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Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase.

Silent information regulator 2 (Sir2) proteins (sirtuins) are nicotinamide adenine dinucleotide-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1 to Sirt7. Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg(105)) and tyrosine residue (Tyr(102)) in the acyl pocket of Sirt5. Several mammalian proteins were identified with mass spectrometry to have succinyl or malonyl lysine modifications. Deletion of Sirt5 in mice appeared to increase the level of succinylation on carbamoyl phosphate synthase 1, which is a known target of Sirt5. Thus, protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo.

Pubmed ID: 22076378


  • Du J
  • Zhou Y
  • Su X
  • Yu JJ
  • Khan S
  • Jiang H
  • Kim J
  • Woo J
  • Kim JH
  • Choi BH
  • He B
  • Chen W
  • Zhang S
  • Cerione RA
  • Auwerx J
  • Hao Q
  • Lin H


Science (New York, N.Y.)

Publication Data

November 11, 2011

Associated Grants

  • Agency: European Research Council, Id: 231138
  • Agency: NIDDK NIH HHS, Id: DK58920
  • Agency: NCRR NIH HHS, Id: P41 RR001646
  • Agency: NCRR NIH HHS, Id: P41 RR001646-27
  • Agency: NIGMS NIH HHS, Id: R01 GM086703
  • Agency: NIGMS NIH HHS, Id: R01 GM086703-03
  • Agency: NIGMS NIH HHS, Id: R01 GM086703-03S1
  • Agency: NIGMS NIH HHS, Id: R01GM086703
  • Agency: NCRR NIH HHS, Id: RR01646

Mesh Terms

  • Acetylation
  • Animals
  • Carbamoyl-Phosphate Synthase (Ammonia)
  • Cattle
  • Crystallography, X-Ray
  • Histones
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Lysine
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondria, Liver
  • NAD
  • Peptides
  • Protein Processing, Post-Translational
  • Sirtuins
  • Succinic Acid