GENERAL INFORMATIONi
Gene namei SIRT1
Synonyms SIR2L1
Gene descriptioni Sirtuin 1
Protein classi Enzymes
Metabolic proteins
Predicted locationi Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi
Chromosome 10
Cytoband q21.3
Chromosome location (bp) 67884656 - 67918390
Number of transcriptsi 4
Ensembl ENSG00000096717 (version 109)
Entrez gene 23411
HGNC HGNC:14929
UniProt Q96EB6 (UniProt - Evidence at protein level)
neXtProt NX_Q96EB6
GeneCards SIRT1
Antibodypedia SIRT1 antibodies


PROTEIN FUNCTION
Protein function (UniProt)i NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression 55. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively 56, 57, 58. Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction 59. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT) (By similarity). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes 60. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus 61, 62. Deacetylates 'Lys-266' of SUV39H1, leading to its activation 63. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1 64. Deacetylates H2A and 'Lys-26' of H1-4 65. Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression 66. Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting (By similarity). Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1 67, 68. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2 69, 70. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response 71, 72. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence 73, 74. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I (By similarity). Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability 75, 76. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation 77, 78, 79. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis 80. Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing 81. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha 82. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1 83, 84, 85, 86. Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver 87. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation 88. Involved in HES1- and HEY2-mediated transcriptional repression 89. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62' 90. Deacetylates MEF2D 91. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3 92. Represses HNF1A-mediated transcription (By similarity). Required for the repression of ESRRG by CREBZF 93. Deacetylates NR1H3 and NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed 94. Involved in lipid metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol synthesis 95, 96. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2 (By similarity). Deacetylates p300/EP300 and PRMT1 (By similarity). Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation 97. Involved in liver and muscle metabolism. Through deacetylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletal muscle under low-glucose conditions and is involved in glucose homeostasis 98. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression 99, 100. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and facilitating recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2 101, 102, 103, 104, 105, 106. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN 107, 108, 109. Promotes DNA double-strand breaks by mediating deacetylation of SIRT6 110. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage 111. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1 112. Catalyzes deacetylation of ERCC4/XPF, thereby impairing interaction with ERCC1 and nucleotide excision repair (NER) 113. Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8 114. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation 115. Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear 116, 117. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability 118. Deacetylates MECOM/EVI1 119. Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization 120. During the neurogenic transition, represses selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation. Regulates the circadian expression of several core clock genes, including BMAL1, RORC, PER2 and CRY1 and plays a critical role in maintaining a controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling 121. Deacetylates BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator (By similarity). Deacetylates PER2, facilitating its ubiquitination and degradation by the proteosome (By similarity). Protects cardiomyocytes against palmitate-induced apoptosis (By similarity). Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity 122. Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis 123. Involved in the CCAR2-mediated regulation of PCK1 and NR1D1 124. Deacetylates CTNB1 at 'Lys-49' 125. In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling (By similarity). In addition to protein deacetylase activity, also acts as protein-lysine deacylase by mediating protein depropionylation and decrotonylation 126. Mediates depropionylation of Osterix (SP7) (By similarity). Catalyzes decrotonylation of histones; it however does not represent a major histone decrotonylase 127. Deacetylates SOX9; promoting SOX9 nuclear localization and transactivation activity (By similarity). Involved in the regulation of centrosome duplication. Deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly 128. Deacetylates NDC80/HEC1 129. show less
Molecular function (UniProt)i Developmental protein, Transferase
Biological process (UniProt)i Apoptosis, Biological rhythms, Differentiation, Host-virus interaction, Myogenesis, Transcription, Transcription regulation
Ligand (UniProt)i Metal-binding, NAD, Zinc
Gene summary (Entrez)i 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] show less
PROTEIN INFORMATIONi
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)		 Transmembrane regions
(predicted)
SIRT1-201
ENSP00000212015
ENST00000212015
Q96EB6
[Direct mapping] NAD-dependent protein deacetylase sirtuin-1 SirtT1 75 kDa fragment
Show all
A0A024QZQ1
[Target identity:100%; Query identity:100%] Sirtuin (Silent mating type information regulation 2 homolog) 1 (S. cerevisiae), isoform CRA_a
Show all
Enzymes
   ENZYME proteins
   Transferases
Metabolic proteins
   SPOCTOPUS predicted secreted proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000012 [single strand break repair]
GO:0000122 [negative regulation of transcription by RNA polymerase II]
GO:0000183 [rDNA heterochromatin formation]
GO:0000720 [pyrimidine dimer repair by nucleotide-excision repair]
GO:0000731 [DNA synthesis involved in DNA repair]
GO:0000785 [chromatin]
GO:0000791 [euchromatin]
GO:0000792 [heterochromatin]
GO:0000978 [RNA polymerase II cis-regulatory region sequence-specific DNA binding]
GO:0001525 [angiogenesis]
GO:0001542 [ovulation from ovarian follicle]
GO:0001650 [fibrillar center]
GO:0001678 [cellular glucose homeostasis]
GO:0001934 [positive regulation of protein phosphorylation]
GO:0001938 [positive regulation of endothelial cell proliferation]
GO:0002039 [p53 binding]
GO:0002821 [positive regulation of adaptive immune response]
GO:0003713 [transcription coactivator activity]
GO:0003714 [transcription corepressor activity]
GO:0004407 [histone deacetylase activity]
GO:0005515 [protein binding]
GO:0005634 [nucleus]
GO:0005635 [nuclear envelope]
GO:0005637 [nuclear inner membrane]
GO:0005654 [nucleoplasm]
GO:0005677 [chromatin silencing complex]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005739 [mitochondrion]
GO:0005829 [cytosol]
GO:0006325 [chromatin organization]
GO:0006346 [DNA methylation-dependent heterochromatin formation]
GO:0006476 [protein deacetylation]
GO:0006642 [triglyceride mobilization]
GO:0006915 [apoptotic process]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0006979 [response to oxidative stress]
GO:0007179 [transforming growth factor beta receptor signaling pathway]
GO:0007283 [spermatogenesis]
GO:0007346 [regulation of mitotic cell cycle]
GO:0007517 [muscle organ development]
GO:0007623 [circadian rhythm]
GO:0008022 [protein C-terminus binding]
GO:0008284 [positive regulation of cell population proliferation]
GO:0008630 [intrinsic apoptotic signaling pathway in response to DNA damage]
GO:0009267 [cellular response to starvation]
GO:0010629 [negative regulation of gene expression]
GO:0010824 [regulation of centrosome duplication]
GO:0010875 [positive regulation of cholesterol efflux]
GO:0010883 [regulation of lipid storage]
GO:0010906 [regulation of glucose metabolic process]
GO:0014068 [positive regulation of phosphatidylinositol 3-kinase signaling]
GO:0016239 [positive regulation of macroautophagy]
GO:0016567 [protein ubiquitination]
GO:0016575 [histone deacetylation]
GO:0016605 [PML body]
GO:0016740 [transferase activity]
GO:0016922 [nuclear receptor binding]
GO:0017136 [NAD-dependent histone deacetylase activity]
GO:0018394 [peptidyl-lysine acetylation]
GO:0019213 [deacetylase activity]
GO:0019899 [enzyme binding]
GO:0019904 [protein domain specific binding]
GO:0030154 [cell differentiation]
GO:0030225 [macrophage differentiation]
GO:0030308 [negative regulation of cell growth]
GO:0030512 [negative regulation of transforming growth factor beta receptor signaling pathway]
GO:0031062 [positive regulation of histone methylation]
GO:0031065 [positive regulation of histone deacetylation]
GO:0031393 [negative regulation of prostaglandin biosynthetic process]
GO:0031507 [heterochromatin formation]
GO:0031648 [protein destabilization]
GO:0032007 [negative regulation of TOR signaling]
GO:0032071 [regulation of endodeoxyribonuclease activity]
GO:0032088 [negative regulation of NF-kappaB transcription factor activity]
GO:0032868 [response to insulin]
GO:0032922 [circadian regulation of gene expression]
GO:0032991 [protein-containing complex]
GO:0033210 [leptin-mediated signaling pathway]
GO:0033553 [rDNA heterochromatin]
GO:0033558 [protein lysine deacetylase activity]
GO:0034391 [regulation of smooth muscle cell apoptotic process]
GO:0034979 [NAD-dependent protein deacetylase activity]
GO:0034983 [peptidyl-lysine deacetylation]
GO:0035098 [ESC/E(Z) complex]
GO:0035356 [cellular triglyceride homeostasis]
GO:0035358 [regulation of peroxisome proliferator activated receptor signaling pathway]
GO:0042127 [regulation of cell population proliferation]
GO:0042149 [cellular response to glucose starvation]
GO:0042326 [negative regulation of phosphorylation]
GO:0042393 [histone binding]
GO:0042542 [response to hydrogen peroxide]
GO:0042595 [behavioral response to starvation]
GO:0042632 [cholesterol homeostasis]
GO:0042771 [intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator]
GO:0042802 [identical protein binding]
GO:0042981 [regulation of apoptotic process]
GO:0043065 [positive regulation of apoptotic process]
GO:0043066 [negative regulation of apoptotic process]
GO:0043124 [negative regulation of I-kappaB kinase/NF-kappaB signaling]
GO:0043161 [proteasome-mediated ubiquitin-dependent protein catabolic process]
GO:0043280 [positive regulation of cysteine-type endopeptidase activity involved in apoptotic process]
GO:0043398 [HLH domain binding]
GO:0043425 [bHLH transcription factor binding]
GO:0043433 [negative regulation of DNA-binding transcription factor activity]
GO:0043518 [negative regulation of DNA damage response, signal transduction by p53 class mediator]
GO:0043536 [positive regulation of blood vessel endothelial cell migration]
GO:0044321 [response to leptin]
GO:0045348 [positive regulation of MHC class II biosynthetic process]
GO:0045599 [negative regulation of fat cell differentiation]
GO:0045722 [positive regulation of gluconeogenesis]
GO:0045739 [positive regulation of DNA repair]
GO:0045766 [positive regulation of angiogenesis]
GO:0045786 [negative regulation of cell cycle]
GO:0045892 [negative regulation of DNA-templated transcription]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0046015 [regulation of transcription by glucose]
GO:0046628 [positive regulation of insulin receptor signaling pathway]
GO:0046872 [metal ion binding]
GO:0046969 [NAD-dependent histone deacetylase activity (H3-K9 specific)]
GO:0048511 [rhythmic process]
GO:0050872 [white fat cell differentiation]
GO:0051019 [mitogen-activated protein kinase binding]
GO:0051097 [negative regulation of helicase activity]
GO:0051152 [positive regulation of smooth muscle cell differentiation]
GO:0051574 [positive regulation of histone H3-K9 methylation]
GO:0051898 [negative regulation of protein kinase B signaling]
GO:0055089 [fatty acid homeostasis]
GO:0060766 [negative regulation of androgen receptor signaling pathway]
GO:0060907 [positive regulation of macrophage cytokine production]
GO:0061773 [eNoSc complex]
GO:0070301 [cellular response to hydrogen peroxide]
GO:0070403 [NAD+ binding]
GO:0070857 [regulation of bile acid biosynthetic process]
GO:0070914 [UV-damage excision repair]
GO:0070932 [histone H3 deacetylation]
GO:0071356 [cellular response to tumor necrosis factor]
GO:0071441 [negative regulation of histone H3-K14 acetylation]
GO:0071456 [cellular response to hypoxia]
GO:0071479 [cellular response to ionizing radiation]
GO:0071900 [regulation of protein serine/threonine kinase activity]
GO:0090335 [regulation of brown fat cell differentiation]
GO:0090400 [stress-induced premature senescence]
GO:0097009 [energy homeostasis]
GO:0106230 [protein depropionylation]
GO:0106231 [protein-propionyllysine depropionylase activity]
GO:0140297 [DNA-binding transcription factor binding]
GO:0160011 [NAD-dependent protein decrotonylase activity]
GO:0160012 [NAD-dependent histone decrotonylase activity]
GO:1900034 [regulation of cellular response to heat]
GO:1900113 [negative regulation of histone H3-K9 trimethylation]
GO:1901215 [negative regulation of neuron death]
GO:1901984 [negative regulation of protein acetylation]
GO:1902166 [negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator]
GO:1902176 [negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway]
GO:1902237 [positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway]
GO:1904179 [positive regulation of adipose tissue development]
GO:1990254 [keratin filament binding]
GO:1990830 [cellular response to leukemia inhibitory factor]
GO:1990841 [promoter-specific chromatin binding]
GO:2000111 [positive regulation of macrophage apoptotic process]
GO:2000480 [negative regulation of cAMP-dependent protein kinase activity]
GO:2000481 [positive regulation of cAMP-dependent protein kinase activity]
GO:2000619 [negative regulation of histone H4-K16 acetylation]
GO:2000655 [negative regulation of cellular response to testosterone stimulus]
GO:2000757 [negative regulation of peptidyl-lysine acetylation]
GO:2000773 [negative regulation of cellular senescence]
GO:2000774 [positive regulation of cellular senescence]
Show all
 747 aa
81.7 kDa 		No 0
SIRT1-202
ENSP00000384063
ENST00000403579
B0QZ35
[Direct mapping] NAD-dependent protein deacetylase sirtuin-1; cDNA FLJ90324 fis, clone NT2RP2001817, highly similar to NAD-dependent deacetylase sirtuin-1
Show all
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0001650 [fibrillar center]
GO:0005654 [nucleoplasm]
GO:0005829 [cytosol]
GO:0016740 [transferase activity]
GO:0070403 [NAD+ binding]
Show all
 444 aa
49.2 kDa 		No 0
SIRT1-203
ENSP00000384508
ENST00000406900
B0QZ35
[Direct mapping] NAD-dependent protein deacetylase sirtuin-1; cDNA FLJ90324 fis, clone NT2RP2001817, highly similar to NAD-dependent deacetylase sirtuin-1
Show all
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0001650 [fibrillar center]
GO:0005654 [nucleoplasm]
GO:0005829 [cytosol]
GO:0016740 [transferase activity]
GO:0070403 [NAD+ binding]
Show all
 444 aa
49.2 kDa 		No 0
SIRT1-204
ENSP00000409208
ENST00000432464
E9PC49
[Direct mapping] NAD-dependent protein deacetylase sirtuin-1
Show all
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0001650 [fibrillar center]
GO:0005654 [nucleoplasm]
GO:0005829 [cytosol]
GO:0016740 [transferase activity]
GO:0070403 [NAD+ binding]
Show all
 452 aa
50.5 kDa 		No 0

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