Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 190 (02 Jun 2021)
Sequence version 2 (31 Oct 2003)
Previous versions | rss
Add a publicationFeedback

NAD-dependent protein deacetylase sirtuin-1



Mus musculus (Mouse)
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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, metabolism, apoptosis and autophagy (PubMed:11250901, PubMed:11672522, PubMed:12651913, PubMed:12887892, PubMed:12960381, PubMed:15175761, PubMed:15220471, PubMed:15632193, PubMed:15744310, PubMed:15788402, PubMed:16098828, PubMed:16366736, PubMed:16790548, PubMed:16892051, PubMed:17098745, PubMed:17347648, PubMed:17620057, PubMed:17901049, PubMed:17936707, PubMed:18004385, PubMed:18296641, PubMed:18371449, PubMed:18477450, PubMed:18662546, PubMed:18662547, PubMed:18687677, PubMed:19299583, PubMed:19356714, PubMed:20817729, PubMed:21176092, PubMed:21187328, PubMed:21189328, PubMed:21622680, PubMed:23160044, PubMed:20167603, PubMed:28883095).

Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression (By similarity).

Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively (By similarity).

Serves as a sensor of the cytosolic ratio of NAD+/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction (By similarity).

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) (PubMed:12887892, PubMed:18477450).

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 (By similarity).

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 (PubMed:18004385).

Deacetylates 'Lys-266' of SUV39H1, leading to its activation (By similarity).

Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1 (PubMed:12887892).

Deacetylates H2A and 'Lys-26' of H1-4 (By similarity).

Deacetylates 'Lys-16' of histone H4 (in vitro) (By similarity).

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 (By similarity).

Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting (PubMed:21187328).

Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1 (By similarity).

Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2 (By similarity).

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 (By similarity).

Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence (PubMed:11672522, PubMed:12960381).

Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I (PubMed:11250901).

Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability (By similarity).

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 (By similarity).

Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis (By similarity).

Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing (By similarity).

Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha (By similarity).

Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1 (PubMed:17620057).

Deacetylates FOXO1, which increases its DNA binding ability and enhances its transcriptional activity leading to increased gluconeogenesis in liver (PubMed:15220471, PubMed:15788402).

Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation (PubMed:16892051).

Involved in HES1- and HEY2-mediated transcriptional repression (By similarity).

In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62' (By similarity).

Deacetylates MEF2D (By similarity).

Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3 (By similarity).

Represses HNF1A-mediated transcription (PubMed:21176092).

Required for the repression of ESRRG by CREBZF (By similarity).

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 (PubMed:17936707).

Involved in lipid metabolism (By similarity).

Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2 (PubMed:15175761).

Deacetylates p300/EP300 and PRMT1 (PubMed:15632193, PubMed:28883095).

Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation (PubMed:16790548).

Involved in liver and muscle metabolism (By similarity).

Through deacetylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletal muscle under low-glucose conditions and is involved in glucose homeostasis (PubMed:15744310, PubMed:17347648).

Involved in regulation of PPARA and fatty acid beta-oxidation in liver (PubMed:19356714).

Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2 (PubMed:16098828, PubMed:16366736, PubMed:17901049).

Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation (PubMed:17901049).

Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression (By similarity).

Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and facilitating 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 (By similarity).

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 (By similarity).

Transcriptional suppression of TP73 probably involves E2F4 and PCAF (By similarity).

Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage (By similarity).

Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1 (By similarity).

Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria (By similarity).

Deacetylates XRCC6/Ku70 at 'Lys-537' and 'Lys-540' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis (By similarity).

Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8 (PubMed:18296641, PubMed:21189328).

Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation (By similarity).

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 (PubMed:18687677).

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 (By similarity).

In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation (By similarity).

Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation (PubMed:17098745).

Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability (By similarity).

Deacetylates MECOM/EVI1 (By similarity).

Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization (By similarity).

During the neurogenic transition, represses selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation (By similarity).

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 (PubMed:18662546, PubMed:18662547, PubMed:19299583).

Deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator (PubMed:18662546, PubMed:18662547, PubMed:19299583).

Deacetylates PER2, facilitating its ubiquitination and degradation by the proteosome (PubMed:18662546).

Protects cardiomyocytes against palmitate-induced apoptosis (PubMed:21622680).

Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity (By similarity).

Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis (PubMed:30193097).

Involved in the CCAR2-mediated regulation of PCK1 and NR1D1 (By similarity).

Deacetylates CTNB1 at 'Lys-49' (By similarity).

In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling (PubMed:20620997).

In addition to protein deacetylase activity, also acts as protein-lysine deacylase: acts as a protein depropionylase by mediating depropionylation of Osterix (SP7) (PubMed:30026585).

Deacetylates SOX9; promoting SOX9 nuclear localization and transactivation activity (PubMed:26910618).

Involved in the regulation of centrosome duplication. Deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly (By similarity).

By similarity40 Publications

Deacetylates '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.

By similarity

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

<p>This subsection of the <a href="">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

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

<p>This subsection of the <a href="">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei355Proton acceptor4 Publications1
<p>This subsection of the <a href="">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi363ZincPROSITE-ProRule annotation1
Metal bindingi366ZincPROSITE-ProRule annotation1
Metal bindingi387ZincPROSITE-ProRule annotation1
Metal bindingi390ZincPROSITE-ProRule annotation1
<p>This subsection of the <a href="">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei474NAD; via amide nitrogenBy similarity1


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi253 – 272NADBy similarityAdd BLAST20
Nucleotide bindingi337 – 340NADBy similarity4
Nucleotide bindingi432 – 434NADBy similarity3
Nucleotide bindingi457 – 459NADBy similarity3

<p>The <a href="">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDevelopmental protein, Transferase
Biological processApoptosis, Biological rhythms, Differentiation, Myogenesis, Transcription, Transcription regulation
LigandMetal-binding, NAD, Zinc

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

BRENDAi, 3474

Reactome - a knowledgebase of biological pathways and processes

R-MMU-3371453, Regulation of HSF1-mediated heat shock response
R-MMU-9617629, Regulation of FOXO transcriptional activity by acetylation

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-1 (EC: Publications)
Alternative name(s):
NAD-dependent protein deacylase sirtuin-1 (EC:2.3.1.-1 Publication)
Regulatory protein SIR2 homolog 1
SIR2-like protein 1
Short name:
Short name:
Cleaved into the following chain:
SirtT1 75 kDa fragment
Short name:
<p>This subsection of the <a href="">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
<p>This subsection of the <a href="">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="">Names and taxonomy</a> section is present for entries that are part of a <a href="">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 10

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

MGI:2135607, Sirt1

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

High degree 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. Conditional knockout in POMC neurons leads to an increase of body weight compare to controls when animals are challenged with high-fat diet (PubMed:20620997).6 Publications


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi37 – 38RR → AA: Abolishes nuclear localization; when associated with A-227; A-228; A-229 and A-230. 2
Mutagenesisi138 – 145LLLTDGLL → AAATGAA: Abolishes nuclear export; when associated with A-425; A-427; A-428; A-429; A-430 and A-431. 1 Publication8
Mutagenesisi154S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-649; A-651 and A-683. 1 Publication1
Mutagenesisi227 – 230KKRK → AAAA: Abolishes nuclear localization; when associated with A-37 and A-38. 1 Publication4
Mutagenesisi230K → R: Decreased acetylation, leading to increased protein deacetylase activity. 1 Publication1
Mutagenesisi355H → Y: Loss of deacetylation activity. Loss of inhibition of E2F1 and loss of coactivation of FOXO1-mediated transcription. 4 Publications1
Mutagenesisi363C → S: Does not affect S-nitrosylation. 1 Publication1
Mutagenesisi366C → S: Does not affect S-nitrosylation. 1 Publication1
Mutagenesisi369K → R: Does not affect protein deacetylase activity. 1 Publication1
Mutagenesisi387C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-390. 1 Publication1
Mutagenesisi390C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-387. 1 Publication1
Mutagenesisi425 – 431VDLLIVI → ADAAAAA: Abolishes nuclear export; when associated with A-138; A-139; A-140; A-144 and A-145. 1 Publication7
Mutagenesisi505K → R: Does not affect protein deacetylase activity. 1 Publication1
Mutagenesisi522T → D: Increased deacetylase activity toward p53/TP53 and increases resistance to genotoxic stress (mimicks residue phosphorylation). 1 Publication1
Mutagenesisi522T → V: Reduces phosphorylation. Impairs deacetylase activity toward p53/TP53 and decreases resistance to genotoxic stress. Does not change nuclear localization. 1 Publication1
Mutagenesisi600K → R: Does not affect protein deacetylase activity. 1 Publication1
Mutagenesisi649S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-651 and A-683. 1 Publication1
Mutagenesisi651S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-683. 1 Publication1
Mutagenesisi683S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-651. 1 Publication1

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedBy similarity
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001102572 – 737NAD-dependent protein deacetylase sirtuin-1Add BLAST736
ChainiPRO_00004152902 – 525SirtT1 75 kDa fragmentBy similarityAdd BLAST524

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="">lipids</a>, <a href="">glycans</a> and <a href="">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylalanineBy similarity1
Modified residuei14PhosphoserineBy similarity1
Modified residuei25PhosphoserineBy similarity1
Modified residuei46Phosphoserine; by MAPK8By similarity1
Modified residuei151PhosphoserineCombined sources1
Modified residuei154PhosphoserineCombined sources1
Modified residuei164PhosphoserineBy similarity1
Modified residuei165PhosphoserineBy similarity1
Modified residuei230N6-acetyllysine1 Publication1
Modified residuei369N6-acetyllysine1 Publication1
Modified residuei387S-nitrosocysteine1 Publication1
Modified residuei390S-nitrosocysteine1 Publication1
Modified residuei422N6-acetyllysine1 Publication1
Modified residuei505N6-acetyllysine1 Publication1
Modified residuei522Phosphothreonine; by DYRK1A, DYRK3 and MAPK81 Publication1
Modified residuei527PhosphoserineBy similarity1
Modified residuei536PhosphothreonineBy similarity1
Modified residuei600N6-acetyllysine1 Publication1
Modified residuei649Phosphoserine; by CaMK21 Publication1
Modified residuei651Phosphoserine; by CaMK2By similarity1
Modified residuei737PhosphoserineBy similarity1

<p>This subsection of the <a href="">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53.By similarity
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 (PubMed:20167603). 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).By similarity1 Publication
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.1 Publication
Acetylated at various Lys residues (PubMed:28923965). Deacetylated via an autocatalytic mechanism (PubMed:28923965). Autodeacetylation at Lys-230 promotes its protein deacetylase activity (PubMed:28923965).1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, S-nitrosylation

Proteomic databases

Encyclopedia of Proteome Dynamics


jPOST - Japan Proteome Standard Repository/Database


PaxDb, a database of protein abundance averages across all three domains of life




PRoteomics IDEntifications database


ProteomicsDB: a multi-organism proteome resource

257181 [Q923E4-1]
257182 [Q923E4-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context


Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.


<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="">P92958</a>, <a href="">Q8TDN4</a>, <a href="">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

By calorie restriction which induces endothelial nitric oxide synthase (eNOS) expression. Induced in liver by pyruvate during fasting. Expressed in a circadian manner in the liver with maximal and minimal levels reached at around Zeitgeber time (ZT) 16 and ZT4, respectively. Its deacetylase activity in the liver is also regulated in a circadian manner, with a peak at ZT15. Down-regulated by palmitate; palmitate down-regulation is mediated by the induction of miR-195 that directly targets SIRT1.5 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

ENSMUSG00000020063, Expressed in cleaving embryo and 294 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

Q923E4, MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with XBP1 isoform 2 (By similarity).

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.

Interacts with CLOCK, ARNTL/BMAL1 and PER2.

Interacts with PPARA; the interaction seems to be modulated by NAD+ levels.

Interacts with NR1H3 and this interaction is inhibited in the presence of CCAR2.

Interacts with CHEK2 and p53/TP53. Exhibits a preferential interaction with sumoylated CCAR2 over its unmodified form (By similarity).

Interacts with PACS2 (By similarity).

Interacts with SIRT7 (PubMed:28842251, PubMed:28923965).

By similarity18 Publications

<p>This subsection of the '<a href="">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="">IntAct database</a>. It is updated at every <a href="">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

220297, 47 interactors

ComplexPortal: manually curated resource of macromolecular complexes

CPX-468, eNoSc complex

CORUM comprehensive resource of mammalian protein complexes


Database of interacting proteins


Protein interaction database and analysis system

Q923E4, 53 interactors

STRING: functional protein association networks


Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

Q923E4, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models


Database of comparative protein structure models


<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini236 – 490Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST255


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 56DisorderedSequence analysisAdd BLAST56
Regioni2 – 268Interaction with H1-4By similarityAdd BLAST267
Regioni2 – 131Interaction with CLOCK1 PublicationAdd BLAST130
Regioni75 – 125DisorderedSequence analysisAdd BLAST51
Regioni135 – 533Interaction with CCAR2By similarityAdd BLAST399
Regioni152 – 171DisorderedSequence analysisAdd BLAST20
Regioni248 – 251Required for interaction with the sumoylated form of CCAR2By similarity4
Regioni514 – 539DisorderedSequence analysisAdd BLAST26
Regioni653 – 713DisorderedSequence analysisAdd BLAST61


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi32 – 39Nuclear localization signal8
Motifi138 – 145Nuclear export signal8
Motifi223 – 230Nuclear localization signal8
Motifi425 – 431Nuclear export signal7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi28 – 42Basic and acidic residuesSequence analysisAdd BLAST15
Compositional biasi524 – 539Polar residuesSequence analysisAdd BLAST16
Compositional biasi653 – 676Polar residuesSequence analysisAdd BLAST24
Compositional biasi677 – 691Acidic residuesSequence analysisAdd BLAST15

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the sirtuin family. Class I subfamily.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

KOG2684, Eukaryota

Ensembl GeneTree


The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms


InParanoid: Eukaryotic Ortholog Groups


Database for complete collections of gene phylogenies


Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

3.30.1600.10, 1 hit

Integrated resource of protein families, domains and functional sites

View protein in InterPro
IPR029035, DHS-like_NAD/FAD-binding_dom
IPR003000, Sirtuin
IPR026591, Sirtuin_cat_small_dom_sf
IPR026590, Ssirtuin_cat_dom

Pfam protein domain database

View protein in Pfam
PF02146, SIR2, 1 hit

Superfamily database of structural and functional annotation

SSF52467, SSF52467, 1 hit

PROSITE; a protein domain and family database

View protein in PROSITE
PS50305, SIRTUIN, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="">length</a> and <a href="">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="">Sequence</a> section indicates if the <a href="">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="">Sequence</a> section indicates if the <a href="">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q923E4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
60 70 80 90 100
110 120 130 140 150
160 170 180 190 200
210 220 230 240 250
260 270 280 290 300
310 320 330 340 350
360 370 380 390 400
410 420 430 440 450
460 470 480 490 500
510 520 530 540 550
560 570 580 590 600
610 620 630 640 650
660 670 680 690 700
710 720 730
Mass (Da):80,372
Last modified:October 31, 2003 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i7F15625E29433119
Isoform 2 (identifier: Q923E4-2) [UniParc]FASTAAdd to basket
Also known as: delta-exon8

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

Show »
Mass (Da):59,875

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
NAD-dependent protein deacetylase s...
698Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
NAD-dependent protein deacetylase s...
140Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_042190446 – 629Missing in isoform 2. CuratedAdd BLAST184

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database


GenBank nucleotide sequence database


DNA Data Bank of Japan; a nucleotide sequence database

Links Updated
AF214646 mRNA Translation: AAF24983.1
BC006584 mRNA Translation: AAH06584.1

The Consensus CDS (CCDS) project

CCDS23898.1 [Q923E4-1]

NCBI Reference Sequences

NP_062786.1, NM_019812.3 [Q923E4-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

ENSMUST00000020257; ENSMUSP00000020257; ENSMUSG00000020063 [Q923E4-1]
ENSMUST00000120239; ENSMUSP00000112595; ENSMUSG00000020063 [Q923E4-1]
ENSMUST00000177694; ENSMUSP00000137565; ENSMUSG00000020063 [Q923E4-2]

Database of genes from NCBI RefSeq genomes


KEGG: Kyoto Encyclopedia of Genes and Genomes


UCSC genome browser

uc007fke.2, mouse [Q923E4-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
Links Updated
AF214646 mRNA Translation: AAF24983.1
BC006584 mRNA Translation: AAH06584.1
CCDSiCCDS23898.1 [Q923E4-1]
RefSeqiNP_062786.1, NM_019812.3 [Q923E4-1]

3D structure databases


Protein-protein interaction databases

BioGRIDi220297, 47 interactors
ComplexPortaliCPX-468, eNoSc complex
IntActiQ923E4, 53 interactors

PTM databases


Proteomic databases

ProteomicsDBi257181 [Q923E4-1]
257182 [Q923E4-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

1637, 1122 antibodies

The DNASU plasmid repository


Genome annotation databases

EnsembliENSMUST00000020257; ENSMUSP00000020257; ENSMUSG00000020063 [Q923E4-1]
ENSMUST00000120239; ENSMUSP00000112595; ENSMUSG00000020063 [Q923E4-1]
ENSMUST00000177694; ENSMUSP00000137565; ENSMUSG00000020063 [Q923E4-2]
UCSCiuc007fke.2, mouse [Q923E4-1]

Organism-specific databases

Comparative Toxicogenomics Database

MGIiMGI:2135607, Sirt1

Phylogenomic databases

eggNOGiKOG2684, Eukaryota

Enzyme and pathway databases

BRENDAi2.3.1.286, 3474
ReactomeiR-MMU-3371453, Regulation of HSF1-mediated heat shock response
R-MMU-9617629, Regulation of FOXO transcriptional activity by acetylation

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

93759, 2 hits in 55 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

Sirt1, mouse

Protein Ontology

RNActiQ923E4, protein

The Stanford Online Universal Resource for Clones and ESTs


Gene expression databases

BgeeiENSMUSG00000020063, Expressed in cleaving embryo and 294 other tissues
GenevisibleiQ923E4, MM

Family and domain databases

Gene3Di3.30.1600.10, 1 hit
InterProiView protein in InterPro
IPR029035, DHS-like_NAD/FAD-binding_dom
IPR003000, Sirtuin
IPR026591, Sirtuin_cat_small_dom_sf
IPR026590, Ssirtuin_cat_dom
PfamiView protein in Pfam
PF02146, SIR2, 1 hit
SUPFAMiSSF52467, SSF52467, 1 hit
PROSITEiView protein in PROSITE
PS50305, SIRTUIN, 1 hit

MobiDB: a database of protein disorder and mobility annotations


<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSIR1_MOUSE
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q923E4
Secondary accession number(s): Q9QXG8
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: June 2, 2021
This is version 190 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome


  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again