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 189 (03 Jul 2019)
Sequence version 2 (31 Oct 2003)
Previous versions | rss
Other tutorials and videosHelp videoFeedback
Protein

NAD-dependent protein deacetylase sirtuin-1

Gene

SIRT1

Organism
Homo sapiens (Human)
Status
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: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:17290224, 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:20955178, PubMed:21149730, PubMed:21245319, PubMed:21471201, PubMed:21504832, PubMed:21555002, PubMed:21698133, PubMed:21701047, PubMed:21775285, PubMed:21807113, PubMed:21841822, PubMed:21890893, PubMed:21947282, PubMed:22274616, PubMed:24415752, PubMed:24824780). Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression (PubMed:15469825). Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively (PubMed:15152190, PubMed:14980222, PubMed:14976264). Serves as a sensor of the cytosolic ratio of NAD+/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction (PubMed:15205477). 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) (By similarity). 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 (PubMed:18485871). 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:18485871, PubMed:21504832). Deacetylates 'Lys-266' of SUV39H1, leading to its activation (PubMed:21504832). Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1 (PubMed:19188449). Deacetylates H2A and 'Lys-26' of HIST1H1E (PubMed:15469825). 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 (PubMed:20375098). Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting (By similarity). Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1 (PubMed:15469825, PubMed:18004385). Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2 (PubMed:18004385, PubMed:21504832). 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 (PubMed:18004385, PubMed:21504832). Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence (PubMed:11672523, PubMed:12006491). Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I (By similarity). Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability (PubMed:19364925, PubMed:21807113). 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 (PubMed:14980222, PubMed:14976264, PubMed:21841822). Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis (PubMed:15126506). Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing (PubMed:21947282). Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha (PubMed:15152190). Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1 (PubMed:17620057, PubMed:17283066, PubMed:20100829, PubMed:20620956). Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver (PubMed:15692560). Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation (PubMed:16892051). Involved in HES1- and HEY2-mediated transcriptional repression (PubMed:12535671). In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62' (PubMed:21698133). Deacetylates MEF2D (PubMed:16166628). Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3 (PubMed:17505061). Represses HNF1A-mediated transcription (By similarity). Required for the repression of ESRRG by CREBZF (PubMed:19690166). 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 (PubMed:20817729). Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2 (By similarity). Deacetylates p300/EP300 and PRMT1 (By similarity). Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation (PubMed:21701047). Involved in liver and muscle metabolism. Through deacetylation 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 (PubMed:17290224, PubMed:20817729). 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 (PubMed:15205477, PubMed:17334224, PubMed:16998810, PubMed:17612497, PubMed:20670893, PubMed:21149730). Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN (PubMed:15205477, PubMed:17334224, PubMed:20097625). 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 (PubMed:18203716). Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1 (PubMed:19934257). 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 (PubMed:18296641). Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation (PubMed:21775285). 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 (PubMed:18687677, PubMed:20203304). 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 (PubMed:21890893). Deacetylates MECOM/EVI1 (PubMed:21555002). Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization (PubMed:22274616). 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 (PubMed:18662546). Deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator (By similarity). Deacetylates PER2, facilitating its ubiquitination and degradation by the proteosome (By similarity). Protects cardiomyocytes against palmitate-induced apoptosis (By similarity). Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity (PubMed:20955178). Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis (PubMed:30193097). 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 similarity55 Publications
Isoform 2: 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.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

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

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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="http://www.uniprot.org/help/function_section">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

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
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 sitei363Proton acceptor9 Publications1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 bindingi371ZincPROSITE-ProRule annotation1
Metal bindingi374ZincPROSITE-ProRule annotation1
Metal bindingi395ZincPROSITE-ProRule annotation1
Metal bindingi398ZincPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 sitei482NAD; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 bindingi261 – 280NADBy similarityAdd BLAST20
Nucleotide bindingi345 – 348NADBy similarity4
Nucleotide bindingi440 – 442NADBy similarity3
Nucleotide bindingi465 – 467NADBy similarity3

<p>The <a href="http://www.geneontology.org/">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="http://www.uniprot.org/keywords">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, Hydrolase
Biological processApoptosis, Biological rhythms, Differentiation, Host-virus interaction, Myogenesis, rRNA processing, Transcription, Transcription regulation
LigandMetal-binding, NAD, Zinc

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-400253 Circadian Clock
R-HSA-427359 SIRT1 negatively regulates rRNA expression
R-HSA-9617629 Regulation of FOXO transcriptional activity by acetylation

SABIO-RK: Biochemical Reaction Kinetics Database

More...
SABIO-RKi
Q96EB6

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...
SignaLinki
Q96EB6

SIGNOR Signaling Network Open Resource

More...
SIGNORi
Q96EB6

<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="http://www.uniprot.org/help/names_and_taxonomy_section">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: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
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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
Name:SIRT1
Synonyms:SIR2L1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">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
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">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

Human Gene Nomenclature Database

More...
HGNCi
HGNC:14929 SIRT1

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
604479 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q96EB6

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'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>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

DisGeNET

More...
DisGeNETi
23411

Open Targets

More...
OpenTargetsi
ENSG00000096717

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA37935

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL4506

Drug and drug target database

More...
DrugBanki
DB05073 SRT501

IUPHAR/BPS Guide to PHARMACOLOGY

More...
GuidetoPHARMACOLOGYi
2707

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
SIRT1

Domain mapping of disease mutations (DMDM)

More...
DMDMi
38258633

<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="http://www.uniprot.org/help/ptm_processing_section">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 methionineiRemovedCombined sources
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001102562 – 747NAD-dependent protein deacetylase sirtuin-1Add BLAST746
ChainiPRO_00004152892 – 533SirtT1 75 kDa fragmentAdd BLAST532

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="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>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

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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.
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).1 Publication
S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein, S-nitrosylation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
Q96EB6

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
Q96EB6

MaxQB - The MaxQuant DataBase

More...
MaxQBi
Q96EB6

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

More...
PaxDbi
Q96EB6

PeptideAtlas

More...
PeptideAtlasi
Q96EB6

PRoteomics IDEntifications database

More...
PRIDEi
Q96EB6

ProteomicsDB human proteome resource

More...
ProteomicsDBi
76393
76394 [Q96EB6-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q96EB6

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

More...
PhosphoSitePlusi
Q96EB6

<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="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed.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

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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000096717 Expressed in 213 organ(s), highest expression level in right adrenal gland

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
Q96EB6 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
Q96EB6 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB003855
HPA006295
HPA052351

<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="http://www.uniprot.org/help/interaction_section">'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="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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 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.

Interacts with PACS2 (PubMed:29656858).

By similarity28 Publications

(Microbial infection)

Interacts with HIV-1 Tat.

2 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">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="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
ACACAQ130853EBI-1802965,EBI-717681
AKT1P317495EBI-1802965,EBI-296087
APEX1P276956EBI-1802965,EBI-1048805
ATG7O953523EBI-1802965,EBI-987834
CCAR2Q8N16316EBI-1802965,EBI-355410
CIITAP330764EBI-1802965,EBI-1538819
CREBZFQ9NS373EBI-1802965,EBI-632965
CSNK2A1P684005EBI-1802965,EBI-347804
CSNK2BP678705EBI-1802965,EBI-348169
DNMT1P2635811EBI-1802965,EBI-719459
DVL1O146402EBI-1802965,EBI-723489
DVL3Q929973EBI-1802965,EBI-739789
E2F1Q010943EBI-1802965,EBI-448924
EP300Q094724EBI-1802965,EBI-447295
FHL2Q141922EBI-1802965,EBI-701903
FOXO1Q127784EBI-1802965,EBI-1108782
Foxo1Q9R1E02EBI-1802965,EBI-1371343From Mus musculus.
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
KMT2AQ031645EBI-1802965,EBI-591370
MAP1LC3BQ9GZQ82EBI-1802965,EBI-373144
MECOMQ031122EBI-1802965,EBI-1384862
MTORP423452EBI-1802965,EBI-359260
MYCP011064EBI-1802965,EBI-447544
MYCNP041983EBI-1802965,EBI-878369
NBNO609345EBI-1802965,EBI-494844
Ncor1Q609742EBI-1802965,EBI-349004From Mus musculus.
NHLH2Q025772EBI-1802965,EBI-5378683
NMNAT1Q9HAN93EBI-1802965,EBI-3917542
NR0B2Q154666EBI-1802965,EBI-3910729
Nr1h2Q606442EBI-1802965,EBI-5276809From Mus musculus.
Nr1h3Q9Z0Y92EBI-1802965,EBI-5276764From Mus musculus.
PIK3R1P279863EBI-1802965,EBI-79464
PPARGP372315EBI-1802965,EBI-781384
PpargP372383EBI-1802965,EBI-5260705From Mus musculus.
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
SETD7Q8WTS611EBI-1802965,EBI-1268586
SNW1Q135737EBI-1802965,EBI-632715
SREBF1P36956-32EBI-1802965,EBI-948338
SUV39H1O434635EBI-1802965,EBI-349968
tatP046083EBI-1802965,EBI-6164389From Human immunodeficiency virus type 1 group M subtype B (isolate HXB2).
TLE1Q047244EBI-1802965,EBI-711424
TP53P0463718EBI-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

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
116983, 267 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...
ComplexPortali
CPX-467 eNoSc complex

CORUM comprehensive resource of mammalian protein complexes

More...
CORUMi
Q96EB6

Database of interacting proteins

More...
DIPi
DIP-29757N

Protein interaction database and analysis system

More...
IntActi
Q96EB6, 145 interactors

Molecular INTeraction database

More...
MINTi
Q96EB6

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000212015

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
Q96EB6

<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

Secondary structure

1747
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

More...
SMRi
Q96EB6

Database of comparative protein structure models

More...
ModBasei
Search...

<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="http://www.uniprot.org/help/family_and_domains_section">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>Domaini244 – 498Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST255

Region

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>Regioni2 – 268Interaction with HIST1H1E1 PublicationAdd 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
<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 signalBy similarity8
Motifi138 – 145Nuclear export signalBy similarity8
Motifi223 – 230Nuclear localization signalBy similarity8
Motifi425 – 431Nuclear export signalBy similarity7

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 amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi54 – 98Ala-richAdd BLAST45
Compositional biasi122 – 127Poly-Asp6
Compositional biasi128 – 134Poly-Glu7

<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

More...
eggNOGi
KOG2684 Eukaryota
COG0846 LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000159406

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000038016

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q96EB6

KEGG Orthology (KO)

More...
KOi
K11411

Identification of Orthologs from Complete Genome Data

More...
OMAi
KCWPARL

Database of Orthologous Groups

More...
OrthoDBi
973532at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q96EB6

TreeFam database of animal gene trees

More...
TreeFami
TF105896

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.30.1600.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
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

More...
Pfami
View protein in Pfam
PF02146 SIR2, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF52467 SSF52467, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
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="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">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="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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: Q96EB6-1) [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
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
<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="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

<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
E9PC49E9PC49_HUMAN
NAD-dependent protein deacetylase s...
SIRT1
452Annotation score:

Annotation score:2 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>
B0QZ35B0QZ35_HUMAN
NAD-dependent protein deacetylase s...
SIRT1
444Annotation score:

Annotation score:2 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>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti386 – 389DIFN → ALFS in AAH12499 (PubMed:15489334).Curated4

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_0251483D → E1 PublicationCorresponds to variant dbSNP:rs35671182Ensembl.1
Natural variantiVAR_051976484V → D. Corresponds to variant dbSNP:rs1063111Ensembl.1

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_042189454 – 639Missing in isoform 2. CuratedAdd BLAST186

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AF083106 mRNA Translation: AAD40849.2
AF235040 mRNA Translation: AAG38486.1
DQ278604 Genomic DNA Translation: ABB72675.1
AL133551 Genomic DNA No translation available.
BC012499 mRNA Translation: AAH12499.1 Different initiation.

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS7273.1 [Q96EB6-1]

NCBI Reference Sequences

More...
RefSeqi
NP_001135970.1, NM_001142498.1
NP_001300978.1, NM_001314049.1
NP_036370.2, NM_012238.4 [Q96EB6-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000212015; ENSP00000212015; ENSG00000096717 [Q96EB6-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
23411

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:23411

UCSC genome browser

More...
UCSCi
uc001jnd.3 human [Q96EB6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<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="http://www.uniprot.org/help/uniref">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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>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 No translation available.
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]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
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[»]
SMRiQ96EB6
ModBaseiSearch...

Protein-protein interaction databases

BioGridi116983, 267 interactors
ComplexPortaliCPX-467 eNoSc complex
CORUMiQ96EB6
DIPiDIP-29757N
IntActiQ96EB6, 145 interactors
MINTiQ96EB6
STRINGi9606.ENSP00000212015

Chemistry databases

BindingDBiQ96EB6
ChEMBLiCHEMBL4506
DrugBankiDB05073 SRT501
GuidetoPHARMACOLOGYi2707

PTM databases

iPTMnetiQ96EB6
PhosphoSitePlusiQ96EB6

Polymorphism and mutation databases

BioMutaiSIRT1
DMDMi38258633

Proteomic databases

EPDiQ96EB6
jPOSTiQ96EB6
MaxQBiQ96EB6
PaxDbiQ96EB6
PeptideAtlasiQ96EB6
PRIDEiQ96EB6
ProteomicsDBi76393
76394 [Q96EB6-2]

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

Comparative Toxicogenomics Database

More...
CTDi
23411
DisGeNETi23411

GeneCards: human genes, protein and diseases

More...
GeneCardsi
SIRT1
HGNCiHGNC:14929 SIRT1
HPAiCAB003855
HPA006295
HPA052351
MIMi604479 gene
neXtProtiNX_Q96EB6
OpenTargetsiENSG00000096717
PharmGKBiPA37935

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG2684 Eukaryota
COG0846 LUCA
GeneTreeiENSGT00940000159406
HOGENOMiHOG000038016
InParanoidiQ96EB6
KOiK11411
OMAiKCWPARL
OrthoDBi973532at2759
PhylomeDBiQ96EB6
TreeFamiTF105896

Enzyme and pathway databases

ReactomeiR-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-400253 Circadian Clock
R-HSA-427359 SIRT1 negatively regulates rRNA expression
R-HSA-9617629 Regulation of FOXO transcriptional activity by acetylation
SABIO-RKiQ96EB6
SignaLinkiQ96EB6
SIGNORiQ96EB6

Miscellaneous databases

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
Sirtuin_1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
23411

Protein Ontology

More...
PROi
PR:Q96EB6

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000096717 Expressed in 213 organ(s), highest expression level in right adrenal gland
ExpressionAtlasiQ96EB6 baseline and differential
GenevisibleiQ96EB6 HS

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

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<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_HUMAN
<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: Q96EB6
Secondary accession number(s): Q2XNF6
, Q5JVQ0, Q9GZR9, Q9Y6F0
<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="http://www.uniprot.org/help/canonical_and_isoforms">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: July 3, 2019
This is version 189 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
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.

<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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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