Sirtuin 4

Sirtuin 4, also known as SIRT4, is a mitochondrial protein which in humans is encoded by the SIRT4 gene.^[5][6] SIRT4 is member of the mammalian sirtuin family of proteins, which are homologs to the yeast Sir2 protein. SIRT4 exhibits NAD+-dependent deacetylase activity.

SIRT4
Identifiers
Aliases	SIRT4, SIR2L4, sirtuin 4
External IDs	OMIM: 604482; MGI: 1922637; HomoloGene: 8164; GeneCards: SIRT4; OMA:SIRT4 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.23-q24.31 Start 120,302,316 bp[1] End 120,313,249 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 F Start 115,478,010 bp[2] End 115,484,725 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle apex of heart muscle of thigh gastrocnemius muscle right adrenal gland sperm left ventricle right adrenal cortex left adrenal gland left adrenal cortex Top expressed in neural layer of retina primary visual cortex superior frontal gyrus right kidney lip spermatid zygote muscle of thigh ventricular zone seminiferous tubule More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity NAD-dependent protein deacetylase activity metal ion binding protein binding NAD+ binding lipoamidase activity NAD+ ADP-ribosyltransferase activity hydrolase activity biotinidase activity zinc ion binding Cellular component mitochondrion mitochondrial inner membrane mitochondrial matrix Biological process peptidyl-lysine deacetylation negative regulation of insulin secretion positive regulation of lipid biosynthetic process protein ADP-ribosylation regulation of glutamine family amino acid metabolic process negative regulation of fatty acid oxidation regulation of pyruvate dehydrogenase activity cellular response to DNA damage stimulus negative regulation of protein processing involved in protein targeting to mitochondrion negative regulation of cardiac muscle cell apoptotic process glutamine metabolic process tricarboxylic acid metabolic process cellular response to hypoxia mitochondrion organization protein deacetylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23409 75387 Ensembl ENSG00000089163 ENSMUSG00000029524 UniProt Q9Y6E7 Q8R216 RefSeq (mRNA) NM_012240 NM_001385733 NM_001385734 NM_001385735 NM_001167691 NM_133760 RefSeq (protein) NP_036372 NP_001161163 NP_598521 Location (UCSC) Chr 12: 120.3 – 120.31 Mb Chr 5: 115.48 – 115.48 Mb PubMed search [3] [4]
Wikidata
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Function

SIRT4 is a mitochondrial ADP-ribosyltransferase that inhibits mitochondrial glutamate dehydrogenase 1 activity, thereby downregulating insulin secretion in response to amino acids.^[7] A deacetylation of malonyl-CoA decarboxylase enzyme by SIRT4 represses the enzyme activity, inhibiting fatty acid oxidation in muscle and liver cells.^[8][9] SIRT4 has a suppressive effect on peroxisome proliferator-activated receptor alpha (PPAR-α) which downregulates fatty acid oxidation in liver cells.^[9] Deacetylation of ADP/ATP translocase 2 (ANT2) increases cellular ATP by dampening mitochondrial uncoupling.^[9]

Clinical significance

SIRT4 is a mitochondrial tumor suppressor protein.^[9] Overexpression of SIRT4 inhibits cancer cell proliferation by inhibition of glutamine metabolism.^[9][10]