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Protein

NAD-dependent protein deacetylase sirtuin-1

Gene

SIRT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. Involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62'. Deacetylates MEF2D. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3. Represses HNF1A-mediated transcription. Required for the repression of ESRRG by CREBZF. Modulates AP-1 transcription factor activity. Deacetylates NR1H3 AND NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed. Involved in lipid metabolism. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates ACSS2 leading to its activation, and HMGCS1. Involved in liver and muscle metabolism. Through deacteylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletel muscle under low-glucose conditions and is involved in glucose homeostasis. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and faciliting recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability. Deacteylates MECOM/EVI1. 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. Regulates the circadian expression of several core clock genes, including ARNTL/BMAL1, RORC, PER2 and CRY1 and plays a critical role in maintaining a controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling. Deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator. Deacetylates PER2, facilitating its ubiquitination and degradation by the proteosome. Protects cardiomyocytes against palmitate-induced apoptosis (PubMed:11672523, PubMed:12006491, PubMed:14976264, PubMed:14980222, PubMed:15126506, PubMed:15152190, PubMed:15205477, PubMed:15469825, PubMed:15692560, PubMed:16079181, PubMed:16166628, PubMed:16892051, PubMed:16998810, PubMed:17283066, PubMed:17334224, PubMed:17505061, PubMed:17612497, PubMed:17620057, PubMed:17936707, PubMed:18203716, PubMed:18296641, PubMed:18662546, PubMed:18687677, PubMed:19188449, PubMed:19220062, PubMed:19364925, PubMed:19690166, PubMed:19934257, PubMed:20097625, PubMed:20100829, PubMed:20203304, PubMed:20375098, PubMed:20620956, PubMed:20670893, PubMed:20817729, PubMed:21149730, PubMed:21245319, PubMed:21471201, PubMed:21504832, PubMed:21555002, PubMed:21698133, PubMed:21701047, PubMed:21775285, PubMed:21807113, PubMed:21841822, PubMed:21890893, PubMed:21909281, PubMed:21947282, PubMed:22274616). Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity (PubMed:20955178). Involved in the CCAR2-mediated regulation of PCK1 and NR1D1 (PubMed:24415752). Deacetylates CTNB1 at 'Lys-49' (PubMed:24824780). In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling (By similarity).By similarity53 Publications
Isoform 2: 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.1 Publication
(Microbial infection) In case of HIV-1 infection, interacts with and deacetylates the viral Tat protein. The viral Tat protein inhibits SIRT1 deacetylation activity toward RELA/NF-kappa-B p65, thereby potentiates its transcriptional activity and SIRT1 is proposed to contribute to T-cell hyperactivation during infection.1 Publication
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.1 Publication

Catalytic activityi

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.PROSITE-ProRule annotation1 Publication

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Inhibited by nicotinamide. Activated by resveratrol (3,5,4'-trihydroxy-trans-stilbene), butein (3,4,2',4'-tetrahydroxychalcone), piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene), Isoliquiritigenin (4,2',4'-trihydroxychalcone), fisetin (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'-pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive regulators of deacetylation activity. Negatively regulated by CCAR2.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei363Proton acceptor1
Metal bindingi371ZincPROSITE-ProRule annotation1
Metal bindingi374ZincPROSITE-ProRule annotation1
Metal bindingi395ZincPROSITE-ProRule annotation1
Metal bindingi398ZincPROSITE-ProRule annotation1
Binding sitei482NAD; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi261 – 280NADBy similarityAdd BLAST20
Nucleotide bindingi345 – 348NADBy similarity4
Nucleotide bindingi440 – 442NADBy similarity3
Nucleotide bindingi465 – 467NADBy similarity3

GO - Molecular functioni

  • bHLH transcription factor binding Source: UniProtKB
  • core promoter sequence-specific DNA binding Source: Ensembl
  • deacetylase activity Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • histone deacetylase activity Source: BHF-UCL
  • HLH domain binding Source: BHF-UCL
  • identical protein binding Source: BHF-UCL
  • keratin filament binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • mitogen-activated protein kinase binding Source: BHF-UCL
  • NAD+ binding Source: InterPro
  • NAD-dependent histone deacetylase activity Source: BHF-UCL
  • NAD-dependent histone deacetylase activity (H3-K9 specific) Source: UniProtKB
  • NAD-dependent protein deacetylase activity Source: UniProtKB
  • nuclear hormone receptor binding Source: UniProtKB
  • p53 binding Source: BHF-UCL
  • protein C-terminus binding Source: UniProtKB
  • protein deacetylase activity Source: UniProtKB
  • transcription corepressor activity Source: BHF-UCL
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • behavioral response to starvation Source: Ensembl
  • cell aging Source: BHF-UCL
  • cellular glucose homeostasis Source: UniProtKB
  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to hydrogen peroxide Source: BHF-UCL
  • cellular response to hypoxia Source: UniProtKB
  • cellular response to ionizing radiation Source: UniProtKB
  • cellular response to starvation Source: BHF-UCL
  • cellular response to tumor necrosis factor Source: UniProtKB
  • cellular triglyceride homeostasis Source: UniProtKB
  • cholesterol homeostasis Source: UniProtKB
  • chromatin organization Source: UniProtKB
  • chromatin silencing Source: ProtInc
  • chromatin silencing at rDNA Source: UniProtKB
  • circadian regulation of gene expression Source: UniProtKB
  • DNA repair Source: BHF-UCL
  • DNA replication Source: BHF-UCL
  • DNA synthesis involved in DNA repair Source: UniProtKB
  • establishment of chromatin silencing Source: BHF-UCL
  • fatty acid homeostasis Source: UniProtKB
  • histone deacetylation Source: UniProtKB
  • histone H3 deacetylation Source: BHF-UCL
  • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
  • leptin-mediated signaling pathway Source: UniProtKB
  • macrophage cytokine production Source: UniProtKB
  • macrophage differentiation Source: UniProtKB
  • maintenance of chromatin silencing Source: BHF-UCL
  • methylation-dependent chromatin silencing Source: UniProtKB
  • muscle organ development Source: UniProtKB-KW
  • negative regulation of androgen receptor signaling pathway Source: BHF-UCL
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cAMP-dependent protein kinase activity Source: UniProtKB
  • negative regulation of cell growth Source: BHF-UCL
  • negative regulation of cellular response to testosterone stimulus Source: BHF-UCL
  • negative regulation of cellular senescence Source: UniProtKB
  • negative regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
  • negative regulation of fat cell differentiation Source: BHF-UCL
  • negative regulation of gene expression Source: CACAO
  • negative regulation of helicase activity Source: UniProtKB
  • negative regulation of histone H3-K14 acetylation Source: CACAO
  • negative regulation of histone H4-K16 acetylation Source: CACAO
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: BHF-UCL
  • negative regulation of neuron death Source: Ensembl
  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: BHF-UCL
  • negative regulation of peptidyl-lysine acetylation Source: UniProtKB
  • negative regulation of phosphorylation Source: UniProtKB
  • negative regulation of prostaglandin biosynthetic process Source: UniProtKB
  • negative regulation of protein acetylation Source: CACAO
  • negative regulation of protein kinase B signaling Source: UniProtKB
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of TOR signaling Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
  • ovulation from ovarian follicle Source: Ensembl
  • peptidyl-lysine acetylation Source: UniProtKB
  • peptidyl-lysine deacetylation Source: BHF-UCL
  • positive regulation of adaptive immune response Source: UniProtKB
  • positive regulation of adipose tissue development Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cAMP-dependent protein kinase activity Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of cellular senescence Source: UniProtKB
  • positive regulation of cholesterol efflux Source: UniProtKB
  • positive regulation of chromatin silencing Source: BHF-UCL
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • positive regulation of DNA repair Source: UniProtKB
  • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: Ensembl
  • positive regulation of endothelial cell proliferation Source: AgBase
  • positive regulation of histone H3-K9 methylation Source: UniProtKB
  • positive regulation of insulin receptor signaling pathway Source: UniProtKB
  • positive regulation of macroautophagy Source: UniProtKB
  • positive regulation of macrophage apoptotic process Source: UniProtKB
  • positive regulation of MHC class II biosynthetic process Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein deacetylation Source: UniProtKB
  • protein destabilization Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • pyrimidine dimer repair by nucleotide-excision repair Source: UniProtKB
  • regulation of bile acid biosynthetic process Source: UniProtKB
  • regulation of brown fat cell differentiation Source: UniProtKB
  • regulation of cell proliferation Source: BHF-UCL
  • regulation of cellular response to heat Source: Reactome
  • regulation of endodeoxyribonuclease activity Source: UniProtKB
  • regulation of glucose metabolic process Source: UniProtKB
  • regulation of lipid storage Source: UniProtKB
  • regulation of mitotic cell cycle Source: UniProtKB
  • regulation of peroxisome proliferator activated receptor signaling pathway Source: BHF-UCL
  • regulation of protein import into nucleus, translocation Source: UniProtKB
  • regulation of protein serine/threonine kinase activity Source: AgBase
  • regulation of smooth muscle cell apoptotic process Source: UniProtKB
  • response to hydrogen peroxide Source: UniProtKB
  • response to insulin Source: UniProtKB
  • response to leptin Source: UniProtKB
  • response to oxidative stress Source: UniProtKB
  • rRNA processing Source: UniProtKB-KW
  • single strand break repair Source: UniProtKB
  • spermatogenesis Source: Ensembl
  • stress-induced premature senescence Source: CACAO
  • transcription, DNA-templated Source: UniProtKB-KW
  • triglyceride mobilization Source: BHF-UCL
  • UV-damage excision repair Source: CACAO
  • viral process Source: UniProtKB-KW
  • white fat cell differentiation Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase

Keywords - Biological processi

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

Keywords - Ligandi

Metal-binding, NAD, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1368082. RORA activates gene expression.
R-HSA-3371453. Regulation of HSF1-mediated heat shock response.
R-HSA-400253. Circadian Clock.
R-HSA-427359. SIRT1 negatively regulates rRNA Expression.
SignaLinkiQ96EB6.
SIGNORiQ96EB6.

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-1 (EC:3.5.1.-)
Short name:
hSIRT1
Alternative name(s):
Regulatory protein SIR2 homolog 1
SIR2-like protein 1
Short name:
hSIR2
Cleaved into the following chain:
SirtT1 75 kDa fragment
Short name:
75SirT1
Gene namesi
Name:SIRT1
Synonyms:SIR2L1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:14929. SIRT1.

Subcellular locationi

SirtT1 75 kDa fragment :

GO - Cellular componenti

  • chromatin silencing complex Source: UniProtKB
  • cytoplasm Source: BHF-UCL
  • mitochondrion Source: HPA
  • nuclear chromatin Source: UniProtKB
  • nuclear envelope Source: BHF-UCL
  • nuclear euchromatin Source: UniProtKB
  • nuclear heterochromatin Source: UniProtKB
  • nuclear inner membrane Source: UniProtKB
  • nucleolus Source: BHF-UCL
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • PML body Source: BHF-UCL
  • rDNA heterochromatin Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27S → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-47 and A-530. 1 Publication1
Mutagenesisi47S → A: Blocks residue phosphorylation, restores deacetylation activity and inhibits DNA damage-induced apoptosis. 2 Publications1
Mutagenesisi47S → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-530. 2 Publications1
Mutagenesisi233K → R: Impairs in vitro methylation by SETD7; when associated with R-235, R-236 and R-238. 1 Publication1
Mutagenesisi235K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-236 and R-238. 1 Publication1
Mutagenesisi236K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-235 and R-238. 1 Publication1
Mutagenesisi238K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-235a and R-236. 1 Publication1
Mutagenesisi256 – 257II → KK: Loss of interaction with the sumoylated form of CCAR2. No effect on its deacetylation activity. 1 Publication2
Mutagenesisi363H → Y: Loss of function. Reduces the interaction with CCAR2 and APEX1. Increases acetylation of APEX1. 9 Publications1
Mutagenesisi474F → A: Abolishes phosphorylation at Ser-47, restores deacetylation activity and inhibits DNA damage-induced apoptosis. 1 Publication1
Mutagenesisi530T → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-47. 2 Publications1
Mutagenesisi530T → A: Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-540. 2 Publications1
Mutagenesisi540S → A: Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-530. 1 Publication1
Mutagenesisi659S → A: Reduces in vitro phosphorylation by CaMK2; when associated with S-661. Greatly reduces in vivo phosphorylation; when associated with A-661. 1 Publication1
Mutagenesisi661S → A: Reduces in vitro phosphorylation by CaMK2; when associated with S-659. Greatly reduces in vivo phosphorylation; when associated with A-659. 1 Publication1
Mutagenesisi684S → A: No effect on phosphorylation (in vitro and in vivo). 1 Publication1

Organism-specific databases

DisGeNETi23411.
OpenTargetsiENSG00000096717.
PharmGKBiPA37935.

Chemistry databases

ChEMBLiCHEMBL4506.
GuidetoPHARMACOLOGYi2707.

Polymorphism and mutation databases

BioMutaiSIRT1.
DMDMi38258633.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001102562 – 747NAD-dependent protein deacetylase sirtuin-1Add BLAST746
ChainiPRO_00004152892 – 533SirtT1 75 kDa fragmentAdd BLAST532

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei14PhosphoserineCombined sources1 Publication1
Modified residuei26Phosphoserine1 Publication1
Modified residuei27Phosphoserine; by MAPK8Combined sources3 Publications1
Modified residuei47Phosphoserine; by MAPK8Combined sources4 Publications1
Modified residuei159Phosphoserine1 Publication1
Modified residuei162Phosphoserine1 Publication1
Modified residuei172Phosphoserine1 Publication1
Modified residuei173Phosphoserine1 Publication1
Modified residuei395S-nitrosocysteineBy similarity1
Modified residuei398S-nitrosocysteineBy similarity1
Modified residuei530Phosphothreonine; by DYRK1A, DYRK3 and MAPK8Combined sources2 Publications1
Modified residuei535PhosphoserineCombined sources1
Modified residuei544Phosphothreonine1 Publication1
Modified residuei545Phosphoserine1 Publication1
Modified residuei659Phosphoserine; by CaMK2By similarity1
Modified residuei661Phosphoserine; by CaMK21 Publication1
Modified residuei719PhosphothreonineCombined sources1 Publication1
Modified residuei747Phosphoserine1 Publication1

Post-translational modificationi

Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53.
Phosphorylated. Phosphorylated by STK4/MST1, resulting in inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by MAPK8/JNK1 at Ser-27, Ser-47, and Thr-530 leads to increased nuclear localization and enzymatic activity. Phosphorylation at Thr-530 by DYRK1A and DYRK3 activates deacetylase activity and promotes cell survival. Phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) at Ser-47 inhibits deacetylation activity. Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation activity (By similarity). Phosphorylation at Ser-27 implicating MAPK9 is linked to protein stability. There is some ambiguity for some phosphosites: Ser-159/Ser-162 and Thr-544/Ser-545.By similarity6 Publications
Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1).
S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein, S-nitrosylation

Proteomic databases

EPDiQ96EB6.
MaxQBiQ96EB6.
PaxDbiQ96EB6.
PeptideAtlasiQ96EB6.
PRIDEiQ96EB6.

PTM databases

iPTMnetiQ96EB6.
PhosphoSitePlusiQ96EB6.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

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

Gene expression databases

BgeeiENSG00000096717.
CleanExiHS_SIRT1.
ExpressionAtlasiQ96EB6. baseline and differential.
GenevisibleiQ96EB6. HS.

Organism-specific databases

HPAiCAB003855.
HPA006295.
HPA052351.

Interactioni

Subunit structurei

Interacts with XBP1 isoform 2 (PubMed:20955178). Found in a complex with PCAF and MYOD1. Interacts with FOXO1; the interaction deacetylates FOXO1, resulting in its nuclear retention and promotion of its transcriptional activity Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML. Interacts with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus); the interaction disrupts the interaction between SIRT1 and p53/TP53. Interacts with SETD7; the interaction induces the dissociation of SIRT1 from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN, NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient restriction. Interacts with SUZ12; the interaction mediates the association with the PRC4 histone methylation complex which is specific as an association with PCR2 and PCR3 complex variants is not found. Interacts with HIV-1 tat. Interacts with BCL6; leads to a epigenetic repression of specific target genes. Interacts with CLOCK, ARNTL/BMAL1 and PER2 (By similarity). Interacts with PPARA; the interaction seems to be modulated by NAD+ levels (PubMed:24043310). Interacts with NR1H3 and this interaction is inhibited in the presence of CCAR2. Interacts with CHEK2. Interacts with p53/TP53. Exhibits a preferential interaction with sumoylated CCAR2 over its unmodified form.By similarity29 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ACACAQ130853EBI-1802965,EBI-717681
AKT1P317495EBI-1802965,EBI-296087
APEX1P276956EBI-1802965,EBI-1048805
CCAR2Q8N1639EBI-1802965,EBI-355410
CIITAP330764EBI-1802965,EBI-1538819
CREBZFQ9NS373EBI-1802965,EBI-632965
CSNK2A1P684004EBI-1802965,EBI-347804
CSNK2BP678705EBI-1802965,EBI-348169
DNMT1P2635811EBI-1802965,EBI-719459
E2F1Q010943EBI-1802965,EBI-448924
EP300Q094722EBI-1802965,EBI-447295
FHL2Q141922EBI-1802965,EBI-701903
FOXO1Q127783EBI-1802965,EBI-1108782
Foxo1Q9R1E02EBI-1802965,EBI-1371343From a different organism.
FOXO3O435245EBI-1802965,EBI-1644164
FOXO4P981773EBI-1802965,EBI-4481939
HCFC1P516102EBI-1802965,EBI-396176
HES1Q144694EBI-1802965,EBI-2832522
HEY2Q9UBP53EBI-1802965,EBI-750630
IRS2Q9Y4H22EBI-1802965,EBI-1049582
KAT2BQ928313EBI-1802965,EBI-477430
MECOMQ031122EBI-1802965,EBI-1384862
MTORP423452EBI-1802965,EBI-359260
MYCP011064EBI-1802965,EBI-447544
MYCNP041983EBI-1802965,EBI-878369
NBNO609345EBI-1802965,EBI-494844
Ncor1Q609742EBI-1802965,EBI-349004From a different organism.
NHLH2Q025772EBI-1802965,EBI-5378683
NMNAT1Q9HAN93EBI-1802965,EBI-3917542
NR0B2Q154666EBI-1802965,EBI-3910729
Nr1h2Q606442EBI-1802965,EBI-5276809From a different organism.
Nr1h3Q9Z0Y92EBI-1802965,EBI-5276764From a different organism.
PIK3R1P279863EBI-1802965,EBI-79464
PpargP372383EBI-1802965,EBI-5260705From a different organism.
PpargP37238-12EBI-1802965,EBI-6267861From a different organism.
RARAP102763EBI-1802965,EBI-413374
RELAQ042065EBI-1802965,EBI-73886
RPS19BP1Q86WX311EBI-1802965,EBI-4479407
RPTORQ8N1223EBI-1802965,EBI-1567928
RRP8O431593EBI-1802965,EBI-2008793
SNW1Q135737EBI-1802965,EBI-632715
SREBF1P36956-32EBI-1802965,EBI-948338
Suv39h1O548644EBI-1802965,EBI-302230From a different organism.
tatP046083EBI-1802965,EBI-6164389From a different organism.
TLE1Q047244EBI-1802965,EBI-711424
TP53P0463713EBI-1802965,EBI-366083
TP73O153504EBI-1802965,EBI-389606
TSC2P498152EBI-1802965,EBI-396587
WRNQ141919EBI-1802965,EBI-368417
XPAP230258EBI-1802965,EBI-295222
XRCC6P129567EBI-1802965,EBI-353208

GO - Molecular functioni

  • bHLH transcription factor binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • HLH domain binding Source: BHF-UCL
  • identical protein binding Source: BHF-UCL
  • keratin filament binding Source: UniProtKB
  • mitogen-activated protein kinase binding Source: BHF-UCL
  • nuclear hormone receptor binding Source: UniProtKB
  • p53 binding Source: BHF-UCL
  • protein C-terminus binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116983. 240 interactors.
DIPiDIP-29757N.
IntActiQ96EB6. 127 interactors.
MINTiMINT-3052322.
STRINGi9606.ENSP00000212015.

Chemistry databases

BindingDBiQ96EB6.

Structurei

Secondary structure

1747
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi184 – 194Combined sources11
Helixi198 – 205Combined sources8
Helixi217 – 228Combined sources12
Helixi243 – 252Combined sources10
Beta strandi254 – 260Combined sources7
Helixi262 – 268Combined sources7
Beta strandi273 – 275Combined sources3
Turni276 – 278Combined sources3
Helixi279 – 286Combined sources8
Beta strandi290 – 292Combined sources3
Helixi293 – 297Combined sources5
Helixi299 – 304Combined sources6
Helixi307 – 312Combined sources6
Helixi313 – 316Combined sources4
Beta strandi318 – 320Combined sources3
Helixi325 – 335Combined sources11
Beta strandi339 – 344Combined sources6
Helixi350 – 354Combined sources5
Beta strandi358 – 361Combined sources4
Beta strandi364 – 371Combined sources8
Turni372 – 374Combined sources3
Beta strandi377 – 379Combined sources3
Helixi380 – 382Combined sources3
Helixi384 – 388Combined sources5
Beta strandi396 – 398Combined sources3
Beta strandi406 – 411Combined sources6
Helixi420 – 429Combined sources10
Turni430 – 432Combined sources3
Beta strandi435 – 440Combined sources6
Helixi448 – 450Combined sources3
Helixi451 – 454Combined sources4
Beta strandi461 – 467Combined sources7
Beta strandi475 – 480Combined sources6
Helixi482 – 493Combined sources12
Helixi495 – 500Combined sources6
Beta strandi506 – 510Combined sources5
Beta strandi643 – 645Combined sources3
Turni646 – 648Combined sources3
Beta strandi649 – 651Combined sources3
Helixi656 – 658Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4I5IX-ray2.50A/B241-516[»]
4IF6X-ray2.25A234-510[»]
B641-665[»]
4IG9X-ray2.64A/C/E/G234-510[»]
B/D/F/H641-665[»]
4KXQX-ray1.85A234-510[»]
B641-663[»]
4ZZHX-ray3.10A183-505[»]
4ZZIX-ray2.73A183-505[»]
4ZZJX-ray2.74A183-505[»]
5BTRX-ray3.20A/B/C143-665[»]
ProteinModelPortaliQ96EB6.
SMRiQ96EB6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini244 – 498Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST255

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 268Interaction with HIST1H1EAdd BLAST267
Regioni2 – 139Interaction with CLOCKBy similarityAdd BLAST138
Regioni143 – 541Interaction with CCAR2Add BLAST399
Regioni256 – 259Required for interaction with the sumoylated form of CCAR21 Publication4
Regioni538 – 540Phosphorylated at one of three serine residues3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 39Nuclear localization signalBy similarity8
Motifi138 – 145Nuclear export signalBy similarity8
Motifi223 – 230Nuclear localization signalBy similarity8
Motifi425 – 431Nuclear export signalBy similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi54 – 98Ala-richAdd BLAST45
Compositional biasi122 – 127Poly-Asp6
Compositional biasi128 – 134Poly-Glu7

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2684. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00850000132399.
HOGENOMiHOG000038016.
HOVERGENiHBG054192.
InParanoidiQ96EB6.
KOiK11411.
OMAiNYPSNKS.
OrthoDBiEOG091G07CT.
PhylomeDBiQ96EB6.
TreeFamiTF105896.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 2 hits.
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. AlignAdd to basket

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

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MADEAALALQ PGGSPSAAGA DREAASSPAG EPLRKRPRRD GPGLERSPGE
60 70 80 90 100
PGGAAPEREV PAAARGCPGA AAAALWREAE AEAAAAGGEQ EAQATAAAGE
110 120 130 140 150
GDNGPGLQGP SREPPLADNL YDEDDDDEGE EEEEAAAAAI GYRDNLLFGD
160 170 180 190 200
EIITNGFHSC ESDEEDRASH ASSSDWTPRP RIGPYTFVQQ HLMIGTDPRT
210 220 230 240 250
ILKDLLPETI PPPELDDMTL WQIVINILSE PPKRKKRKDI NTIEDAVKLL
260 270 280 290 300
QECKKIIVLT GAGVSVSCGI PDFRSRDGIY ARLAVDFPDL PDPQAMFDIE
310 320 330 340 350
YFRKDPRPFF KFAKEIYPGQ FQPSLCHKFI ALSDKEGKLL RNYTQNIDTL
360 370 380 390 400
EQVAGIQRII QCHGSFATAS CLICKYKVDC EAVRGDIFNQ VVPRCPRCPA
410 420 430 440 450
DEPLAIMKPE IVFFGENLPE QFHRAMKYDK DEVDLLIVIG SSLKVRPVAL
460 470 480 490 500
IPSSIPHEVP QILINREPLP HLHFDVELLG DCDVIINELC HRLGGEYAKL
510 520 530 540 550
CCNPVKLSEI TEKPPRTQKE LAYLSELPPT PLHVSEDSSS PERTSPPDSS
560 570 580 590 600
VIVTLLDQAA KSNDDLDVSE SKGCMEEKPQ EVQTSRNVES IAEQMENPDL
610 620 630 640 650
KNVGSSTGEK NERTSVAGTV RKCWPNRVAK EQISRRLDGN QYLFLPPNRY
660 670 680 690 700
IFHGAEVYSD SEDDVLSSSS CGSNSDSGTC QSPSLEEPME DESEIEEFYN
710 720 730 740
GLEDEPDVPE RAGGAGFGTD GDDQEAINEA ISVKQEVTDM NYPSNKS
Length:747
Mass (Da):81,681
Last modified:October 31, 2003 - v2
Checksum:i2D3BEA6D73DA229F
GO
Isoform 2 (identifier: Q96EB6-2) [UniParc]FASTAAdd to basket
Also known as: delta-exon8

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

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

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti386 – 389DIFN → ALFS in AAH12499 (PubMed:15489334).Curated4

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0251483D → E.1 PublicationCorresponds to variant rs35671182dbSNPEnsembl.1
Natural variantiVAR_051976484V → D.Corresponds to variant rs1063111dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042189454 – 639Missing in isoform 2. CuratedAdd BLAST186

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF083106 mRNA. Translation: AAD40849.2.
AF235040 mRNA. Translation: AAG38486.1.
DQ278604 Genomic DNA. Translation: ABB72675.1.
AL133551 Genomic DNA. Translation: CAI16036.1.
BC012499 mRNA. Translation: AAH12499.1. Different initiation.
CCDSiCCDS7273.1. [Q96EB6-1]
RefSeqiNP_001135970.1. NM_001142498.1.
NP_001300978.1. NM_001314049.1.
NP_036370.2. NM_012238.4. [Q96EB6-1]
UniGeneiHs.369779.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF083106 mRNA. Translation: AAD40849.2.
AF235040 mRNA. Translation: AAG38486.1.
DQ278604 Genomic DNA. Translation: ABB72675.1.
AL133551 Genomic DNA. Translation: CAI16036.1.
BC012499 mRNA. Translation: AAH12499.1. Different initiation.
CCDSiCCDS7273.1. [Q96EB6-1]
RefSeqiNP_001135970.1. NM_001142498.1.
NP_001300978.1. NM_001314049.1.
NP_036370.2. NM_012238.4. [Q96EB6-1]
UniGeneiHs.369779.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4I5IX-ray2.50A/B241-516[»]
4IF6X-ray2.25A234-510[»]
B641-665[»]
4IG9X-ray2.64A/C/E/G234-510[»]
B/D/F/H641-665[»]
4KXQX-ray1.85A234-510[»]
B641-663[»]
4ZZHX-ray3.10A183-505[»]
4ZZIX-ray2.73A183-505[»]
4ZZJX-ray2.74A183-505[»]
5BTRX-ray3.20A/B/C143-665[»]
ProteinModelPortaliQ96EB6.
SMRiQ96EB6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116983. 240 interactors.
DIPiDIP-29757N.
IntActiQ96EB6. 127 interactors.
MINTiMINT-3052322.
STRINGi9606.ENSP00000212015.

Chemistry databases

BindingDBiQ96EB6.
ChEMBLiCHEMBL4506.
GuidetoPHARMACOLOGYi2707.

PTM databases

iPTMnetiQ96EB6.
PhosphoSitePlusiQ96EB6.

Polymorphism and mutation databases

BioMutaiSIRT1.
DMDMi38258633.

Proteomic databases

EPDiQ96EB6.
MaxQBiQ96EB6.
PaxDbiQ96EB6.
PeptideAtlasiQ96EB6.
PRIDEiQ96EB6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23411.
DisGeNETi23411.
GeneCardsiSIRT1.
HGNCiHGNC:14929. SIRT1.
HPAiCAB003855.
HPA006295.
HPA052351.
MIMi604479. gene.
neXtProtiNX_Q96EB6.
OpenTargetsiENSG00000096717.
PharmGKBiPA37935.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2684. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00850000132399.
HOGENOMiHOG000038016.
HOVERGENiHBG054192.
InParanoidiQ96EB6.
KOiK11411.
OMAiNYPSNKS.
OrthoDBiEOG091G07CT.
PhylomeDBiQ96EB6.
TreeFamiTF105896.

Enzyme and pathway databases

ReactomeiR-HSA-1368082. RORA activates gene expression.
R-HSA-3371453. Regulation of HSF1-mediated heat shock response.
R-HSA-400253. Circadian Clock.
R-HSA-427359. SIRT1 negatively regulates rRNA Expression.
SignaLinkiQ96EB6.
SIGNORiQ96EB6.

Miscellaneous databases

GeneWikiiSirtuin_1.
GenomeRNAii23411.
PROiQ96EB6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000096717.
CleanExiHS_SIRT1.
ExpressionAtlasiQ96EB6. baseline and differential.
GenevisibleiQ96EB6. HS.

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. 2 hits.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSIR1_HUMAN
AccessioniPrimary (citable) accession number: Q96EB6
Secondary accession number(s): Q2XNF6
, Q5JVQ0, Q9GZR9, Q9Y6F0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: November 2, 2016
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Red wine, which contains resveratrol, may participate in activation of sirtuin proteins, and may therefore participate in an extended lifespan as it has been observed in yeast.
Calf histone H1 is used as substrate in the in vitro deacetylation assay (PubMed:15469825). As, in vivo, interaction occurs between SIRT1 with HIST1H1E, deacetylation has been validated only for HIST1H1E.1 Publication
The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.