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Q96EB6

- SIR1_HUMAN

UniProt

Q96EB6 - SIR1_HUMAN

Protein

NAD-dependent protein deacetylase sirtuin-1

Gene

SIRT1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 2 (31 Oct 2003)
      Previous versions | rss
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    Functioni

    NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metobolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD+/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD+/NADP+ ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. Deacetylates H2A and 'Lys-26' of HIST1H1E. Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting. Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis. Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. Involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62'. Deacetylates MEF2D. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3. Represses HNF1A-mediated transcription. Required for the repression of ESRRG by CREBZF. Modulates AP-1 transcription factor activity. Deacetylates NR1H3 AND NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed. Involved in lipid metabolism. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates ACSS2 leading to its activation, and HMGCS1. Involved in liver and muscle metabolism. Through deacteylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletel muscle under low-glucose conditions and is involved in glucose homeostasis. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and faciliting recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability. Deacteylates MECOM/EVI1. Isoform 2 is shown to deacetylate 'Lys-382' of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop. In case of HIV-1 infection, interacts with and deacetylates the viral Tat protein. The viral Tat protein inhibits SIRT1 deacetylation activity toward RELA/NF-kappa-B p65, thereby potentiates its transcriptional activity and SIRT1 is proposed to contribute to T-cell hyperactivation during infection. Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization. During the neurogenic transition, repress selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation.
    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 activityi

    NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.1 PublicationPROSITE-ProRule annotation

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Enzyme regulationi

    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 CCAR2.4 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei363 – 3631Proton acceptor
    Metal bindingi371 – 3711ZincPROSITE-ProRule annotation
    Metal bindingi374 – 3741ZincPROSITE-ProRule annotation
    Metal bindingi395 – 3951ZincPROSITE-ProRule annotation
    Metal bindingi398 – 3981ZincPROSITE-ProRule annotation
    Binding sitei482 – 4821NAD; via amide nitrogenBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi261 – 28020NADBy similarityAdd
    BLAST
    Nucleotide bindingi345 – 3484NADBy similarity
    Nucleotide bindingi440 – 4423NADBy similarity
    Nucleotide bindingi465 – 4673NADBy similarity

    GO - Molecular functioni

    1. bHLH transcription factor binding Source: UniProtKB
    2. deacetylase activity Source: UniProtKB
    3. enzyme binding Source: UniProt
    4. histone binding Source: BHF-UCL
    5. histone deacetylase activity Source: BHF-UCL
    6. HLH domain binding Source: BHF-UCL
    7. identical protein binding Source: BHF-UCL
    8. keratin filament binding Source: UniProt
    9. metal ion binding Source: UniProtKB-KW
    10. mitogen-activated protein kinase binding Source: BHF-UCL
    11. NAD+ binding Source: InterPro
    12. NAD-dependent histone deacetylase activity Source: BHF-UCL
    13. NAD-dependent histone deacetylase activity (H3-K9 specific) Source: UniProtKB
    14. NAD-dependent protein deacetylase activity Source: UniProtKB
    15. p53 binding Source: BHF-UCL
    16. protein binding Source: UniProtKB
    17. protein C-terminus binding Source: UniProtKB
    18. protein deacetylase activity Source: UniProtKB
    19. transcription corepressor activity Source: BHF-UCL
    20. transcription factor binding Source: UniProt

    GO - Biological processi

    1. angiogenesis Source: UniProtKB
    2. cell aging Source: BHF-UCL
    3. cellular glucose homeostasis Source: UniProtKB
    4. cellular response to DNA damage stimulus Source: UniProtKB
    5. cellular response to hydrogen peroxide Source: BHF-UCL
    6. cellular response to hypoxia Source: UniProtKB
    7. cellular response to ionizing radiation Source: UniProtKB
    8. cellular response to starvation Source: BHF-UCL
    9. cellular response to tumor necrosis factor Source: UniProtKB
    10. cellular triglyceride homeostasis Source: UniProtKB
    11. cholesterol homeostasis Source: UniProtKB
    12. chromatin organization Source: UniProt
    13. chromatin silencing Source: ProtInc
    14. chromatin silencing at rDNA Source: UniProtKB
    15. DNA repair Source: BHF-UCL
    16. DNA replication Source: BHF-UCL
    17. DNA synthesis involved in DNA repair Source: UniProtKB
    18. establishment of chromatin silencing Source: BHF-UCL
    19. fatty acid homeostasis Source: UniProtKB
    20. histone deacetylation Source: UniProtKB
    21. histone H3 deacetylation Source: BHF-UCL
    22. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
    23. maintenance of chromatin silencing Source: BHF-UCL
    24. methylation-dependent chromatin silencing Source: UniProtKB
    25. muscle organ development Source: UniProtKB-KW
    26. negative regulation of androgen receptor signaling pathway Source: BHF-UCL
    27. negative regulation of apoptotic process Source: UniProtKB
    28. negative regulation of cAMP-dependent protein kinase activity Source: UniProtKB
    29. negative regulation of cell growth Source: BHF-UCL
    30. negative regulation of cellular response to testosterone stimulus Source: BHF-UCL
    31. negative regulation of cellular senescence Source: UniProtKB
    32. negative regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
    33. negative regulation of fat cell differentiation Source: BHF-UCL
    34. negative regulation of helicase activity Source: UniProtKB
    35. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    36. negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: BHF-UCL
    37. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
    38. negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: BHF-UCL
    39. negative regulation of peptidyl-lysine acetylation Source: UniProtKB
    40. negative regulation of phosphorylation Source: UniProtKB
    41. negative regulation of prostaglandin biosynthetic process Source: UniProtKB
    42. negative regulation of protein kinase B signaling Source: UniProtKB
    43. negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    44. negative regulation of TOR signaling Source: UniProtKB
    45. negative regulation of transcription, DNA-templated Source: BHF-UCL
    46. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    47. negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
    48. ovulation from ovarian follicle Source: Ensembl
    49. peptidyl-lysine acetylation Source: UniProtKB
    50. peptidyl-lysine deacetylation Source: BHF-UCL
    51. positive regulation of adaptive immune response Source: UniProtKB
    52. positive regulation of apoptotic process Source: UniProtKB
    53. positive regulation of cAMP-dependent protein kinase activity Source: UniProtKB
    54. positive regulation of cell proliferation Source: UniProtKB
    55. positive regulation of cellular senescence Source: UniProtKB
    56. positive regulation of cholesterol efflux Source: UniProtKB
    57. positive regulation of chromatin silencing Source: BHF-UCL
    58. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    59. positive regulation of DNA repair Source: UniProtKB
    60. positive regulation of histone H3-K9 methylation Source: UniProt
    61. positive regulation of insulin receptor signaling pathway Source: UniProtKB
    62. positive regulation of macroautophagy Source: UniProtKB
    63. positive regulation of macrophage apoptotic process Source: UniProtKB
    64. positive regulation of MHC class II biosynthetic process Source: UniProtKB
    65. positive regulation of protein phosphorylation Source: UniProtKB
    66. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    67. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
    68. protein deacetylation Source: UniProtKB
    69. protein destabilization Source: UniProtKB
    70. protein ubiquitination Source: UniProtKB
    71. pyrimidine dimer repair by nucleotide-excision repair Source: UniProtKB
    72. regulation of bile acid biosynthetic process Source: UniProtKB
    73. regulation of cell proliferation Source: BHF-UCL
    74. regulation of endodeoxyribonuclease activity Source: UniProtKB
    75. regulation of glucose metabolic process Source: UniProtKB
    76. regulation of mitotic cell cycle Source: UniProtKB
    77. regulation of peroxisome proliferator activated receptor signaling pathway Source: BHF-UCL
    78. regulation of protein import into nucleus, translocation Source: UniProtKB
    79. regulation of smooth muscle cell apoptotic process Source: UniProtKB
    80. response to hydrogen peroxide Source: UniProtKB
    81. response to insulin Source: UniProtKB
    82. response to oxidative stress Source: UniProtKB
    83. rRNA processing Source: UniProtKB-KW
    84. single strand break repair Source: UniProtKB
    85. spermatogenesis Source: Ensembl
    86. transcription, DNA-templated Source: UniProtKB-KW
    87. triglyceride mobilization Source: BHF-UCL
    88. viral process Source: UniProtKB-KW
    89. white fat cell differentiation Source: BHF-UCL

    Keywords - Molecular functioni

    Developmental protein, Hydrolase

    Keywords - Biological processi

    Apoptosis, Differentiation, Host-virus interaction, Myogenesis, rRNA processing, Transcription, Transcription regulation

    Keywords - Ligandi

    Metal-binding, NAD, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_200780. Regulation of HSF1-mediated heat shock response.
    REACT_200827. SIRT1 negatively regulates rRNA Expression.
    SignaLinkiQ96EB6.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NAD-dependent protein deacetylase sirtuin-1 (EC:3.5.1.-)
    Short name:
    hSIRT1
    Alternative name(s):
    Regulatory protein SIR2 homolog 1
    SIR2-like protein 1
    Short name:
    hSIR2
    Cleaved into the following chain:
    SirtT1 75 kDa fragment
    Short name:
    75SirT1
    Gene namesi
    Name:SIRT1
    Synonyms:SIR2L1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:14929. SIRT1.

    Subcellular locationi

    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.

    GO - Cellular componenti

    1. chromatin silencing complex Source: UniProtKB
    2. cytoplasm Source: BHF-UCL
    3. mitochondrion Source: HPA
    4. nuclear chromatin Source: BHF-UCL
    5. nuclear envelope Source: BHF-UCL
    6. nuclear euchromatin Source: UniProtKB
    7. nuclear heterochromatin Source: UniProtKB
    8. nuclear inner membrane Source: UniProtKB
    9. nucleolus Source: BHF-UCL
    10. nucleoplasm Source: UniProtKB
    11. nucleus Source: UniProtKB
    12. PML body Source: BHF-UCL
    13. rDNA heterochromatin Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi27 – 271S → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-47 and A-530. 1 Publication
    Mutagenesisi47 – 471S → A: Blocks residue phosphorylation, restores deacetylation activity and inhibits DNA damage-induced apoptosis. 2 Publications
    Mutagenesisi47 – 471S → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-530. 2 Publications
    Mutagenesisi233 – 2331K → R: Impairs in vitro methylation by SETD7; when associated with R-235, R-236 and R-238. 1 Publication
    Mutagenesisi235 – 2351K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-236 and R-238. 1 Publication
    Mutagenesisi236 – 2361K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-235 and R-238. 1 Publication
    Mutagenesisi238 – 2381K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-235a and R-236. 1 Publication
    Mutagenesisi363 – 3631H → Y: Loss of function. Reduces the interaction with CCAR2 and APEX1. Increases acetylation of APEX1. 7 Publications
    Mutagenesisi474 – 4741F → A: Abolishes phosphorylation at Ser-47, restores deacetylation activity and inhibits DNA damage-induced apoptosis. 1 Publication
    Mutagenesisi530 – 5301T → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-47. 2 Publications
    Mutagenesisi530 – 5301T → A: Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-540. 2 Publications
    Mutagenesisi540 – 5401S → A: Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-530. 1 Publication
    Mutagenesisi659 – 6591S → A: Reduces in vitro phosphorylation by CaMK2; when associated with S-661. Greatly reduces in vivo phosphorylation; when associated with A-661. 1 Publication
    Mutagenesisi661 – 6611S → A: Reduces in vitro phosphorylation by CaMK2; when associated with S-659. Greatly reduces in vivo phosphorylation; when associated with A-659. 1 Publication
    Mutagenesisi684 – 6841S → A: No effect on phosphorylation (in vitro and in vivo). 1 Publication

    Organism-specific databases

    PharmGKBiPA37935.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed5 Publications
    Chaini2 – 747746NAD-dependent protein deacetylase sirtuin-1PRO_0000110256Add
    BLAST
    Chaini2 – 533532SirtT1 75 kDa fragmentPRO_0000415289Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine5 Publications
    Modified residuei14 – 141Phosphoserine4 Publications
    Modified residuei26 – 261Phosphoserine2 Publications
    Modified residuei27 – 271Phosphoserine; by MAPK84 Publications
    Modified residuei47 – 471Phosphoserine; by MAPK88 Publications
    Modified residuei159 – 1591Phosphoserine2 Publications
    Modified residuei162 – 1621Phosphoserine2 Publications
    Modified residuei172 – 1721Phosphoserine2 Publications
    Modified residuei173 – 1731Phosphoserine2 Publications
    Modified residuei395 – 3951S-nitrosocysteineBy similarity
    Modified residuei398 – 3981S-nitrosocysteineBy similarity
    Modified residuei530 – 5301Phosphothreonine; by DYRK1A, DYRK3 and MAPK84 Publications
    Modified residuei535 – 5351Phosphoserine2 Publications
    Modified residuei544 – 5441Phosphothreonine2 Publications
    Modified residuei545 – 5451Phosphoserine2 Publications
    Modified residuei659 – 6591Phosphoserine; by CaMK2By similarity
    Modified residuei661 – 6611Phosphoserine; by CaMK22 Publications
    Modified residuei719 – 7191Phosphothreonine5 Publications
    Modified residuei747 – 7471Phosphoserine2 Publications

    Post-translational modificationi

    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.By similarity11 Publications
    Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1).
    S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity.By similarity

    Keywords - PTMi

    Acetylation, Methylation, Phosphoprotein, S-nitrosylation

    Proteomic databases

    MaxQBiQ96EB6.
    PaxDbiQ96EB6.
    PeptideAtlasiQ96EB6.
    PRIDEiQ96EB6.

    PTM databases

    PhosphoSiteiQ96EB6.

    Expressioni

    Tissue specificityi

    Widely expressed.1 Publication

    Inductioni

    Up-regulated by methyl methanesulfonate (MMS). In H293T cells by presence of rat calorie restriction (CR) serum.2 Publications

    Gene expression databases

    ArrayExpressiQ96EB6.
    BgeeiQ96EB6.
    CleanExiHS_SIRT1.
    GenevestigatoriQ96EB6.

    Organism-specific databases

    HPAiCAB003855.
    HPA006295.
    HPA052351.

    Interactioni

    Subunit structurei

    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.24 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    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
    RPS19BP1Q86WX311EBI-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

    Protein-protein interaction databases

    BioGridi116983. 269 interactions.
    DIPiDIP-29757N.
    IntActiQ96EB6. 112 interactions.
    MINTiMINT-3052322.
    STRINGi9606.ENSP00000212015.

    Structurei

    Secondary structure

    1
    747
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi243 – 25210
    Beta strandi254 – 2607
    Helixi262 – 2687
    Beta strandi273 – 2753
    Turni276 – 2783
    Helixi279 – 2868
    Beta strandi290 – 2923
    Helixi293 – 2975
    Helixi299 – 3046
    Helixi307 – 3126
    Helixi313 – 3164
    Beta strandi318 – 3203
    Helixi325 – 33511
    Beta strandi339 – 3446
    Helixi350 – 3545
    Beta strandi358 – 3614
    Beta strandi364 – 3718
    Turni372 – 3743
    Beta strandi377 – 3793
    Helixi380 – 3823
    Helixi384 – 3885
    Beta strandi396 – 3983
    Beta strandi406 – 4116
    Helixi420 – 42910
    Turni430 – 4323
    Beta strandi435 – 4406
    Helixi448 – 4503
    Helixi451 – 4544
    Beta strandi461 – 4677
    Beta strandi475 – 4806
    Helixi482 – 49312
    Helixi495 – 5006
    Beta strandi643 – 6453
    Turni646 – 6483
    Beta strandi649 – 6513
    Helixi656 – 6583

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ96EB6.
    SMRiQ96EB6. Positions 234-510.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini244 – 498255Deacetylase sirtuin-typePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 268267Interaction with HIST1H1EAdd
    BLAST
    Regioni143 – 541399Interaction with CCAR2Add
    BLAST
    Regioni538 – 5403Phosphorylated at one of three serine residues

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi32 – 398Nuclear localization signalBy similarity
    Motifi138 – 1458Nuclear export signalBy similarity
    Motifi223 – 2308Nuclear localization signalBy similarity
    Motifi425 – 4317Nuclear export signalBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi54 – 9845Ala-richAdd
    BLAST
    Compositional biasi122 – 1276Poly-Asp
    Compositional biasi128 – 1347Poly-Glu

    Sequence similaritiesi

    Belongs to the sirtuin family. Class I subfamily.Curated
    Contains 1 deacetylase sirtuin-type domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0846.
    HOGENOMiHOG000038016.
    HOVERGENiHBG054192.
    InParanoidiQ96EB6.
    KOiK11411.
    OMAiNYPSNKS.
    OrthoDBiEOG7WX09C.
    PhylomeDBiQ96EB6.
    TreeFamiTF105896.

    Family and domain databases

    Gene3Di3.30.1600.10. 2 hits.
    3.40.50.1220. 3 hits.
    InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR003000. Sirtuin.
    IPR026591. Sirtuin_cat_small_dom.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view]
    PANTHERiPTHR11085. PTHR11085. 1 hit.
    PfamiPF02146. SIR2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52467. SSF52467. 1 hit.
    PROSITEiPS50305. SIRTUIN. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q96EB6-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MADEAALALQ PGGSPSAAGA DREAASSPAG EPLRKRPRRD GPGLERSPGE    50
    PGGAAPEREV PAAARGCPGA AAAALWREAE AEAAAAGGEQ EAQATAAAGE 100
    GDNGPGLQGP SREPPLADNL YDEDDDDEGE EEEEAAAAAI GYRDNLLFGD 150
    EIITNGFHSC ESDEEDRASH ASSSDWTPRP RIGPYTFVQQ HLMIGTDPRT 200
    ILKDLLPETI PPPELDDMTL WQIVINILSE PPKRKKRKDI NTIEDAVKLL 250
    QECKKIIVLT GAGVSVSCGI PDFRSRDGIY ARLAVDFPDL PDPQAMFDIE 300
    YFRKDPRPFF KFAKEIYPGQ FQPSLCHKFI ALSDKEGKLL RNYTQNIDTL 350
    EQVAGIQRII QCHGSFATAS CLICKYKVDC EAVRGDIFNQ VVPRCPRCPA 400
    DEPLAIMKPE IVFFGENLPE QFHRAMKYDK DEVDLLIVIG SSLKVRPVAL 450
    IPSSIPHEVP QILINREPLP HLHFDVELLG DCDVIINELC HRLGGEYAKL 500
    CCNPVKLSEI TEKPPRTQKE LAYLSELPPT PLHVSEDSSS PERTSPPDSS 550
    VIVTLLDQAA KSNDDLDVSE SKGCMEEKPQ EVQTSRNVES IAEQMENPDL 600
    KNVGSSTGEK NERTSVAGTV RKCWPNRVAK EQISRRLDGN QYLFLPPNRY 650
    IFHGAEVYSD SEDDVLSSSS CGSNSDSGTC QSPSLEEPME DESEIEEFYN 700
    GLEDEPDVPE RAGGAGFGTD GDDQEAINEA ISVKQEVTDM NYPSNKS 747
    Length:747
    Mass (Da):81,681
    Last modified:October 31, 2003 - v2
    Checksum:i2D3BEA6D73DA229F
    GO
    Isoform 2 (identifier: Q96EB6-2) [UniParc]FASTAAdd to Basket

    Also known as: delta-exon8

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

    Show »
    Length:561
    Mass (Da):61,066
    Checksum:iBFD54C8E408F23BD
    GO

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti386 – 3894DIFN → ALFS in AAH12499. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti3 – 31D → E.1 Publication
    Corresponds to variant rs35671182 [ dbSNP | Ensembl ].
    VAR_025148
    Natural varianti484 – 4841V → D.
    Corresponds to variant rs1063111 [ dbSNP | Ensembl ].
    VAR_051976

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei454 – 639186Missing in isoform 2. CuratedVSP_042189Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS7273.1. [Q96EB6-1]
    RefSeqiNP_001135970.1. NM_001142498.1.
    NP_036370.2. NM_012238.4. [Q96EB6-1]
    UniGeneiHs.369779.

    Genome annotation databases

    EnsembliENST00000212015; ENSP00000212015; ENSG00000096717. [Q96EB6-1]
    GeneIDi23411.
    KEGGihsa:23411.
    UCSCiuc001jnd.3. human. [Q96EB6-1]

    Polymorphism databases

    DMDMi38258633.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs
    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSi CCDS7273.1. [Q96EB6-1 ]
    RefSeqi NP_001135970.1. NM_001142498.1.
    NP_036370.2. NM_012238.4. [Q96EB6-1 ]
    UniGenei Hs.369779.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4I5I X-ray 2.50 A/B 241-516 [» ]
    4IF6 X-ray 2.25 A 234-510 [» ]
    B 641-665 [» ]
    4IG9 X-ray 2.64 A/C/E/G 234-510 [» ]
    B/D/F/H 641-665 [» ]
    4KXQ X-ray 1.85 A 234-510 [» ]
    B 641-663 [» ]
    ProteinModelPortali Q96EB6.
    SMRi Q96EB6. Positions 234-510.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116983. 269 interactions.
    DIPi DIP-29757N.
    IntActi Q96EB6. 112 interactions.
    MINTi MINT-3052322.
    STRINGi 9606.ENSP00000212015.

    Chemistry

    BindingDBi Q96EB6.
    ChEMBLi CHEMBL4506.

    PTM databases

    PhosphoSitei Q96EB6.

    Polymorphism databases

    DMDMi 38258633.

    Proteomic databases

    MaxQBi Q96EB6.
    PaxDbi Q96EB6.
    PeptideAtlasi Q96EB6.
    PRIDEi Q96EB6.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000212015 ; ENSP00000212015 ; ENSG00000096717 . [Q96EB6-1 ]
    GeneIDi 23411.
    KEGGi hsa:23411.
    UCSCi uc001jnd.3. human. [Q96EB6-1 ]

    Organism-specific databases

    CTDi 23411.
    GeneCardsi GC10P069644.
    HGNCi HGNC:14929. SIRT1.
    HPAi CAB003855.
    HPA006295.
    HPA052351.
    MIMi 604479. gene.
    neXtProti NX_Q96EB6.
    PharmGKBi PA37935.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0846.
    HOGENOMi HOG000038016.
    HOVERGENi HBG054192.
    InParanoidi Q96EB6.
    KOi K11411.
    OMAi NYPSNKS.
    OrthoDBi EOG7WX09C.
    PhylomeDBi Q96EB6.
    TreeFami TF105896.

    Enzyme and pathway databases

    Reactomei REACT_200780. Regulation of HSF1-mediated heat shock response.
    REACT_200827. SIRT1 negatively regulates rRNA Expression.
    SignaLinki Q96EB6.

    Miscellaneous databases

    GeneWikii Sirtuin_1.
    GenomeRNAii 23411.
    NextBioi 45603.
    PROi Q96EB6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96EB6.
    Bgeei Q96EB6.
    CleanExi HS_SIRT1.
    Genevestigatori Q96EB6.

    Family and domain databases

    Gene3Di 3.30.1600.10. 2 hits.
    3.40.50.1220. 3 hits.
    InterProi IPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR003000. Sirtuin.
    IPR026591. Sirtuin_cat_small_dom.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view ]
    PANTHERi PTHR11085. PTHR11085. 1 hit.
    Pfami PF02146. SIR2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52467. SSF52467. 1 hit.
    PROSITEi PS50305. SIRTUIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Cited for: FUNCTION IN DEACETYLATION OF CIITA.
    83. 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. 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.

    Entry informationi

    Entry nameiSIR1_HUMAN
    AccessioniPrimary (citable) accession number: Q96EB6
    Secondary accession number(s): Q2XNF6
    , Q5JVQ0, Q9GZR9, Q9Y6F0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 31, 2003
    Last sequence update: October 31, 2003
    Last modified: October 1, 2014
    This is version 138 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    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 (PubMed:15469825). As, in vivo, interaction occurs between SIRT1 with HIST1H1E, deacetylation has been validated only for HIST1H1E.1 Publication
    The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3