SIRT1 Gene

Name	sirtuin 1
Description	This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. 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 determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSIRT1 is a conserved NAD⁺‐dependent deacetylase that plays a central role in coupling nutrient sensing to cellular energy homeostasis. It has been shown to be activated by small‐molecule polyphenols such as resveratrol, although its activation in vitro may depend on subtle substrate features (15749705). SIRT1 activation enhances mitochondrial oxidative phosphorylation and biogenesis through deacetylation of key regulators including PGC-1α, thereby improving aerobic capacity and whole-body metabolic homeostasis (17112576, 18482975, 18687677, 20103737, 20421294, 20817729, 26831453)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its metabolic functions, SIRT1 governs cell survival and stress responses by modulating the activity of several transcription factors. It deacetylates members of the FOXO family to shift cellular outcomes toward stress resistance, while simultaneously regulating the tumor suppressor p53 and NF-κB signaling to counteract excessive apoptosis (11672522, 14976264, 14980222, 15152190, 15205477, 16354677). Furthermore, SIRT1 is regulated by and forms feedback loops with other factors such as E2F1, AROS, and DBC1, which fine-tune its deacetylase activity and thereby influence the transcriptional control of cell cycle and apoptotic pathways (16892051, 17964266, 18235501, 18755897)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSIRT1 also exerts widespread protective effects against cellular stress, inflammation, and tissue degeneration. It promotes endothelial function by deacetylating eNOS and thereby enhancing nitric oxide production for vasodilation (17785417). SIRT1 induces autophagy via the deacetylation of core autophagic proteins, thereby contributing to cell survival under nutrient deficiency (18296641), and it modulates hypoxic and inflammatory signaling pathways—dampening HIF-1α activation in low oxygen scenarios (19498162) while suppressing NF-κB–dependent proinflammatory cytokine release (16183991, 17041012, 17581637, 18174544, 19104446, 19996091, 23770291, 24141423, 24507186)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, the role of SIRT1 in cancer biology and genomic stability appears to be complex and context dependent. SIRT1 contributes to DNA repair and limits genomic instability, thereby exerting tumor‐suppressive functions (16207712, 17638871, 18414679, 18835033). However, depending on cellular context and p53 status, elevated SIRT1 expression has been associated with tumor survival and progression in some malignancies, such as colon and prostate cancers, making it a potential target for therapeutic intervention (19132007, 22340598)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "31", "end_ref": "36"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Margie T Borra, Brian C Smith, John M Denu "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of human SIRT1 activation by resveratrol."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M501250200"}], "href": "https://doi.org/10.1074/jbc.M501250200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15749705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15749705"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marie Lagouge, Carmen Argmann, Zachary Gerhart-Hines, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2006.11.013"}], "href": "https://doi.org/10.1016/j.cell.2006.11.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17112576"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17112576"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiuyun Hou, Shanqin Xu, Karlene A Maitland-Toolan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M802187200"}], "href": "https://doi.org/10.1074/jbc.M802187200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18482975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18482975"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fan Lan, Jose M Cacicedo, Neil Ruderman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M805711200"}], "href": "https://doi.org/10.1074/jbc.M805711200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18687677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18687677"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Neil B Ruderman, X Julia Xu, Lauren Nelson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK and SIRT1: a long-standing partnership?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00745.2009"}], "href": "https://doi.org/10.1152/ajpendo.00745.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20103737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20103737"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhenggang Yang, Barbara B Kahn, Hang Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Macrophage alpha1 AMP-activated protein kinase (alpha1AMPK) antagonizes fatty acid-induced inflammation through SIRT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.123620"}], "href": "https://doi.org/10.1074/jbc.M110.123620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20421294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20421294"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Bhaskar Ponugoti, Dong-Hyun Kim, Zhen Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.122978"}], "href": "https://doi.org/10.1074/jbc.M110.122978"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20817729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20817729"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Bor Luen Tang "}, {"type": "b", "children": [{"type": "t", "text": "Sirt1 and the Mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cells (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14348/molcells.2016.2318"}], "href": "https://doi.org/10.14348/molcells.2016.2318"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26831453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26831453"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "J Luo, A Y Nikolaev, S Imai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Negative control of p53 by Sir2alpha promotes cell survival under stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(01)00524-4"}], "href": "https://doi.org/10.1016/s0092-8674(01"}, {"type": "t", "text": "00524-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11672522"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11672522"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Anne Brunet, Lora B Sweeney, J Fitzhugh Sturgill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1094637"}], "href": "https://doi.org/10.1126/science.1094637"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14976264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14976264"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Maria Carla Motta, Nullin Divecha, Madeleine Lemieux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian SIRT1 represses forkhead transcription factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(04)00126-6"}], "href": "https://doi.org/10.1016/s0092-8674(04"}, {"type": "t", "text": "00126-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14980222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14980222"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Fan Yeung, Jamie E Hoberg, Catherine S Ramsey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600244"}], "href": "https://doi.org/10.1038/sj.emboj.7600244"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15152190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15152190"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Haim Y Cohen, Christine Miller, Kevin J Bitterman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1099196"}], "href": "https://doi.org/10.1126/science.1099196"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15205477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15205477"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jonathan M Solomon, Rao Pasupuleti, Lei Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.1.28-38.2006"}], "href": "https://doi.org/10.1128/MCB.26.1.28-38.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16354677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16354677"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Chuangui Wang, Lihong Chen, Xinghua Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1468"}], "href": "https://doi.org/10.1038/ncb1468"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16892051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16892051"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Eun-Joo Kim, Jeong-Hoon Kho, Moo-Rim Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.08.030"}], "href": "https://doi.org/10.1016/j.molcel.2007.08.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17964266"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17964266"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Ja-Eun Kim, Junjie Chen, Zhenkun Lou "}, {"type": "b", "children": [{"type": "t", "text": "DBC1 is a negative regulator of SIRT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06500"}], "href": "https://doi.org/10.1038/nature06500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18235501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18235501"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Munekazu Yamakuchi, Marcella Ferlito, Charles J Lowenstein "}, {"type": "b", "children": [{"type": "t", "text": "miR-34a repression of SIRT1 regulates apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0801613105"}], "href": "https://doi.org/10.1073/pnas.0801613105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18755897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18755897"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jennifer Chen, Yungui Zhou, Sarah Mueller-Steiner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M509329200"}], "href": "https://doi.org/10.1074/jbc.M509329200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16183991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16183991"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Se-Ran Yang, Jessica Wright, Mark Bauter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NF-kappaB in macrophages in vitro and in rat lungs in vivo: implications for chronic inflammation and aging."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00308.2006"}], "href": "https://doi.org/10.1152/ajplung.00308.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17041012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17041012"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Dohoon Kim, Minh Dang Nguyen, Matthew M Dobbin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601758"}], "href": "https://doi.org/10.1038/sj.emboj.7601758"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17581637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17581637"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Ilwola Mattagajasingh, Cuk-Seong Kim, Asma Naqvi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0704329104"}], "href": "https://doi.org/10.1073/pnas.0704329104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17785417"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17785417"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Saravanan Rajendrasozhan, Se-Ran Yang, Vuokko L Kinnula, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Crit Care Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1164/rccm.200708-1269OC"}], "href": "https://doi.org/10.1164/rccm.200708-1269OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18174544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18174544"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "In Hye Lee, Liu Cao, Raul Mostoslavsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0712145105"}], "href": "https://doi.org/10.1073/pnas.0712145105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18296641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18296641"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Carl Julien, Cyntia Tremblay, Vincent Emond, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuropathol Exp Neurol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/NEN.0b013e3181922348"}], "href": "https://doi.org/10.1097/NEN.0b013e3181922348"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19104446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19104446"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Elhadji M Dioum, Rui Chen, Matthew S Alexander, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1169956"}], "href": "https://doi.org/10.1126/science.1169956"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19498162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19498162"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Jorg van Loosdregt, Yvonne Vercoulen, Teun Guichelaar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-02-207118"}], "href": "https://doi.org/10.1182/blood-2009-02-207118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19996091"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19996091"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Anu Kauppinen, Tiina Suuronen, Johanna Ojala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2013.06.007"}], "href": "https://doi.org/10.1016/j.cellsig.2013.06.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23770291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23770291"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Kazuhiro Hasegawa, Shu Wakino, Petra Simic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3363"}], "href": "https://doi.org/10.1038/nm.3363"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24141423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24141423"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "A Zara Herskovits, Leonard Guarente "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 in neurodevelopment and brain senescence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2014.01.028"}], "href": "https://doi.org/10.1016/j.neuron.2014.01.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24507186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24507186"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Jyothish B Pillai, Ayman Isbatan, Shin-ichiro Imai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M506162200"}], "href": "https://doi.org/10.1074/jbc.M506162200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16207712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16207712"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Derek M Huffman, William E Grizzle, Marcas M Bamman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 is significantly elevated in mouse and human prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-0085"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-0085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17638871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17638871"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Ron Firestein, Gil Blander, Shaday Michan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0002020"}], "href": "https://doi.org/10.1371/journal.pone.0002020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18414679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18414679"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Rui-Hong Wang, Kundan Sengupta, Cuiling Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2008.09.001"}], "href": "https://doi.org/10.1016/j.ccr.2008.09.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18835033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18835033"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Christopher L Brooks, Wei Gu "}, {"type": "b", "children": [{"type": "t", "text": "How does SIRT1 affect metabolism, senescence and cancer?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrc2562"}], "href": "https://doi.org/10.1038/nrc2562"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19132007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19132007"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Ling Li, Lisheng Wang, Liang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of p53 by SIRT1 inhibition enhances elimination of CML leukemia stem cells in combination with imatinib."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2011.12.020"}], "href": "https://doi.org/10.1016/j.ccr.2011.12.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22340598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22340598"}]}]}]}
Synonyms	SIR2alpha, SIR2L1, HSIR2
Proteins	SIR1_HUMAN
NCBI Gene ID	23411
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SIRT1 has 16,486 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 130 datasets.

Click the + buttons to view associations for SIRT1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SIRT1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by SIRT1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SIRT1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SIRT1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SIRT1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SIRT1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SIRT1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving SIRT1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SIRT1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SIRT1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SIRT1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SIRT1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SIRT1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with SIRT1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SIRT1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SIRT1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SIRT1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SIRT1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SIRT1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SIRT1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SIRT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SIRT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SIRT1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SIRT1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SIRT1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SIRT1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing SIRT1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SIRT1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SIRT1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SIRT1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SIRT1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SIRT1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SIRT1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SIRT1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SIRT1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SIRT1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SIRT1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for SIRT1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SIRT1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SIRT1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SIRT1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.