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Sirtuin 4
Symbols SIRT4 ; SIR2L4
External IDs OMIM604482 MGI1922637 HomoloGene8164 IUPHAR: 2710 GeneCards: SIRT4 Gene
EC number 2.4.2.-
Species Human Mouse
Entrez 23409 75387
Ensembl ENSG00000089163 ENSMUSG00000029524
UniProt Q9Y6E7 Q8R216
RefSeq (mRNA) NM_012240 NM_001167691
RefSeq (protein) NP_036372 NP_001161163
Location (UCSC) Chr 12:
120.74 – 120.75 Mb
Chr 5:
115.48 – 115.48 Mb
PubMed search [1] [2]

Sirtuin 4, also known as SIRT4 is a protein which in humans is encoded by the SIRT4 gene.[1][2]


This gene encodes a member of the sirtuin family of proteins which are homologs of the Sir2 gene in budding yeast. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been fully determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA.[3] Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity.[1][3] The protein encoded by this gene is included in class IV of the sirtuin family.[2]

SIRT4 is a mitochondrial ADP-ribosyltransferase that inhibits mitochondrial glutamate dehydrogenase 1 activity, thereby downregulating insulin secretion in response to amino acids.[4] It has been shown that SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells.[5]


  1. ^ a b Frye RA (June 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. 
  2. ^ a b "Entrez Gene: Sirtuin 4". 
  3. ^ a b Tanny JC, Dowd GJ, Huang J, Hilz H, Moazed D (December 1999). "An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing". Cell 99 (7): 735–45. doi:10.1016/S0092-8674(00)81671-2. PMID 10619427. 
  4. ^ Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L (September 2006). "SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells". Cell 126 (5): 941–54. doi:10.1016/j.cell.2006.06.057. PMID 16959573. 
  5. ^ Nasrin N, Wu X, Fortier E, Feng Y, Bare' OC, Chen S, Ren X, Wu Z, Streeper RS, Bordone L (October 2010). "SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells. In primary myotubes and hepatocytes, knockdown of SIRT4 results in increased Fatty Acid Oxidation, cellular respiration, and pAMPK levels. SIRT4 inhibition increases fat oxidative capacity in liver and mitochondrial function in muscle, which might provide therapeutic benefits for diseases associated with ectopic lipid storage such as type 2 diabetes.". J. Biol. Chem. 285 (42): 31995–2002. doi:10.1074/jbc.M110.124164. PMC 2952200. PMID 20685656. 

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.