Human Gene SIRT1 (uc001jnd.3) Description and Page Index
  Description: Homo sapiens sirtuin 1 (SIRT1), transcript variant 1, mRNA.
RefSeq Summary (NM_012238): 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].
Transcript (Including UTRs)
   Position: hg19 chr10:69,644,427-69,678,147 Size: 33,721 Total Exon Count: 9 Strand: +
Coding Region
   Position: hg19 chr10:69,644,480-69,676,350 Size: 31,871 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:69,644,427-69,678,147)mRNA (may differ from genome)Protein (747 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: SIR1_HUMAN
DESCRIPTION: RecName: Full=NAD-dependent protein deacetylase sirtuin-1; Short=hSIRT1; EC=3.5.1.-; AltName: Full=Regulatory protein SIR2 homolog 1; AltName: Full=SIR2-like protein 1; Short=hSIR2; Contains: RecName: Full=SirtT1 75 kDa fragment; Short=75SirT1;
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 transacivation 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.
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.
COFACTOR: Binds 1 zinc ion per subunit (By similarity).
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 KIAA1967/DBC1.
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 KIAA1967/DBC1 (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.
INTERACTION: Q13085:ACACA; NbExp=3; IntAct=EBI-1802965, EBI-717681; P31749:AKT1; NbExp=5; IntAct=EBI-1802965, EBI-296087; P27695:APEX1; NbExp=6; IntAct=EBI-1802965, EBI-1048805; P33076:CIITA; NbExp=4; IntAct=EBI-1802965, EBI-1538819; Q9NS37:CREBZF; NbExp=3; IntAct=EBI-1802965, EBI-632965; P68400:CSNK2A1; NbExp=2; IntAct=EBI-1802965, EBI-347804; P26358:DNMT1; NbExp=11; IntAct=EBI-1802965, EBI-719459; Q01094:E2F1; NbExp=3; IntAct=EBI-1802965, EBI-448924; Q09472:EP300; NbExp=2; IntAct=EBI-1802965, EBI-447295; Q14192:FHL2; NbExp=2; IntAct=EBI-1802965, EBI-701903; Q12778:FOXO1; NbExp=3; IntAct=EBI-1802965, EBI-1108782; Q9R1E0:Foxo1 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-1371343; O43524:FOXO3; NbExp=5; IntAct=EBI-1802965, EBI-1644164; P98177:FOXO4; NbExp=3; IntAct=EBI-1802965, EBI-4481939; P51610:HCFC1; NbExp=2; IntAct=EBI-1802965, EBI-396176; Q14469:HES1; NbExp=4; IntAct=EBI-1802965, EBI-2832522; Q9UBP5:HEY2; NbExp=3; IntAct=EBI-1802965, EBI-750630; Q9Y4H2:IRS2; NbExp=2; IntAct=EBI-1802965, EBI-1049582; Q92831:KAT2B; NbExp=3; IntAct=EBI-1802965, EBI-477430; Q8N163:KIAA1967; NbExp=9; IntAct=EBI-1802965, EBI-355410; Q03112:MECOM; NbExp=2; IntAct=EBI-1802965, EBI-1384862; P42345:MTOR; NbExp=2; IntAct=EBI-1802965, EBI-359260; P01106:MYC; NbExp=4; IntAct=EBI-1802965, EBI-447544; P04198:MYCN; NbExp=3; IntAct=EBI-1802965, EBI-878369; O60934:NBN; NbExp=5; IntAct=EBI-1802965, EBI-494844; Q60974:Ncor1 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-349004; Q02577:NHLH2; NbExp=2; IntAct=EBI-1802965, EBI-5378683; Q9HAN9:NMNAT1; NbExp=3; IntAct=EBI-1802965, EBI-3917542; Q15466:NR0B2; NbExp=6; IntAct=EBI-1802965, EBI-3910729; Q60644:Nr1h2 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-5276809; Q9Z0Y9:Nr1h3 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-5276764; P27986:PIK3R1; NbExp=3; IntAct=EBI-1802965, EBI-79464; P10276:RARA; NbExp=3; IntAct=EBI-1802965, EBI-413374; Q04206:RELA; NbExp=4; IntAct=EBI-1802965, EBI-73886; Q86WX3:RPS19BP1; NbExp=9; IntAct=EBI-1802965, EBI-4479407; Q8N122:RPTOR; NbExp=3; IntAct=EBI-1802965, EBI-1567928; O43159:RRP8; NbExp=3; IntAct=EBI-1802965, EBI-2008793; Q13573:SNW1; NbExp=7; IntAct=EBI-1802965, EBI-632715; P36956-3:SREBF1; NbExp=2; IntAct=EBI-1802965, EBI-948338; O54864:Suv39h1 (xeno); NbExp=4; IntAct=EBI-1802965, EBI-302230; P04608:tat (xeno); NbExp=3; IntAct=EBI-1802965, EBI-6164389; Q04724:TLE1; NbExp=4; IntAct=EBI-1802965, EBI-711424; P04637:TP53; NbExp=13; IntAct=EBI-1802965, EBI-366083; O15350:TP73; NbExp=4; IntAct=EBI-1802965, EBI-389606; P49815:TSC2; NbExp=2; IntAct=EBI-1802965, EBI-396587; Q14191:WRN; NbExp=9; IntAct=EBI-1802965, EBI-368417; P23025:XPA; NbExp=8; IntAct=EBI-1802965, EBI-295222; P12956:XRCC6; NbExp=7; IntAct=EBI-1802965, EBI-353208;
SUBCELLULAR LOCATION: 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.
SUBCELLULAR LOCATION: SirtT1 75 kDa fragment: Cytoplasm. Mitochondrion.
TISSUE SPECIFICITY: Widely expressed.
INDUCTION: Up-regulated by methyl methanesulfonate (MMS). In H293T cells by presence of rat calorie restriction (CR) serum.
PTM: Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53.
PTM: 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 acivates 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.
PTM: Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1).
PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity (By similarity).
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).
SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
SIMILARITY: Contains 1 deacetylase sirtuin-type domain.
SEQUENCE CAUTION: Sequence=AAH12499.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/sirt1/";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): SIRT1
CDC HuGE Published Literature: SIRT1

-  MalaCards Disease Associations
  MalaCards Gene Search: SIRT1
Diseases sorted by gene-association score: xeroderma pigmentosum, group d (6), ovarian endodermal sinus tumor (4), ovarian primitive germ cell tumor (4), hiv-1 (2), diabetes mellitus, noninsulin-dependent (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 15.51 RPKM in Testis
Total median expression: 319.13 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -10.0053-0.189 Picture PostScript Text
3' UTR -413.271797-0.230 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003000 - Sirtuin
IPR026591 - Sirtuin_cat_small_dom
IPR026590 - Ssirtuin_cat_dom

Pfam Domains:
PF02146 - Sir2 family

SCOP Domains:
52467 - DHS-like NAD/FAD-binding domain

ModBase Predicted Comparative 3D Structure on Q96EB6
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details  Gene DetailsGene Details 
Gene Sorter  Gene SorterGene Sorter 
  EnsemblFlyBaseWormBase 
  Protein SequenceProtein SequenceProtein Sequence 
  AlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001046 core promoter sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0002039 p53 binding
GO:0003714 transcription corepressor activity
GO:0004407 histone deacetylase activity
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0008134 transcription factor binding
GO:0016787 hydrolase activity
GO:0017136 NAD-dependent histone deacetylase activity
GO:0019213 deacetylase activity
GO:0019899 enzyme binding
GO:0019904 protein domain specific binding
GO:0033558 protein deacetylase activity
GO:0034979 NAD-dependent protein deacetylase activity
GO:0035257 nuclear hormone receptor binding
GO:0042393 histone binding
GO:0042802 identical protein binding
GO:0043398 HLH domain binding
GO:0043425 bHLH transcription factor binding
GO:0046872 metal ion binding
GO:0046969 NAD-dependent histone deacetylase activity (H3-K9 specific)
GO:0051019 mitogen-activated protein kinase binding
GO:0070403 NAD+ binding
GO:1990254 keratin filament binding
GO:0003950 NAD+ ADP-ribosyltransferase activity

Biological Process:
GO:0000012 single strand break repair
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000183 chromatin silencing at rDNA
GO:0000720 pyrimidine dimer repair by nucleotide-excision repair
GO:0000731 DNA synthesis involved in DNA repair
GO:0001525 angiogenesis
GO:0001542 ovulation from ovarian follicle
GO:0001678 cellular glucose homeostasis
GO:0001934 positive regulation of protein phosphorylation
GO:0001938 positive regulation of endothelial cell proliferation
GO:0002821 positive regulation of adaptive immune response
GO:0006325 chromatin organization
GO:0006342 chromatin silencing
GO:0006343 establishment of chromatin silencing
GO:0006344 maintenance of chromatin silencing
GO:0006346 methylation-dependent chromatin silencing
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006364 rRNA processing
GO:0006366 transcription from RNA polymerase II promoter
GO:0006476 protein deacetylation
GO:0006642 triglyceride mobilization
GO:0006915 apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0006979 response to oxidative stress
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007275 multicellular organism development
GO:0007283 spermatogenesis
GO:0007346 regulation of mitotic cell cycle
GO:0007517 muscle organ development
GO:0007569 cell aging
GO:0007623 circadian rhythm
GO:0008284 positive regulation of cell proliferation
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009267 cellular response to starvation
GO:0010629 negative regulation of gene expression
GO:0010875 positive regulation of cholesterol efflux
GO:0010883 regulation of lipid storage
GO:0010906 regulation of glucose metabolic process
GO:0010934 macrophage cytokine production
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:0016032 viral process
GO:0016239 positive regulation of macroautophagy
GO:0016567 protein ubiquitination
GO:0016575 histone deacetylation
GO:0018394 peptidyl-lysine acetylation
GO:0030154 cell differentiation
GO:0030225 macrophage differentiation
GO:0030308 negative regulation of cell growth
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
GO:0031393 negative regulation of prostaglandin biosynthetic process
GO:0031648 protein destabilization
GO:0031937 positive regulation of chromatin silencing
GO:0032007 negative regulation of TOR signaling
GO:0032071 regulation of endodeoxyribonuclease activity
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032868 response to insulin
GO:0032922 circadian regulation of gene expression
GO:0033158 regulation of protein import into nucleus, translocation
GO:0033210 leptin-mediated signaling pathway
GO:0034391 regulation of smooth muscle cell apoptotic process
GO:0034983 peptidyl-lysine deacetylation
GO:0035356 cellular triglyceride homeostasis
GO:0035358 regulation of peroxisome proliferator activated receptor signaling pathway
GO:0042127 regulation of cell proliferation
GO:0042326 negative regulation of phosphorylation
GO:0042542 response to hydrogen peroxide
GO:0042595 behavioral response to starvation
GO:0042632 cholesterol homeostasis
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0042981 regulation of apoptotic process
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043518 negative regulation of DNA damage response, signal transduction by p53 class mediator
GO:0043536 positive regulation of blood vessel endothelial cell migration
GO:0044321 response to leptin
GO:0045348 positive regulation of MHC class II biosynthetic process
GO:0045599 negative regulation of fat cell differentiation
GO:0045739 positive regulation of DNA repair
GO:0045766 positive regulation of angiogenesis
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046628 positive regulation of insulin receptor signaling pathway
GO:0048511 rhythmic process
GO:0050872 white fat cell differentiation
GO:0051097 negative regulation of helicase activity
GO:0051152 positive regulation of smooth muscle cell differentiation
GO:0051574 positive regulation of histone H3-K9 methylation
GO:0051898 negative regulation of protein kinase B signaling
GO:0055089 fatty acid homeostasis
GO:0060766 negative regulation of androgen receptor signaling pathway
GO:0061647 histone H3-K9 modification
GO:0070301 cellular response to hydrogen peroxide
GO:0070857 regulation of bile acid biosynthetic process
GO:0070914 UV-damage excision repair
GO:0070932 histone H3 deacetylation
GO:0071356 cellular response to tumor necrosis factor
GO:0071441 negative regulation of histone H3-K14 acetylation
GO:0071456 cellular response to hypoxia
GO:0071479 cellular response to ionizing radiation
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0090335 regulation of brown fat cell differentiation
GO:0090400 stress-induced premature senescence
GO:1900034 regulation of cellular response to heat
GO:1900113 negative regulation of histone H3-K9 trimethylation
GO:1901215 negative regulation of neuron death
GO:1901984 negative regulation of protein acetylation
GO:1902166 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:1902237 positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1904179 positive regulation of adipose tissue development
GO:1990619 histone H3-K9 deacetylation
GO:1990830 cellular response to leukemia inhibitory factor
GO:2000111 positive regulation of macrophage apoptotic process
GO:2000480 negative regulation of cAMP-dependent protein kinase activity
GO:2000481 positive regulation of cAMP-dependent protein kinase activity
GO:2000619 negative regulation of histone H4-K16 acetylation
GO:2000655 negative regulation of cellular response to testosterone stimulus
GO:2000757 negative regulation of peptidyl-lysine acetylation
GO:2000773 negative regulation of cellular senescence
GO:2000774 positive regulation of cellular senescence
GO:0006471 protein ADP-ribosylation

Cellular Component:
GO:0000785 chromatin
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005635 nuclear envelope
GO:0005637 nuclear inner membrane
GO:0005654 nucleoplasm
GO:0005677 chromatin silencing complex
GO:0005719 nuclear euchromatin
GO:0005720 nuclear heterochromatin
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0016605 PML body
GO:0033553 rDNA heterochromatin
GO:0035098 ESC/E(Z) complex


-  Descriptions from all associated GenBank mRNAs
  JD227474 - Sequence 208498 from Patent EP1572962.
AF083106 - Homo sapiens sirtuin type 1 (SIRT1) mRNA, complete cds.
AF235040 - Homo sapiens SIR2alpha protein (SIR2ALPHA) mRNA, complete cds.
JD408107 - Sequence 389131 from Patent EP1572962.
JD138988 - Sequence 120012 from Patent EP1572962.
JD472878 - Sequence 453902 from Patent EP1572962.
JD445689 - Sequence 426713 from Patent EP1572962.
JD407351 - Sequence 388375 from Patent EP1572962.
AL136741 - Homo sapiens mRNA; cDNA DKFZp434F1411 (from clone DKFZp434F1411).
BC012499 - Homo sapiens sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae), mRNA (cDNA clone MGC:21066 IMAGE:4518906), complete cds.
AK289743 - Homo sapiens cDNA FLJ76335 complete cds, highly similar to Homo sapiens sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae), mRNA.
CU680344 - Synthetic construct Homo sapiens gateway clone IMAGE:100019856 5' read SIRT1 mRNA.
JQ768366 - Homo sapiens sirtuin 1 (SIRT1) mRNA, partial cds.
KJ904690 - Synthetic construct Homo sapiens clone ccsbBroadEn_14084 SIRT1 gene, encodes complete protein.
JD026022 - Sequence 7046 from Patent EP1572962.
JD032842 - Sequence 13866 from Patent EP1572962.
AK074805 - Homo sapiens cDNA FLJ90324 fis, clone NT2RP2001817, highly similar to NAD-dependent deacetylase sirtuin-1 (EC 3.5.1.-).
AK027686 - Homo sapiens cDNA FLJ14780 fis, clone NT2RP4000449, highly similar to NAD-dependent deacetylase sirtuin-1 (EC 3.5.1.-).
BX648554 - Homo sapiens mRNA; cDNA DKFZp779P1254 (from clone DKFZp779P1254).
JD535927 - Sequence 516951 from Patent EP1572962.
JD308335 - Sequence 289359 from Patent EP1572962.
JD283982 - Sequence 265006 from Patent EP1572962.
JD204954 - Sequence 185978 from Patent EP1572962.
JD410621 - Sequence 391645 from Patent EP1572962.
JD524101 - Sequence 505125 from Patent EP1572962.
JD146754 - Sequence 127778 from Patent EP1572962.
JD516118 - Sequence 497142 from Patent EP1572962.
JD562293 - Sequence 543317 from Patent EP1572962.
JD328576 - Sequence 309600 from Patent EP1572962.
JD333445 - Sequence 314469 from Patent EP1572962.
JD553821 - Sequence 534845 from Patent EP1572962.
JD330377 - Sequence 311401 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_pmlPathway - Regulation of transcriptional activity by PML

Reactome (by CSHL, EBI, and GO)

Protein Q96EB6 (Reactome details) participates in the following event(s):

R-HSA-427528 Formation of energy-dependent Nucleolar Silencing Complex (eNoSC)
R-HSA-3371518 SIRT1 binds to HSF1
R-HSA-3371537 DBC1 binds SIRT1
R-HSA-3371467 SIRT1 deacetylates HSF1
R-HSA-5211239 SIRT1 deacetylates TAF1B in SL1 complex
R-HSA-427514 eNoSC deacetylates histone H3
R-HSA-427527 eNoSC dimethylates histone H3 at lysine-9
R-HSA-427359 SIRT1 negatively regulates rRNA expression
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-5250941 Negative epigenetic regulation of rRNA expression
R-HSA-3371556 Cellular response to heat stress
R-HSA-212165 Epigenetic regulation of gene expression
R-HSA-2262752 Cellular responses to stress
R-HSA-74160 Gene expression (Transcription)
R-HSA-8953897 Cellular responses to external stimuli

-  Other Names for This Gene
  Alternate Gene Symbols: NM_012238, NP_001135970, Q2XNF6, Q5JVQ0, Q96EB6, Q9GZR9, Q9Y6F0, SIR1_HUMAN, SIR2L1
UCSC ID: uc001jnd.3
RefSeq Accession: NM_012238
Protein: Q96EB6 (aka SIR1_HUMAN)
CCDS: CCDS7273.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_012238.4
exon count: 9CDS single in 3' UTR: no RNA size: 4110
ORF size: 2244CDS single in intron: no Alignment % ID: 99.98
txCdsPredict score: 3589.00frame shift in genome: no % Coverage: 99.61
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.