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SIR1_RAT Reviewed; 555 AA.
A0A0G2JZ79;
08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
08-JUN-2016, sequence version 2.
02-DEC-2020, entry version 44.
RecName: Full=NAD-dependent protein deacetylase sirtuin-1 {ECO:0000250|UniProtKB:Q923E4};
EC=2.3.1.286 {ECO:0000250|UniProtKB:Q96EB6};
AltName: Full=NAD-dependent protein deacylase sirtuin-1;
EC=2.3.1.- {ECO:0000250|UniProtKB:Q923E4};
Name=Sirt1 {ECO:0000312|RGD:1308542};
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Brown Norway;
PubMed=15057822; DOI=10.1038/nature02426;
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
Mockrin S., Collins F.S.;
"Genome sequence of the Brown Norway rat yields insights into mammalian
evolution.";
Nature 428:493-521(2004).
-!- FUNCTION: NAD-dependent protein deacetylase that links transcriptional
regulation directly to intracellular energetics and participates in the
coordination of several separated cellular functions such as cell
cycle, response to DNA damage, metabolism, apoptosis and autophagy. Can
modulate chromatin function through deacetylation of histones and can
promote alterations in the methylation of histones and DNA, leading to
transcriptional repression. Deacetylates a broad range of transcription
factors and coregulators, thereby regulating target gene expression
positively and negatively. Serves as a sensor of the cytosolic ratio of
NAD(+)/NADH which is altered by glucose deprivation and metabolic
changes associated with caloric restriction. Is essential in skeletal
muscle cell differentiation and in response to low nutrients mediates
the inhibitory effect on skeletal myoblast differentiation which also
involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide
phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-
dependent nucleolar silencing) complex, a complex that mediates
silencing of rDNA in response to intracellular energy status and acts
by recruiting histone-modifying enzymes. The eNoSC complex is able to
sense the energy status of cell: upon glucose starvation, elevation of
NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3
deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by
SUV39H1 and the formation of silent chromatin in the rDNA locus.
Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits
skeletal muscle differentiation by deacetylating PCAF and MYOD1.
Deacetylates H2A and 'Lys-26' of H1-4. Deacetylates 'Lys-16' of histone
H4 (in vitro). Involved in NR0B2/SHP corepression function through
chromatin remodeling: Recruited to LRH1 target gene promoters by
NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading
to transcriptional repression. Proposed to contribute to genomic
integrity via positive regulation of telomere length; however, reports
on localization to pericentromeric heterochromatin are conflicting.
Proposed to play a role in constitutive heterochromatin (CH) formation
and/or maintenance through regulation of the available pool of nuclear
SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation
by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in
SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to
accelerate renewal of the heterochromatin which correlates with greater
genomic integrity during stress response. Deacetylates 'Lys-382' of
p53/TP53 and impairs its ability to induce transcription-dependent
proapoptotic program and modulate cell senescence. Deacetylates TAF1B
and thereby represses rDNA transcription by the RNA polymerase I.
Deacetylates MYC, promotes the association of MYC with MAX and
decreases MYC stability leading to compromised transformational
capability. Deacetylates FOXO3 in response to oxidative stress thereby
increasing its ability to induce cell cycle arrest and resistance to
oxidative stress but inhibiting FOXO3-mediated induction of apoptosis
transcriptional activity; also leading to FOXO3 ubiquitination and
protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4
in regulation of transcriptional activity and apoptosis. Deacetylates
DNMT1; thereby impairs DNMT1 methyltransferase-independent
transcription repressor activity, modulates DNMT1 cell cycle regulatory
function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-
B p65 thereby inhibiting its transactivating potential and augments
apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1
and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and
enhancement of its transcriptional activity leading to increased
gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and
apoptotic function, possibly by deacetylation. Involved in HES1- and
HEY2-mediated transcriptional repression. In cooperation with MYCN
seems to be involved in transcriptional repression of DUSP6/MAPK3
leading to MYCN stabilization by phosphorylation at 'Ser-62'.
Deacetylates MEF2D. Required for antagonist-mediated transcription
suppression of AR-dependent genes which may be linked to local
deacetylation of histone H3. Represses HNF1A-mediated transcription.
Required for the repression of ESRRG by CREBZF. Deacetylates NR1H3 AND
NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates
transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal
degradation and results in cholesterol efflux; a promoter clearing
mechanism after reach round of transcription is proposed. Involved in
lipid metabolism. Implicated in regulation of adipogenesis and fat
mobilization in white adipocytes by repression of PPARG which probably
involves association with NCOR1 and SMRT/NCOR2. Deacetylates p300/EP300
and PRMT1. Deacetylates ACSS2 leading to its activation, and HMGCS1
deacetylation. Involved in liver and muscle metabolism. 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. Involved in regulation of PPARA and
fatty acid beta-oxidation in liver. Involved in positive regulation of
insulin secretion in pancreatic beta cells in response to glucose; the
function seems to imply transcriptional repression of UCP2. Proposed to
deacetylate IRS2 thereby facilitating its insulin-induced tyrosine
phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby
decreasing its stability and transactivation in lipogenic gene
expression. Involved in DNA damage response by repressing genes which
are involved in DNA repair, such as XPC and TP73, deacetylating
XRCC6/Ku70, and 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.
Also involved in DNA repair of DNA double-strand breaks by homologous
recombination and specifically single-strand annealing independently of
XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably
involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT)
signaling. Transcriptional suppression of TP73 probably involves E2F4
and PCAF. Deacetylates WRN thereby regulating its helicase and
exonuclease activities and regulates WRN nuclear translocation in
response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and
stimulates cellular AP endonuclease activity by promoting the
association of APEX1 to XRCC1. Increases p53/TP53-mediated
transcription-independent apoptosis by blocking nuclear translocation
of cytoplasmic p53/TP53 and probably redirecting it to mitochondria.
Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to
sequester BAX away from mitochondria thereby inhibiting stress-induced
apoptosis. Is involved in autophagy, presumably by deacetylating ATG5,
ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced
binding of AKT1 and PDK1 to PIP3 and promotes their activation.
Proposed to play role in regulation of STK11/LBK1-dependent AMPK
signaling pathways implicated in cellular senescence which seems to
involve the regulation of the acetylation status of STK11/LBK1. Can
deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic
localization and association with STRAD; however, the relevance of such
activity in normal cells is unclear. In endothelial cells is shown to
inhibit STK11/LBK1 activity and to promote its degradation.
Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its
degradation. Deacetylates CIITA and augments its MHC class II
transactivation and contributes to its stability. Deacetylates
MECOM/EVI1. Deacetylates PML at 'Lys-487' and this deacetylation
promotes PML control of PER2 nuclear localization. During the
neurogenic transition, represses selective NOTCH1-target genes through
histone deacetylation in a BCL6-dependent manner and leading to
neuronal differentiation. Regulates the circadian expression of several
core clock genes, including ARNTL/BMAL1, RORC, PER2 and CRY1 and plays
a critical role in maintaining a controlled rhythmicity in histone
acetylation, thereby contributing to circadian chromatin remodeling.
Deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters
in order to facilitate repression by inhibitory components of the
circadian oscillator. Deacetylates PER2, facilitating its
ubiquitination and degradation by the proteosome. Protects
cardiomyocytes against palmitate-induced apoptosis. Deacetylates XBP1
isoform 2; deacetylation decreases protein stability of XBP1 isoform 2
and inhibits its transcriptional activity. Deacetylates PCK1 and
directs its activity toward phosphoenolpyruvate production promoting
gluconeogenesis. Involved in the CCAR2-mediated regulation of PCK1 and
NR1D1. Deacetylates CTNB1 at 'Lys-49'. In POMC (pro-opiomelanocortin)
neurons, required for leptin-induced activation of PI3K signaling. In
addition to protein deacetylase activity, also acts as protein-lysine
deacylase: acts as a protein depropionylase by mediating
depropionylation of Osterix (SP7). Deacetylates SOX9; promoting SOX9
nuclear localization and transactivation activity. 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). {ECO:0000250|UniProtKB:Q923E4,
ECO:0000250|UniProtKB:Q96EB6}.
-!- CATALYTIC ACTIVITY:
Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
EC=2.3.1.286; Evidence={ECO:0000250|UniProtKB:Q96EB6,
ECO:0000255|PROSITE-ProRule:PRU00236};
-!- CATALYTIC ACTIVITY:
Reaction=H2O + N(6)-propanoyl-L-lysyl-[protein] + NAD(+) = 3''-O-
propanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
Xref=Rhea:RHEA:23500, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13758,
ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
ChEBI:CHEBI:57540, ChEBI:CHEBI:138019, ChEBI:CHEBI:145015;
Evidence={ECO:0000250|UniProtKB:Q923E4};
PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23501;
Evidence={ECO:0000250|UniProtKB:Q923E4};
-!- COFACTOR:
Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q8IXJ6};
-!- ACTIVITY REGULATION: 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.
{ECO:0000250|UniProtKB:Q96EB6}.
-!- SUBUNIT: Interacts with XBP1 isoform 2 (By similarity). Found in a
complex with PCAF and MYOD1. Interacts with FOXO1; the interaction
deacetylates FOXO1, resulting in its nuclear retention and promotion of
its transcriptional activity Component of the eNoSC complex, composed
of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML.
Interacts with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus);
the interaction disrupts the interaction between SIRT1 and p53/TP53.
Interacts with SETD7; the interaction induces the dissociation of SIRT1
from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN,
NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and
NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient
restriction. Interacts with SUZ12; the interaction mediates the
association with the PRC4 histone methylation complex which is specific
as an association with PCR2 and PCR3 complex variants is not found.
Interacts with HIV-1 tat. Interacts with BCL6; leads to a epigenetic
repression of specific target genes. Interacts with CLOCK, ARNTL/BMAL1
and PER2 (By similarity). Interacts with PPARA; the interaction seems
to be modulated by NAD(+) levels. Interacts with NR1H3 and this
interaction is inhibited in the presence of CCAR2. Interacts with
CHEK2. Interacts with p53/TP53. Exhibits a preferential interaction
with sumoylated CCAR2 over its unmodified form (By similarity).
Interacts with PACS2 (By similarity). Interacts with SIRT7 (By
similarity). {ECO:0000250|UniProtKB:Q923E4,
ECO:0000250|UniProtKB:Q96EB6}.
-!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250|UniProtKB:Q96EB6}.
Cytoplasm {ECO:0000250|UniProtKB:Q96EB6}. Nucleus
{ECO:0000250|UniProtKB:Q96EB6}. Note=Recruited to the nuclear bodies
via its interaction with PML. Colocalized with APEX1 in the nucleus.
May be found in nucleolus, nuclear euchromatin, heterochromatin and
inner membrane (By similarity). Shuttles between nucleus and cytoplasm
(By similarity). Colocalizes in the nucleus with XBP1 isoform 2 (By
similarity). {ECO:0000250|UniProtKB:Q923E4,
ECO:0000250|UniProtKB:Q96EB6}.
-!- PTM: Methylated on multiple lysine residues; methylation is enhanced
after DNA damage and is dispensable for deacetylase activity toward
p53/TP53. {ECO:0000250|UniProtKB:Q96EB6}.
-!- PTM: Phosphorylated. Phosphorylated by STK4/MST1, resulting in
inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by
MAPK8/JNK1 at Thr-338 leads to increased nuclear localization and
enzymatic activity. Phosphorylation at Thr-338 by DYRK1A and DYRK3
activates deacetylase activity and promotes cell survival.
Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B
p65/RELA deacetylation activity (By similarity).
{ECO:0000250|UniProtKB:Q923E4, ECO:0000250|UniProtKB:Q96EB6}.
-!- PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent
protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.
-!- PTM: Acetylated at various Lys residues. Deacetylated via an
autocatalytic mechanism. Autodeacetylation at Lys-46 promotes its
protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.
-!- MISCELLANEOUS: Red wine, which contains resveratrol, may participate in
activation of sirtuin proteins, and may therefore contribute to an
extended lifespan as has been observed in yeast.
{ECO:0000250|UniProtKB:Q96EB6}.
-!- MISCELLANEOUS: Calf histone H1 is used as substrate in the in vitro
deacetylation assay. As, in vivo, interaction occurs between SIRT1 with
H1-4, deacetylation has been validated only for H1-4.
{ECO:0000250|UniProtKB:Q96EB6}.
-!- MISCELLANEOUS: The reported ADP-ribosyltransferase activity of sirtuins
is likely to be an inefficient side reaction of the deacetylase
activity and may not be physiologically relevant.
{ECO:0000250|UniProtKB:Q96EB6}.
-!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
{ECO:0000305}.
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EMBL; AABR07044925; -; NOT_ANNOTATED_CDS; Genomic_DNA.
SMR; A0A0G2JZ79; -.
STRING; 10116.ENSRNOP00000000427; -.
PaxDb; A0A0G2JZ79; -.
RGD; 1308542; Sirt1.
eggNOG; KOG2684; Eukaryota.
Reactome; R-RNO-3371453; Regulation of HSF1-mediated heat shock response.
Reactome; R-RNO-427359; SIRT1 negatively regulates rRNA expression.
Reactome; R-RNO-9617629; Regulation of FOXO transcriptional activity by acetylation.
PRO; PR:A0A0G2JZ79; -.
Proteomes; UP000002494; Unplaced.
Bgee; ENSRNOG00000051592; Expressed in thymus and 20 other tissues.
GO; GO:0030424; C:axon; IDA:RGD.
GO; GO:0000785; C:chromatin; ISO:RGD.
GO; GO:0005677; C:chromatin silencing complex; ISO:RGD.
GO; GO:0005737; C:cytoplasm; ISO:RGD.
GO; GO:0005829; C:cytosol; IDA:RGD.
GO; GO:0030426; C:growth cone; IDA:RGD.
GO; GO:0005739; C:mitochondrion; ISO:RGD.
GO; GO:0000790; C:nuclear chromatin; ISO:RGD.
GO; GO:0005635; C:nuclear envelope; ISO:RGD.
GO; GO:0005719; C:nuclear euchromatin; ISO:RGD.
GO; GO:0005720; C:nuclear heterochromatin; ISO:RGD.
GO; GO:0005637; C:nuclear inner membrane; ISO:RGD.
GO; GO:0005730; C:nucleolus; ISO:RGD.
GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
GO; GO:0005634; C:nucleus; IDA:RGD.
GO; GO:0016605; C:PML body; ISO:RGD.
GO; GO:0032991; C:protein-containing complex; ISO:RGD.
GO; GO:0033553; C:rDNA heterochromatin; ISO:RGD.
GO; GO:0043425; F:bHLH transcription factor binding; ISO:RGD.
GO; GO:0019213; F:deacetylase activity; ISO:RGD.
GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
GO; GO:0042393; F:histone binding; ISO:RGD.
GO; GO:0004407; F:histone deacetylase activity; ISO:RGD.
GO; GO:0043398; F:HLH domain binding; ISO:RGD.
GO; GO:0042802; F:identical protein binding; ISO:RGD.
GO; GO:1990254; F:keratin filament binding; ISO:RGD.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:RGD.
GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:RGD.
GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); ISO:RGD.
GO; GO:0034979; F:NAD-dependent protein deacetylase activity; ISO:RGD.
GO; GO:0035257; F:nuclear hormone receptor binding; ISO:RGD.
GO; GO:0002039; F:p53 binding; ISO:RGD.
GO; GO:1990841; F:promoter-specific chromatin binding; ISO:RGD.
GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
GO; GO:0033558; F:protein deacetylase activity; ISO:RGD.
GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
GO; GO:0043422; F:protein kinase B binding; IDA:RGD.
GO; GO:0106231; F:protein-propionyllysine depropionylase activity; ISS:UniProtKB.
GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
GO; GO:0003713; F:transcription coactivator activity; ISO:RGD.
GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
GO; GO:0008134; F:transcription factor binding; ISO:RGD.
GO; GO:0001525; P:angiogenesis; ISO:RGD.
GO; GO:0042595; P:behavioral response to starvation; ISO:RGD.
GO; GO:0007569; P:cell aging; IEP:RGD.
GO; GO:0001678; P:cellular glucose homeostasis; ISO:RGD.
GO; GO:1904646; P:cellular response to amyloid-beta; IMP:ARUK-UCL.
GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
GO; GO:1904644; P:cellular response to curcumin; IEP:RGD.
GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
GO; GO:0071456; P:cellular response to hypoxia; ISO:RGD.
GO; GO:0071479; P:cellular response to ionizing radiation; ISO:RGD.
GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
GO; GO:1904648; P:cellular response to rotenone; IEP:RGD.
GO; GO:0009267; P:cellular response to starvation; ISO:RGD.
GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
GO; GO:0071303; P:cellular response to vitamin B3; IEP:RGD.
GO; GO:0035356; P:cellular triglyceride homeostasis; ISO:RGD.
GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
GO; GO:0006325; P:chromatin organization; ISO:RGD.
GO; GO:0032922; P:circadian regulation of gene expression; ISO:RGD.
GO; GO:0007623; P:circadian rhythm; ISO:RGD.
GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISO:RGD.
GO; GO:0055089; P:fatty acid homeostasis; ISO:RGD.
GO; GO:0031507; P:heterochromatin assembly; ISO:RGD.
GO; GO:0070829; P:heterochromatin maintenance; ISO:RGD.
GO; GO:0016575; P:histone deacetylation; ISO:RGD.
GO; GO:0070932; P:histone H3 deacetylation; IMP:RGD.
GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD.
GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
GO; GO:0033210; P:leptin-mediated signaling pathway; ISO:RGD.
GO; GO:0010934; P:macrophage cytokine production; ISO:RGD.
GO; GO:0030225; P:macrophage differentiation; ISO:RGD.
GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISO:RGD.
GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; ISO:RGD.
GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:RGD.
GO; GO:0060548; P:negative regulation of cell death; IMP:RGD.
GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
GO; GO:2000655; P:negative regulation of cellular response to testosterone stimulus; ISO:RGD.
GO; GO:2000773; P:negative regulation of cellular senescence; ISO:RGD.
GO; GO:0043392; P:negative regulation of DNA binding; IMP:RGD.
GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISO:RGD.
GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:RGD.
GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IMP:RGD.
GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
GO; GO:0060125; P:negative regulation of growth hormone secretion; IMP:RGD.
GO; GO:0051097; P:negative regulation of helicase activity; ISO:RGD.
GO; GO:0071441; P:negative regulation of histone H3-K14 acetylation; ISO:RGD.
GO; GO:1900113; P:negative regulation of histone H3-K9 trimethylation; ISO:RGD.
GO; GO:2000619; P:negative regulation of histone H4-K16 acetylation; ISO:RGD.
GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:ARUK-UCL.
GO; GO:1901215; P:negative regulation of neuron death; ISO:RGD.
GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; ISO:RGD.
GO; GO:0042326; P:negative regulation of phosphorylation; ISO:RGD.
GO; GO:0031393; P:negative regulation of prostaglandin biosynthetic process; ISO:RGD.
GO; GO:1901984; P:negative regulation of protein acetylation; IMP:RGD.
GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:RGD.
GO; GO:1900181; P:negative regulation of protein localization to nucleus; IMP:RGD.
GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IMP:RGD.
GO; GO:0032007; P:negative regulation of TOR signaling; ISO:RGD.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:RGD.
GO; GO:0001542; P:ovulation from ovarian follicle; ISO:RGD.
GO; GO:0018394; P:peptidyl-lysine acetylation; ISO:RGD.
GO; GO:0034983; P:peptidyl-lysine deacetylation; ISO:RGD.
GO; GO:0002821; P:positive regulation of adaptive immune response; ISO:RGD.
GO; GO:1904179; P:positive regulation of adipose tissue development; ISO:RGD.
GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
GO; GO:0097755; P:positive regulation of blood vessel diameter; IMP:RGD.
GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; ISO:RGD.
GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IMP:RGD.
GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
GO; GO:2000774; P:positive regulation of cellular senescence; ISO:RGD.
GO; GO:0010875; P:positive regulation of cholesterol efflux; ISO:RGD.
GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
GO; GO:0045739; P:positive regulation of DNA repair; ISO:RGD.
GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
GO; GO:0045722; P:positive regulation of gluconeogenesis; IMP:RGD.
GO; GO:0010460; P:positive regulation of heart rate; IMP:RGD.
GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; ISO:RGD.
GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:RGD.
GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD.
GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD.
GO; GO:2000111; P:positive regulation of macrophage apoptotic process; ISO:RGD.
GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISO:RGD.
GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
GO; GO:0090312; P:positive regulation of protein deacetylation; IMP:RGD.
GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
GO; GO:0014858; P:positive regulation of skeletal muscle cell proliferation; IMP:RGD.
GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; ISO:RGD.
GO; GO:2000614; P:positive regulation of thyroid-stimulating hormone secretion; IMP:RGD.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:RGD.
GO; GO:0006476; P:protein deacetylation; IDA:RGD.
GO; GO:0106230; P:protein depropionylation; ISS:UniProtKB.
GO; GO:0031648; P:protein destabilization; ISO:RGD.
GO; GO:0016567; P:protein ubiquitination; ISO:RGD.
GO; GO:0000720; P:pyrimidine dimer repair by nucleotide-excision repair; ISO:RGD.
GO; GO:0000183; P:rDNA heterochromatin assembly; ISO:RGD.
GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
GO; GO:0070857; P:regulation of bile acid biosynthetic process; ISO:RGD.
GO; GO:0090335; P:regulation of brown fat cell differentiation; ISO:RGD.
GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
GO; GO:0010824; P:regulation of centrosome duplication; ISS:UniProtKB.
GO; GO:0032071; P:regulation of endodeoxyribonuclease activity; ISO:RGD.
GO; GO:0010906; P:regulation of glucose metabolic process; ISO:RGD.
GO; GO:0010883; P:regulation of lipid storage; ISO:RGD.
GO; GO:0007346; P:regulation of mitotic cell cycle; ISO:RGD.
GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; ISO:RGD.
GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; ISO:RGD.
GO; GO:0034391; P:regulation of smooth muscle cell apoptotic process; ISO:RGD.
GO; GO:0045471; P:response to ethanol; IDA:RGD.
GO; GO:1902617; P:response to fluoride; IEP:RGD.
GO; GO:0042542; P:response to hydrogen peroxide; ISO:RGD.
GO; GO:0032868; P:response to insulin; ISO:RGD.
GO; GO:1904373; P:response to kainic acid; IEP:RGD.
GO; GO:0044321; P:response to leptin; ISO:RGD.
GO; GO:0010046; P:response to mycotoxin; IEP:RGD.
GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
GO; GO:1904638; P:response to resveratrol; IEP:RGD.
GO; GO:0000012; P:single strand break repair; ISO:RGD.
GO; GO:0007283; P:spermatogenesis; ISO:RGD.
GO; GO:0090400; P:stress-induced premature senescence; ISO:RGD.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
GO; GO:0006642; P:triglyceride mobilization; ISO:RGD.
GO; GO:0070914; P:UV-damage excision repair; ISO:RGD.
GO; GO:0050872; P:white fat cell differentiation; ISO:RGD.
Gene3D; 3.30.1600.10; -; 1.
InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
InterPro; IPR003000; Sirtuin.
InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
InterPro; IPR026590; Ssirtuin_cat_dom.
Pfam; PF02146; SIR2; 1.
SUPFAM; SSF52467; SSF52467; 1.
PROSITE; PS50305; SIRTUIN; 1.
3: Inferred from homology;
Acetylation; Apoptosis; Biological rhythms; Cytoplasm;
Developmental protein; Differentiation; Metal-binding; Methylation;
Myogenesis; NAD; Nucleus; Phosphoprotein; Reference proteome;
S-nitrosylation; Transcription; Transcription regulation; Transferase;
Zinc.
CHAIN 1..555
/note="NAD-dependent protein deacetylase sirtuin-1"
/id="PRO_0000436411"
DOMAIN 52..306
/note="Deacetylase sirtuin-type"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
NP_BIND 69..88
/note="NAD"
/evidence="ECO:0000250|UniProtKB:Q8IXJ6"
NP_BIND 153..156
/note="NAD"
/evidence="ECO:0000250|UniProtKB:Q8IXJ6"
NP_BIND 248..250
/note="NAD"
/evidence="ECO:0000250|UniProtKB:Q8IXJ6"
NP_BIND 273..275
/note="NAD"
/evidence="ECO:0000250|UniProtKB:Q8IXJ6"
REGION 64..67
/note="Required for interaction with the sumoylated form of
CCAR2"
/evidence="ECO:0000250|UniProtKB:Q96EB6"
MOTIF 39..46
/note="Nuclear localization signal"
/evidence="ECO:0000250|UniProtKB:Q923E4"
MOTIF 241..247
/note="Nuclear export signal"
/evidence="ECO:0000250|UniProtKB:Q923E4"
ACT_SITE 171
/note="Proton acceptor"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
METAL 179
/note="Zinc"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
METAL 182
/note="Zinc"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
METAL 203
/note="Zinc"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
METAL 206
/note="Zinc"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
BINDING 290
/note="NAD; via amide nitrogen"
/evidence="ECO:0000250"
MOD_RES 46
/note="N6-acetyllysine"
/evidence="ECO:0000250|UniProtKB:Q923E4"
MOD_RES 185
/note="N6-acetyllysine"
/evidence="ECO:0000250|UniProtKB:Q923E4"
MOD_RES 203
/note="S-nitrosocysteine"
/evidence="ECO:0000250|UniProtKB:Q923E4"
MOD_RES 206
/note="S-nitrosocysteine"
/evidence="ECO:0000250|UniProtKB:Q923E4"
MOD_RES 238
/note="N6-acetyllysine"
/evidence="ECO:0000250|UniProtKB:Q923E4"
MOD_RES 321
/note="N6-acetyllysine"
/evidence="ECO:0000250|UniProtKB:Q923E4"
MOD_RES 338
/note="Phosphothreonine"
/evidence="ECO:0000250|UniProtKB:Q96EB6"
MOD_RES 343
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:Q96EB6"
MOD_RES 352
/note="Phosphothreonine"
/evidence="ECO:0000250|UniProtKB:Q96EB6"
MOD_RES 417
/note="N6-acetyllysine"
/evidence="ECO:0000250|UniProtKB:Q923E4"
MOD_RES 466
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:Q923E4"
MOD_RES 468
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:Q96EB6"
MOD_RES 552
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:Q96EB6"
SEQUENCE 555 AA; 62059 MW; A408C8A746AB812F CRC64;
MIGTDPRTIL KDLLPETIPP PELDDMTLWQ IVINILSEPP KRKKRKDINT IEDAVKLLQE
CKKIIVLTGA GVSVSCGIPD FRSRDGIYAR LAVDFPDLPD PQAMFDIEYF RKDPRPFFKF
AKEIYPGQFQ PSLCHKFIAL SDKEGKLLRN YTQNIDTLEQ VAGIQRIIQC HGSFATASCL
ICKYKVDCEA VRGDIFNQVV PRCPRCPADE PLAIMKPEIV FFGENLPEQF HRAMKYDKDE
VDLLIVIGSS LKVRPVALIP SSIPHEVPQI LINREPLPHL HFDVELLGDC DVIINELCHR
LGGEYAKLCC NPVKLSEITE KPPRTQKELV HLSELPPTPL HISEDSSSPE RTVPQDSSVI
ATLVDQTIKN KVDDLEVSEP KSCVEEKSQE VQTYRNVESI NVENPDFKAV GSSTGDKNER
TSVAETVRKC WPNRLAKEQI SKRLDGNQYL FVPPNRYIFH GAEVYSDSED DALSSSSCGS
NSDSGTCQSP SLEEPLEDES EIEEFYNGLE DDADRPECAG GSGADGGDQE AVNEAIAMKQ
ELTDVNCTPD KSEHY