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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 IUPHAR: 2708 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:
39.37 – 39.39 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 et al. (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 et al. (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 et al. (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 et al. (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]