Sequence Detail

ID/Version

P59941 (UniProt | EBI)

Last sequence update: 2003-10-31
Last annotation update: 2024-11-27

Sequence description from provider

RecName: Full=NAD-dependent protein deacylase sirtuin-6 {ECO:0000305}; EC=2.3.1.- {ECO:0000250|UniProtKB:Q8N6T7};AltName: Full=NAD-dependent protein deacetylase sirtuin-6 {ECO:0000305}; EC=2.3.1.286 {ECO:0000255|PROSITE-ProRule:PRU00236, E

Provider

SWISS-PROT

Sequence

Polypeptide 334 aa

Source

Organism mouse

See UniProt | EBI for source

Annotated genes and markers

Follow the symbol links to get more information on the GO terms, expression assays, orthologs, phenotypic alleles, and other information for the genes or markers below.

Type	Symbol	Name	GO Terms	Expression Assays	Orthologs	Phenotypic Alleles
Gene	Sirt6	sirtuin 6	157	107	3	30

Sequence references in MGI

J:99908 Liszt G, et al., Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem. 2005 Jun 3;280(22):21313-20
J:112817 Mostoslavsky R, et al., Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell. 2006 Jan 27;124(2):315-29
J:146526 Van Gool F, et al., Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner. Nat Med. 2009 Feb;15(2):206-10
J:147591 Kawahara TL, et al., SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell. 2009 Jan 9;136(1):62-74
J:166368 Kim HS, et al., Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metab. 2010 Sep 8;12(3):224-36
J:167023 Xiao C, et al., SIRT6 deficiency results in severe hypoglycemia by enhancing both basal and insulin-stimulated glucose uptake in mice. J Biol Chem. 2010 Nov 19;285(47):36776-84
J:167155 Schwer B, et al., Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity. Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21790-4
J:167957 Zhong L, et al., The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell. 2010 Jan 22;140(2):280-93
J:173531 Mao Z, et al., SIRT6 promotes DNA repair under stress by activating PARP1. Science. 2011 Jun 17;332(6036):1443-6
J:181684 Kanfi Y, et al., The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012 Mar 8;483(7388):218-21
J:193985 Dominy JE Jr, et al., The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis. Mol Cell. 2012 Dec 28;48(6):900-13
J:196437 Jiang H, et al., SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl lysine. Nature. 2013 Apr 4;496(7443):110-3
J:202697 Toiber D, et al., SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling. Mol Cell. 2013 Aug 22;51(4):454-68
J:203942 Tao R, et al., FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression. J Biol Chem. 2013 Oct 11;288(41):29252-9
J:212254 Zhang P, et al., Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10684-9
J:214604 Masri S, et al., Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism. Cell. 2014 Jul 31;158(3):659-72
J:219058 Sebastian C, et al., The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell. 2012 Dec 7;151(6):1185-99
J:234471 Kugel S, et al., SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b. Cell. 2016 Jun 2;165(6):1401-15
J:246935 Kuang J, et al., Fat-Specific Sirt6 Ablation Sensitizes Mice to High-Fat Diet-Induced Obesity and Insulin Resistance by Inhibiting Lipolysis. Diabetes. 2017 May;66(5):1159-1171
J:247143 Peshti V, et al., Characterization of physiological defects in adult SIRT6-/- mice. PLoS One. 2017;12(4):e0176371
J:249895 Yao L, et al., Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat. Cell Rep. 2017 Jul 18;20(3):641-654
J:250994 Chen Q, et al., SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion. Cell Rep. 2017 Mar 28;18(13):3155-3166
J:253685 Liu M, et al., Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling. Nat Commun. 2017 Sep 04;8(1):413
J:254113 Song MY, et al., Insulin secretion impairment in Sirt6 knockout pancreatic beta cells is mediated by suppression of the FoxO1-Pdx1-Glut2 pathway. Sci Rep. 2016 Jul 26;6:30321
J:264146 Ghosh S, et al., Haploinsufficiency of Trp53 dramatically extends the lifespan of Sirt6-deficient mice. Elife. 2018 Feb 23;7:e32127
J:274744 Chen L, et al., Hepatocyte-specific Sirt6 deficiency impairs ketogenesis. J Biol Chem. 2019 Feb 1;294(5):1579-1589
J:275081 Simon M, et al., LINE1 Derepression in Aged Wild-Type and SIRT6-Deficient Mice Drives Inflammation. Cell Metab. 2019 Apr 2;29(4):871-885.e5
J:278647 Etchegaray JP, et al., The Histone Deacetylase SIRT6 Restrains Transcription Elongation via Promoter-Proximal Pausing. Mol Cell. 2019 Aug 22;75(4):683-699.e7
J:281991 Jung SM, et al., Non-canonical mTORC2 Signaling Regulates Brown Adipocyte Lipid Catabolism through SIRT6-FoxO1. Mol Cell. 2019 Aug 22;75(4):807-822.e8
J:288674 Naiman S, et al., SIRT6 Promotes Hepatic Beta-Oxidation via Activation of PPARalpha. Cell Rep. 2019 Dec 17;29(12):4127-4143.e8
J:291806 Sun S, et al., Sirt6 deacetylase activity regulates circadian rhythms via Per2. Biochem Biophys Res Commun. 2019 Apr 2;511(2):234-238
J:322365 Etchegaray JP, et al., The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine. Nat Cell Biol. 2015 May;17(5):545-57
J:322373 Rezazadeh S, et al., SIRT6 mono-ADP ribosylates KDM2A to locally increase H3K36me2 at DNA damage sites to inhibit transcription and promote repair. Aging (Albany NY). 2020 Jun 25;12(12):11165-11184
J:322374 Rezazadeh S, et al., SIRT6 promotes transcription of a subset of NRF2 targets by mono-ADP-ribosylating BAF170. Nucleic Acids Res. 2019 Sep 5;47(15):7914-7928
J:322375 Ferrer CM, et al., An inactivating mutation in the histone deacetylase SIRT6 causes human perinatal lethality. Genes Dev. 2018 Mar 1;32(5-6):373-388
J:322377 Van Meter M, et al., SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nat Commun. 2014 Sep 23;5:5011
J:322389 Tian X, et al., SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species. Cell. 2019 Apr 18;177(3):622-638.e22
J:341999 Roichman A, et al., Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nat Commun. 2021 May 28;12(1):3208