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SIRT1 Gene

protein-coding   GIFtS: 71
GCID: GC10P069644

Sirtuin 1

(Previous names: sirtuin (silent mating type information regulation 2, S....)
Microbiology & Infectious Diseases Congress
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Sirtuin 11 2     Sirtuin (Silent Mating Type Information Regulation 2, S. Cerevisiae,
Homolog) 11
SIR2L12 3 5     SIR2alpha2
Regulatory Protein SIR2 Homolog 12 3     NAD-Dependent Deacetylase Sirtuin-12
hSIR22 3     NAD-Dependent Protein Deacetylase Sirtuin-12
hSIRT12 3     Sir2-Like 12
SIR2-Like Protein 12 3     Sirtuin Type 12
Sirtuin (Silent Mating Type Information Regulation 2 Homolog) 1 (S.
Cerevisiae)1
     EC 3.5.1.-3

External Ids:    HGNC: 149291   Entrez Gene: 234112   Ensembl: ENSG000000967177   OMIM: 6044795   UniProtKB: Q96EB63   

Export aliases for SIRT1 gene to outside databases

Previous GC identifers: GC10P068455 GC10P068731 GC10P069536 GC10P068989 GC10P069314 GC10P063643


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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, and hyperphosphatemia. GO annotations related to this gene include protein C-terminus binding and identical protein binding. An important paralog of this gene is SIRT4.

UniProtKB/Swiss-Prot: SIR1_HUMAN, Q96EB6
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 insuline-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
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

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 (Sirtuin 1) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000010.11  NT_030059.14  NC_018921.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the SIRT1 gene promoter:
         N-Myc   MyoD   C/EBPalpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): SIRT1 promoter sequence
   Search Chromatin IP Primers for SIRT1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SIRT1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 10q21.3   Ensembl cytogenetic band:  10q21.3   HGNC cytogenetic band: 10q21

SIRT1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SIRT1 gene location

GeneLoc information about chromosome 10         GeneLoc Exon Structure

GeneLoc location for GC10P069644:  view genomic region     (about GC identifiers)

Start:
69,644,427 bp from pter      End:
69,678,147 bp from pter
Size:
33,721 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: SIR1_HUMAN, Q96EB6 (See protein sequence)
Recommended Name: NAD-dependent protein deacetylase sirtuin-1  
Size: 747 amino acids; 81681 Da
Cofactor: Binds 1 zinc ion per subunit (By similarity)
Subunit: 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
Miscellaneous: 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
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
Miscellaneous: The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction
of the deacetylase activity and may not be physiologically relevant (PubMed:19220062)
Sequence caution: Sequence=AAH12499.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
4 PDB 3D structures from and Proteopedia for SIRT1:
4I5I (3D)        4IF6 (3D)        4IG9 (3D)        4KXQ (3D)    
Secondary accessions: Q2XNF6 Q5JVQ0 Q9GZR9 Q9Y6F0
Alternative splicing: 2 isoforms:  Q96EB6-1   Q96EB6-2   

Explore the universe of human proteins at neXtProt for SIRT1: NX_Q96EB6

Explore proteomics data for SIRT1 at MOPED

Post-translational modifications: 

  • Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for
    deacetylase activity toward p53/TP531
  • 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-5451
  • Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75
    kDa fragment (75SirT1)1
  • S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity (By similarity)1
  • Ubiquitination2 at Lys238, Lys311, Lys601, Lys610
  • Modification sites at PhosphoSitePlus

  • See SIRT1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001135970.1  NP_036370.2  

    ENSEMBL proteins: 
     ENSP00000212015   ENSP00000384508   ENSP00000384063   ENSP00000409208  
    Reactome Protein details: Q96EB6

    SIRT1 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for SIRT1 (Sirtuin 1/SIRT1)
    Enzo Life Sciences proteins for SIRT1
    OriGene Purified Protein for SIRT1
    OriGene Protein Over-expression Lysate for SIRT1
    OriGene MassSpec for SIRT1
    OriGene Custom Protein Services for SIRT1
    GenScript Custom Purified and Recombinant Proteins Services for SIRT1
    Novus Biologicals SIRT1 Proteins
    Novus Biologicals SIRT1 Lysate
    Sino Biological Recombinant Protein for SIRT1
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for SIRT1

    SIRT1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of SIRT1
    R&D Systems Antibodies for SIRT1 (Sirtuin 1/SIRT1)
    OriGene Antibodies for SIRT1
    OriGene Custom Antibody Services for SIRT1
    Novus Biologicals SIRT1 Antibodies
    Abcam antibodies for SIRT1
    Cloud-Clone Corp. Antibodies for SIRT1
    ThermoFisher Antibody for SIRT1
    LSBio Antibodies in human, mouse, rat for SIRT1

    SIRT1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for SIRT1
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for SIRT1
    Enzo Life Sciences assays for SIRT1
    Cloud-Clone Corp. ELISAs for SIRT1
    Cloud-Clone Corp. CLIAs for SIRT1


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    3 InterPro protein domains:
     IPR026591 Sirtuin_cat_small_dom
     IPR003000 Sirtuin
     IPR026590 Ssirtuin_cat_dom

    Graphical View of Domain Structure for InterPro Entry Q96EB6

    ProtoNet protein and cluster: Q96EB6

    1 Blocks protein domain: IPB003000 Silent information regulator protein Sir2

    UniProtKB/Swiss-Prot: SIR1_HUMAN, Q96EB6
    Similarity: Belongs to the sirtuin family. Class I subfamily
    Similarity: Contains 1 deacetylase sirtuin-type domain


    SIRT1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
    About This Section

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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: SIR1_HUMAN, Q96EB6
    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 insuline-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
    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
    Catalytic activity: NAD(+) + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein
    Enzyme regulation: 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
    Induction: Up-regulated by methyl methanesulfonate (MMS). In H293T cells by presence of rat calorie restriction
    (CR) serum

         Enzyme Number (IUBMB): EC 3.5.1.-1

         Gene Ontology (GO): Selected molecular function terms (see all 20):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002039p53 binding IPI11672523
    GO:0003714transcription corepressor activity ISS--
    GO:0003950NOT NAD+ ADP-ribosyltransferase activity TAS17456799
    GO:0004407histone deacetylase activity IDA--
    GO:0005515protein binding IPI11672523
         
    SIRT1 for ontologies           About GeneDecksing


    Phenotypes:
         3 GenomeRNAi human phenotypes for SIRT1:
     G0/1 arrest  High actin ratio cells  Increased G1 DNA content 

         Selected MGI mutant phenotypes (inferred from 13 alleles(MGI details for Sirt1) (see all 24):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  craniofacial 
     digestive/alimentary  embryogenesis  endocrine/exocrine gland  growth/size/body  hematopoietic system 
     homeostasis/metabolism  immune system  integument  limbs/digits/tail  liver/biliary system 

    SIRT1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for SIRT1: Sirt1tm1.1Cxd Sirt1tm1Fwa Sirt1tm1.1Ygu Sirt1tm1Mcby Sirt1tm2Fwa Sirt1tm2.1Fwa

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SIRT1
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       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for SIRT1

    miRNA
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    miRTarBase miRNAs that target SIRT1:
    hsa-mir-192-5p (MIRT026849), hsa-mir-449b-5p (MIRT006349), hsa-mir-34a-5p (MIRT002098), hsa-mir-199a-5p (MIRT052646), hsa-mir-181a-5p (MIRT006213), hsa-mir-215-5p (MIRT024509), hsa-mir-128-3p (MIRT007324), hsa-let-7c-5p (MIRT051790), hsa-mir-181b-5p (MIRT006272), hsa-mir-124-3p (MIRT023069), hsa-mir-217 (MIRT000144), hsa-mir-216a-5p (MIRT005018), hsa-mir-449a (MIRT006348), hsa-mir-181c-5p (MIRT006878), hsa-mir-132-3p (MIRT000333), hsa-mir-331-3p (MIRT043458), hsa-mir-138-5p (MIRT006271), hsa-mir-9-5p (MIRT006892)

    Block miRNA regulation of human, mouse, rat SIRT1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate SIRT1 (see all 51):
    hsa-miR-607 hsa-miR-3607-3p hsa-miR-200a hsa-miR-128 hsa-miR-30d hsa-miR-29b-1* hsa-miR-570 hsa-miR-141
    SwitchGear 3'UTR luciferase reporter plasmidSIRT1 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector (see all 2): SIRT1 (NM_012238)
    Browse Sino Biological Human cDNA Clones
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
    About This Section

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    Subcellular locations from UniProtKB/Swiss-Prot
    SIR1_HUMAN, Q96EB6: Nucleus, PML body. Cytoplasm. 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
    SIR1_HUMAN, Q96EB6: SirtT1 75 kDa fragment: Cytoplasm. Mitochondrion
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    mitochondrion5
    nucleus5
    cytosol3
    peroxisome2
    endoplasmic reticulum1
    extracellular1
    plasma membrane1
    vacuole1

    Gene Ontology (GO): Selected cellular component terms (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000785chromatin ----
    GO:0000790nuclear chromatin IDA17505061
    GO:0005634nucleus IDA--
    GO:0005635nuclear envelope IDA15469825
    GO:0005637nuclear inner membrane IDA15469825

    SIRT1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
    About This Section

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    SuperPaths for SIRT1 About   (see all 26)  
    See pathways by source

    SuperPathContained pathways About
    1p53 Signaling
    p53 Signaling0.38
    p53 Pathway0.38
    2Amphetamine addiction
    Amphetamine addiction0.44
    3Nicotinate and nicotinamide metabolism
    NAD metabolism0.43
    4Non-homologous end-joining
    DNA damage NHEJ mechanisms of DSBs repair0.37
    5Regulation of Cholesterol Biosynthesis by SREBP (SREBF)
    SREBP signalling0.31

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for SIRT1
        Notch Signaling Pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for SIRT1
        p53 Signaling
    SUMO Pathway

    3 Cell Signaling Technology (CST) Pathways for SIRT1
        Chromatin Regulation / Acetylation
    Apoptosis and Autophagy
    Glucose / Energy Metabolism

    2 GeneGo (Thomson Reuters) Pathways for SIRT1
        NAD metabolism
    DNA damage NHEJ mechanisms of DSBs repair

    Selected BioSystems Pathways for SIRT1 (see all 13)
        Integrated Breast Cancer Pathway
    SREBP signalling
    SREBF and miR33 in cholesterol and lipid homeostasis
    Androgen receptor signaling pathway
    Energy Metabolism

    1 Sino Biological Pathway for SIRT1
        p53 Pathway

    2 Reactome Pathways for SIRT1
        Regulation of HSF1-mediated heat shock response
    SIRT1 negatively regulates rRNA Expression

    1 PharmGKB Pathway for SIRT1
        Metformin Pathway, Pharmacodynamic

    3 Kegg Pathways  (Kegg details for SIRT1):
        FoxO signaling pathway
    Amphetamine addiction
    MicroRNAs in cancer


    SIRT1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SIRT1 (see all 9): 
              Epigenetic Chromatin Modification Enzymes in human mouse rat
              Polycomb & Trithorax Complexes in human mouse rat
              DNA Damage Signaling Pathway in human mouse rat
              Cancer PathwayFinder in human mouse rat
              Adipogenesis in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for SIRT1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for SIRT1 (Q96EB61, 2, 3 ENSP000002120154) via UniProtKB, MINT, STRING, and/or I2D (see all 619)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CSNK2BP678701, 2, 3EBI-1802965,EBI-348169 MINT-8206425 MINT-8206396 MINT-8206373 MINT-8206385 MINT-8206442 MINT-8206407 I2D: score=1 
    ENSG00000206406P678701, 2, 3EBI-1802965,EBI-348169 MINT-8206425 MINT-8206396 MINT-8206373 MINT-8206385 MINT-8206442 MINT-8206407 I2D: score=1 
    ENSG00000224398P678701, 2, 3EBI-1802965,EBI-348169 MINT-8206425 MINT-8206396 MINT-8206373 MINT-8206385 MINT-8206442 MINT-8206407 I2D: score=1 
    ENSG00000228875P678701, 2, 3EBI-1802965,EBI-348169 MINT-8206425 MINT-8206396 MINT-8206373 MINT-8206385 MINT-8206442 MINT-8206407 I2D: score=1 
    ENSG00000230700P678701, 2, 3EBI-1802965,EBI-348169 MINT-8206425 MINT-8206396 MINT-8206373 MINT-8206385 MINT-8206442 MINT-8206407 I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 91):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000012single strand break repair IMP--
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IMP--
    GO:0000183chromatin silencing at rDNA IDA18485871
    GO:0000720pyrimidine dimer repair by nucleotide-excision repair IMP--
    GO:0000731DNA synthesis involved in DNA repair ISS--

    SIRT1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for SIRT1
    6 ApexBio Compounds for SIRT1     About this table
    CompoundAction CAS #
    EX 527 (SEN0014196)novel, potential, and specific small-molecule inhibitor of SIRT1[49843-98-3]
    Sirtinolspecific SIRT1 and SIRT2 inhibitor[410536-97-9]
    sirtuin modulatorsirtuin modulator[1093403-33-8]
    SRT1720activating the sirtuin subtype SIRT1 in vitro. [1001645-58-4]
    Tenovin-3Tenovin-3 [1011301-27-1]
    Tenovin-6a potent SIRT1 and SIRT2 inhibitor as well as p53 activator. [1011557-82-6]

    Compounds for SIRT1 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    SirtinolSelective sirtuin family deacetylase inhibitor[410536-97-9]
    EX 527Selective SIRT1 inhibitor[49843-98-3]
    AK 7Selective SIRT2 inhibitor; brain penetrant[420831-40-9]
    SplitomicinSir2p inhibitor[5690-03-9]
    AGK 2Selective SIRT2 inhibitor[304896-28-4]

    4 HMDB Compounds for SIRT1    About this table
    CompoundSynonyms CAS #PubMed Ids
    NAD3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate (see all 28)53-84-9--
    NADH1,4-Dihydronicotinamide adenine dinucleotide (see all 17)58-68-4--
    Quercetin2-(3,4-Dihydroxy-phenyl)-3,5,7-trihydroxy-chromen-4-one (see all 13)117-39-5--
    Resveratrol3,4',5-Trihydroxystilbene (see all 3)501-36-0--

    Selected Novoseek inferred chemical compound relationships for SIRT1 gene (see all 12)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    resveratrol 88.7 111 15749705 (6), 20061378 (4), 19749157 (4), 18997065 (3) (see all 39)
    nicotinamide 80.5 26 17620057 (3), 12297502 (2), 18957417 (2), 19720090 (2) (see all 14)
    nad+ 77.8 47 19664641 (4), 17595514 (2), 19716821 (2), 20068143 (2) (see all 14)
    lysine 51.7 3 15744310 (1), 17098745 (1), 19578370 (1)
    nadh 41 8 19664641 (2), 20107110 (1), 19928762 (1), 19188449 (1)
    fatty acid 28.6 8 17646659 (2), 20160399 (1), 18709650 (1), 20033348 (1)
    glucose 23.7 25 18423418 (4), 19071085 (3), 20068143 (3), 15744310 (3) (see all 11)
    lipid 17.9 10 17936707 (2), 17646659 (2), 20033348 (1), 18239056 (1) (see all 6)
    estrogen 3.77 1 19690166 (1)
    oxygen 0 1 18922599 (1), 19303870 (1)



    SIRT1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for SIRT1 gene (2 alternative transcripts): 
    NM_001142498.1  NM_012238.4  

    Unigene Cluster for SIRT1:

    Sirtuin 1
    Hs.369779  [show with all ESTs]
    Unigene Representative Sequence: NM_012238
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000212015(uc001jnd.3 uc009xpp.3) ENST00000497639 ENST00000473922
    ENST00000406900(uc001jne.3) ENST00000403579 ENST00000432464(uc010qis.2)

    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate SIRT1 (see all 51):
    hsa-miR-607 hsa-miR-3607-3p hsa-miR-200a hsa-miR-128 hsa-miR-30d hsa-miR-29b-1* hsa-miR-570 hsa-miR-141
    SwitchGear 3'UTR luciferase reporter plasmidSIRT1 3' UTR sequence
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    Additional mRNA sequence: 

    AF083106.2 AF235040.1 AK027686.1 AK074805.1 AK289743.1 AL136741.1 BC012499.1 BX648554.1 
    JQ768366.1 

    7 DOTS entries:

    DT.312320  DT.100749000  DT.97824709  DT.100748999  DT.91751505  DT.121247108  DT.100658352 

    Selected AceView cDNA sequences (see all 87):

    BU186744 CK820052 AA828109 BF445130 AA608812 AW615289 BQ219206 BM980158 
    NM_012238 AI282390 AA452304 AA461259 AI367389 AF235040 BU735905 BM354077 
    BQ632248 AF083106 BM273130 BC012499 BG036612 AI381553 BI258271 AA236993 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for SIRT1 (see all 6)    About this scheme

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


    ECgene alternative splicing isoforms for SIRT1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    SIRT1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    SIRT1 Expression
    About this image


    SIRT1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 6) fully expand
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Cerebral Cortex
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Ovary (Reproductive System)
             Oviduct
     
     Pancreas (Endocrine System)
             Islets of Langerhans
     
     Bone (Muscoskeletal System)
             Bone Marrow
    SIRT1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SIRT1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.369779

    UniProtKB/Swiss-Prot: SIR1_HUMAN, Q96EB6
    Tissue specificity: Widely expressed

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SIRT1 (see all 9): 
              Epigenetic Chromatin Modification Enzymes in human mouse rat
              Polycomb & Trithorax Complexes in human mouse rat
              DNA Damage Signaling Pathway in human mouse rat
              Cancer PathwayFinder in human mouse rat
              Adipogenesis in human mouse rat

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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SIRT1

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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

    Orthologs for SIRT1 gene from Selected species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Sirt11 , 5 sirtuin 1 (silent mating type information regulation more5
    sirtuin 11
    86.12(n)1
    85.85(a)1
      10 (32.57 cM)5
    937591  NM_019812.21  NP_062786.11 
     633190055 
    chicken
    (Gallus gallus)
    Aves SIRT11 sirtuin 1 77.44(n)
    79.9(a)
      423646  NM_001004767.1  NP_001004767.1 
    lizard
    (Anolis carolinensis)
    Reptilia SIRT16
    sirtuin 1
    70(a)
    1 ↔ 1
    GL343215.1(1273714-1294087)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia BX715176.12   -- 74.64(n)    BX715176.1 
    zebrafish
    (Danio rerio)
    Actinopterygii BI476700.12   -- 74.16(n)    BI476700.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Sir23 histone deacetylation NAD-dependent
    histone deacetylase
    57(a)   34A7   --
    worm
    (Caenorhabditis elegans)
    Secernentea sir-2.13 Yeast regulatory protein SIR2 like 44(a)   IV(10363661-10366363)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes HST1(YOL068C)4 NAD(+)-dependent histone deacetylase; essential subunit more   --   15(201879-200368) 854086  NP_014573.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section

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    Paralogs for SIRT1 gene
    SIRT42  SIRT52  
    3 SIMAP similar genes for SIRT1 using alignment to 4 protein entries:     SIR1_HUMAN (see all proteins):
    SIR2    SIRT3    SIRT2

    SIRT1 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
    About This Section

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    Selected SNPs for SIRT1 (see all 1031)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 10 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1875505451,2
    --69642556(+) TTTTTA/TAATTT 1 -- us2k10--------
    rs1933010591,2
    --69642577(+) ATACAA/GGTGCA 1 -- us2k10--------
    rs1851323161,2
    --69642643(+) ATCAAC/GCCCTC 1 -- us2k10--------
    rs107402801,2
    C,H--69642668(+) TATATA/TTTTTT 1 -- us2k1 tfbs311Minor allele frequency- T:0.05NA WA CSA EA 373
    rs1903768441,2
    --69642791(+) GTAGCC/TGGGAT 1 -- us2k10--------
    rs1818066261,2
    --69642819(+) ACGCCC/GGGCTA 1 -- us2k10--------
    rs1479155571,2
    C--69645699(+) GGTTT-/CTTTTT 2 -- int10--------
    rs3763331721,2
    C--69646871(+) GGTGA-/CCGCCT 1 -- int10--------
    rs1113544061,2
    F--69647488(+) TGCCAC/ATACGC 1 -- int12Minor allele frequency- A:0.50CSA 4
    rs1129088441,2
    F--69647492(+) ACTACG/TCCCGG 1 -- int12Minor allele frequency- T:0.50CSA 4

    HapMap Linkage Disequilibrium report for SIRT1 (69644427 - 69678147 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for SIRT1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv825437CNV Gain20364138

    Human Gene Mutation Database (HGMD): SIRT1
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing SIRT1
    DNA2.0 Custom Variant and Variant Library Synthesis for SIRT1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 604479    OMIM disorders: --

    Selected diseases for SIRT1 (see all 76):    
    About MalaCards
    xeroderma pigmentosum, group d    hyperphosphatemia    nijmegen breakage syndrome    differentiating neuroblastoma
    tauopathy    ventricular septal defect    bronchopulmonary dysplasia    papillary renal cell carcinoma
    cockayne syndrome    werner syndrome    inclusion body myositis    fatty liver disease
    morbid obesity    xeroderma pigmentosum    adult t-cell leukemia    major depressive disorder
    mood disorder    myocarditis    myositis    diabetic nephropathy

    4 diseases from the University of Copenhagen DISEASES database for SIRT1:
    Diabetes mellitus     Fatty liver disease     Vascular disease     Cancer

    SIRT1 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    8 Novoseek inferred disease relationships for SIRT1 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cancer 32.4 38 16596166 (3), 16288037 (3), 19149601 (2), 19060927 (2) (see all 16)
    metabolic disorder 31.7 4 19260974 (2), 17646659 (1), 19749157 (1)
    neurodegeneration 28.3 5 17581637 (2), 20061622 (2), 17936707 (1), 18838864 (1) (see all 7)
    insulin sensitivity 14.5 6 20107110 (4), 17646659 (1), 20439735 (1), 18928399 (1)
    tumors 6.42 20 19433578 (4), 19047049 (3), 12297502 (1), 19285066 (1) (see all 9)
    cardiovascular diseases 0.294 8 19260974 (2), 20061622 (1), 19815564 (1)
    insulin resistance 0 2 20107110 (1), 19260974 (1), 20068143 (1), 15850715 (1)
    stroke 0 2 20306310 (1), 18537630 (1)

    Genetic Association Database (GAD): SIRT1
    Human Genome Epidemiology (HuGE) Navigator: SIRT1 (23 documents)

    Export disorders for SIRT1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for SIRT1 gene, integrated from 10 sources (see all 613):
    (articles sorted by number of sources associating them with SIRT1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. (PubMed id 10381378)1, 2, 3 Frye R.A. (Biochem. Biophys. Res. Commun. 1999)
    2. JNK2-dependent regulation of SIRT1 protein stability. (PubMed id 18838864)1, 2, 9 Ford J.... Milner J. (Cell Cycle 2008)
    3. JNK1 phosphorylates SIRT1 and promotes its enzymatic activity. (PubMed id 20027304)1, 2, 9 Nasrin N.... Bordone L. (PLoS ONE 2009)
    4. Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear receptor estrogen receptor-related receptor gamma transactivation. (PubMed id 19690166)1, 2, 9 Xie Y.B.... Choi H.S. (J. Biol. Chem. 2009)
    5. hSirT1-dependent regulation of the PCAF-E2F1-p73 apoptotic pathway in response to DNA damage. (PubMed id 19188449)1, 2, 9 Pediconi N.... Levrero M. (Mol. Cell. Biol. 2009)
    6. Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity. (PubMed id 16257164)1, 4, 9 Flachsbart F....Nebel A. (Exp. Gerontol. 2006)
    7. SIRT1 regulates HIV transcription via Tat deacetylation. (PubMed id 15719057)1, 2, 9 Pagans S.... Ott M. (PLoS Biol. 2005)
    8. Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2. (PubMed id 19236849)1, 2, 9 Zschoernig B. and Mahlknecht U. (Biochem. Biophys. Res. Commun. 2009)
    9. Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity. (PubMed id 17964266)1, 2, 9 Kim E.-J.... Um S.-J. (Mol. Cell 2007)
    10. SIRT1 deacetylates and positively regulates the nuclear receptor LXR. (PubMed id 17936707)1, 2, 9 Li X.... Guarente L. (Mol. Cell 2007)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 23411 HGNC: 14929 AceView: SIRT1 Ensembl:ENSG00000096717 euGenes: HUgn23411
    ECgene: SIRT1 Kegg: 23411 H-InvDB: SIRT1

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for SIRT1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for SIRT1 Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPshttp://egp.gs.washington.edu/data/sirt1/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for SIRT1 gene:
    Search GeneIP for patents involving SIRT1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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