Sirtuin 4

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AliasesSIRT4, SIR2L4, sirtuin 4
External IDsMGI: 1922637 HomoloGene: 8164 GeneCards: SIRT4
Gene location (Human)
Chromosome 12 (human)
Chr.Chromosome 12 (human)[1]
Chromosome 12 (human)
Genomic location for SIRT4
Genomic location for SIRT4
Band12q24.23-q24.31Start120,302,316 bp[1]
End120,313,249 bp[1]
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 12: 120.3 – 120.31 MbChr 5: 115.48 – 115.48 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Sirtuin 4, also known as SIRT4, is a protein which in humans is encoded by the SIRT4 gene.[5][6]


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.[7] Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity.[5][7] The protein encoded by this gene is included in class IV of the sirtuin family.[6]

SIRT4 is a mitochondrial ADP-ribosyltransferase that inhibits mitochondrial glutamate dehydrogenase 1 activity, thereby downregulating insulin secretion in response to amino acids.[8] It has been shown that SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells.[9]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000089163 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029524 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ 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): 273–79. doi:10.1006/bbrc.1999.0897. PMID 10381378.
  6. ^ a b "Entrez Gene: Sirtuin 4".
  7. ^ 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.
  8. ^ 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.
  9. ^ 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): 31995–32002. 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.