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Aliases for SIRT1 Gene

Aliases for SIRT1 Gene

  • Sirtuin 1 2 3
  • SIR2L1 3 4 6
  • Regulatory Protein SIR2 Homolog 1 3 4
  • SIR2-Like Protein 1 3 4
  • HSIRT1 3 4
  • HSIR2 3 4
  • Sirtuin (Silent Mating Type Information Regulation 2, S. Cerevisiae, Homolog) 1 2
  • Sirtuin (Silent Mating Type Information Regulation 2 Homolog) 1 (S. Cerevisiae) 2
  • NAD-Dependent Protein Deacetylase Sirtuin-1 3
  • NAD-Dependent Deacetylase Sirtuin-1 3
  • Sirtuin Type 1 3
  • Sir2-Like 1 3
  • EC 3.5.1.- 4
  • SIR2alpha 3

External Ids for SIRT1 Gene

Summaries for SIRT1 Gene

Entrez Gene Summary for SIRT1 Gene

  • 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]

GeneCards Summary for SIRT1 Gene

SIRT1 (Sirtuin 1) is a Protein Coding gene. Diseases associated with SIRT1 include xeroderma pigmentosum, group d. Among its related pathways are MicroRNAs in cancer and Integrated Pancreatic Cancer Pathway. GO annotations related to this gene include identical protein binding and protein C-terminus binding. An important paralog of this gene is SIRT5.

UniProtKB/Swiss-Prot for SIRT1 Gene

  • 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, metobolism, 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). 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 HIST1H1E. 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. 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. 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. Required for the repression of ESRRG by CREBZF. Modulates AP-1 transcription factor activity. 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. Involved in lipid metabolism. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates ACSS2 leading to its activation, and HMGCS1. Involved in liver and muscle metabolism. Through deacteylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletel 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 faciliting 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. 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. 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. Deacteylates MECOM/EVI1. Isoform 2 is shown to deacetylate 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. 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. Deacetylates PML at Lys-487 and this deacetylation promotes PML control of PER2 nuclear localization. During the neurogenic transition, repress 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 ARNTL/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 ARNTL/BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator. Deacetylates PER2, facilitating its ubiquitination and degradation by the proteosome. Protects cardiomyocytes against palmitate-induced apoptosis (PubMed:11672523, PubMed:12006491, PubMed:14976264, PubMed:14980222, PubMed:15126506, PubMed:15152190, PubMed:15205477, PubMed:15469825, PubMed:15692560, PubMed:16079181, PubMed:16166628, PubMed:16892051, PubMed:16998810, PubMed:17283066, PubMed:17334224, PubMed:17505061, PubMed:17612497, PubMed:17620057, PubMed:17936707, PubMed:18203716, PubMed:18296641, PubMed:18662546, PubMed:18687677, PubMed:19188449, PubMed:19220062, PubMed:19364925, PubMed:19690166, PubMed:19934257, PubMed:20097625, PubMed:20100829, PubMed:20203304, PubMed:20375098, PubMed:20620956, PubMed:20670893, PubMed:20817729, PubMed:20975832, PubMed:21149730, PubMed:21245319, PubMed:21471201, PubMed:21504832, PubMed:21555002, PubMed:21698133, PubMed:21701047, PubMed:21775285, PubMed:21807113, PubMed:21841822, PubMed:21890893, PubMed:21909281, PubMed:21947282, PubMed:22274616). Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity (PubMed:20955178).

  • 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.

Tocris Summary for SIRT1 Gene

  • Silent information regulator (Sir2)-like family deacetylases (also known as sirtuins) are a group of enzymes closely related to histone deacetylases. These enzymes can be found in the cytoplasm, mitochondria or nucleus and are ubiquitously expressed. Sir2-like family deacetylases catalyze the removal of acetyl groups from lysine residues in histones and non-histone proteins, which is coupled to NAD+ hydrolysis. In general, sirtuins do not act autonomously but as components of large multiprotein complexes, such as pRb-E2F and mSin3A, that mediate important transcription regulatory pathways. Sirtuins have a role in regulation of transcription and apoptosis leading to substantial interest in inhibitors of these enzymes as possible antineoplastic agents. In addition, Sir2-like family deacteylases are involved in the normal ageing process through their role in resistance to cellular stress.

Gene Wiki entry for SIRT1 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SIRT1 Gene

Genomics for SIRT1 Gene

Genomic Location for SIRT1 Gene

Start:
67,884,669 bp from pter
End:
67,918,390 bp from pter
Size:
33,722 bases
Orientation:
Plus strand

Genomic View for SIRT1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SIRT1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIRT1 Gene

Regulatory Elements for SIRT1 Gene

Proteins for SIRT1 Gene

  • Protein details for SIRT1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96EB6-SIR1_HUMAN
    Recommended name:
    NAD-dependent protein deacetylase sirtuin-1
    Protein Accession:
    Q96EB6
    Secondary Accessions:
    • Q2XNF6
    • Q5JVQ0
    • Q9GZR9
    • Q9Y6F0

    Protein attributes for SIRT1 Gene

    Size:
    747 amino acids
    Molecular mass:
    81681 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
    Quaternary structure:
    • Interacts with XBP1 isoform 2 (PubMed:20955178). Found in a complex with PCAF and MYOD1. Interacts with FOXO1; the interaction deacetylates FOXO1, resulting in its nuclear retention and promotion of its transcriptional activity Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML. Interacts with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus); the interaction disrupts the interaction between SIRT1 and p53/TP53. Interacts with SETD7; the interaction induces the dissociation of SIRT1 from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN, NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient restriction. Interacts with SUZ12; the interaction mediates the association with the PRC4 histone methylation complex which is specific as an association with PCR2 and PCR3 complex variants is not found. Interacts with HIV-1 tat. Interacts with BCL6; leads to a epigenetic repression of specific target genes. Interacts with CLOCK, ARNTL/BMAL1 and PER2 (By similarity).
    Miscellaneous:
    • Calf histone H1 is used as substrate in the in vitro deacetylation assay (PubMed:15469825). As, in vivo, interaction occurs between SIRT1 with HIST1H1E, deacetylation has been validated only for HIST1H1E.
    • Red wine, which contains resveratrol, may participate in activation of sirtuin proteins, and may therefore participate in an extended lifespan as it has been observed in yeast
    • The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant.
    SequenceCaution:
    • Sequence=AAH12499.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SIRT1 Gene

    Alternative splice isoforms for SIRT1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SIRT1 Gene

Proteomics data for SIRT1 Gene at MOPED

Post-translational modifications for SIRT1 Gene

  • Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53
  • Phosphorylated. Phosphorylated by STK4/MST1, resulting in inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by MAPK8/JNK1 at Ser-27, Ser-47, and Thr-530 leads to increased nuclear localization and enzymatic activity. Phosphorylation at Thr-530 by DYRK1A and DYRK3 activates deacetylase activity and promotes cell survival. Phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) at Ser-47 inhibits deacetylation activity. Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation activity (By similarity). Phosphorylation at Ser-27 implicating MAPK9 is linked to protein stability. There is some ambiguity for some phosphosites: Ser-159/Ser-162 and Thr-544/Ser-545.
  • Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1)
  • S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys238, Lys311, Lys601, and Lys610

Other Protein References for SIRT1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for SIRT1 Gene

Domains for SIRT1 Gene

UniProtKB/Swiss-Prot:

SIR1_HUMAN
Domain:
  • Contains 1 deacetylase sirtuin-type domain.:
    • Q96EB6
Family:
  • Belongs to the sirtuin family. Class I subfamily.:
    • Q96EB6
genes like me logo Genes that share domains with SIRT1: view

No data available for Gene Families for SIRT1 Gene

Function for SIRT1 Gene

Molecular function for SIRT1 Gene

UniProtKB/Swiss-Prot CatalyticActivity: NAD(+) + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.
UniProtKB/Swiss-Prot EnzymeRegulation: Inhibited by nicotinamide. Activated by resveratrol (3,5,4-trihydroxy-trans-stilbene), butein (3,4,2,4-tetrahydroxychalcone), piceatannol (3,5,3,4-tetrahydroxy-trans-stilbene), Isoliquiritigenin (4,2,4-trihydroxychalcone), fisetin (3,7,3,4-tetrahydroxyflavone) and quercetin (3,5,7,3,4-pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive regulators of deacetylation activity. Negatively regulated by CCAR2.
UniProtKB/Swiss-Prot Function: 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, metobolism, 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). 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 HIST1H1E. 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. 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. 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. Required for the repression of ESRRG by CREBZF. Modulates AP-1 transcription factor activity. 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. Involved in lipid metabolism. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates ACSS2 leading to its activation, and HMGCS1. Involved in liver and muscle metabolism. Through deacteylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletel 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 faciliting 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. 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. 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. Deacteylates MECOM/EVI1. Isoform 2 is shown to deacetylate 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. 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. Deacetylates PML at Lys-487 and this deacetylation promotes PML control of PER2 nuclear localization. During the neurogenic transition, repress 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 ARNTL/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 ARNTL/BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator. Deacetylates PER2, facilitating its ubiquitination and degradation by the proteosome. Protects cardiomyocytes against palmitate-induced apoptosis (PubMed:11672523, PubMed:12006491, PubMed:14976264, PubMed:14980222, PubMed:15126506, PubMed:15152190, PubMed:15205477, PubMed:15469825, PubMed:15692560, PubMed:16079181, PubMed:16166628, PubMed:16892051, PubMed:16998810, PubMed:17283066, PubMed:17334224, PubMed:17505061, PubMed:17612497, PubMed:17620057, PubMed:17936707, PubMed:18203716, PubMed:18296641, PubMed:18662546, PubMed:18687677, PubMed:19188449, PubMed:19220062, PubMed:19364925, PubMed:19690166, PubMed:19934257, PubMed:20097625, PubMed:20100829, PubMed:20203304, PubMed:20375098, PubMed:20620956, PubMed:20670893, PubMed:20817729, PubMed:20975832, PubMed:21149730, PubMed:21245319, PubMed:21471201, PubMed:21504832, PubMed:21555002, PubMed:21698133, PubMed:21701047, PubMed:21775285, PubMed:21807113, PubMed:21841822, PubMed:21890893, PubMed:21909281, PubMed:21947282, PubMed:22274616). Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity (PubMed:20955178).
UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction: Up-regulated by methyl methanesulfonate (MMS). In H293T cells by presence of rat calorie restriction (CR) serum.

Enzyme Numbers (IUBMB) for SIRT1 Gene

Gene Ontology (GO) - Molecular Function for SIRT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001046 core promoter sequence-specific DNA binding IEA --
GO:0002039 p53 binding IPI 11672523
GO:0003714 transcription corepressor activity ISS --
GO:0003950 NOT NAD+ ADP-ribosyltransferase activity TAS 17456799
GO:0004407 histone deacetylase activity IDA 20027304
genes like me logo Genes that share ontologies with SIRT1: view
genes like me logo Genes that share phenotypes with SIRT1: view

Animal Models for SIRT1 Gene

MGI Knock Outs for SIRT1:

No data available for Transcription Factor Targeting and HOMER Transcription for SIRT1 Gene

Localization for SIRT1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIRT1 Gene

Nucleus, PML body. Cytoplasm. Nucleus. Note=Recruited to the nuclear bodies via its interaction with PML. Colocalized with APEX1 in the nucleus. May be found in nucleolus, nuclear euchromatin, heterochromatin and inner membrane. Shuttles between nucleus and cytoplasm (By similarity). Colocalizes in the nucleus with XBP1 isoform 2 (PubMed:20955178). {ECO:0000250 UniProtKB:Q923E4, ECO:0000269 PubMed:20955178}.
SirtT1 75 kDa fragment: Cytoplasm. Mitochondrion.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SIRT1 Gene COMPARTMENTS Subcellular localization image for SIRT1 gene
Compartment Confidence
mitochondrion 5
nucleus 5
cytosol 3
peroxisome 2
endoplasmic reticulum 1
extracellular 1
plasma membrane 1
vacuole 1

Gene Ontology (GO) - Cellular Components for SIRT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin --
GO:0000790 nuclear chromatin IDA 17505061
GO:0005634 nucleus IDA --
GO:0005635 nuclear envelope IDA 15469825
GO:0005637 nuclear inner membrane IDA 15469825
genes like me logo Genes that share ontologies with SIRT1: view

Pathways for SIRT1 Gene

genes like me logo Genes that share pathways with SIRT1: view

Pathways by source for SIRT1 Gene

2 GeneGo (Thomson Reuters Life Sciences Research) pathways for SIRT1 Gene
1 R&D Systems pathway for SIRT1 Gene
1 Sino Biological pathway for SIRT1 Gene
2 Qiagen pathways for SIRT1 Gene

Gene Ontology (GO) - Biological Process for SIRT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000012 single strand break repair IMP 20097625
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IMP 21947282
GO:0000183 chromatin silencing at rDNA TAS --
GO:0000720 pyrimidine dimer repair by nucleotide-excision repair IMP 21149730
GO:0000731 DNA synthesis involved in DNA repair ISS --
genes like me logo Genes that share ontologies with SIRT1: view

Compounds for SIRT1 Gene

(6) ApexBio Compounds for SIRT1 Gene

Compound Action Cas Number
EX 527 (SEN0014196) novel, potential, and specific small-molecule inhibitor of SIRT1 [49843-98-3]
Sirtinol specific SIRT1 and SIRT2 inhibitor [410536-97-9]
sirtuin modulator sirtuin modulator. [1093403-33-8]
SRT1720 activating the sirtuin subtype SIRT1 in vitro. [1001645-58-4]
Tenovin-3 Tenovin-3 [1011301-27-1]
Tenovin-6 a potent SIRT1 and SIRT2 inhibitor as well as p53 activator. [1011557-82-6]

(5) Tocris Compounds for SIRT1 Gene

Compound Action Cas Number
AGK 2 Selective SIRT2 inhibitor [304896-28-4]
AK 7 Selective SIRT2 inhibitor; brain penetrant [420831-40-9]
EX 527 Selective SIRT1 inhibitor [49843-98-3]
Sirtinol Selective sirtuin family deacetylase inhibitor [410536-97-9]
Splitomicin Sir2p inhibitor [5690-03-9]

(4) HMDB Compounds for SIRT1 Gene

Compound Synonyms Cas Number PubMed IDs
NAD
  • 3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate
53-84-9
NADH
  • 1,4-Dihydronicotinamide adenine dinucleotide
58-68-4
Quercetin
  • 2-(3,4-Dihydroxy-phenyl)-3,5,7-trihydroxy-chromen-4-one
117-39-5
Resveratrol
  • 3,4',5-Trihydroxystilbene
501-36-0

(12) Novoseek inferred chemical compound relationships for SIRT1 Gene

Compound -log(P) Hits PubMed IDs
resveratrol 88.7 72
nicotinamide 80.5 19
nad+ 77.8 21
lysine 51.7 3
nadh 41 5
genes like me logo Genes that share compounds with SIRT1: view

Transcripts for SIRT1 Gene

Unigene Clusters for SIRT1 Gene

Sirtuin 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SIRT1 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c ^ 4a · 4b · 4c ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9 ^ 10
SP1: -
SP2:
SP3: - -
SP4: - -
SP5: - - - - -
SP6:

Relevant External Links for SIRT1 Gene

GeneLoc Exon Structure for
SIRT1
ECgene alternative splicing isoforms for
SIRT1

Expression for SIRT1 Gene

mRNA expression in normal human tissues for SIRT1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for SIRT1 Gene

SOURCE GeneReport for Unigene cluster for SIRT1 Gene Hs.369779

mRNA Expression by UniProt/SwissProt for SIRT1 Gene

Q96EB6-SIR1_HUMAN
Tissue specificity: Widely expressed.
genes like me logo Genes that share expressions with SIRT1: view

Orthologs for SIRT1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SIRT1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SIRT1 36
  • 99.15 (n)
  • 98.93 (a)
SIRT1 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SIRT1 36
  • 90.71 (n)
  • 90.16 (a)
SIRT1 37
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SIRT1 36
  • 91.09 (n)
  • 90.28 (a)
SIRT1 37
  • 91 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Sirt1 36
  • 86.12 (n)
  • 85.85 (a)
Sirt1 16
Sirt1 37
  • 85 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SIRT1 37
  • 75 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 37
  • 17 (a)
ManyToMany
rat
(Rattus norvegicus)
Mammalia Sirt1 36
  • 89.96 (n)
  • 91.56 (a)
chicken
(Gallus gallus)
Aves SIRT1 36
  • 77.44 (n)
  • 79.9 (a)
SIRT1 37
  • 75 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SIRT1 37
  • 70 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sirt1 36
  • 69.74 (n)
  • 74.12 (a)
zebrafish
(Danio rerio)
Actinopterygii sirt1 36
  • 62.59 (n)
  • 66.23 (a)
sirt1 37
  • 47 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Sir2 37
  • 29 (a)
OneToOne
Sir2 38
  • 57 (a)
worm
(Caenorhabditis elegans)
Secernentea sir-2.1 37
  • 33 (a)
OneToOne
sir-2.1 38
  • 44 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HST1 37
  • 25 (a)
ManyToMany
HST1 39
SIR2 37
  • 24 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 63 (a)
OneToMany
-- 37
  • 42 (a)
OneToMany
Species with no ortholog for SIRT1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SIRT1 Gene

ENSEMBL:
Gene Tree for SIRT1 (if available)
TreeFam:
Gene Tree for SIRT1 (if available)

Paralogs for SIRT1 Gene

Paralogs for SIRT1 Gene

Selected SIMAP similar genes for SIRT1 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with SIRT1: view

Variants for SIRT1 Gene

Sequence variations from dbSNP and Humsavar for SIRT1 Gene

SNP ID Clin Chr 10 pos Sequence Context AA Info Type MAF
rs737477 -- 67,887,847(+) CTGGG(A/C)TTACA intron-variant
rs752578 -- 67,917,303(+) TGTAG(C/T)AATGT utr-variant-3-prime
rs768471 -- 67,891,977(+) AGAAT(A/G)GGAAG intron-variant
rs911738 -- 67,888,231(-) GAACA(C/T)AAAAA intron-variant
rs932657 -- 67,887,574(-) AAAAA(A/C)CGTAC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SIRT1 Gene

Variant ID Type Subtype PubMed ID
nsv825437 CNV Gain 20364138

Relevant External Links for SIRT1 Gene

HapMap Linkage Disequilibrium report
SIRT1
Human Gene Mutation Database (HGMD)
SIRT1

Disorders for SIRT1 Gene

(4) University of Copenhagen DISEASES for SIRT1 Gene

(8) Novoseek inferred disease relationships for SIRT1 Gene

Disease -log(P) Hits PubMed IDs
cancer 32.4 25
metabolic disorder 31.7 4
neurodegeneration 28.3 9
insulin sensitivity 14.5 7
tumors 6.42 14

Relevant External Links for SIRT1

Genetic Association Database (GAD)
SIRT1
Human Genome Epidemiology (HuGE) Navigator
SIRT1
genes like me logo Genes that share disorders with SIRT1: view

No data available for UniProtKB/Swiss-Prot for SIRT1 Gene

Publications for SIRT1 Gene

  1. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. (PMID: 12297502) Bitterman K.J. … Sinclair D.A. (J. Biol. Chem. 2002) 3 4 23
  2. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. (PMID: 14976264) Brunet A. … Greenberg M.E. (Science 2004) 3 4 23
  3. SIRT1 regulates HIV transcription via Tat deacetylation. (PMID: 15719057) Pagans S. … Ott M. (PLoS Biol. 2005) 3 4 23
  4. Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity. (PMID: 16257164) Flachsbart F. … Nebel A. (Exp. Gerontol. 2006) 3 23 49
  5. Sirtuin 1 is required for antagonist-induced transcriptional repression of androgen-responsive genes by the androgen receptor. (PMID: 17505061) Dai Y. … Faller D.V. (Mol. Endocrinol. 2007) 3 4 23

Products for SIRT1 Gene

  • Addgene plasmids for SIRT1

Sources for SIRT1 Gene

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