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Sirtuin 2
Protein SIRT2 PDB 1j8f.png
PDB rendering based on 1j8f.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols SIRT2 ; SIR2; SIR2L; SIR2L2
External IDs OMIM604480 MGI1927664 HomoloGene40823 ChEMBL: 4462 GeneCards: SIRT2 Gene
EC number 3.5.1.-
RNA expression pattern
PBB GE SIRT2 220605 s at tn.png
More reference expression data
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 [1] [2]

NAD-dependent deacetylase sirtuin-2 is an enzyme that in humans is encoded by the SIRT2 gene.[1][2][3]


This 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. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Two transcript variants result from alternative splicing of this gene.[3]

Model organisms[edit]

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.

A conditional knockout mouse line, called Sirt2tm1a(EUCOMM)Wtsi[6][7] 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.[8][9][10] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][11] Twenty five tests were carried out on homozygous mutant adult mice, however no significant abnormalities were observed.[4]

Selective ligands[edit]


  • 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]


  1. ^ Afshar G, Murnane JP (Aug 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 (Jul 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". Biochem Biophys Res Commun 260 (1): 273–9. doi:10.1006/bbrc.1999.0897. PMID 10381378. 
  3. ^ a b "Entrez Gene: SIRT2 sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae)". 
  4. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. 
  5. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  6. ^ "International Knockout Mouse Consortium". 
  7. ^ "Mouse Genome Informatics". 
  8. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750. 
  9. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  10. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  11. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  12. ^ Cui H, Kamal Z, Ai T, Xu Y, More SS, Wilson DJ, Chen L (2014). "Discovery of Potent and Selective Sirtuin 2 (SIRT2) Inhibitors Using a Fragment-Based Approach". J. Med. Chem. doi:10.1021/jm500777s. PMID 25275824. 
  13. ^ Fridén-Saxin M, Seifert T, Landergren MR, Suuronen T, Lahtela-Kakkonen M, Jarho EM, Luthman K (2012). "Synthesis and Evaluation of Substituted Chroman-4-one and Chromone Derivatives as Sirtuin 2-Selective Inhibitors". J. Med. Chem. 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 (2012). "Design, synthesis, and biological activity of a novel series of human sirtuin-2-selective inhibitors". J. Med. Chem. 55 (12): 5760–73. doi:10.1021/jm3002108. PMID 22642300. 

Further reading[edit]