SIRT1 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0097009Biological processenergy homeostasis
GO_0042542Biological processresponse to hydrogen peroxide
GO_0045786Biological processnegative regulation of cell cycle
GO_0006642Biological processtriglyceride mobilization
GO_0051097Biological processnegative regulation of helicase activity
GO_0032071Biological processregulation of endodeoxyribonuclease activity
GO_0000183Biological processrDNA heterochromatin formation
GO_0030225Biological processmacrophage differentiation
GO_2000773Biological processnegative regulation of cellular senescence
GO_0006346Biological processDNA methylation-dependent heterochromatin formation
GO_0046015Biological processregulation of transcription by glucose
GO_0009267Biological processcellular response to starvation
GO_0051152Biological processpositive regulation of smooth muscle cell differentiation
GO_2000655Biological processnegative regulation of cellular response to testosterone stimulus
GO_0032088Biological processnegative regulation of NF-kappaB transcription factor activity
GO_2000757Biological processnegative regulation of peptidyl-lysine acetylation
GO_0045722Biological processpositive regulation of gluconeogenesis
GO_0043066Biological processnegative regulation of apoptotic process
GO_0007346Biological processregulation of mitotic cell cycle
GO_0060766Biological processnegative regulation of androgen receptor signaling pathway
GO_1902166Biological processnegative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO_0051897Biological processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO_0006979Biological processresponse to oxidative stress
GO_0031393Biological processnegative regulation of prostaglandin biosynthetic process
GO_0043161Biological processproteasome-mediated ubiquitin-dependent protein catabolic process
GO_0070301Biological processcellular response to hydrogen peroxide
GO_2000480Biological processnegative regulation of cAMP-dependent protein kinase activity
GO_0050872Biological processwhite fat cell differentiation
GO_1901797Biological processnegative regulation of signal transduction by p53 class mediator
GO_0001525Biological processangiogenesis
GO_0010868Biological processnegative regulation of triglyceride biosynthetic process
GO_0045348Biological processpositive regulation of MHC class II biosynthetic process
GO_0090335Biological processregulation of brown fat cell differentiation
GO_0010629Biological processnegative regulation of gene expression
GO_0045766Biological processpositive regulation of angiogenesis
GO_0070914Biological processUV-damage excision repair
GO_0032007Biological processnegative regulation of TOR signaling
GO_0045599Biological processnegative regulation of fat cell differentiation
GO_0034391Biological processregulation of smooth muscle cell apoptotic process
GO_0071900Biological processregulation of protein serine/threonine kinase activity
GO_0031507Biological processheterochromatin formation
GO_0035358Biological processregulation of peroxisome proliferator activated receptor signaling pathway
GO_1900034Biological processregulation of cellular response to heat
GO_0051658Biological processmaintenance of nucleus location
GO_0042981Biological processregulation of apoptotic process
GO_0016239Biological processpositive regulation of macroautophagy
GO_0010883Biological processregulation of lipid storage
GO_0000731Biological processDNA synthesis involved in DNA repair
GO_0042595Biological processbehavioral response to starvation
GO_0071479Biological processcellular response to ionizing radiation
GO_2000481Biological processpositive regulation of cAMP-dependent protein kinase activity
GO_0043124Biological processnegative regulation of canonical NF-kappaB signal transduction
GO_0043518Biological processnegative regulation of DNA damage response, signal transduction by p53 class mediator
GO_1904179Biological processpositive regulation of adipose tissue development
GO_0042149Biological processcellular response to glucose starvation
GO_0016567Biological processprotein ubiquitination
GO_0055089Biological processfatty acid homeostasis
GO_0001542Biological processovulation from ovarian follicle
GO_0043536Biological processpositive regulation of blood vessel endothelial cell migration
GO_0140861Biological processDNA repair-dependent chromatin remodeling
GO_0045739Biological processpositive regulation of DNA repair
GO_1990830Biological processcellular response to leukemia inhibitory factor
GO_0042771Biological processintrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO_0006476Biological processprotein deacetylation
GO_0001934Biological processpositive regulation of protein phosphorylation
GO_0031648Biological processprotein destabilization
GO_0043433Biological processnegative regulation of DNA-binding transcription factor activity
GO_0001678Biological processintracellular glucose homeostasis
GO_1902237Biological processpositive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO_0010824Biological processregulation of centrosome duplication
GO_0033210Biological processleptin-mediated signaling pathway
GO_0007517Biological processmuscle organ development
GO_0002821Biological processpositive regulation of adaptive immune response
GO_0046628Biological processpositive regulation of insulin receptor signaling pathway
GO_0060907Biological processpositive regulation of macrophage cytokine production
GO_0008284Biological processpositive regulation of cell population proliferation
GO_0043524Biological processnegative regulation of neuron apoptotic process
GO_0043065Biological processpositive regulation of apoptotic process
GO_2000781Biological processpositive regulation of double-strand break repair
GO_0045892Biological processnegative regulation of DNA-templated transcription
GO_0042127Biological processregulation of cell population proliferation
GO_0071456Biological processcellular response to hypoxia
GO_0045944Biological processpositive regulation of transcription by RNA polymerase II
GO_0006325Biological processchromatin organization
GO_2000111Biological processpositive regulation of macrophage apoptotic process
GO_0007283Biological processspermatogenesis
GO_0000012Biological processsingle strand break repair
GO_2000774Biological processpositive regulation of cellular senescence
GO_0030512Biological processnegative regulation of transforming growth factor beta receptor signaling pathway
GO_0044321Biological processresponse to leptin
GO_0006974Biological processDNA damage response
GO_0106230Biological processprotein depropionylation
GO_0032868Biological processresponse to insulin
GO_1902176Biological processnegative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO_0010906Biological processregulation of glucose metabolic process
GO_0000720Biological processpyrimidine dimer repair by nucleotide-excision repair
GO_0090400Biological processstress-induced premature senescence
GO_0000122Biological processnegative regulation of transcription by RNA polymerase II
GO_0043280Biological processpositive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO_0018394Biological processpeptidyl-lysine acetylation
GO_0042326Biological processnegative regulation of phosphorylation
GO_0032922Biological processcircadian regulation of gene expression
GO_0051898Biological processnegative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO_0071356Biological processcellular response to tumor necrosis factor
GO_0001938Biological processpositive regulation of endothelial cell proliferation
GO_0010875Biological processpositive regulation of cholesterol efflux
GO_0070857Biological processregulation of bile acid biosynthetic process
GO_0007179Biological processtransforming growth factor beta receptor signaling pathway
GO_1901984Biological processnegative regulation of protein acetylation
GO_0035356Biological processintracellular triglyceride homeostasis
GO_0042632Biological processcholesterol homeostasis
GO_0035098Cellular componentESC/E(Z) complex
GO_0016605Cellular componentPML body
GO_0005634Cellular componentnucleus
GO_0005730Cellular componentnucleolus
GO_0005654Cellular componentnucleoplasm
GO_0001650Cellular componentfibrillar center
GO_0061773Cellular componenteNoSc complex
GO_0005739Cellular componentmitochondrion
GO_0000792Cellular componentheterochromatin
GO_0000791Cellular componenteuchromatin
GO_0005737Cellular componentcytoplasm
GO_0033553Cellular componentrDNA heterochromatin
GO_0000785Cellular componentchromatin
GO_0005677Cellular componentchromatin silencing complex
GO_0005637Cellular componentnuclear inner membrane
GO_0005635Cellular componentnuclear envelope
GO_0005829Cellular componentcytosol
GO_0140297Molecular functionDNA-binding transcription factor binding
GO_0042802Molecular functionidentical protein binding
GO_0106231Molecular functionprotein-propionyllysine depropionylase activity
GO_0046970Molecular functionNAD-dependent histone H4K16 deacetylase activity
GO_0140937Molecular functionhistone H4K12 deacetylase activity
GO_1990404Molecular functionNAD+-protein ADP-ribosyltransferase activity
GO_0000978Molecular functionRNA polymerase II cis-regulatory region sequence-specific DNA binding
GO_1990841Molecular functionpromoter-specific chromatin binding
GO_0042393Molecular functionhistone binding
GO_0070577Molecular functionlysine-acetylated histone binding
GO_0160012Molecular functionNAD-dependent histone decrotonylase activity
GO_0046969Molecular functionNAD-dependent histone H3K9 deacetylase activity
GO_0046872Molecular functionmetal ion binding
GO_0032041Molecular functionNAD-dependent histone H3K14 deacetylase activity
GO_1990254Molecular functionkeratin filament binding
GO_0019899Molecular functionenzyme binding
GO_0019213Molecular functiondeacetylase activity
GO_0003950Molecular functionNAD+ ADP-ribosyltransferase activity
GO_0004407Molecular functionhistone deacetylase activity
GO_0017136Molecular functionNAD-dependent histone deacetylase activity
GO_0070403Molecular functionNAD+ binding
GO_0034979Molecular functionNAD-dependent protein lysine deacetylase activity
GO_0002039Molecular functionp53 binding
GO_0005515Molecular functionprotein binding
GO_0033558Molecular functionprotein lysine deacetylase activity
GO_0016922Molecular functionnuclear receptor binding
GO_0043425Molecular functionbHLH transcription factor binding
GO_0141050Molecular functionhistone H3K deacetylase activity
GO_0003714Molecular functiontranscription corepressor activity
GO_0051019Molecular functionmitogen-activated protein kinase binding
GO_0003713Molecular functiontranscription coactivator activity
GO_0043398Molecular functionHLH domain binding

IV. Literature review

[source]
Gene nameSIRT1
Protein nameSirtuin 1 (cDNA FLJ90324 fis, clone NT2RP2001817, highly similar to NAD-dependent deacetylase sirtuin-1)
Sirtuin 1
NAD-dependent protein deacetylase sirtuin-1 (hSIRT1) (EC 2.3.1.286) (NAD-dependent protein deacylase sirtuin-1) (EC 2.3.1.-) (Regulatory protein SIR2 homolog 1) (SIR2-like protein 1) (hSIR2) [Cleaved into: SirtT1 75 kDa fragment (75SirT1)]
SynonymsSIR2L1
DescriptionFUNCTION: 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 . Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression . Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively . Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction . 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 . 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 . Deacetylates 'Lys-266' of SUV39H1, leading to its activation . Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1 . Deacetylates H2A and 'Lys-26' of H1-4 . 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 . 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 . Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2 . 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 . Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence . 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 . 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 . Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis . Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing . Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha . Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1 . Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver . Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation . Involved in HES1- and HEY2-mediated transcriptional repression . In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62' . Deacetylates MEF2D . Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3 . Represses HNF1A-mediated transcription (By similarity). Required for the repression of ESRRG by CREBZF . Deacetylates NR1H3 and NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteasomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed . Involved in lipid metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol synthesis . 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 . 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 . 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 . 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 . Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN . Promotes DNA double-strand breaks by mediating deacetylation of SIRT6 . 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 . Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1 . Catalyzes deacetylation of ERCC4/XPF, thereby impairing interaction with ERCC1 and nucleotide excision repair (NER) . 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 . Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation . 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 . 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 . Deacetylates MECOM/EVI1 . Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization . 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 . 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 proteasome (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 . Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis . Involved in the CCAR2-mediated regulation of PCK1 and NR1D1 . Deacetylates CTNB1 at 'Lys-49' . In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling (By similarity). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by mediating protein depropionylation and decrotonylation . Mediates depropionylation of Osterix (SP7) (By similarity). Catalyzes decrotonylation of histones; it however does not represent a major histone decrotonylase . 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 . Deacetylates NDC80/HEC1 . .; FUNCTION: [Isoform 2]: Deacetylates 'Lys-382' of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop. .; FUNCTION: [SirtT1 75 kDa fragment]: Catalytically inactive 75SirT1 may be involved in regulation of apoptosis. May be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly. .; FUNCTION: (Microbial infection) In case of HIV-1 infection, interacts with and deacetylates the viral Tat protein. The viral Tat protein inhibits SIRT1 deacetylation activity toward RELA/NF-kappa-B p65, thereby potentiates its transcriptional activity and SIRT1 is proposed to contribute to T-cell hyperactivation during infection. .

AccessionsE9PC49
ENST00000406900.5
ENST00000403579.1
Q96EB6
ENST00000212015.11 [Q96EB6-1]
I1Y8W7
B0QZ35
ENST00000432464.5