Q923E4 (SIR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 122. History...
Names and origin
|Protein names||Recommended name:|
NAD-dependent protein deacetylase sirtuin-1
Regulatory protein SIR2 homolog 1
SIR2-like protein 1
Cleaved into the following chain:
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||737 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.
Binds 1 zinc ion per subunit By similarity.
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
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
Nucleus › PML 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
Widely expressed. Weakly expressed in liver and skeletal muscle. Ref.6
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.
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
Contains 1 deacetylase sirtuin-type domain.
|E2F1||Q01094||3||EBI-1802585,EBI-448924||From a different organism.|
|FOXO1||Q12778||2||EBI-1802585,EBI-1108782||From a different organism.|
|RB1||P06400||4||EBI-1802585,EBI-491274||From a different organism.|
|RBL1||P28749||2||EBI-1802585,EBI-971402||From a different organism.|
|RBL2||Q08999||2||EBI-1802585,EBI-971439||From a different organism.|
|TP53||P04637||4||EBI-1802585,EBI-366083||From a different organism.|
|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:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 737||736||NAD-dependent protein deacetylase sirtuin-1||PRO_0000110257|
|Chain||2 – 525||524||SirtT1 75 kDa fragment By similarity||PRO_0000415290|
|Domain||236 – 490||255||Deacetylase sirtuin-type|
|Nucleotide binding||253 – 272||20||NAD By similarity|
|Nucleotide binding||337 – 340||4||NAD By similarity|
|Nucleotide binding||432 – 434||3||NAD By similarity|
|Nucleotide binding||457 – 459||3||NAD By similarity|
|Region||2 – 268||267||Interaction with HIST1H1E|
|Motif||32 – 39||8||Nuclear localization signal|
|Motif||138 – 145||8||Nuclear export signal|
|Motif||223 – 230||8||Nuclear localization signal|
|Motif||425 – 431||7||Nuclear export signal|
|Compositional bias||2 – 131||130||Ala-rich|
|Compositional bias||155 – 158||4||Poly-Asp|
|Active site||355||1||Proton acceptor|
|Metal binding||363||1||Zinc By similarity|
|Metal binding||366||1||Zinc By similarity|
|Metal binding||387||1||Zinc By similarity|
|Metal binding||390||1||Zinc By similarity|
|Binding site||474||1||NAD; via amide nitrogen By similarity|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine By similarity|
|Modified residue||14||1||Phosphoserine By similarity|
|Modified residue||25||1||Phosphoserine By similarity|
|Modified residue||46||1||Phosphoserine; by MAPK8 By similarity|
|Modified residue||164||1||Phosphoserine By similarity|
|Modified residue||165||1||Phosphoserine By similarity|
|Modified residue||387||1||S-nitrosocysteine Ref.39|
|Modified residue||390||1||S-nitrosocysteine Ref.39|
|Modified residue||522||1||Phosphothreonine; by DYRK1A, DYRK3 and MAPK8 Ref.38|
|Modified residue||527||1||Phosphoserine By similarity|
|Modified residue||649||1||Phosphoserine; by CaMK2 Ref.35|
|Modified residue||651||1||Phosphoserine; by CaMK2 By similarity|
|Modified residue||737||1||Phosphoserine By similarity|
|Alternative sequence||446 – 629||184||Missing in isoform 2.||VSP_042190|
|Mutagenesis||37 – 38||2||RR → AA: Abolishes nuclear localization; when associated with A-227; A-228; A-229 and A-230.|
|Mutagenesis||138 – 145||8||LLLTDGLL → AAATGAA: Abolishes nuclear export; when associated with A-425; A-427; A-428; A-429; A-430 and A-431.|
|Mutagenesis||154||1||S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-649; A-651 and A-683. Ref.35|
|Mutagenesis||227 – 230||4||KKRK → AAAA: Abolishes nuclear localization; when associated with A-37 and A-38. Ref.25|
|Mutagenesis||355||1||H → 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|
|Mutagenesis||363||1||C → S: Does not affect S-nitrosylation. Ref.39|
|Mutagenesis||366||1||C → S: Does not affect S-nitrosylation. Ref.39|
|Mutagenesis||387||1||C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-390. Ref.39|
|Mutagenesis||390||1||C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-387. Ref.39|
|Mutagenesis||425 – 431||7||VDLLIVI → ADAAAAA: Abolishes nuclear export; when associated with A-138; A-139; A-140; A-144 and A-145. Ref.25|
|Mutagenesis||522||1||T → D: Increased deacetylase activity toward p53/TP53 and increases restistance to genotoxic stress (mimicks residue phosphorylation). Ref.38|
|Mutagenesis||522||1||T → V: Reduces phosphorylation. Impairs deacetylase activity toward p53/TP53 and decreases restistance to genotoxic stress. Ref.38|
|Mutagenesis||649||1||S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-651 and A-683. Ref.35|
|Mutagenesis||651||1||S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-683. Ref.35|
|Mutagenesis||683||1||S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-651. Ref.35|
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"The direct involvement of SirT1 in insulin-induced insulin receptor substrate-2 tyrosine phosphorylation."|
J. Biol. Chem. 282:34356-34364(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH IRS1 AND IRS2.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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).
|||"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.
|||"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.
|||"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.
|||"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.|
|AF214646 mRNA. Translation: AAF24983.1.|
BC006584 mRNA. Translation: AAH06584.1.
|RefSeq||NP_062786.1. NM_019812.2. |
3D structure databases
|SMR||Q923E4. Positions 233-504. |
Protein-protein interaction databases
|BioGrid||220297. 28 interactions.|
|IntAct||Q923E4. 42 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000020257; ENSMUSP00000020257; ENSMUSG00000020063. |
ENSMUST00000120239; ENSMUSP00000112595; ENSMUSG00000020063.
ENSMUST00000177694; ENSMUSP00000137565; ENSMUSG00000020063.
|UCSC||uc007fke.2. mouse. |
|MGI||MGI:2135607. Sirt1. |
Gene expression databases
Family and domain databases
|Gene3D||3.30.1600.10. 2 hits. |
|InterPro||IPR003000. Sirtuin. |
|PANTHER||PTHR11085. PTHR11085. 1 hit. |
|Pfam||PF02146. SIR2. 1 hit. |
|PROSITE||PS50305. SIRTUIN. 1 hit. |
|Accession||Primary (citable) accession number: Q923E4|
Secondary accession number(s): Q9QXG8
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|