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Q923E4

- SIR1_MOUSE

UniProt

Q923E4 - SIR1_MOUSE

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Protein
NAD-dependent protein deacetylase sirtuin-1
Gene
Sirt1, Sir2l1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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, which increases its DNA binding ability and enhances 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-537' and 'Lys-540' 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. 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.30 Publications
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 By similarity.30 Publications

Catalytic activityi

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

Cofactori

Binds 1 zinc ion per subunit By similarity.

Enzyme regulationi

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 By similarity. Inhibited by nicotinamide. Negatively regulated by CCAR2 By similarity.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei355 – 3551Proton acceptor
Metal bindingi363 – 3631Zinc By similarity
Metal bindingi366 – 3661Zinc By similarity
Metal bindingi387 – 3871Zinc By similarity
Metal bindingi390 – 3901Zinc By similarity
Binding sitei474 – 4741NAD; via amide nitrogen By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi253 – 27220NAD By similarity
Add
BLAST
Nucleotide bindingi337 – 3404NAD By similarity
Nucleotide bindingi432 – 4343NAD By similarity
Nucleotide bindingi457 – 4593NAD By similarity

GO - Molecular functioni

  1. NAD+ binding Source: InterPro
  2. NAD-dependent histone deacetylase activity Source: MGI
  3. NAD-dependent histone deacetylase activity (H3-K9 specific) Source: UniProtKB
  4. NAD-dependent protein deacetylase activity Source: UniProtKB
  5. bHLH transcription factor binding Source: UniProtKB
  6. deacetylase activity Source: UniProtKB
  7. enzyme binding Source: UniProtKB
  8. metal ion binding Source: UniProtKB-KW
  9. p53 binding Source: BHF-UCL
  10. protein binding Source: UniProtKB
  11. protein deacetylase activity Source: UniProtKB
  12. protein domain specific binding Source: BHF-UCL
  13. transcription corepressor activity Source: BHF-UCL

GO - Biological processi

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

Keywords - Molecular functioni

Developmental protein, Hydrolase

Keywords - Biological processi

Apoptosis, Differentiation, Myogenesis, rRNA processing, Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, NAD, Zinc

Enzyme and pathway databases

ReactomeiREACT_222185. Regulation of HSF1-mediated heat shock response.
REACT_224328. SIRT1 negatively regulates rRNA Expression.

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-1 (EC:3.5.1.-)
Alternative name(s):
Regulatory protein SIR2 homolog 1
SIR2-like protein 1
SIR2alpha
Short name:
Sir2
Short name:
mSIR2a
Cleaved into the following chain:
SirtT1 75 kDa fragment
Short name:
75SirT1
Gene namesi
Name:Sirt1
Synonyms:Sir2l1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 10

Organism-specific databases

MGIiMGI:2135607. Sirt1.

Subcellular locationi

NucleusPML body. Cytoplasm By similarity
Note: Recruited to the nuclear bodies via its interaction with PML. Colocalized with APEX1 in the nucleus. May be found in nucleolus, nuclear euchromatin, heterochromatin and inner membrane. Shuttles between nucleus and cytoplasm By similarity.3 Publications
Chain SirtT1 75 kDa fragment : Cytoplasm By similarity. Mitochondrion By similarity 3 Publications

GO - Cellular componenti

  1. ESC/E(Z) complex Source: Ensembl
  2. PML body Source: UniProtKB-SubCell
  3. chromatin Source: UniProtKB
  4. chromatin silencing complex Source: Ensembl
  5. cytoplasm Source: UniProtKB
  6. mitochondrion Source: UniProtKB-SubCell
  7. nuclear euchromatin Source: UniProtKB
  8. nuclear heterochromatin Source: UniProtKB
  9. nuclear inner membrane Source: UniProtKB
  10. nucleolus Source: Ensembl
  11. nucleoplasm Source: UniProtKB
  12. nucleus Source: UniProtKB
  13. rDNA heterochromatin Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

High degeree of embryonic and postnatal lethality. Decreased levels of histone H3 containing a trimethyl group at its lysine 9 position (H3K9me3) in regions of heterochromatin. Attenuates spermatogenesis but not oogenesis with reduced numbers of mature sperm and spermatogenic precursors. Mice develop an autoimmune-like condition with late onset diabetes insipidus. Prostatic intraepithelial neoplasia associated with reduced autophagy.5 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi37 – 382RR → AA: Abolishes nuclear localization; when associated with A-227; A-228; A-229 and A-230.
Mutagenesisi138 – 1458LLLTDGLL → AAATGAA: Abolishes nuclear export; when associated with A-425; A-427; A-428; A-429; A-430 and A-431.
Mutagenesisi154 – 1541S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-649; A-651 and A-683. 1 Publication
Mutagenesisi227 – 2304KKRK → AAAA: Abolishes nuclear localization; when associated with A-37 and A-38. 1 Publication
Mutagenesisi355 – 3551H → Y: Loss of deacetylation activity. Loss of inhibition of E2F1 and loss of coactivation of FOXO1-mediated transcription. 4 Publications
Mutagenesisi363 – 3631C → S: Does not affect S-nitrosylation. 1 Publication
Mutagenesisi366 – 3661C → S: Does not affect S-nitrosylation. 1 Publication
Mutagenesisi387 – 3871C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-390. 1 Publication
Mutagenesisi390 – 3901C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-387. 1 Publication
Mutagenesisi425 – 4317VDLLIVI → ADAAAAA: Abolishes nuclear export; when associated with A-138; A-139; A-140; A-144 and A-145. 1 Publication
Mutagenesisi522 – 5221T → D: Increased deacetylase activity toward p53/TP53 and increases restistance to genotoxic stress (mimicks residue phosphorylation). 1 Publication
Mutagenesisi522 – 5221T → V: Reduces phosphorylation. Impairs deacetylase activity toward p53/TP53 and decreases restistance to genotoxic stress. 1 Publication
Mutagenesisi649 – 6491S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-651 and A-683. 1 Publication
Mutagenesisi651 – 6511S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-683. 1 Publication
Mutagenesisi683 – 6831S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-651. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 737736NAD-dependent protein deacetylase sirtuin-1
PRO_0000110257Add
BLAST
Chaini2 – 525524SirtT1 75 kDa fragment By similarity
PRO_0000415290Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By similarity
Modified residuei14 – 141Phosphoserine By similarity
Modified residuei25 – 251Phosphoserine By similarity
Modified residuei46 – 461Phosphoserine; by MAPK8 By similarity
Modified residuei164 – 1641Phosphoserine By similarity
Modified residuei165 – 1651Phosphoserine By similarity
Modified residuei387 – 3871S-nitrosocysteine1 Publication
Modified residuei390 – 3901S-nitrosocysteine1 Publication
Modified residuei522 – 5221Phosphothreonine; by DYRK1A, DYRK3 and MAPK81 Publication
Modified residuei527 – 5271Phosphoserine By similarity
Modified residuei649 – 6491Phosphoserine; by CaMK21 Publication
Modified residuei651 – 6511Phosphoserine; by CaMK2 By similarity
Modified residuei737 – 7371Phosphoserine By similarity

Post-translational modificationi

Phosphorylated. Phosphorylated by STK4/MST1, resulting in inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by MAPK8/JNK1 at Ser-46 and Thr-522 leads to increased nuclear localization and enzymatic activity. Phosphorylation at Thr-522 by DYRK1A and DYRK3 activates deacetylase activity and promotes cell survival. Phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) at Ser-46 inhibits deacetylation activity. Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation activity By similarity.2 Publications
Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1) By similarity.
S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity.

Keywords - PTMi

Acetylation, Phosphoprotein, S-nitrosylation

Proteomic databases

PaxDbiQ923E4.
PRIDEiQ923E4.

PTM databases

PhosphoSiteiQ923E4.

Expressioni

Tissue specificityi

Widely expressed. Weakly expressed in liver and skeletal muscle.1 Publication

Inductioni

By calorie restriction which induces endothelial nitric oxide synthase (eNOS) expression. Induced in liver by pyruvate during fasting.3 Publications

Gene expression databases

ArrayExpressiQ923E4.
BgeeiQ923E4.
GenevestigatoriQ923E4.

Interactioni

Subunit structurei

Found in a complex with PCAF and MYOD1 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 FOXO1; the interaction deacetylates FOXO1, enhances its DNA-binding ability and increases its transcriptional activity. Interacts with BCL6; leads to a epigenetic repression of specific target genes.13 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ClockO0878511EBI-1802585,EBI-79859
Dyrk1aQ612144EBI-1802585,EBI-80344
Dyrk3Q922Y07EBI-1802585,EBI-5242007
E2F1Q010943EBI-1802585,EBI-448924From a different organism.
FOXO1Q127782EBI-1802585,EBI-1108782From a different organism.
Hic1Q9R1Y52EBI-1802585,EBI-5236187
Hnf1aP223615EBI-1802585,EBI-5272860
Irs2P811222EBI-1802585,EBI-1369862
Nhlh2Q642212EBI-1802585,EBI-5378529
Nr0b2Q622272EBI-1802585,EBI-4310440
PpargP372382EBI-1802585,EBI-5260705
Ppargc1aO703436EBI-1802585,EBI-1371053
RB1P064004EBI-1802585,EBI-491274From a different organism.
RBL1P287492EBI-1802585,EBI-971402From a different organism.
RBL2Q089992EBI-1802585,EBI-971439From a different organism.
Smad7O352536EBI-1802585,EBI-5274835
Srebf1Q9WTN32EBI-1802585,EBI-5273743
TP53P046374EBI-1802585,EBI-366083From a different organism.

Protein-protein interaction databases

BioGridi220297. 28 interactions.
DIPiDIP-47052N.
IntActiQ923E4. 42 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ923E4.
SMRiQ923E4. Positions 226-502.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini236 – 490255Deacetylase sirtuin-type
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 268267Interaction with HIST1H1E
Add
BLAST

Motif

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

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi2 – 131130Ala-rich
Add
BLAST
Compositional biasi155 – 1584Poly-Asp

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0846.
GeneTreeiENSGT00740000115330.
HOGENOMiHOG000038016.
HOVERGENiHBG054192.
InParanoidiQ923E4.
KOiK11411.
OMAiNYPSNKS.
OrthoDBiEOG7WX09C.
PhylomeDBiQ923E4.

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: Q923E4-1) [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.

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MADEVALALQ AAGSPSAAAA MEAASQPADE PLRKRPRRDG PGLGRSPGEP    50
SAAVAPAAAG CEAASAAAPA ALWREAAGAA ASAEREAPAT AVAGDGDNGS 100
GLRREPRAAD DFDDDEGEEE DEAAAAAAAA AIGYRDNLLL TDGLLTNGFH 150
SCESDDDDRT SHASSSDWTP RPRIGPYTFV QQHLMIGTDP RTILKDLLPE 200
TIPPPELDDM TLWQIVINIL SEPPKRKKRK DINTIEDAVK LLQECKKIIV 250
LTGAGVSVSC GIPDFRSRDG IYARLAVDFP DLPDPQAMFD IEYFRKDPRP 300
FFKFAKEIYP GQFQPSLCHK FIALSDKEGK LLRNYTQNID TLEQVAGIQR 350
ILQCHGSFAT ASCLICKYKV DCEAVRGDIF NQVVPRCPRC PADEPLAIMK 400
PEIVFFGENL PEQFHRAMKY DKDEVDLLIV IGSSLKVRPV ALIPSSIPHE 450
VPQILINREP LPHLHFDVEL LGDCDVIINE LCHRLGGEYA KLCCNPVKLS 500
EITEKPPRPQ KELVHLSELP PTPLHISEDS SSPERTVPQD SSVIATLVDQ 550
ATNNNVNDLE VSESSCVEEK PQEVQTSRNV ENINVENPDF KAVGSSTADK 600
NERTSVAETV RKCWPNRLAK EQISKRLEGN QYLFVPPNRY IFHGAEVYSD 650
SEDDVLSSSS CGSNSDSGTC QSPSLEEPLE DESEIEEFYN GLEDDTERPE 700
CAGGSGFGAD GGDQEVVNEA IATRQELTDV NYPSDKS 737
Length:737
Mass (Da):80,372
Last modified:October 31, 2003 - v2
Checksum:i7F15625E29433119
GO
Isoform 2 (identifier: Q923E4-2) [UniParc]FASTAAdd to Basket

Also known as: delta-exon8

The sequence of this isoform differs from the canonical sequence as follows:
     446-629: Missing.

Show »
Length:553
Mass (Da):59,875
Checksum:i3426394C5CF062E9
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei446 – 629184Missing in isoform 2.
VSP_042190Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF214646 mRNA. Translation: AAF24983.1.
BC006584 mRNA. Translation: AAH06584.1.
CCDSiCCDS23898.1. [Q923E4-1]
RefSeqiNP_062786.1. NM_019812.2. [Q923E4-1]
UniGeneiMm.351459.

Genome annotation databases

EnsembliENSMUST00000020257; ENSMUSP00000020257; ENSMUSG00000020063. [Q923E4-1]
ENSMUST00000120239; ENSMUSP00000112595; ENSMUSG00000020063. [Q923E4-1]
ENSMUST00000177694; ENSMUSP00000137565; ENSMUSG00000020063. [Q923E4-2]
GeneIDi93759.
KEGGimmu:93759.
UCSCiuc007fke.2. mouse. [Q923E4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF214646 mRNA. Translation: AAF24983.1 .
BC006584 mRNA. Translation: AAH06584.1 .
CCDSi CCDS23898.1. [Q923E4-1 ]
RefSeqi NP_062786.1. NM_019812.2. [Q923E4-1 ]
UniGenei Mm.351459.

3D structure databases

ProteinModelPortali Q923E4.
SMRi Q923E4. Positions 226-502.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 220297. 28 interactions.
DIPi DIP-47052N.
IntActi Q923E4. 42 interactions.

PTM databases

PhosphoSitei Q923E4.

Proteomic databases

PaxDbi Q923E4.
PRIDEi Q923E4.

Protocols and materials databases

DNASUi 93759.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000020257 ; ENSMUSP00000020257 ; ENSMUSG00000020063 . [Q923E4-1 ]
ENSMUST00000120239 ; ENSMUSP00000112595 ; ENSMUSG00000020063 . [Q923E4-1 ]
ENSMUST00000177694 ; ENSMUSP00000137565 ; ENSMUSG00000020063 . [Q923E4-2 ]
GeneIDi 93759.
KEGGi mmu:93759.
UCSCi uc007fke.2. mouse. [Q923E4-1 ]

Organism-specific databases

CTDi 23411.
MGIi MGI:2135607. Sirt1.

Phylogenomic databases

eggNOGi COG0846.
GeneTreei ENSGT00740000115330.
HOGENOMi HOG000038016.
HOVERGENi HBG054192.
InParanoidi Q923E4.
KOi K11411.
OMAi NYPSNKS.
OrthoDBi EOG7WX09C.
PhylomeDBi Q923E4.

Enzyme and pathway databases

Reactomei REACT_222185. Regulation of HSF1-mediated heat shock response.
REACT_224328. SIRT1 negatively regulates rRNA Expression.

Miscellaneous databases

NextBioi 351639.
PROi Q923E4.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q923E4.
Bgeei Q923E4.
Genevestigatori Q923E4.

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

« Hide 'large scale' publications
  1. "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase."
    Imai S., Armstrong C.M., Kaeberlein M., Guarente L.
    Nature 403:795-800(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Swiss Webster / NIH.
  2. "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 545-737.
    Tissue: Mammary tumor.
  3. "Negative control of p53 by Sir2alpha promotes cell survival under stress."
    Luo J., Nikolaev A.Y., Imai S., Chen D., Su F., Shiloh A., Guarente L., Gu W.
    Cell 107:137-148(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TP53, ENZYME REGULATION, MUTAGENESIS OF HIS-355.
  4. "Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase I transcription."
    Muth V., Nadaud S., Grummt I., Voit R.
    EMBO J. 20:1353-1362(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DEACETYLATION OF TAF1B.
  5. "The absence of SIR2alpha protein has no effect on global gene silencing in mouse embryonic stem cells."
    McBurney M.W., Yang X., Jardine K., Bieman M., Th'ng J., Lemieux M.
    Mol. Cancer Res. 1:402-409(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis."
    McBurney M.W., Yang X., Jardine K., Hixon M., Boekelheide K., Webb J.R., Lansdorp P.M., Lemieux M.
    Mol. Cell. Biol. 23:38-54(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
  7. "Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state."
    Fulco M., Schiltz R.L., Iezzi S., King M.T., Zhao P., Kashiwaya Y., Hoffman E., Veech R.L., Sartorelli V.
    Mol. Cell 12:51-62(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MYOD1 AND PCAF, MUTAGENESIS OF HIS-355.
  8. "Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice."
    Cheng H.-L., Mostoslavsky R., Saito S., Manis J.P., Gu Y., Patel P., Bronson R., Appella E., Alt F.W., Chua K.F.
    Proc. Natl. Acad. Sci. U.S.A. 100:10794-10799(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma."
    Picard F., Kurtev M., Chung N., Topark-Ngarm A., Senawong T., Machado De Oliveira R., Leid M., McBurney M.W., Guarente L.
    Nature 429:771-776(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ADIPODIGENESIS, FUNCTION IN FAT MOBILIZATION, INTERACTION WITH PPARG AND NCOR1.
  10. "Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases."
    Hallows W.C., Lee S., Denu J.M.
    Proc. Natl. Acad. Sci. U.S.A. 103:10230-10235(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DEACETYLATION OF ACSS2, FUNCTION IN REGULATION OF ACCS2.
  11. "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, FUNCTION IN REGULATION OF NR1H3.
  12. "SIRT1 regulates apoptosis and Nanog expression in mouse embryonic stem cells by controlling p53 subcellular localization."
    Han M.K., Song E.K., Guo Y., Ou X., Mantel C., Broxmeyer H.E.
    Cell Stem Cell 2:241-251(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN APOPTOSIS.
  13. "Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity."
    Daitoku H., Hatta M., Matsuzaki H., Aratani S., Ohshima T., Miyagishi M., Nakajima T., Fukamizu A.
    Proc. Natl. Acad. Sci. U.S.A. 101:10042-10047(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FOXO1, FUNCTION IN DEACETYLATION OF FOXO1, MUTAGENESIS OF HIS-355.
  14. "Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses."
    Chen W.Y., Wang D.H., Yen R.C., Luo J., Gu W., Baylin S.B.
    Cell 123:437-448(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HIC1.
  15. "Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice."
    Moynihan K.A., Grimm A.A., Plueger M.M., Bernal-Mizrachi E., Ford E., Cras-Meneur C., Permutt M.A., Imai S.
    Cell Metab. 2:105-117(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN REGULATION OF INSULIN SECRETION.
  16. "SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1."
    Bouras T., Fu M., Sauve A.A., Wang F., Quong A.A., Perkins N.D., Hay R.T., Gu W., Pestell R.G.
    J. Biol. Chem. 280:10264-10276(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  17. "Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes."
    Frescas D., Valenti L., Accili D.
    J. Biol. Chem. 280:20589-20595(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN REGULATION OF FOXO1.
  18. "Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1."
    Rodgers J.T., Lerin C., Haas W., Gygi S.P., Spiegelman B.M., Puigserver P.
    Nature 434:113-118(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DEACETYLATION OF PPARGC1A, FUNCTION IN REGULATION OF GLUCOSE HOMEOSTASIS, INDUCTION.
  19. "Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS."
    Nisoli E., Tonello C., Cardile A., Cozzi V., Bracale R., Tedesco L., Falcone S., Valerio A., Cantoni O., Clementi E., Moncada S., Carruba M.O.
    Science 310:314-317(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  20. "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, MUTAGENESIS OF HIS-355.
  21. Cited for: FUNCTION IN REGULATION OF INSULIN SECRETION.
  22. "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.
  23. "Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha."
    Gerhart-Hines Z., Rodgers J.T., Bare O., Lerin C., Kim S.H., Mostoslavsky R., Alt F.W., Wu Z., Puigserver P.
    EMBO J. 26:1913-1923(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DEACETYLATION OF PPARGC1A, FUNCTION IN REGULATION OF MUSCLE METABOLISM.
  24. "SIRT1 inhibits transforming growth factor beta-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation."
    Kume S., Haneda M., Kanasaki K., Sugimoto T., Araki S., Isshiki K., Isono M., Uzu T., Guarente L., Kashiwagi A., Koya D.
    J. Biol. Chem. 282:151-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DEACETYLATION OF SMAD7.
  25. "Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1."
    Tanno M., Sakamoto J., Miura T., Shimamoto K., Horio Y.
    J. Biol. Chem. 282:6823-6832(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 38-ARG-ARG-39; 138-LEU--LEU-145; 227-LYS--LYS-230 AND 425-VAL--ILE-431.
  26. "The direct involvement of SirT1 in insulin-induced insulin receptor substrate-2 tyrosine phosphorylation."
    Zhang J.
    J. Biol. Chem. 282:34356-34364(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH IRS1 AND IRS2.
  27. "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: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
  28. "Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt."
    Fulco M., Cen Y., Zhao P., Hoffman E.P., McBurney M.W., Sauve A.A., Sartorelli V.
    Dev. Cell 14:661-673(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  29. Cited for: DISRUPTION PHENOTYPE.
  30. "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, FUNCTION IN POSSIBLE REGULATION OF STK11.
  31. "Sirt1 deficiency attenuates spermatogenesis and germ cell function."
    Coussens M., Maresh J.G., Yanagimachi R., Maeda G., Allsopp R.
    PLoS ONE 3:E1571-E1571(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  32. "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 AUTOPHAGY.
  33. "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: FUNCTION IN REGULATION OF PPARA, INTERACTION WITH PPARA.
  34. "Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters."
    Zhang T., Berrocal J.G., Frizzell K.M., Gamble M.J., DuMond M.E., Krishnakumar R., Yang T., Sauve A.A., Kraus W.L.
    J. Biol. Chem. 284:20408-20417(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NMNAT1.
  35. "CK2 is the regulator of SIRT1 substrate-binding affinity, deacetylase activity and cellular response to DNA-damage."
    Kang H., Jung J.W., Kim M.K., Chung J.H.
    PLoS ONE 4:E6611-E6611(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-649, MUTAGENESIS OF SER-154; SER-649; SER-651 AND SER-683.
  36. "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, FUNCTION IN REGULATION OF SREBF1.
  37. "SIRT1 contributes to telomere maintenance and augments global homologous recombination."
    Palacios J.A., Herranz D., De Bonis M.L., Velasco S., Serrano M., Blasco M.A.
    J. Cell Biol. 191:1299-1313(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN TELOMERE MAINTENANCE.
  38. "DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1."
    Guo X., Williams J.G., Schug T.T., Li X.
    J. Biol. Chem. 285:13223-13232(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-522, MUTAGENESIS OF THR-522.
  39. Cited for: S-NITROSYLATION AT CYS-387 AND CYS-390, MUTAGENESIS OF CYS-363; CYS-366; CYS-387 AND CYS-390.
  40. "KRIT1 regulates the homeostasis of intracellular reactive oxygen species."
    Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P., Retta S.F.
    PLoS ONE 5:E11786-E11786(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FOXO1.
  41. "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).
  42. "A nutrient-sensitive interaction between Sirt1 and HNF-1alpha regulates Crp expression."
    Grimm A.A., Brace C.S., Wang T., Stormo G.D., Imai S.
    Aging Cell 10:305-317(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HNF1A.
  43. "Disruption of a Sirt1-dependent autophagy checkpoint in the prostate results in prostatic intraepithelial neoplasia lesion formation."
    Powell M.J., Casimiro M.C., Cordon-Cardo C., He X., Yeow W.S., Wang C., McCue P.A., McBurney M.W., Pestell R.G.
    Cancer Res. 71:964-975(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN AUTOPHAGY, DISRUPTION PHENOTYPE.
  44. "Novel repressor regulates insulin sensitivity through interaction with Foxo1."
    Nakae J., Cao Y., Hakuno F., Takemori H., Kawano Y., Sekioka R., Abe T., Kiyonari H., Tanaka T., Sakai J., Takahashi S., Itoh H.
    EMBO J. 31:2275-2295(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FOXO1.
  45. "BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets."
    Tiberi L., van den Ameele J., Dimidschstein J., Piccirilli J., Gall D., Herpoel A., Bilheu A., Bonnefont J., Iacovino M., Kyba M., Bouschet T., Vanderhaeghen P.
    Nat. Neurosci. 15:1627-1635(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN NEUROGENESIS, INTERACTION WITH BCL6.

Entry informationi

Entry nameiSIR1_MOUSE
AccessioniPrimary (citable) accession number: Q923E4
Secondary accession number(s): Q9QXG8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: September 3, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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