondevila D, Muñoz P, Krüger M, Tischfield JA, Vaquero A (Mar 2013). "The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation". Genes & Development 27 (6): 639–53. doi:10.1101/gad.211342.112. PMID 23468428.
8. Vempati RK, Jayani RS, Notani D, Sengupta A, Galande S, Haldar D (Sep 2010). "p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals". The Journal of Biological Chemistry 285 (37): 28553–64. doi:10.1074/jbc.M110.149393. PMID 20587414.
9. Black JC, Mosley A, Kitada T, Washburn M, Carey M (Nov 2008). "The SIRT2 deacetylase regulates autoacetylation of p300". Molecular Cell 32 (3): 449–55. doi:10.1016/j.molcel.2008.09.018. PMID 18995842.
10. Rack JG, VanLinden MR, Lutter T, Aasland R, Ziegler M (Apr 2014). "Constitutive nuclear localization of an alternatively spliced sirtuin-2 isoform". Journal of Molecular Biology 426 (8): 1677–91. doi:10.1016/j.jmb.2013.10.027. PMID 24177535.
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12. Cui H, Kamal Z, Ai T, Xu Y, More SS, Wilson DJ, Chen L (Oct 2014). "Discovery of potent and selective sirtuin 2 (SIRT2) inhibitors using a fragment-based approach". Journal of Medicinal Chemistry 57 (20): 8340–57. doi:10.1021/jm500777s. PMID 25275824.
13. Fridén-Saxin M, Seifert T, Landergren MR, Suuronen T, Lahtela-Kakkonen M, Jarho EM, Luthman K (Aug 2012). "Synthesis and evaluation of substituted chroman-4-one and chromone derivatives as sirtuin 2-selective inhibitors". Journal of Medicinal Chemistry 55 (16): 7104–13. doi:10.1021/jm3005288. PMC 3426190. PMID 22746324.
14. Suzuki T, Khan MN, Sawada H, Imai E, Itoh Y, Yamatsuta K, Tokuda N, Takeuchi J, Seko T, Nakagawa H, Miyata N (Jun 2012). "Design, synthesis, and biological activity of a novel series of human sirtuin-2-selective inhibitors". Journal of Medicinal Chemistry 55 (12): 5760–73. doi:10.1021/jm3002108. PMID 22642300.
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22. Gomes P, Outeiro TF, Cavadas C (Nov 2015). "Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism". Trends in Pharmacological Sciences 36 (11): 756–68. doi:10.1016/j.tips.2015.08.001. PMID 26538315.
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24. Inoue T, Hiratsuka M, Osaki M, Yamada H, Kishimoto I, Yamaguchi S, Nakano S, Katoh M, Ito H, Oshimura M (Feb 2007). "SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress". Oncogene 26 (7): 945–57. doi:10.1038/sj.onc.1209857. PMID 16909107.
25. Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA (May 2003). "Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle". Molecular and Cellular Biology 23 (9): 3173–85. PMID 12697818.
26. 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 (Oct 2011). "SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity". Cancer Cell 20 (4): 487–99. doi:10.1016/j.ccr.2011.09.004. PMID 22014574.
27. Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, Young AB, Abagyan R, Feany MB, Hyman BT, Kazantsev AG (Jul 2007). "Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease". Science 317 (5837): 516–9. doi:10.1126/science.1143780. PMID 17588900.
28. Luthi-Carter R, Taylor DM, Pallos J, Lambert E, Amore A, Parker A, Moffitt H, Smith DL, Runne H, Gokce O, Kuhn A, Xiang Z, Maxwell MM, Reeves SA, Bates GP, Neri C, Thompson LM, Marsh JL, Kazantsev AG (Apr 2010). "SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis". Proceedings of the National Academy of Sciences of the United States of America 107 (17): 7927–32. doi:10.1073/pnas.1002924107. PMID 20378838.
29. Chen X, Wales P, Quinti L, Zuo F, Moniot S, Herisson F, Rauf NA, Wang H, Silverman RB, Ayata C, Maxwell MM, Steegborn C, Schwarzschild MA, Outeiro TF, Kazantsev AG (2015). "The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson's disease but not amyotrophic lateral sclerosis and cerebral ischemia". PLOS ONE 10 (1): e0116919. doi:10.1371/journal.pone.0116919. PMID 25608039.
30. Yuan Q, Zhan L, Zhou QY, Zhang LL, Chen XM, Hu XM, Yuan XC (Oct 2015). "SIRT2 regulates microtubule stabilization in diabetic cardiomyopathy". European Journal of Pharmacology 764: 554–61. doi:10.1016/j.ejphar.2015.07.045. PMID 26209361.
31. Belman JP, Bian RR, Habtemichael EN, Li DT, Jurczak MJ, Alcázar-Román A, McNally LJ, Shulman GI, Bogan JS (Feb 2015). "Acetylation of TUG protein promotes the accumulation of GLUT4 glucose transporters in an insulin-responsive intracellular compartment". The Journal of Biological Chemistry 290 (7): 4447–63. doi:10.1074/jbc.M114.603977. PMID 25561724.
32. Nguyen P, Lee S, Lorang-Leins D, Trepel J, Smart DK (Sep 2014). "SIRT2 interacts with β-catenin to inhibit Wnt signaling output in response to radiation-induced stress". Molecular Cancer Research 12 (9): 1244–53. doi:10.1158/1541-7786.MCR-14-0223-T. PMID 24866770.
33. Xu Y, Li F, Lv L, Li T, Zhou X, Deng CX, Guan KL, Lei QY, Xiong Y (Jul 2014). "Oxidative stress activates SIRT2 to deacetylate and stimulate phosphoglycerate mutase". Cancer Research 74 (13): 3630–42. doi:10.1158/0008-5472.CAN-13-3615. PMID 24786789.
34. Saxena M, Dykes SS, Malyarchuk S, Wang AE, Cardelli JA, Pruitt K (Jan 2015). "The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration". Oncogene 34 (2): 188–98. doi:10.1038/onc.2013.549. PMID 24362520.
35. Theendakara V, Patent A, Peters Libeu CA, Philpot B, Flores S, Descamps O, Poksay KS, Zhang Q, Cailing G, Hart M, John V, Rao RV, Bredesen DE (Nov 2013). "Neuroprotective Sirtuin ratio reversed by ApoE4". Proceedings of the National Academy of Sciences of the United States of America 110 (45): 18303–8. doi:10.1073/pnas.1314145110. PMID 24145446.
36. van Leeuwen IM, Higgins M, Campbell J, McCarthy AR, Sachweh MC, Navarro AM, Laín S (Apr 2013). "Modulation of p53 C-terminal acetylation by mdm2, p14ARF, and cytoplasmic SirT2". Molecular Cancer Therapeutics 12 (4): 471–80. doi:10.1158/1535-7163.MCT-12-0904. PMID 23416275.
37. Jiang W, Wang S, Xiao M, Lin Y, Zhou L, Lei Q, Xiong Y, Guan KL, Zhao S (Jul 2011). "Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase". Molecular Cell 43 (1): 33–44. doi:10.1016/j.molcel.2011.04.028. PMID 21726808.
38. Wang F, Tong Q (Feb 2009). "SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma". Molecular Biology of the Cell 20 (3): 801–8. doi:10.1091/mbc.E08-06-0647. PMID 19037106.
39. Han Y, Jin YH, Kim YJ, Kang BY, Choi HJ, Kim DW, Yeo CY, Lee KY (Oct 2008). "Acetylation of Sirt2 by p300 attenuates its deacetylase activity". Biochemical and Biophysical Research Communications 375 (4): 576–80. doi:10.1016/j.bbrc.2008.08.042. PMID 18722353.
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41. Shimazu T, Horinouchi S, Yoshida M (Feb 2007). "Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing". The Journal of Biological Chemistry 282 (7): 4470–8. doi:10.1074/jbc.M609745200. PMID 17172643.

Further reading

• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (Apr 1997). "Large-scale concatenation cDNA sequencing". Genome Research 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Frye RA (Jul 2000). "Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins". Biochemical and Biophysical Research Communications 273 (2): 793–8. doi:10.1006/bbrc.2000.3000. PMID 10873683.
• 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 (Aug 2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America 97 (17): 9543–8. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
• Finnin MS, Donigian JR, Pavletich NP (Jul 2001). "Structure of the histone deacetylase SIRT2". Nature Structural Biology 8 (7): 621–5. doi:10.1038/89668. PMID 11427894.
• Grozinger CM, Chao ED, Blackwell HE, Moazed D, Schreiber SL (Oct 2001). "Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening". The Journal of Biological Chemistry 276 (42): 38837–43. doi:10.1074/jbc.M106779200. PMID 11483616.
• Borra MT, O'Neill FJ, Jackson MD, Marshall B, Verdin E, Foltz KR, Denu JM (Apr 2002). "Conserved enzymatic production and biological effect of O-acetyl-ADP-ribose by silent information regulator 2-like NAD+-dependent deacetylases". The Journal of Biological Chemistry 277 (15): 12632–41. doi:10.1074/jbc.M111830200. PMID 11812793.
• De Smet C, Nishimori H, Furnari FB, Bögler O, Huang HJ, Cavenee WK (May 2002). "A novel seven transmembrane receptor induced during the early steps of astrocyte differentiation identified by differential expression". Journal of Neurochemistry 81 (3): 575–88. doi:10.1046/j.1471-4159.2002.00847.x. PMID 12065666.
• North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (Feb 2003). "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase". Molecular Cell 11 (2): 437–44. doi:10.1016/S1097-2765(03)00038-8. PMID 12620231.
• Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA (May 2003). "Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle". Molecular and Cellular Biology 23 (9): 3173–85. doi:10.1128/MCB.23.9.3173-3185.2003. PMC 153197. PMID 12697818.
• Fulco M, Schiltz RL, Iezzi S, King MT, Zhao P, Kashiwaya Y, Hoffman E, Veech RL, Sartorelli V (Jul 2003). "Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state". Molecular Cell 12 (1): 51–62. doi:10.1016/S1097-2765(03)00226-0. PMID 12887892.
• Hiratsuka M, Inoue T, Toda T, Kimura N, Shirayoshi Y, Kamitani H, Watanabe T, Ohama E, Tahimic CG, Kurimasa A, Oshimura M (Sep 2003). "Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene". Biochemical and Biophysical Research Communications 309 (3): 558–66. doi:10.1016/j.bbrc.2003.08.029. PMID 12963026.
• van der Horst A, Tertoolen LG, de Vries-Smits LM, Frye RA, Medema RH, Burgering BM (Jul 2004). "FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)". The Journal of Biological Chemistry 279 (28): 28873–9. doi:10.1074/jbc.M401138200. PMID 15126506.
• Bae NS, Swanson MJ, Vassilev A, Howard BH (Jun 2004). "Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10". Journal of Biochemistry 135 (6): 695–700. doi:10.1093/jb/mvh084. PMID 15213244.
• de Oliveira RM, Sarkander J, Kazantsev AG, Outeiro TF (2012). "SIRT2 as a Therapeutic Target for Age-Related Disorders". Frontiers in Pharmacology 3: 82. doi:10.3389/fphar.2012.00082. PMC 3342661. PMID 22563317.