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Q923E4 (SIR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

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

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:

  1. SirtT1 75 kDa fragment
    Short name=75SirT1
Gene names
Name:Sirt1
Synonyms:Sir2l1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length737 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metobolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD+/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD+/NADP+ ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. Deacetylates H2A and 'Lys-26' of HIST1H1E. Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting. Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis. Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1. Deacetylates FOXO1, 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 insuline-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1Cthereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and faciliting recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-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. Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.30 Ref.32 Ref.33 Ref.36 Ref.37 Ref.42 Ref.43 Ref.45

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. Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.30 Ref.32 Ref.33 Ref.36 Ref.37 Ref.42 Ref.43 Ref.45

Catalytic activity

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

Cofactor

Binds 1 zinc ion per subunit By similarity.

Enzyme regulation

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. Ref.3

Subunit structure

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. Ref.3 Ref.7 Ref.9 Ref.13 Ref.14 Ref.20 Ref.26 Ref.33 Ref.34 Ref.40 Ref.42 Ref.44 Ref.45

Subcellular location

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. Ref.25 Ref.26 Ref.27

SirtT1 75 kDa fragment: Cytoplasm By similarity. Mitochondrion By similarity Ref.25 Ref.26 Ref.27.

Tissue specificity

Widely expressed. Weakly expressed in liver and skeletal muscle. Ref.6

Induction

By calorie restriction which induces endothelial nitric oxide synthase (eNOS) expression. Induced in liver by pyruvate during fasting. Ref.3 Ref.18 Ref.19

Post-translational modification

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. Ref.35 Ref.38

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.

Disruption phenotype

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. Ref.6 Ref.27 Ref.29 Ref.31 Ref.43

Sequence similarities

Belongs to the sirtuin family. Class I subfamily.

Contains 1 deacetylase sirtuin-type domain.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
Myogenesis
rRNA processing
Transcription
Transcription regulation
   Cellular componentCytoplasm
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
   LigandMetal-binding
NAD
Zinc
   Molecular functionDevelopmental protein
Hydrolase
   PTMAcetylation
Phosphoprotein
S-nitrosylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA synthesis involved in DNA repair

Inferred from mutant phenotype PubMed 17612497. Source: UniProtKB

angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cell death

Inferred from genetic interaction PubMed 22956852. Source: MGI

cellular glucose homeostasis

Inferred from mutant phenotype Ref.18. Source: UniProtKB

cellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to ionizing radiation

Inferred from mutant phenotype PubMed 17612497. Source: UniProtKB

cellular response to starvation

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

cellular response to tumor necrosis factor

Inferred from sequence or structural similarity. Source: UniProtKB

cellular triglyceride homeostasis

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cholesterol homeostasis

Inferred from mutant phenotype Ref.11. Source: UniProtKB

chromatin silencing at rDNA

Inferred from electronic annotation. Source: Ensembl

establishment of chromatin silencing

Inferred from electronic annotation. Source: Ensembl

fatty acid homeostasis

Inferred from mutant phenotype Ref.23. Source: UniProtKB

histone deacetylation

Inferred from direct assay Ref.39. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from direct assay Ref.14. Source: UniProtKB

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

Inferred from sequence or structural similarity. Source: UniProtKB

maintenance of chromatin silencing

Inferred from electronic annotation. Source: Ensembl

muscle organ development

Inferred from electronic annotation. Source: UniProtKB-KW

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

Inferred from electronic annotation. Source: Ensembl

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

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of TOR signaling

Inferred from mutant phenotype PubMed 20169165. Source: UniProtKB

negative regulation of androgen receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cAMP-dependent protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of cellular response to testosterone stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of cellular senescence

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of fat cell differentiation

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

negative regulation of helicase activity

Inferred from electronic annotation. Source: Ensembl

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

Inferred from mutant phenotype Ref.3. Source: BHF-UCL

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

Inferred from electronic annotation. Source: Ensembl

negative regulation of peptidyl-lysine acetylation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of phosphorylation

Inferred from mutant phenotype PubMed 17612497. Source: UniProtKB

negative regulation of prostaglandin biosynthetic process

Inferred from mutant phenotype PubMed 20042607. Source: UniProtKB

negative regulation of protein kinase B signaling

Inferred from mutant phenotype PubMed 21149730. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15381699. Source: MGI

negative regulation of transforming growth factor beta receptor signaling pathway

Inferred from direct assay Ref.24. Source: UniProtKB

ovulation from ovarian follicle

Inferred from mutant phenotype Ref.6. Source: MGI

peptidyl-lysine acetylation

Inferred from electronic annotation. Source: Ensembl

peptidyl-lysine deacetylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA repair

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of MHC class II biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cAMP-dependent protein kinase activity

Inferred from direct assay Ref.30. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cellular senescence

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cholesterol efflux

Inferred from mutant phenotype Ref.11. Source: UniProtKB

positive regulation of chromatin silencing

Inferred from electronic annotation. Source: Ensembl

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

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of macroautophagy

Inferred from direct assay Ref.32Ref.43. Source: UniProtKB

positive regulation of macrophage apoptotic process

Inferred from mutant phenotype PubMed 20042607. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from mutant phenotype Ref.26. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.13. Source: UniProtKB

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein deacetylation

Inferred from direct assay PubMed 11672523. Source: BHF-UCL

protein destabilization

Inferred from direct assay Ref.11. Source: UniProtKB

protein ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

pyrimidine dimer repair by nucleotide-excision repair

Inferred from mutant phenotype PubMed 21149730. Source: UniProtKB

rRNA processing

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of bile acid biosynthetic process

Inferred from mutant phenotype PubMed 20375098. Source: UniProtKB

regulation of endodeoxyribonuclease activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of glucose metabolic process

Inferred from mutant phenotype Ref.23. Source: UniProtKB

regulation of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of peroxisome proliferator activated receptor signaling pathway

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

regulation of protein import into nucleus, translocation

Inferred from electronic annotation. Source: Ensembl

regulation of smooth muscle cell apoptotic process

Inferred from direct assay Ref.24. Source: UniProtKB

response to hydrogen peroxide

Inferred from sequence or structural similarity. Source: UniProtKB

response to insulin

Inferred from direct assay Ref.26. Source: UniProtKB

single strand break repair

Inferred from sequence or structural similarity. Source: UniProtKB

spermatogenesis

Inferred from mutant phenotype Ref.6. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

triglyceride mobilization

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

white fat cell differentiation

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

   Cellular_componentESC/E(Z) complex

Inferred from electronic annotation. Source: Ensembl

PML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

chromatin

Inferred from direct assay Ref.14. Source: UniProtKB

chromatin silencing complex

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay Ref.25. Source: UniProtKB

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear euchromatin

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear heterochromatin

Inferred from direct assay Ref.27. Source: UniProtKB

nuclear inner membrane

Inferred from sequence or structural similarity. Source: UniProtKB

nucleolus

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay Ref.27. Source: UniProtKB

rDNA heterochromatin

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionNAD+ binding

Inferred from electronic annotation. Source: InterPro

NAD-dependent histone deacetylase activity

Inferred from direct assay Ref.1. Source: MGI

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

Inferred from direct assay Ref.39. Source: UniProtKB

NAD-dependent protein deacetylase activity

Inferred from direct assay Ref.13. Source: UniProtKB

bHLH transcription factor binding

Inferred from sequence or structural similarity. Source: UniProtKB

deacetylase activity

Inferred from mutant phenotype Ref.27. Source: UniProtKB

enzyme binding

Inferred from physical interaction PubMed 19578370Ref.39. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

p53 binding

Inferred from physical interaction Ref.3. Source: BHF-UCL

protein deacetylase activity

Inferred from direct assay PubMed 19578370. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction Ref.9. Source: BHF-UCL

transcription corepressor activity

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q923E4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q923E4-2)

Also known as: delta-exon8;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 737736NAD-dependent protein deacetylase sirtuin-1
PRO_0000110257
Chain2 – 525524SirtT1 75 kDa fragment By similarity
PRO_0000415290

Regions

Domain236 – 490255Deacetylase sirtuin-type
Nucleotide binding253 – 27220NAD By similarity
Nucleotide binding337 – 3404NAD By similarity
Nucleotide binding432 – 4343NAD By similarity
Nucleotide binding457 – 4593NAD By similarity
Region2 – 268267Interaction with HIST1H1E
Motif32 – 398Nuclear localization signal
Motif138 – 1458Nuclear export signal
Motif223 – 2308Nuclear localization signal
Motif425 – 4317Nuclear export signal
Compositional bias2 – 131130Ala-rich
Compositional bias155 – 1584Poly-Asp

Sites

Active site3551Proton acceptor
Metal binding3631Zinc By similarity
Metal binding3661Zinc By similarity
Metal binding3871Zinc By similarity
Metal binding3901Zinc By similarity
Binding site4741NAD; via amide nitrogen By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue141Phosphoserine By similarity
Modified residue251Phosphoserine By similarity
Modified residue461Phosphoserine; by MAPK8 By similarity
Modified residue1641Phosphoserine By similarity
Modified residue1651Phosphoserine By similarity
Modified residue3871S-nitrosocysteine Ref.39
Modified residue3901S-nitrosocysteine Ref.39
Modified residue5221Phosphothreonine; by DYRK1A, DYRK3 and MAPK8 Ref.38
Modified residue5271Phosphoserine By similarity
Modified residue6491Phosphoserine; by CaMK2 Ref.35
Modified residue6511Phosphoserine; by CaMK2 By similarity
Modified residue7371Phosphoserine By similarity

Natural variations

Alternative sequence446 – 629184Missing in isoform 2.
VSP_042190

Experimental info

Mutagenesis37 – 382RR → AA: Abolishes nuclear localization; when associated with A-227; A-228; A-229 and A-230.
Mutagenesis138 – 1458LLLTDGLL → AAATGAA: Abolishes nuclear export; when associated with A-425; A-427; A-428; A-429; A-430 and A-431.
Mutagenesis1541S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-649; A-651 and A-683. Ref.35
Mutagenesis227 – 2304KKRK → AAAA: Abolishes nuclear localization; when associated with A-37 and A-38. Ref.25
Mutagenesis3551H → Y: Loss of deacetylation activity. Loss of inhibition of E2F1 and loss of coactivation of FOXO1-mediated transcription. Ref.3 Ref.7 Ref.13 Ref.20
Mutagenesis3631C → S: Does not affect S-nitrosylation. Ref.39
Mutagenesis3661C → S: Does not affect S-nitrosylation. Ref.39
Mutagenesis3871C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-390. Ref.39
Mutagenesis3901C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-387. Ref.39
Mutagenesis425 – 4317VDLLIVI → ADAAAAA: Abolishes nuclear export; when associated with A-138; A-139; A-140; A-144 and A-145. Ref.25
Mutagenesis5221T → D: Increased deacetylase activity toward p53/TP53 and increases restistance to genotoxic stress (mimicks residue phosphorylation). Ref.38
Mutagenesis5221T → V: Reduces phosphorylation. Impairs deacetylase activity toward p53/TP53 and decreases restistance to genotoxic stress. Ref.38
Mutagenesis6491S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-651 and A-683. Ref.35
Mutagenesis6511S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-683. Ref.35
Mutagenesis6831S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-651. Ref.35

Sequences

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

Last modified October 31, 2003. Version 2.
Checksum: 7F15625E29433119

FASTA73780,372
        10         20         30         40         50         60 
MADEVALALQ AAGSPSAAAA MEAASQPADE PLRKRPRRDG PGLGRSPGEP SAAVAPAAAG 

        70         80         90        100        110        120 
CEAASAAAPA ALWREAAGAA ASAEREAPAT AVAGDGDNGS GLRREPRAAD DFDDDEGEEE 

       130        140        150        160        170        180 
DEAAAAAAAA AIGYRDNLLL TDGLLTNGFH SCESDDDDRT SHASSSDWTP RPRIGPYTFV 

       190        200        210        220        230        240 
QQHLMIGTDP RTILKDLLPE TIPPPELDDM TLWQIVINIL SEPPKRKKRK DINTIEDAVK 

       250        260        270        280        290        300 
LLQECKKIIV LTGAGVSVSC GIPDFRSRDG IYARLAVDFP DLPDPQAMFD IEYFRKDPRP 

       310        320        330        340        350        360 
FFKFAKEIYP GQFQPSLCHK FIALSDKEGK LLRNYTQNID TLEQVAGIQR ILQCHGSFAT 

       370        380        390        400        410        420 
ASCLICKYKV DCEAVRGDIF NQVVPRCPRC PADEPLAIMK PEIVFFGENL PEQFHRAMKY 

       430        440        450        460        470        480 
DKDEVDLLIV IGSSLKVRPV ALIPSSIPHE VPQILINREP LPHLHFDVEL LGDCDVIINE 

       490        500        510        520        530        540 
LCHRLGGEYA KLCCNPVKLS EITEKPPRPQ KELVHLSELP PTPLHISEDS SSPERTVPQD 

       550        560        570        580        590        600 
SSVIATLVDQ ATNNNVNDLE VSESSCVEEK PQEVQTSRNV ENINVENPDF KAVGSSTADK 

       610        620        630        640        650        660 
NERTSVAETV RKCWPNRLAK EQISKRLEGN QYLFVPPNRY IFHGAEVYSD SEDDVLSSSS 

       670        680        690        700        710        720 
CGSNSDSGTC QSPSLEEPLE DESEIEEFYN GLEDDTERPE CAGGSGFGAD GGDQEVVNEA 

       730 
IATRQELTDV NYPSDKS 

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Isoform 2 (delta-exon8) [UniParc].

Checksum: 3426394C5CF062E9
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FASTA55359,875

References

« Hide 'large scale' references
[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]"Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells."
Bordone L., Motta M.C., Picard F., Robinson A., Jhala U.S., Apfeld J., McDonagh T., Lemieux M., McBurney M., Szilvasi A., Easlon E.J., Lin S.J., Guarente L.
PLoS Biol. 4:E31-E31(2006) [PubMed] [Europe PMC] [Abstract]
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]"sirt1-null mice develop an autoimmune-like condition."
Sequeira J., Boily G., Bazinet S., Saliba S., He X., Jardine K., Kennedy C., Staines W., Rousseaux C., Mueller R., McBurney M.W.
Exp. Cell Res. 314:3069-3074(2008) [PubMed] [Europe PMC] [Abstract]
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]"GAPDH mediates nitrosylation of nuclear proteins."
Kornberg M.D., Sen N., Hara M.R., Juluri K.R., Nguyen J.V., Snowman A.M., Law L., Hester L.D., Snyder S.H.
Nat. Cell Biol. 12:1094-1100(2010) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF214646 mRNA. Translation: AAF24983.1.
BC006584 mRNA. Translation: AAH06584.1.
RefSeqNP_062786.1. NM_019812.2.
UniGeneMm.351459.

3D structure databases

ProteinModelPortalQ923E4.
SMRQ923E4. Positions 173-502.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid220297. 28 interactions.
DIPDIP-47052N.
IntActQ923E4. 42 interactions.

PTM databases

PhosphoSiteQ923E4.

Proteomic databases

PaxDbQ923E4.
PRIDEQ923E4.

Protocols and materials databases

DNASU93759.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020257; ENSMUSP00000020257; ENSMUSG00000020063. [Q923E4-1]
ENSMUST00000120239; ENSMUSP00000112595; ENSMUSG00000020063. [Q923E4-1]
ENSMUST00000177694; ENSMUSP00000137565; ENSMUSG00000020063. [Q923E4-2]
GeneID93759.
KEGGmmu:93759.
UCSCuc007fke.2. mouse. [Q923E4-1]

Organism-specific databases

CTD23411.
MGIMGI:2135607. Sirt1.

Phylogenomic databases

eggNOGCOG0846.
GeneTreeENSGT00740000115330.
HOGENOMHOG000038016.
HOVERGENHBG054192.
InParanoidQ923E4.
KOK11411.
OMANYPSNKS.
OrthoDBEOG7WX09C.
PhylomeDBQ923E4.

Gene expression databases

ArrayExpressQ923E4.
BgeeQ923E4.
GenevestigatorQ923E4.

Family and domain databases

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

Other

NextBio351639.
PROQ923E4.
SOURCESearch...

Entry information

Entry nameSIR1_MOUSE
AccessionPrimary (citable) accession number: Q923E4
Secondary accession number(s): Q9QXG8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: April 16, 2014
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot