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Q96EB6 (SIR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
NAD-dependent protein deacetylase sirtuin-1

Short name=hSIRT1
EC=3.5.1.-
Alternative name(s):
Regulatory protein SIR2 homolog 1
SIR2-like protein 1
Short name=hSIR2

Cleaved into the following chain:

  1. SirtT1 75 kDa fragment
    Short name=75SirT1
Gene names
Name:SIRT1
Synonyms:SIR2L1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length747 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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-1Cthereby 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. Ref.6 Ref.7 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.34 Ref.36 Ref.37 Ref.38 Ref.43 Ref.46 Ref.48 Ref.49 Ref.50 Ref.53 Ref.54 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60 Ref.61 Ref.63 Ref.64 Ref.66 Ref.69 Ref.71 Ref.73 Ref.74 Ref.75 Ref.76 Ref.79 Ref.81 Ref.82 Ref.83 Ref.85

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. Ref.6 Ref.7 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.34 Ref.36 Ref.37 Ref.38 Ref.43 Ref.46 Ref.48 Ref.49 Ref.50 Ref.53 Ref.54 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60 Ref.61 Ref.63 Ref.64 Ref.66 Ref.69 Ref.71 Ref.73 Ref.74 Ref.75 Ref.76 Ref.79 Ref.81 Ref.82 Ref.83 Ref.85

Catalytic activity

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.7

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 CCAR2. Ref.8 Ref.9 Ref.39 Ref.40

Subunit structure

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. Ref.2 Ref.7 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.24 Ref.28 Ref.34 Ref.36 Ref.39 Ref.40 Ref.47 Ref.48 Ref.55 Ref.61 Ref.62 Ref.63 Ref.70 Ref.76 Ref.77 Ref.78 Ref.87

Subcellular location

NucleusPML 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. Ref.6 Ref.7 Ref.13 Ref.17 Ref.51 Ref.60 Ref.81

SirtT1 75 kDa fragment: Cytoplasm. Mitochondrion Ref.6 Ref.7 Ref.13 Ref.17 Ref.51 Ref.60 Ref.81.

Tissue specificity

Widely expressed. Ref.1

Induction

Up-regulated by methyl methanesulfonate (MMS). In H293T cells by presence of rat calorie restriction (CR) serum. Ref.8 Ref.9 Ref.15 Ref.39 Ref.40 Ref.60 Ref.63

Post-translational modification

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. Ref.35 Ref.41 Ref.45 Ref.51 Ref.72 Ref.73

Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1). Ref.67

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.

Calf histone H1 is used as substrate in the in vitro deacetylation assay (Ref.13). As, in vivo, interaction occurs between SIRT1 with HIST1H1E, deacetylation has been validated only for HIST1H1E.

The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant (Ref.46).

Sequence similarities

Belongs to the sirtuin family. Class I subfamily.

Contains 1 deacetylase sirtuin-type domain.

Sequence caution

The sequence AAH12499.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
Host-virus interaction
Myogenesis
rRNA processing
Transcription
Transcription regulation
   Cellular componentCytoplasm
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandMetal-binding
NAD
Zinc
   Molecular functionDevelopmental protein
Hydrolase
   PTMAcetylation
Methylation
Phosphoprotein
S-nitrosylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Traceable author statement PubMed 17317627. Source: BHF-UCL

DNA replication

Traceable author statement PubMed 17317627. Source: BHF-UCL

DNA synthesis involved in DNA repair

Inferred from sequence or structural similarity. Source: UniProtKB

angiogenesis

Inferred from direct assay Ref.58. Source: UniProtKB

cell aging

Traceable author statement Ref.6. Source: BHF-UCL

cellular glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from direct assay Ref.37. Source: UniProtKB

cellular response to hydrogen peroxide

Inferred from direct assay Ref.51. Source: BHF-UCL

cellular response to hypoxia

Inferred from mutant phenotype Ref.58. Source: UniProtKB

cellular response to ionizing radiation

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to starvation

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to tumor necrosis factor

Inferred from direct assay Ref.10. Source: UniProtKB

cellular triglyceride homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

cholesterol homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

chromatin silencing

Traceable author statement Ref.1. Source: ProtInc

chromatin silencing at rDNA

Inferred from direct assay Ref.34. Source: UniProtKB

establishment of chromatin silencing

Inferred from direct assay Ref.13. Source: BHF-UCL

fatty acid homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

histone H3 deacetylation

Inferred from direct assay Ref.51. Source: BHF-UCL

histone deacetylation

Inferred from direct assay Ref.17PubMed 17172643. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from mutant phenotype Ref.56. Source: UniProtKB

maintenance of chromatin silencing

Inferred from mutant phenotype Ref.13. Source: BHF-UCL

methylation-dependent chromatin silencing

Traceable author statement Ref.75. Source: UniProtKB

muscle organ development

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of DNA damage response, signal transduction by p53 class mediator

Inferred from direct assay Ref.6. Source: BHF-UCL

negative regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay Ref.24. Source: UniProtKB

negative regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.10. Source: UniProtKB

negative regulation of TOR signaling

Inferred from mutant phenotype Ref.62. Source: UniProtKB

negative regulation of androgen receptor signaling pathway

Inferred from mutant phenotype Ref.27. Source: BHF-UCL

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.22Ref.79. Source: UniProtKB

negative regulation of cAMP-dependent protein kinase activity

Inferred from direct assay Ref.53. Source: UniProtKB

negative regulation of cell growth

Inferred from mutant phenotype Ref.27. Source: BHF-UCL

negative regulation of cellular response to testosterone stimulus

Inferred from mutant phenotype Ref.27. Source: BHF-UCL

negative regulation of cellular senescence

Inferred from direct assay Ref.53. Source: UniProtKB

negative regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of helicase activity

Inferred from direct assay Ref.37. Source: UniProtKB

negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from sequence or structural similarity PubMed 11672522. Source: BHF-UCL

negative regulation of intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from mutant phenotype PubMed 17317627. Source: BHF-UCL

negative regulation of peptidyl-lysine acetylation

Inferred from direct assay Ref.56. Source: UniProtKB

negative regulation of phosphorylation

Inferred from mutant phenotype Ref.31. Source: UniProtKB

negative regulation of prostaglandin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein kinase B signaling

Inferred from mutant phenotype Ref.64. Source: UniProtKB

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.6. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.16. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.6. Source: BHF-UCL

negative regulation of transforming growth factor beta receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

ovulation from ovarian follicle

Inferred from electronic annotation. Source: Ensembl

peptidyl-lysine acetylation

Inferred from mutant phenotype Ref.33. Source: UniProtKB

peptidyl-lysine deacetylation

Inferred from direct assay Ref.13. Source: BHF-UCL

positive regulation of DNA repair

Inferred from mutant phenotype Ref.60. Source: UniProtKB

positive regulation of MHC class II biosynthetic process

Inferred from direct assay Ref.82. Source: UniProtKB

positive regulation of adaptive immune response

Inferred from direct assay Ref.82. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay Ref.10. Source: UniProtKB

positive regulation of cAMP-dependent protein kinase activity

Inferred from mutant phenotype Ref.38. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype Ref.71. Source: UniProtKB

positive regulation of cellular senescence

Inferred from direct assay Ref.38. Source: UniProtKB

positive regulation of cholesterol efflux

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of chromatin silencing

Inferred from mutant phenotype Ref.13. Source: BHF-UCL

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 19047049. Source: UniProtKB

positive regulation of insulin receptor signaling pathway

Inferred from direct assay PubMed 21241768. Source: UniProtKB

positive regulation of macroautophagy

Inferred from direct assay Ref.43. Source: UniProtKB

positive regulation of macrophage apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.71. Source: UniProtKB

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype Ref.85. Source: UniProtKB

protein deacetylation

Inferred from direct assay Ref.37Ref.51. Source: UniProtKB

protein destabilization

Inferred from sequence or structural similarity. Source: UniProtKB

protein ubiquitination

Inferred from direct assay Ref.85. Source: UniProtKB

pyrimidine dimer repair by nucleotide-excision repair

Inferred from mutant phenotype Ref.64. Source: UniProtKB

rRNA processing

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of bile acid biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell proliferation

Inferred from mutant phenotype Ref.7. Source: BHF-UCL

regulation of endodeoxyribonuclease activity

Inferred from mutant phenotype Ref.60. Source: UniProtKB

regulation of glucose metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of mitotic cell cycle

Inferred from direct assay Ref.16. Source: UniProtKB

regulation of peroxisome proliferator activated receptor signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of protein import into nucleus, translocation

Inferred from mutant phenotype Ref.37. Source: UniProtKB

regulation of smooth muscle cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

response to hydrogen peroxide

Inferred from direct assay Ref.60. Source: UniProtKB

response to insulin

Inferred from sequence or structural similarity. Source: UniProtKB

response to oxidative stress

Inferred from direct assay Ref.14. Source: UniProtKB

single strand break repair

Inferred from mutant phenotype Ref.54. Source: UniProtKB

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

triglyceride mobilization

Inferred from sequence or structural similarity. Source: BHF-UCL

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

white fat cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentPML body

Inferred from direct assay Ref.7. Source: BHF-UCL

chromatin silencing complex

Inferred from direct assay Ref.34. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.51. Source: BHF-UCL

mitochondrion

Inferred from direct assay. Source: HPA

nuclear chromatin

Inferred from direct assay Ref.27. Source: BHF-UCL

nuclear envelope

Inferred from direct assay Ref.13. Source: BHF-UCL

nuclear euchromatin

Inferred from direct assay Ref.13. Source: UniProtKB

nuclear heterochromatin

Inferred from direct assay Ref.13. Source: UniProtKB

nuclear inner membrane

Inferred from direct assay Ref.13. Source: UniProtKB

nucleolus

Inferred from direct assay Ref.13. Source: BHF-UCL

nucleoplasm

Inferred from direct assay Ref.17. Source: UniProtKB

nucleus

Inferred from direct assay Ref.60. Source: UniProtKB

rDNA heterochromatin

Inferred from direct assay Ref.34. Source: UniProtKB

   Molecular_functionHLH domain binding

Inferred from physical interaction Ref.2. Source: BHF-UCL

NAD+ binding

Inferred from electronic annotation. Source: InterPro

NAD-dependent histone deacetylase activity

Inferred from direct assay Ref.7Ref.13. Source: BHF-UCL

NAD-dependent histone deacetylase activity (H3-K9 specific)

Inferred from sequence or structural similarity. Source: UniProtKB

NAD-dependent protein deacetylase activity

Inferred from direct assay Ref.79. Source: UniProtKB

bHLH transcription factor binding

Inferred from physical interaction Ref.71. Source: UniProtKB

deacetylase activity

Inferred from direct assay Ref.37. Source: UniProtKB

histone binding

Inferred from physical interaction Ref.13. Source: BHF-UCL

histone deacetylase activity

Inferred from direct assay Ref.51. Source: BHF-UCL

identical protein binding

Inferred from physical interaction Ref.13. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

mitogen-activated protein kinase binding

Inferred from physical interaction Ref.51. Source: BHF-UCL

p53 binding

Inferred from physical interaction Ref.6. Source: BHF-UCL

protein C-terminus binding

Inferred from physical interaction Ref.37. Source: UniProtKB

protein deacetylase activity

Inferred from direct assay Ref.60Ref.71. Source: UniProtKB

transcription corepressor activity

Inferred from direct assay Ref.2. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ACACAQ130853EBI-1802965,EBI-717681
AKT1P317495EBI-1802965,EBI-296087
APEX1P276956EBI-1802965,EBI-1048805
CCAR2Q8N1639EBI-1802965,EBI-355410
CIITAP330764EBI-1802965,EBI-1538819
CREBZFQ9NS373EBI-1802965,EBI-632965
CSNK2A1P684004EBI-1802965,EBI-347804
CSNK2BP678705EBI-1802965,EBI-348169
DNMT1P2635811EBI-1802965,EBI-719459
E2F1Q010943EBI-1802965,EBI-448924
EP300Q094722EBI-1802965,EBI-447295
FHL2Q141922EBI-1802965,EBI-701903
FOXO1Q127783EBI-1802965,EBI-1108782
Foxo1Q9R1E02EBI-1802965,EBI-1371343From a different organism.
FOXO3O435245EBI-1802965,EBI-1644164
FOXO4P981773EBI-1802965,EBI-4481939
HCFC1P516102EBI-1802965,EBI-396176
HES1Q144694EBI-1802965,EBI-2832522
HEY2Q9UBP53EBI-1802965,EBI-750630
IRS2Q9Y4H22EBI-1802965,EBI-1049582
KAT2BQ928313EBI-1802965,EBI-477430
MECOMQ031122EBI-1802965,EBI-1384862
MTORP423452EBI-1802965,EBI-359260
MYCP011064EBI-1802965,EBI-447544
MYCNP041983EBI-1802965,EBI-878369
NBNO609345EBI-1802965,EBI-494844
Ncor1Q609742EBI-1802965,EBI-349004From a different organism.
NHLH2Q025772EBI-1802965,EBI-5378683
NMNAT1Q9HAN93EBI-1802965,EBI-3917542
NR0B2Q154666EBI-1802965,EBI-3910729
Nr1h2Q606442EBI-1802965,EBI-5276809From a different organism.
Nr1h3Q9Z0Y92EBI-1802965,EBI-5276764From a different organism.
PIK3R1P279863EBI-1802965,EBI-79464
PpargP372383EBI-1802965,EBI-5260705From a different organism.
PpargP37238-12EBI-1802965,EBI-6267861From a different organism.
RARAP102763EBI-1802965,EBI-413374
RELAQ042064EBI-1802965,EBI-73886
RPS19BP1Q86WX39EBI-1802965,EBI-4479407
RPTORQ8N1223EBI-1802965,EBI-1567928
RRP8O431593EBI-1802965,EBI-2008793
SNW1Q135737EBI-1802965,EBI-632715
SREBF1P36956-32EBI-1802965,EBI-948338
Suv39h1O548644EBI-1802965,EBI-302230From a different organism.
tatP046083EBI-1802965,EBI-6164389From a different organism.
TLE1Q047244EBI-1802965,EBI-711424
TP53P0463713EBI-1802965,EBI-366083
TP73O153504EBI-1802965,EBI-389606
TSC2P498152EBI-1802965,EBI-396587
WRNQ141919EBI-1802965,EBI-368417
XPAP230258EBI-1802965,EBI-295222
XRCC6P129567EBI-1802965,EBI-353208

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96EB6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96EB6-2)

Also known as: delta-exon8;

The sequence of this isoform differs from the canonical sequence as follows:
     454-639: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.44
Chain2 – 747746NAD-dependent protein deacetylase sirtuin-1
PRO_0000110256
Chain2 – 533532SirtT1 75 kDa fragment
PRO_0000415289

Regions

Domain244 – 498255Deacetylase sirtuin-type
Nucleotide binding261 – 28020NAD By similarity
Nucleotide binding345 – 3484NAD By similarity
Nucleotide binding440 – 4423NAD By similarity
Nucleotide binding465 – 4673NAD By similarity
Region2 – 268267Interaction with HIST1H1E
Region143 – 541399Interaction with CCAR2
Region538 – 5403Phosphorylated at one of three serine residues
Motif32 – 398Nuclear localization signal By similarity
Motif138 – 1458Nuclear export signal By similarity
Motif223 – 2308Nuclear localization signal By similarity
Motif425 – 4317Nuclear export signal By similarity
Compositional bias54 – 9845Ala-rich
Compositional bias122 – 1276Poly-Asp
Compositional bias128 – 1347Poly-Glu

Sites

Active site3631Proton acceptor
Metal binding3711Zinc By similarity
Metal binding3741Zinc By similarity
Metal binding3951Zinc By similarity
Metal binding3981Zinc By similarity
Binding site4821NAD; via amide nitrogen By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.44 Ref.65 Ref.80 Ref.84 Ref.86
Modified residue141Phosphoserine Ref.41 Ref.65 Ref.80
Modified residue261Phosphoserine Ref.41
Modified residue271Phosphoserine; by MAPK8 Ref.35 Ref.41 Ref.51
Modified residue471Phosphoserine; by MAPK8 Ref.21 Ref.35 Ref.41 Ref.51 Ref.65 Ref.73 Ref.80
Modified residue1591Phosphoserine Probable
Modified residue1621Phosphoserine Probable
Modified residue1721Phosphoserine Ref.41
Modified residue1731Phosphoserine Ref.41
Modified residue3951S-nitrosocysteine By similarity
Modified residue3981S-nitrosocysteine By similarity
Modified residue5301Phosphothreonine; by DYRK1A, DYRK3 and MAPK8 Ref.41 Ref.51 Ref.52
Modified residue5351Phosphoserine Ref.52
Modified residue5441Phosphothreonine Probable
Modified residue5451Phosphoserine Probable
Modified residue6591Phosphoserine; by CaMK2 By similarity
Modified residue6611Phosphoserine; by CaMK2 Probable
Modified residue7191Phosphothreonine Ref.41 Ref.42 Ref.52 Ref.80
Modified residue7471Phosphoserine Ref.41

Natural variations

Alternative sequence454 – 639186Missing in isoform 2.
VSP_042189
Natural variant31D → E. Ref.3
Corresponds to variant rs35671182 [ dbSNP | Ensembl ].
VAR_025148
Natural variant4841V → D.
Corresponds to variant rs1063111 [ dbSNP | Ensembl ].
VAR_051976

Experimental info

Mutagenesis271S → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-47 and A-530. Ref.51
Mutagenesis471S → A: Blocks residue phosphorylation, restores deacetylation activity and inhibits DNA damage-induced apoptosis. Ref.51 Ref.73
Mutagenesis471S → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-530. Ref.51 Ref.73
Mutagenesis2331K → R: Impairs in vitro methylation by SETD7; when associated with R-235, R-236 and R-238. Ref.78
Mutagenesis2351K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-236 and R-238. Ref.78
Mutagenesis2361K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-235 and R-238. Ref.78
Mutagenesis2381K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-235a and R-236. Ref.78
Mutagenesis3631H → Y: Loss of function. Reduces the interaction with CCAR2 and APEX1. Increases acetylation of APEX1. Ref.2 Ref.6 Ref.7 Ref.33 Ref.34 Ref.39 Ref.60
Mutagenesis4741F → A: Abolishes phosphorylation at Ser-47, restores deacetylation activity and inhibits DNA damage-induced apoptosis. Ref.73
Mutagenesis5301T → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-47. Ref.41 Ref.51
Mutagenesis5301T → A: Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-540. Ref.41 Ref.51
Mutagenesis5401S → A: Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-530. Ref.41
Mutagenesis6591S → A: Reduces in vitro phosphorylation by CaMK2; when associated with S-661. Greatly reduces in vivo phosphorylation; when associated with A-661. Ref.45
Mutagenesis6611S → A: Reduces in vitro phosphorylation by CaMK2; when associated with S-659. Greatly reduces in vivo phosphorylation; when associated with A-659. Ref.45
Mutagenesis6841S → A: No effect on phosphorylation (in vitro and in vivo). Ref.45
Sequence conflict386 – 3894DIFN → ALFS in AAH12499. Ref.5

Secondary structure

............................................................... 747
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 31, 2003. Version 2.
Checksum: 2D3BEA6D73DA229F

FASTA74781,681
        10         20         30         40         50         60 
MADEAALALQ PGGSPSAAGA DREAASSPAG EPLRKRPRRD GPGLERSPGE PGGAAPEREV 

        70         80         90        100        110        120 
PAAARGCPGA AAAALWREAE AEAAAAGGEQ EAQATAAAGE GDNGPGLQGP SREPPLADNL 

       130        140        150        160        170        180 
YDEDDDDEGE EEEEAAAAAI GYRDNLLFGD EIITNGFHSC ESDEEDRASH ASSSDWTPRP 

       190        200        210        220        230        240 
RIGPYTFVQQ HLMIGTDPRT ILKDLLPETI PPPELDDMTL WQIVINILSE PPKRKKRKDI 

       250        260        270        280        290        300 
NTIEDAVKLL QECKKIIVLT GAGVSVSCGI PDFRSRDGIY ARLAVDFPDL PDPQAMFDIE 

       310        320        330        340        350        360 
YFRKDPRPFF KFAKEIYPGQ FQPSLCHKFI ALSDKEGKLL RNYTQNIDTL EQVAGIQRII 

       370        380        390        400        410        420 
QCHGSFATAS CLICKYKVDC EAVRGDIFNQ VVPRCPRCPA DEPLAIMKPE IVFFGENLPE 

       430        440        450        460        470        480 
QFHRAMKYDK DEVDLLIVIG SSLKVRPVAL IPSSIPHEVP QILINREPLP HLHFDVELLG 

       490        500        510        520        530        540 
DCDVIINELC HRLGGEYAKL CCNPVKLSEI TEKPPRTQKE LAYLSELPPT PLHVSEDSSS 

       550        560        570        580        590        600 
PERTSPPDSS VIVTLLDQAA KSNDDLDVSE SKGCMEEKPQ EVQTSRNVES IAEQMENPDL 

       610        620        630        640        650        660 
KNVGSSTGEK NERTSVAGTV RKCWPNRVAK EQISRRLDGN QYLFLPPNRY IFHGAEVYSD 

       670        680        690        700        710        720 
SEDDVLSSSS CGSNSDSGTC QSPSLEEPME DESEIEEFYN GLEDEPDVPE RAGGAGFGTD 

       730        740 
GDDQEAINEA ISVKQEVTDM NYPSNKS 

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Isoform 2 (delta-exon8) [UniParc].

Checksum: BFD54C8E408F23BD
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FASTA56161,066

References

« Hide 'large scale' references
[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."
Frye R.A.
Biochem. Biophys. Res. Commun. 260:273-279(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Testis.
[2]"Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression."
Takata T., Ishikawa F.
Biochem. Biophys. Res. Commun. 301:250-257(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH HES1 AND HEY2, MUTAGENESIS OF HIS-363.
[3]NIEHS SNPs program
Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-3.
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 124-747.
Tissue: Prostate.
[6]"hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase."
Vaziri H., Dessain S.K., Ng Eaton E., Imai S., Frye R.A., Pandita T.K., Guarente L., Weinberg R.A.
Cell 107:149-159(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF TP53, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-363.
[7]"Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence."
Langley E., Pearson M., Faretta M., Bauer U.-M., Frye R.A., Minucci S., Pelicci P.G., Kouzarides T.
EMBO J. 21:2383-2396(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH PML, MUTAGENESIS OF HIS-363.
[8]"Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1."
Bitterman K.J., Anderson R.M., Cohen H.Y., Latorre-Esteves M., Sinclair D.A.
J. Biol. Chem. 277:45099-45107(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[9]"Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan."
Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S., Wood J.G., Zipkin R.E., Chung P., Kisielewski A., Zhang L.-L., Scherer B., Sinclair D.A.
Nature 425:191-196(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[10]"Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase."
Frye R.A., Mayo M.W.
EMBO J. 23:2369-2380(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Mammalian SIRT1 represses forkhead transcription factors."
Motta M.C., Divecha N., Lemieux M., Kamel C., Chen D., Gu W., Bultsma Y., McBurney M., Guarente L.
Cell 116:551-563(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF FOXO3, FUNCTION IN REGULATION OF FOXO3.
[12]"FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)."
van der Horst A., Tertoolen L.G.J., de Vries-Smits L.M.M., Frye R.A., Medema R.H., Burgering B.M.T.
J. Biol. Chem. 279:28873-28879(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF MLLT7.
[13]"Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin."
Vaquero A., Scher M., Lee D., Erdjument-Bromage H., Tempst P., Reinberg D.
Mol. Cell 16:93-105(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]"Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase."
Brunet A., Sweeney L.B., Sturgill J.F., Chua K.F., Greer P.L., Lin Y., Tran H., Ross S.E., Mostoslavsky R., Cohen H.Y., Hu L.S., Cheng H.L., Jedrychowski M.P., Gygi S.P., Sinclair D.A., Alt F.W., Greenberg M.E.
Science 303:2011-2015(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF FOXO3, FUNCTION IN REGULATION OF FOXO3.
[15]"Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase."
Cohen H.Y., Miller C., Bitterman K.J., Wall N.R., Hekking B., Kessler B., Howitz K.T., Gorospe M., de Cabo R., Sinclair D.A.
Science 305:390-392(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF XRCC6, INDUCTION BY CR.
[16]"Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation."
Yang Y., Hou H., Haller E.M., Nicosia S.V., Bai W.
EMBO J. 24:1021-1032(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FHL2, FUNCTION IN DEACETYLATION OF FOXO1, FUNCTION IN REGULATION OF FOXO1.
[17]"Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins."
Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.
Mol. Biol. Cell 16:4623-4635(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[18]"Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications."
Zhao X., Sternsdorf T., Bolger T.A., Evans R.M., Yao T.-P.
Mol. Cell. Biol. 25:8456-8464(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF MEF2D, INTERACTION WITH HDAC4.
[19]"SIRT1 regulates HIV transcription via Tat deacetylation."
Pagans S., Pedal A., North B.J., Kaehlcke K., Marshall B.L., Dorr A., Hetzer-Egger C., Henklein P., Frye R., McBurney M.W., Hruby H., Jung M., Verdin E., Ott M.
PLoS Biol. 3:210-220(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 TAT.
[20]"Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation."
Kuzmichev A., Margueron R., Vaquero A., Preissner T.S., Scher M., Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P.J., Reinberg D.
Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH THE PRC4 COMPLEX, INTERACTION WITH SUZ12.
[21]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage."
Wang C., Chen L., Hou X., Li Z., Kabra N., Ma Y., Nemoto S., Finkel T., Gu W., Cress W.D., Chen J.
Nat. Cell Biol. 8:1025-1031(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH E2F1.
[23]"Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1."
Wong S., Weber J.D.
Biochem. J. 407:451-460(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF RB1.
[24]"Sirt1 interacts with transducin-like enhancer of split-1 to inhibit nuclear factor kappaB-mediated transcription."
Ghosh H.S., Spencer J.V., Ng B., McBurney M.W., Robbins P.D.
Biochem. J. 408:105-111(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TLE1.
[25]"SIRT1 promotes DNA repair activity and deacetylation of Ku70."
Jeong J., Juhn K., Lee H., Kim S.H., Min B.H., Lee K.M., Cho M.H., Park G.H., Lee K.H.
Exp. Mol. Med. 39:8-13(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF XRCC6, FUNCTION IN DNA REPAIR.
[26]"SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity."
Dai J.M., Wang Z.Y., Sun D.C., Lin R.X., Wang S.Q.
J. Cell. Physiol. 210:161-166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF TP73, FUNCTION IN REGULATION OF TP73.
[27]"Sirtuin 1 is required for antagonist-induced transcriptional repression of androgen-responsive genes by the androgen receptor."
Dai Y., Ngo D., Forman L.W., Qin D.C., Jacob J., Faller D.V.
Mol. Endocrinol. 21:1807-1821(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN AR-DEPENDENT REPRESSION.
[28]"Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity."
Kim E.-J., Kho J.-H., Kang M.-R., Um S.-J.
Mol. Cell 28:277-290(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RPS19BP1.
[29]Erratum
Kim E.-J., Kho J.-H., Kang M.-R., Um S.-J.
Mol. Cell 28:513-513(2007)
[30]"SIRT1 deacetylates and positively regulates the nuclear receptor LXR."
Li X., Zhang S., Blander G., Tse J.G., Krieger M., Guarente L.
Mol. Cell 28:91-106(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF NR1H3 AND NR1H2.
[31]"SIRT1 regulates the function of the Nijmegen breakage syndrome protein."
Yuan Z., Zhang X., Sengupta N., Lane W.S., Seto E.
Mol. Cell 27:149-162(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF NBN, FUNCTION IN DNA REPAIR.
[32]"An acetylation/deacetylation-SUMOylation switch through a phylogenetically conserved psiKXEP motif in the tumor suppressor HIC1 regulates transcriptional repression activity."
Stankovic-Valentin N., Deltour S., Seeler J., Pinte S., Vergoten G., Guerardel C., Dejean A., Leprince D.
Mol. Cell. Biol. 27:2661-2675(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF HIC1.
[33]"SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation."
Vaquero A., Scher M., Erdjument-Bromage H., Tempst P., Serrano L., Reinberg D.
Nature 450:440-444(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF HIS-363.
[34]"Epigenetic control of rDNA loci in response to intracellular energy status."
Murayama A., Ohmori K., Fujimura A., Minami H., Yasuzawa-Tanaka K., Kuroda T., Oie S., Daitoku H., Okuwaki M., Nagata K., Fukamizu A., Kimura K., Shimizu T., Yanagisawa J.
Cell 133:627-639(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE ENOSC COMPLEX, FUNCTION, MUTAGENESIS OF HIS-363.
[35]"JNK2-dependent regulation of SIRT1 protein stability."
Ford J., Ahmed S., Allison S., Jiang M., Milner J.
Cell Cycle 7:3091-3097(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-27 AND SER-47.
[36]"Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation."
Kwon H.S., Brent M.M., Getachew R., Jayakumar P., Chen L.F., Schnolzer M., McBurney M.W., Marmorstein R., Greene W.C., Ott M.
Cell Host Microbe 3:158-167(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 TAT, FUNCTION IN T-CELL ACTIVATION.
[37]"Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation."
Li K., Casta A., Wang R., Lozada E., Fan W., Kane S., Ge Q., Gu W., Orren D., Luo J.
J. Biol. Chem. 283:7590-7598(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF WRN, FUNCTION IN DNA DAMAGE.
[38]"SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activation."
Lan F., Cacicedo J.M., Ruderman N., Ido Y.
J. Biol. Chem. 283:27628-27635(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF STK11.
[39]"DBC1 is a negative regulator of SIRT1."
Kim J.-E., Chen J., Lou Z.
Nature 451:583-586(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CCAR2, ENZYME REGULATION, MUTAGENESIS OF HIS-363, IDENTIFICATION BY MASS SPECTROMETRY.
[40]"Negative regulation of the deacetylase SIRT1 by DBC1."
Zhao W., Kruse J.-P., Tang Y., Jung S.Y., Qin J., Gu W.
Nature 451:587-590(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CCAR2, ENZYME REGULATION.
[41]"Phosphorylation regulates SIRT1 function."
Sasaki T., Maier B., Koclega K.D., Chruszcz M., Gluba W., Stukenberg P.T., Minor W., Scrable H.
PLoS ONE 3:E4020-E4020(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-14; SER-26; SER-27; SER-47; SER-159; SER-162; SER-172; SER-173; THR-530; THR-544; SER-545; THR-719 AND SER-747, MUTAGENESIS OF THR-530 AND SER-540.
[42]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[43]"A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy."
Lee I.H., Cao L., Mostoslavsky R., Lombard D.B., Liu J., Bruns N.E., Tsokos M., Alt F.W., Finkel T.
Proc. Natl. Acad. Sci. U.S.A. 105:3374-3379(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF ATG5; ATG7 AND MAP1LC3B, FUNCTION IN AUTOPHAGY.
[44]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[45]"Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2."
Zschoernig B., Mahlknecht U.
Biochem. Biophys. Res. Commun. 381:372-377(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-659 AND SER-661, MUTAGENESIS OF SER-659; SER-661 AND SER-684.
[46]"Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogues and 32P-NAD."
Du J., Jiang H., Lin H.
Biochemistry 48:2878-2890(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[47]"Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation."
Purushotham A., Schug T.T., Xu Q., Surapureddi S., Guo X., Li X.
Cell Metab. 9:327-338(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPARA.
[48]"Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear receptor estrogen receptor-related receptor gamma transactivation."
Xie Y.B., Park J.H., Kim D.K., Hwang J.H., Oh S., Park S.B., Shong M., Lee I.K., Choi H.S.
J. Biol. Chem. 284:28762-28774(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CREBZF.
[49]"A c-Myc-SIRT1 feedback loop regulates cell growth and transformation."
Yuan J., Minter-Dykhouse K., Lou Z.
J. Cell Biol. 185:203-211(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF MYC, FUNCTION IN REGULATION OF MYC.
[50]"hSirT1-dependent regulation of the PCAF-E2F1-p73 apoptotic pathway in response to DNA damage."
Pediconi N., Guerrieri F., Vossio S., Bruno T., Belloni L., Schinzari V., Scisciani C., Fanciulli M., Levrero M.
Mol. Cell. Biol. 29:1989-1998(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF PCAF, FUNCTION IN DNA REPAIR.
[51]"JNK1 phosphorylates SIRT1 and promotes its enzymatic activity."
Nasrin N., Kaushik V.K., Fortier E., Wall D., Pearson K.J., de Cabo R., Bordone L.
PLoS ONE 4:E8414-E8414(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-27; SER-47 AND THR-530, MUTAGENESIS OF SER-27; SER-47 AND THR-530, SUBCELLULAR LOCATION.
[52]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-530; SER-535 AND THR-719, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[53]"SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells."
Zu Y., Liu L., Lee M.Y., Xu C., Liang Y., Man R.Y., Vanhoutte P.M., Wang Y.
Circ. Res. 106:1384-1393(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF STK11.
[54]"Role of SIRT1 in homologous recombination."
Uhl M., Csernok A., Aydin S., Kreienberg R., Wiesmuller L., Gatz S.A.
DNA Repair 9:383-393(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA REPAIR HOMOLOGOUS RECOMBINATION.
[55]"SIRT1 suppresses activator protein-1 transcriptional activity and cyclooxygenase-2 expression in macrophages."
Zhang R., Chen H.Z., Liu J.J., Jia Y.Y., Zhang Z.Q., Yang R.F., Zhang Y., Xu J., Wei Y.S., Liu D.P., Liang C.C.
J. Biol. Chem. 285:7097-7110(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FOS AND JUN.
[56]"SIRT1 regulates autoacetylation and histone acetyltransferase activity of TIP60."
Wang J., Chen J.
J. Biol. Chem. 285:11458-11464(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF KAT5.
[57]"SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism."
Ponugoti B., Kim D.H., Xiao Z., Smith Z., Miao J., Zang M., Wu S.Y., Chiang C.M., Veenstra T.D., Kemper J.K.
J. Biol. Chem. 285:33959-33970(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF SREBF1.
[58]"Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha."
Lim J.H., Lee Y.M., Chun Y.S., Chen J., Kim J.E., Park J.W.
Mol. Cell 38:864-878(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF HIF1A, FUNCTION IN REGULATION OF HIF1A.
[59]"SIRT1 regulates UV-induced DNA repair through deacetylating XPA."
Fan W., Luo J.
Mol. Cell 39:247-258(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF XPA.
[60]"SIRT1 deacetylates APE1 and regulates cellular base excision repair."
Yamamori T., DeRicco J., Naqvi A., Hoffman T.A., Mattagajasingh I., Kasuno K., Jung S.B., Kim C.S., Irani K.
Nucleic Acids Res. 38:832-845(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF APEX1, FUNCTION IN DNA REPAIR, MUTAGENESIS OF HIS-363, INDUCTION, SUBCELLULAR LOCATION.
[61]"Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation."
Chanda D., Xie Y.B., Choi H.S.
Nucleic Acids Res. 38:4607-4619(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NR0B2.
[62]"SIRT1 negatively regulates the mammalian target of rapamycin."
Ghosh H.S., McBurney M., Robbins P.D.
PLoS ONE 5:E9199-E9199(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TSC2.
[63]"SIRT1 undergoes alternative splicing in a novel auto-regulatory loop with p53."
Lynch C.J., Shah Z.H., Allison S.J., Ahmed S.U., Ford J., Warnock L.J., Li H., Serrano M., Milner J.
PLoS ONE 5:E13502-E13502(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION (ISOFORM 2), INDUCTION (ISOFORM 2), INTERACTION WITH TP53 AND RPS19BP1.
[64]"Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C."
Ming M., Shea C.R., Guo X., Li X., Soltani K., Han W., He Y.Y.
Proc. Natl. Acad. Sci. U.S.A. 107:22623-22628(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA REPAIR, SUPPRESSION OF XPC.
[65]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-47, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[66]"SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2."
Hirschey M.D., Shimazu T., Capra J.A., Pollard K.S., Verdin E.
Aging (Albany NY) 3:635-642(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF HMGCS1.
[67]"Tumor necrosis factor alpha-mediated cleavage and inactivation of SirT1 in human osteoarthritic chondrocytes."
Dvir-Ginzberg M., Gagarina V., Lee E.J., Booth R., Gabay O., Hall D.J.
Arthritis Rheum. 63:2363-2373(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PROCESSING.
[68]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[69]"EVI1 up-regulates the stress responsive gene SIRT1 which triggers deacetylation and degradation of EVI1."
Pradhan A.K., Kuila N., Singh S., Chakraborty S.
Biochim. Biophys. Acta 1809:269-275(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF MECOM.
[70]"Energy sensing factors PGC-1alpha and SIRT1 modulate PXR expression and function."
Buler M., Aatsinki S.M., Skoumal R., Hakkola J.
Biochem. Pharmacol. 82:2008-2015(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NR1I2.
[71]"Sirt1 deacetylates c-Myc and promotes c-Myc/Max association."
Mao B., Zhao G., Lv X., Chen H.Z., Xue Z., Yang B., Liu D.P., Liang C.C.
Int. J. Biochem. Cell Biol. 43:1573-1581(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF MYC, FUNCTION IN REGULATION OF MYC.
[72]"MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation."
Yuan F., Xie Q., Wu J., Bai Y., Mao B., Dong Y., Bi W., Ji G., Tao W., Wang Y., Yuan Z.
J. Biol. Chem. 286:6940-6945(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY STK4/MST1.
[73]"Cancer cell survival following DNA damage-mediated premature senescence is regulated by mammalian target of rapamycin (mTOR)-dependent Inhibition of sirtuin 1."
Back J.H., Rezvani H.R., Zhu Y., Guyonnet-Duperat V., Athar M., Ratner D., Kim A.L.
J. Biol. Chem. 286:19100-19108(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS, PHOSPHORYLATION AT SER-47, MUTAGENESIS OF SER-47 AND PHE-474.
[74]"Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and ensures genome protection."
Bosch-Presegue L., Raurell-Vila H., Marazuela-Duque A., Kane-Goldsmith N., Valle A., Oliver J., Serrano L., Vaquero A.
Mol. Cell 42:210-223(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN STABILIZATION OF SUV39H1.
[75]"SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities."
Peng L., Yuan Z., Ling H., Fukasawa K., Robertson K., Olashaw N., Koomen J., Chen J., Lane W.S., Seto E.
Mol. Cell. Biol. 31:4720-4734(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF DNMT1, FUNCTION IN REGULATION OF DNMT1.
[76]"SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability."
Marshall G.M., Liu P.Y., Gherardi S., Scarlett C.J., Bedalov A., Xu N., Iraci N., Valli E., Ling D., Thomas W., van Bekkum M., Sekyere E., Jankowski K., Trahair T., Mackenzie K.L., Haber M., Norris M.D., Biankin A.V., Perini G., Liu T.
PLoS Genet. 7:E1002135-E1002135(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF MYCN, INTERACTION WITH MYCN.
[77]"The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO."
Rizki G., Iwata T.N., Li J., Riedel C.G., Picard C.L., Jan M., Murphy C.T., Lee S.S.
PLoS Genet. 7:E1002235-E1002235(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HCFC1.
[78]"Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1)."
Liu X., Wang D., Zhao Y., Tu B., Zheng Z., Wang L., Wang H., Gu W., Roeder R.G., Zhu W.G.
Proc. Natl. Acad. Sci. U.S.A. 108:1925-1930(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SETD7, MUTAGENESIS OF LYS-233; LYS-235; LYS-236 AND LYS-238.
[79]"The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy."
Sundaresan N.R., Pillai V.B., Wolfgeher D., Samant S., Vasudevan P., Parekh V., Raghuraman H., Cunningham J.M., Gupta M., Gupta M.P.
Sci. Signal. 4:RA46-RA46(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF AKT1, FUNCTION IN REGULATION OF AKT1.
[80]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-47 AND THR-719, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[81]"75kDa SirT1 blocks TNFalpha-mediated apoptosis in human osteoarthritic chondrocytes."
Oppenheimer H., Gabay O., Meir H., Haze A., Kandel L., Liebergall M., Gagarina V., Lee E.J., Dvir-Ginzberg M.
Arthritis Rheum. 64:718-728(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION (SIRTT1 75 KDA FRAGMENT), SUBCELLULAR LOCATION (75SIRT1).
[82]"SIRT1 links CIITA deacetylation to MHC II activation."
Wu X., Kong X., Chen D., Li H., Zhao Y., Xia M., Fang M., Li P., Fang F., Sun L., Tian W., Xu H., Yang Y., Qi X., Gao Y., Sha J., Chen Q., Xu Y.
Nucleic Acids Res. 39:9549-9558(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF CIITA.
[83]"PML regulates PER2 nuclear localization and circadian function."
Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A., Rea M.A., Zhao Z., Lee C.C., Chang K.S.
EMBO J. 31:1427-1439(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF PML.
[84]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[85]"Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation."
Wang F., Chan C.H., Chen K., Guan X., Lin H.K., Tong Q.
Oncogene 31:1546-1557(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF FOXO3, FUNCTION IN REGULATION OF FOXO3.
[86]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[87]"Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of breast cancer cells through impaired responses to UV-induced DNA damage."
Kim W., Kim J.E.
Cancer Lett. 333:180-186(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CCAR2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF083106 mRNA. Translation: AAD40849.2.
AF235040 mRNA. Translation: AAG38486.1.
DQ278604 Genomic DNA. Translation: ABB72675.1.
AL133551 Genomic DNA. Translation: CAI16036.1.
BC012499 mRNA. Translation: AAH12499.1. Different initiation.
RefSeqNP_001135970.1. NM_001142498.1.
NP_036370.2. NM_012238.4.
UniGeneHs.369779.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4I5IX-ray2.50A/B241-516[»]
4IF6X-ray2.25A234-510[»]
B641-665[»]
4IG9X-ray2.64A/C/E/G234-510[»]
B/D/F/H641-665[»]
4KXQX-ray1.85A234-510[»]
B641-663[»]
ProteinModelPortalQ96EB6.
SMRQ96EB6. Positions 181-510.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116983. 267 interactions.
DIPDIP-29757N.
IntActQ96EB6. 112 interactions.
MINTMINT-3052322.
STRING9606.ENSP00000212015.

Chemistry

BindingDBQ96EB6.
ChEMBLCHEMBL4506.

PTM databases

PhosphoSiteQ96EB6.

Polymorphism databases

DMDM38258633.

Proteomic databases

PaxDbQ96EB6.
PeptideAtlasQ96EB6.
PRIDEQ96EB6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000212015; ENSP00000212015; ENSG00000096717. [Q96EB6-1]
GeneID23411.
KEGGhsa:23411.
UCSCuc001jnd.3. human. [Q96EB6-1]

Organism-specific databases

CTD23411.
GeneCardsGC10P069644.
HGNCHGNC:14929. SIRT1.
HPACAB003855.
HPA006295.
HPA052351.
MIM604479. gene.
neXtProtNX_Q96EB6.
PharmGKBPA37935.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0846.
HOGENOMHOG000038016.
HOVERGENHBG054192.
InParanoidQ96EB6.
KOK11411.
OMANYPSNKS.
OrthoDBEOG7WX09C.
PhylomeDBQ96EB6.
TreeFamTF105896.

Enzyme and pathway databases

SignaLinkQ96EB6.

Gene expression databases

ArrayExpressQ96EB6.
BgeeQ96EB6.
CleanExHS_SIRT1.
GenevestigatorQ96EB6.

Family and domain databases

Gene3D3.30.1600.10. 2 hits.
InterProIPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERPTHR11085. PTHR11085. 1 hit.
PfamPF02146. SIR2. 1 hit.
[Graphical view]
PROSITEPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSirtuin_1.
GenomeRNAi23411.
NextBio45603.
PROQ96EB6.
SOURCESearch...

Entry information

Entry nameSIR1_HUMAN
AccessionPrimary (citable) accession number: Q96EB6
Secondary accession number(s): Q2XNF6 expand/collapse secondary AC list , Q5JVQ0, Q9GZR9, Q9Y6F0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: April 16, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM