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Gene Review

SIRT3  -  sirtuin 3

Homo sapiens

Synonyms: NAD-dependent protein deacetylase sirtuin-3, mitochondrial, Regulatory protein SIR2 homolog 3, SIR2-like protein 3, SIR2L3, hSIRT3
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Disease relevance of SIRT3

  • Increased levels of SIRT3 and SIRT7 transcription were also associated with node-positive breast cancer (P<0.05 and P<0.0001, respectively) [1].

High impact information on SIRT3

  • The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase [2].
  • Mitochondrial import of hSIRT3 is dependent on an NH2-terminal amphipathic alpha-helix rich in basic residues. hSIRT3 is proteolytically processed in the mitochondrial matrix to a 28-kD product [2].
  • AceCS2 was completely inactivated upon acetylation and was rapidly reactivated by SIRT3 deacetylation [3].
  • Because SIRT3 is localized to the mitochondria, we investigated whether AceCS2 also might be regulated by acetylation, and specifically deacetylated by mitochondrial SIRT3 [3].
  • The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys-642 both in vitro and in vivo [4].

Biological context of SIRT3


Anatomical context of SIRT3

  • These results suggest a previously unrecognized organelle for sirtuin function and that the role of SIRT3 in mitochondria involves protein deacetylation [9].

Associations of SIRT3 with chemical compounds


  1. Altered sirtuin expression is associated with node-positive breast cancer. Ashraf, N., Zino, S., Macintyre, A., Kingsmore, D., Payne, A.P., George, W.D., Shiels, P.G. Br. J. Cancer (2006) [Pubmed]
  2. The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase. Schwer, B., North, B.J., Frye, R.A., Ott, M., Verdin, E. J. Cell Biol. (2002) [Pubmed]
  3. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Hallows, W.C., Lee, S., Denu, J.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Schwer, B., Bunkenborg, J., Verdin, R.O., Andersen, J.S., Verdin, E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Bellizzi, D., Rose, G., Cavalcante, P., Covello, G., Dato, S., De Rango, F., Greco, V., Maggiolini, M., Feraco, E., Mari, V., Franceschi, C., Passarino, G., De Benedictis, G. Genomics (2005) [Pubmed]
  6. Metabolite of SIR2 reaction modulates TRPM2 ion channel. Grubisha, O., Rafty, L.A., Takanishi, C.L., Xu, X., Tong, L., Perraud, A.L., Scharenberg, A.M., Denu, J.M. J. Biol. Chem. (2006) [Pubmed]
  7. Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13. Bellizzi, D., Dato, S., Cavalcante, P., Covello, G., Di Cianni, F., Passarino, G., Rose, G., De Benedictis, G. Genomics (2007) [Pubmed]
  8. Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Rose, G., Dato, S., Altomare, K., Bellizzi, D., Garasto, S., Greco, V., Passarino, G., Feraco, E., Mari, V., Barbi, C., BonaFe, M., Franceschi, C., Tan, Q., Boiko, S., Yashin, A.I., De Benedictis, G. Exp. Gerontol. (2003) [Pubmed]
  9. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Onyango, P., Celic, I., McCaffery, J.M., Boeke, J.D., Feinberg, A.P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
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