Gene Symbol: Sirt5
Description: sirtuin 5
Alias: 0610012J09Rik, 1500032M05Rik, AV001953, NAD-dependent protein deacylase sirtuin-5, mitochondrial, NAD-dependent deacetylase sirtuin-5, NAD-dependent lysine demalonylase and desuccinylase sirtuin-5, mitochondrial
Species: mouse
Products:     Sirt5

Top Publications

  1. Lombard D, Alt F, Cheng H, Bunkenborg J, Streeper R, Mostoslavsky R, et al. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol. 2007;27:8807-14 pubmed mitochondrial hyperacetylation was detectable in mice lacking the two other mitochondrial sirtuins, SIRT4 and SIRT5. Surprisingly, despite this biochemical phenotype, SIRT3-deficient mice are metabolically unremarkable under basal ..
  2. Nakagawa T, Lomb D, Haigis M, Guarente L. SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell. 2009;137:560-70 pubmed publisher
    ..Here, we show that SIRT5 localizes in the mitochondrial matrix and interacts with carbamoyl phosphate synthetase 1 (CPS1), an enzyme, ..
  3. Du J, Zhou Y, Su X, Yu J, Khan S, Jiang H, et al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science. 2011;334:806-9 pubmed publisher
    ..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...
  4. Park J, Chen Y, Tishkoff D, Peng C, Tan M, Dai L, et al. SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol Cell. 2013;50:919-30 pubmed publisher
    Protein function is regulated by diverse posttranslational modifications. The mitochondrial sirtuin SIRT5 removes malonyl and succinyl moieties from target lysines...
  5. Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker C, Steegborn C. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol. 2008;382:790-801 pubmed publisher
    ..Mammalian mitochondria contain three Sirtuins, Sirt3, Sirt4, and Sirt5. Only one substrate is known for Sirt3 as well as for Sirt4, and up to now, no target for Sirt5 has been reported...
  6. Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, et al. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics. 2011;10:M111.012658 pubmed publisher
    ..In addition, we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation ..
  7. Rardin M, He W, Nishida Y, Newman J, Carrico C, Danielson S, et al. SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab. 2013;18:920-33 pubmed publisher
    ..approach to characterize the lysine succinylome in liver mitochondria and its regulation by the desuccinylase SIRT5. A total of 1,190 unique sites were identified as succinylated, and 386 sites across 140 proteins representing ..
  8. Hershberger K, Abraham D, MARTIN A, Mao L, Liu J, Gu H, et al. Sirtuin 5 is required for mouse survival in response to cardiac pressure overload. J Biol Chem. 2017;292:19767-19781 pubmed publisher
    In mitochondria, the sirtuin SIRT5 is an NAD+-dependent protein deacylase that controls several metabolic pathways...
  9. Nakagawa T, Guarente L. Urea cycle regulation by mitochondrial sirtuin, SIRT5. Aging (Albany NY). 2009;1:578-81 pubmed
    Mammalian sirtuins have diverse roles in aging, metabolism and disease. Recently we reported a new function for SIRT5 in urea cycle regulation...

More Information


  1. Yu J, Sadhukhan S, Noriega L, Moullan N, He B, Weiss R, et al. Metabolic characterization of a Sirt5 deficient mouse model. Sci Rep. 2013;3:2806 pubmed publisher
    b>Sirt5, localized in the mitochondria, is a member of sirtuin family of NAD?-dependent deacetylases. Sirt5 was shown to deacetylate and activate carbamoyl phosphate synthase 1...
  2. Voelter Mahlknecht S, Mahlknecht U. Cloning, chromosomal characterization and FISH mapping of the NAD(+)-dependent histone deacetylase gene sirtuin 5 in the mouse. Int J Oncol. 2013;43:237-45 pubmed publisher
    Sirtuin 5 (SIRT5) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, belonging to the silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (sirtuins)...
  3. Li L, Zhang P, Bao Z, Wang T, Liu S, Huang F. PGC-1? Promotes Ureagenesis in Mouse Periportal Hepatocytes through SIRT3 and SIRT5 in Response to Glucagon. Sci Rep. 2016;6:24156 pubmed publisher
    ..showed that fasting strongly stimulated mice glucagon secretion, hepatic PGC-1?, sirtuin 3 (SIRT3) and sirtuin 5 (SIRT5) expression and ureagenesis enzymatic activity such as carbamoyl phosphate synthetase 1 (CPS1) and ornithine ..
  4. Tan M, Peng C, Anderson K, Chhoy P, Xie Z, Dai L, et al. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 2014;19:605-17 pubmed publisher
    ..We demonstrated that the previously annotated deacetylase, sirtuin 5 (SIRT5), is a lysine deglutarylase...
  5. Sadhukhan S, Liu X, Ryu D, Nelson O, Stupinski J, Li Z, et al. Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function. Proc Natl Acad Sci U S A. 2016;113:4320-5 pubmed publisher
    ..One such PTM is lysine succinylation, which is regulated by sirtuin 5 (SIRT5)...
  6. Witt O, Deubzer H, Milde T, Oehme I. HDAC family: What are the cancer relevant targets?. Cancer Lett. 2009;277:8-21 pubmed publisher
    ..The aim of this review is to discuss individual HDAC family members as drug targets in cancer taking into consideration their function under physiological conditions and their oncogenic potential in malignant disease. ..
  7. Li F, Liu L. SIRT5 Deficiency Enhances Susceptibility to Kainate-Induced Seizures and Exacerbates Hippocampal Neurodegeneration not through Mitochondrial Antioxidant Enzyme SOD2. Front Cell Neurosci. 2016;10:171 pubmed publisher
    ..Sirtuin 5 (SIRT5), localized in mitochondrial matrix, has been considered as an important functional modulator of mitochondria that ..
  8. Nakamura Y, Ogura M, Tanaka D, Inagaki N. Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5. Biochem Biophys Res Commun. 2008;366:174-9 pubmed
    ..regulator 2 (SIR2) is involved in extension of yeast longevity by calorie restriction, and SIRT3, SIRT4, and SIRT5 are mammalian homologs of SIR2 localized in mitochondria...
  9. Zhou L, Wang F, Sun R, Chen X, Zhang M, Xu Q, et al. SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense. EMBO Rep. 2016;17:811-22 pubmed publisher
    ..Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), ..
  10. Takumida M, Takumida H, Katagiri Y, Anniko M. Localization of sirtuins (SIRT1-7) in the aged mouse inner ear. Acta Otolaryngol. 2016;136:120-31 pubmed publisher
    ..In the cochlea, the expression of SIRT1, 3, and 5 (both mRNA and protein) was decreased in the old mice, whereas no noticeable difference was observed regarding SIRT2, 4, 6, or 7. ..
  11. Yang X, Liu B, Zhu W, Luo J. SIRT5, functions in cellular metabolism with a multiple enzymatic activities. Sci China Life Sci. 2015;58:912-4 pubmed publisher
  12. Nishida Y, Rardin M, Carrico C, He W, Sahu A, Gut P, et al. SIRT5 Regulates both Cytosolic and Mitochondrial Protein Malonylation with Glycolysis as a Major Target. Mol Cell. 2015;59:321-32 pubmed publisher
    Protein acylation links energetic substrate flux with cellular adaptive responses. SIRT5 is a NAD(+)-dependent lysine deacylase and removes both succinyl and malonyl groups...
  13. Liu L, Peritore C, Ginsberg J, Shih J, Arun S, Donmez G. Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson's disease. Behav Brain Res. 2015;281:215-21 pubmed publisher
    ..b>SIRT5, which localizes in the mitochondrial matrix, is nicotinamide adenine dinucleotide (NAD(+))-dependent histone ..
  14. Kawamura Y, Uchijima Y, Horike N, Tonami K, Nishiyama K, Amano T, et al. Sirt3 protects in vitro-fertilized mouse preimplantation embryos against oxidative stress-induced p53-mediated developmental arrest. J Clin Invest. 2010;120:2817-28 pubmed publisher
    ..These results indicate that Sirt3 plays a protective role in preimplantation embryos against stress conditions during in vitro fertilization and culture...
  15. Zhang Y, Bharathi S, Rardin M, Uppala R, Verdin E, Gibson B, et al. SIRT3 and SIRT5 regulate the enzyme activity and cardiolipin binding of very long-chain acyl-CoA dehydrogenase. PLoS ONE. 2015;10:e0122297 pubmed publisher
    SIRT3 and SIRT5 have been shown to regulate mitochondrial fatty acid oxidation but the molecular mechanisms behind the regulation are lacking...
  16. Buler M, Aatsinki S, Izzi V, Uusimaa J, Hakkola J. SIRT5 is under the control of PGC-1? and AMPK and is involved in regulation of mitochondrial energy metabolism. FASEB J. 2014;28:3225-37 pubmed publisher
    ..Overexpression of PGC-1? in mouse primary hepatocytes increased SIRT5 mRNA expression 4-fold and also the protein in a peroxisome proliferator-activated receptor ? (PPAR?)- and ..
  17. Scapoli L, Martinelli M, Pezzetti F, Palmieri A, Girardi A, Savoia A, et al. Expression and association data strongly support JARID2 involvement in nonsyndromic cleft lip with or without cleft palate. Hum Mutat. 2010;31:794-800 pubmed publisher
    ..Understanding the molecular role of JARID2 within facial development may offer additional information to further unravel the complex genetics of CL/P...
  18. Ogura M, Nakamura Y, Tanaka D, Zhuang X, Fujita Y, Obara A, et al. Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1. Biochem Biophys Res Commun. 2010;393:73-8 pubmed publisher
    ..In mammals, among the seven SIR2 homologues (SIRT1-7), SIRT3, 4, and 5 are localized to mitochondria. As SIRT5 mRNA levels in liver are increased by fasting, the physiological role of SIRT5 was investigated in liver of SIRT5-..
  19. Nakamura Y, Ogura M, Ogura K, Tanaka D, Inagaki N. SIRT5 deacetylates and activates urate oxidase in liver mitochondria of mice. FEBS Lett. 2012;586:4076-81 pubmed publisher
    We identified urate oxidase (UOX) as a target of SIRT5 by comparing mitochondrial proteins in livers of SIRT5-overexpressing transgenic (SIRT5 Tg) and wild-type mice by using two-dimensional electrophoresis...
  20. Guedouari H, Daigle T, Scorrano L, Hébert Chatelain E. Sirtuin 5 protects mitochondria from fragmentation and degradation during starvation. Biochim Biophys Acta Mol Cell Res. 2017;1864:169-176 pubmed publisher
    ..Here we show that the mitochondrial Sirtuin 5 (Sirt5) is essential for starvation induced mitochondrial elongation...
  21. Boylston J, Sun J, Chen Y, Gucek M, Sack M, Murphy E. Characterization of the cardiac succinylome and its role in ischemia-reperfusion injury. J Mol Cell Cardiol. 2015;88:73-81 pubmed publisher
    Succinylation refers to modification of lysine residues with succinyl groups donated by succinyl-CoA. Sirtuin5 (Sirt5) is a mitochondrial NAD(+)-dependent deacylase that catalyzes the removal of succinyl groups from proteins...
  22. Martin J, Balmer M, Rajendran S, Maurhofer O, Dufour J, St Pierre M. Nutritional stress exacerbates hepatic steatosis induced by deletion of the histidine nucleotide-binding (Hint2) mitochondrial protein. Am J Physiol Gastrointest Liver Physiol. 2016;310:G497-509 pubmed publisher
    ..The absence of Hint2 deregulates the posttranslational modification of several mitochondrial proteins, which impedes the adaptation to episodes of nutritional stress. ..
  23. Zhang Y, Bharathi S, Rardin M, Lu J, Maringer K, Sims Lucas S, et al. Lysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain. J Biol Chem. 2017;292:10239-10249 pubmed publisher
    b>SIRT5 is a lysine desuccinylase known to regulate mitochondrial fatty acid oxidation and the urea cycle. Here, SIRT5 was observed to bind to cardiolipin via an amphipathic helix on its N terminus...