Q96EB6 (SIR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NAD-dependent protein deacetylase sirtuin-1
Short name=hSIRT1
EC=3.5.1.-

Alternative name(s):
Regulatory protein SIR2 homolog 1
SIR2-like protein 1
Short name=hSIR2

Cleaved into the following chain:

1. SirtT1 75 kDa fragment
   Short name=75SirT1

Gene names

Name:	SIRT1
Synonyms:	SIR2L1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	747 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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, metobolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD+/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD+/NADP+ ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. Deacetylates H2A and 'Lys-26' of HIST1H1E. Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting. Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis. Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. Involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62'. Deacetylates MEF2D. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3. Represses HNF1A-mediated transcription. Required for the repression of ESRRG by CREBZF. Modulates AP-1 transcription factor activity. Deacetylates NR1H3 AND NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed. Involved in lipid metabolism. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates ACSS2 leading to its activation, and HMGCS1. Involved in liver and muscle metabolism. Through deacteylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletel muscle under low-glucose conditions and is involved in glucose homeostasis. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insuline-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and faciliting recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transacivation and contributes to its stability. Deacteylates MECOM/EVI1. Isoform 2 is shown to deacetylate 'Lys-382' of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop. 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. Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization. Ref.6 Ref.7 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.34 Ref.36 Ref.37 Ref.38 Ref.43 Ref.45 Ref.47 Ref.48 Ref.49 Ref.52 Ref.53 Ref.55 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60 Ref.62 Ref.63 Ref.65 Ref.68 Ref.70 Ref.72 Ref.73 Ref.74 Ref.75 Ref.78 Ref.80 Ref.81 Ref.82 Ref.83 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. Ref.6 Ref.7 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.34 Ref.36 Ref.37 Ref.38 Ref.43 Ref.45 Ref.47 Ref.48 Ref.49 Ref.52 Ref.53 Ref.55 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60 Ref.62 Ref.63 Ref.65 Ref.68 Ref.70 Ref.72 Ref.73 Ref.74 Ref.75 Ref.78 Ref.80 Ref.81 Ref.82 Ref.83
Catalytic activity	NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.7
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme 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 KIAA1967/DBC1. Ref.8 Ref.9 Ref.39 Ref.40
Subunit structure	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 KIAA1967/DBC1 (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. Ref.2 Ref.7 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.24 Ref.28 Ref.34 Ref.36 Ref.39 Ref.40 Ref.46 Ref.47 Ref.54 Ref.60 Ref.61 Ref.62 Ref.69 Ref.75 Ref.76 Ref.77
Subcellular location	Nucleus › PML body. Cytoplasm. Note: Recruited to the nuclear bodies via its interaction with PML. Colocalized with APEX1 in the nucleus. May be found in nucleolus, nuclear euchromatin, heterochromatin and inner membrane. Shuttles between nucleus and cytoplasm. Ref.6 Ref.7 Ref.13 Ref.17 Ref.50 Ref.59 Ref.80 SirtT1 75 kDa fragment: Cytoplasm. Mitochondrion Ref.6 Ref.7 Ref.13 Ref.17 Ref.50 Ref.59 Ref.80.
Tissue specificity	Widely expressed. Ref.1
Induction	Up-regulated by methyl methanesulfonate (MMS). In H293T cells by presence of rat calorie restriction (CR) serum. Ref.8 Ref.9 Ref.15 Ref.39 Ref.40 Ref.59 Ref.62
Post-translational modification	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 acivates 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. Ref.35 Ref.41 Ref.44 Ref.50 Ref.71 Ref.72 Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1). Ref.66 S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity By similarity.
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 (Ref.13). As, in vivo, interaction occurs between SIRT1 with HIST1H1E, deacetylation has been validated only for HIST1H1E. The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant (Ref.45).
Sequence similarities	Belongs to the sirtuin family. Class I subfamily. Contains 1 deacetylase sirtuin-type domain.
Sequence caution	The sequence AAH12499.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Apoptosis Differentiation Host-virus interaction Myogenesis Transcription Transcription regulation rRNA processing
Cellular component	Cytoplasm Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding NAD Zinc
Molecular function	Developmental protein Hydrolase
PTM	Acetylation Methylation Phosphoprotein S-nitrosylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Traceable author statement PubMed 17317627. Source: BHF-UCL DNA synthesis involved in DNA repair Inferred from sequence or structural similarity. Source: UniProtKB angiogenesis Inferred from direct assay Ref.57. Source: UniProtKB cell aging Traceable author statement Ref.6. Source: BHF-UCL cellular glucose homeostasis Inferred from sequence or structural similarity. Source: UniProtKB cellular response to hydrogen peroxide Inferred from direct assay Ref.50. Source: BHF-UCL cellular response to hypoxia Inferred from mutant phenotype Ref.57. Source: UniProtKB cellular response to ionizing radiation Inferred from sequence or structural similarity. Source: UniProtKB cellular response to starvation Inferred from sequence or structural similarity. Source: BHF-UCL cellular response to tumor necrosis factor Inferred from direct assay Ref.10. Source: UniProtKB cellular triglyceride homeostasis Inferred from sequence or structural similarity. Source: UniProtKB cholesterol homeostasis Inferred from sequence or structural similarity. Source: UniProtKB chromatin silencing at rDNA Inferred from direct assay Ref.34. Source: UniProtKB establishment of chromatin silencing Inferred from direct assay Ref.13. Source: BHF-UCL fatty acid homeostasis Inferred from sequence or structural similarity. Source: UniProtKB intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from mutant phenotype Ref.55. Source: UniProtKB maintenance of chromatin silencing Inferred from mutant phenotype Ref.13. Source: BHF-UCL methylation-dependent chromatin silencing Traceable author statement Ref.74. Source: UniProtKB muscle organ development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of DNA damage response, signal transduction by p53 class mediator Inferred from direct assay Ref.6. Source: BHF-UCL negative regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay Ref.24. Source: UniProtKB negative regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.10. Source: UniProtKB negative regulation of TOR signaling cascade Inferred from mutant phenotype Ref.61. Source: UniProtKB negative regulation of androgen receptor signaling pathway Inferred from mutant phenotype Ref.27. Source: BHF-UCL negative regulation of apoptotic process Inferred from mutant phenotype Ref.22Ref.78. Source: UniProtKB negative regulation of cAMP-dependent protein kinase activity Inferred from direct assay Ref.52. Source: UniProtKB negative regulation of cell growth Inferred from mutant phenotype Ref.27. Source: BHF-UCL negative regulation of cellular response to testosterone stimulus Inferred from mutant phenotype Ref.27. Source: BHF-UCL negative regulation of cellular senescence Inferred from direct assay Ref.52. Source: UniProtKB negative regulation of fat cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of helicase activity Inferred from direct assay Ref.37. Source: UniProtKB negative regulation of peptidyl-lysine acetylation Inferred from direct assay Ref.55. Source: UniProtKB negative regulation of prostaglandin biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from mutant phenotype Ref.63. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.16. Source: UniProtKB negative regulation of transforming growth factor beta receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB ovulation from ovarian follicle Inferred from electronic annotation. Source: Compara peptidyl-lysine acetylation Inferred from mutant phenotype Ref.33. Source: UniProtKB peptidyl-lysine deacetylation Inferred from direct assay Ref.13. Source: BHF-UCL positive regulation of DNA repair Inferred from mutant phenotype Ref.59. Source: UniProtKB positive regulation of MHC class II biosynthetic process Inferred from direct assay Ref.81. Source: UniProtKB positive regulation of adaptive immune response Inferred from direct assay Ref.81. Source: UniProtKB positive regulation of cAMP-dependent protein kinase activity Inferred from mutant phenotype Ref.38. Source: UniProtKB positive regulation of cell proliferation Inferred from mutant phenotype Ref.70. Source: UniProtKB positive regulation of cellular senescence Inferred from direct assay Ref.38. Source: UniProtKB positive regulation of cholesterol efflux Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of chromatin silencing Inferred from mutant phenotype Ref.13. Source: BHF-UCL positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from mutant phenotype PubMed 19047049. Source: UniProtKB positive regulation of insulin receptor signaling pathway Inferred from direct assay PubMed 21241768. Source: UniProtKB positive regulation of macroautophagy Inferred from direct assay Ref.43. Source: UniProtKB positive regulation of macrophage apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.70. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.83. Source: UniProtKB protein destabilization Inferred from sequence or structural similarity. Source: UniProtKB protein ubiquitination Inferred from direct assay Ref.83. Source: UniProtKB pyrimidine dimer repair by nucleotide-excision repair Inferred from mutant phenotype Ref.63. Source: UniProtKB rRNA processing Inferred from electronic annotation. Source: UniProtKB-KW regulation of bile acid biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of endodeoxyribonuclease activity Inferred from mutant phenotype Ref.59. Source: UniProtKB regulation of glucose metabolic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of mitotic cell cycle Inferred from direct assay Ref.16. Source: UniProtKB regulation of peroxisome proliferator activated receptor signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL regulation of protein import into nucleus, translocation Inferred from mutant phenotype Ref.37. Source: UniProtKB regulation of smooth muscle cell apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB response to insulin stimulus Inferred from sequence or structural similarity. Source: UniProtKB single strand break repair Inferred from mutant phenotype Ref.53. Source: UniProtKB spermatogenesis Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW triglyceride mobilization Inferred from sequence or structural similarity. Source: BHF-UCL virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW white fat cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	PML body Inferred from direct assay Ref.7. Source: BHF-UCL chromatin silencing complex Inferred from direct assay Ref.34. Source: UniProtKB cytoplasm Inferred from direct assay Ref.50. Source: BHF-UCL nuclear euchromatin Inferred from direct assay Ref.13. Source: UniProtKB nuclear heterochromatin Inferred from direct assay Ref.13. Source: UniProtKB nuclear inner membrane Inferred from direct assay Ref.13. Source: UniProtKB nucleolus Inferred from direct assay Ref.13. Source: BHF-UCL rDNA heterochromatin Inferred from direct assay Ref.34. Source: UniProtKB
Molecular_function	NAD+ binding Inferred from electronic annotation. Source: InterPro NAD-dependent histone deacetylase activity (H3-K9 specific) Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW transcription corepressor activity Inferred from direct assay Ref.2. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACACA	Q13085	3	EBI-1802965,EBI-717681
AKT1	P31749	5	EBI-1802965,EBI-296087
APEX1	P27695	6	EBI-1802965,EBI-1048805
CIITA	P33076	4	EBI-1802965,EBI-1538819
CREBZF	Q9NS37	3	EBI-1802965,EBI-632965
CSNK2A1	P68400	2	EBI-1802965,EBI-347804
DNMT1	P26358	11	EBI-1802965,EBI-719459
E2F1	Q01094	3	EBI-1802965,EBI-448924
EP300	Q09472	2	EBI-1802965,EBI-447295
FHL2	Q14192	2	EBI-1802965,EBI-701903
FOXO1	Q12778	3	EBI-1802965,EBI-1108782
Foxo1	Q9R1E0	2	EBI-1802965,EBI-1371343	From a different organism.
FOXO3	O43524	5	EBI-1802965,EBI-1644164
FOXO4	P98177	3	EBI-1802965,EBI-4481939
HCFC1	P51610	2	EBI-1802965,EBI-396176
HES1	Q14469	4	EBI-1802965,EBI-2832522
HEY2	Q9UBP5	3	EBI-1802965,EBI-750630
IRS2	Q9Y4H2	2	EBI-1802965,EBI-1049582
KAT2B	Q92831	3	EBI-1802965,EBI-477430
KIAA1967	Q8N163	9	EBI-1802965,EBI-355410
MECOM	Q03112	2	EBI-1802965,EBI-1384862
MTOR	P42345	2	EBI-1802965,EBI-359260
MYC	P01106	4	EBI-1802965,EBI-447544
MYCN	P04198	3	EBI-1802965,EBI-878369
NBN	O60934	5	EBI-1802965,EBI-494844
Ncor1	Q60974	2	EBI-1802965,EBI-349004	From a different organism.
NHLH2	Q02577	2	EBI-1802965,EBI-5378683
NMNAT1	Q9HAN9	3	EBI-1802965,EBI-3917542
NR0B2	Q15466	6	EBI-1802965,EBI-3910729
Nr1h2	Q60644	2	EBI-1802965,EBI-5276809	From a different organism.
Nr1h3	Q9Z0Y9	2	EBI-1802965,EBI-5276764	From a different organism.
PIK3R1	P27986	3	EBI-1802965,EBI-79464
Pparg	P37238	3	EBI-1802965,EBI-5260705	From a different organism.
Pparg	P37238-1	2	EBI-1802965,EBI-6267861	From a different organism.
RARA	P10276	3	EBI-1802965,EBI-413374
RELA	Q04206	4	EBI-1802965,EBI-73886
RPS19BP1	Q86WX3	9	EBI-1802965,EBI-4479407
RPTOR	Q8N122	3	EBI-1802965,EBI-1567928
RRP8	O43159	3	EBI-1802965,EBI-2008793
SNW1	Q13573	7	EBI-1802965,EBI-632715
SREBF1	P36956-3	2	EBI-1802965,EBI-948338
Suv39h1	O54864	4	EBI-1802965,EBI-302230	From a different organism.
tat	P04608	3	EBI-1802965,EBI-6164389	From a different organism.
TLE1	Q04724	4	EBI-1802965,EBI-711424
TP53	P04637	13	EBI-1802965,EBI-366083
TP73	O15350	4	EBI-1802965,EBI-389606
TSC2	P49815	2	EBI-1802965,EBI-396587
WRN	Q14191	9	EBI-1802965,EBI-368417
XPA	P23025	8	EBI-1802965,EBI-295222
XRCC6	P12956	7	EBI-1802965,EBI-353208

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96EB6-1)

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

Isoform 2 (identifier: Q96EB6-2)

Also known as: delta-exon8;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.64

Chain

2 – 747

746

NAD-dependent protein deacetylase sirtuin-1

PRO_0000110256

Chain

2 – 533

532

SirtT1 75 kDa fragment

PRO_0000415289

Regions

Domain

244 – 498

255

Deacetylase sirtuin-type

Nucleotide binding

261 – 280

20

NAD By similarity

Nucleotide binding

345 – 348

4

NAD By similarity

Nucleotide binding

440 – 442

3

NAD By similarity

Nucleotide binding

465 – 467

3

NAD By similarity

Region

2 – 268

267

Interaction with HIST1H1E

Region

143 – 541

399

Interaction with KIAA1967/DBC1

Region

538 – 540

3

Phosphorylated at one of three serine residues

Motif

32 – 39

8

Nuclear localization signal By similarity

Motif

138 – 145

8

Nuclear export signal By similarity

Motif

223 – 230

8

Nuclear localization signal By similarity

Motif

425 – 431

7

Nuclear export signal By similarity

Compositional bias

54 – 98

45

Ala-rich

Compositional bias

122 – 127

6

Poly-Asp

Compositional bias

128 – 134

7

Poly-Glu

Sites

Active site

363

1

Proton acceptor

Metal binding

371

1

Zinc By similarity

Metal binding

374

1

Zinc By similarity

Metal binding

395

1

Zinc By similarity

Metal binding

398

1

Zinc By similarity

Binding site

482

1

NAD; via amide nitrogen By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.64 Ref.79

Modified residue

14

1

Phosphoserine Ref.41 Ref.64 Ref.79

Modified residue

26

1

Phosphoserine Ref.41

Modified residue

27

1

Phosphoserine; by MAPK8 Ref.35 Ref.41 Ref.50

Modified residue

47

1

Phosphoserine; by MAPK8 Ref.21 Ref.35 Ref.41 Ref.50 Ref.64 Ref.72 Ref.79

Modified residue

159

1

Phosphoserine Probable

Modified residue

162

1

Phosphoserine Probable

Modified residue

172

1

Phosphoserine Ref.41

Modified residue

173

1

Phosphoserine Ref.41

Modified residue

395

1

S-nitrosocysteine By similarity

Modified residue

398

1

S-nitrosocysteine By similarity

Modified residue

530

1

Phosphothreonine; by DYRK1A, DYRK3 and MAPK8 Ref.41 Ref.50 Ref.51

Modified residue

535

1

Phosphoserine Ref.51

Modified residue

544

1

Phosphothreonine Probable

Modified residue

545

1

Phosphoserine Probable

Modified residue

659

1

Phosphoserine; by CaMK2 By similarity

Modified residue

661

1

Phosphoserine; by CaMK2 Probable

Modified residue

719

1

Phosphothreonine Ref.41 Ref.42 Ref.51 Ref.79

Modified residue

747

1

Phosphoserine Ref.41

Natural variations

Alternative sequence

454 – 639

186

Missing in isoform 2.

VSP_042189

Natural variant

3

1

D → E. Ref.3
Corresponds to variant rs35671182 [ dbSNP | Ensembl ].

VAR_025148

Natural variant

484

1

V → D.
Corresponds to variant rs1063111 [ dbSNP | Ensembl ].

VAR_051976

Experimental info

Mutagenesis

27

1

S → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-47 and A-530. Ref.50

Mutagenesis

47

1

S → A: Blocks residue phosphorylation, restores deacetylation activity and inhibits DNA damage-induced apoptosis. Ref.50 Ref.72

Mutagenesis

47

1

S → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-530. Ref.50 Ref.72

Mutagenesis

233

1

K → R: Impairs in vitro methylation by SETD7; when associated with R-235, R-236 and R-238. Ref.77

Mutagenesis

235

1

K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-236 and R-238. Ref.77

Mutagenesis

236

1

K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-235 and R-238. Ref.77

Mutagenesis

238

1

K → R: Impairs in vitro methylation by SETD7; when associated with R-233, R-235a and R-236. Ref.77

Mutagenesis

363

1

H → Y: Loss of function. Reduces the interaction with KIAA1967/DBC1 and APEX1. Increases acetylation of APEX1. Ref.2 Ref.6 Ref.7 Ref.33 Ref.34 Ref.39 Ref.59

Mutagenesis

474

1

F → A: Abolishes phosphorylation at Ser-47, restores deacetylation activity and inhibits DNA damage-induced apoptosis. Ref.72

Mutagenesis

530

1

T → A: Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-47. Ref.41 Ref.50

Mutagenesis

530

1

T → A: Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-540. Ref.41 Ref.50

Mutagenesis

540

1

S → A: Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-530. Ref.41

Mutagenesis

659

1

S → A: Reduces in vitro phosphorylation by CaMK2; when associated with S-661. Greatly reduces in vivo phosphorylation; when associated with A-661. Ref.44

Mutagenesis

661

1

S → A: Reduces in vitro phosphorylation by CaMK2; when associated with S-659. Greatly reduces in vivo phosphorylation; when associated with A-659. Ref.44

Mutagenesis

684

1

S → A: No effect on phosphorylation (in vitro and in vivo). Ref.44

Sequence conflict

386 – 389

4

DIFN → ALFS in AAH12499. Ref.5

Secondary structure

1

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747

Helix Strand Turn

Details...

Helix

243 – 252

10

Beta strand

254 – 260

7

Helix

262 – 265

4

Turn

266 – 269

4

Beta strand

273 – 275

3

Helix

279 – 286

8

Beta strand

290 – 292

3

Helix

293 – 297

5

Helix

299 – 304

6

Helix

307 – 312

6

Helix

313 – 315

3

Beta strand

318 – 320

3

Helix

325 – 335

11

Beta strand

339 – 344

6

Helix

350 – 354

5

Beta strand

358 – 361

4

Beta strand

364 – 371

8

Turn

372 – 374

3

Beta strand

377 – 379

3

Helix

381 – 388

8

Beta strand

396 – 398

3

Beta strand

406 – 411

6

Helix

420 – 429

10

Turn

430 – 432

3

Beta strand

434 – 440

7

Helix

448 – 450

3

Helix

451 – 454

4

Beta strand

461 – 467

7

Beta strand

475 – 480

6

Helix

482 – 493

12

Helix

497 – 500

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 31, 2003. Version 2. Checksum: 2D3BEA6D73DA229F	FASTA	747	81,681
	10 20 30 40 50 60 MADEAALALQ PGGSPSAAGA DREAASSPAG EPLRKRPRRD GPGLERSPGE PGGAAPEREV 70 80 90 100 110 120 PAAARGCPGA AAAALWREAE AEAAAAGGEQ EAQATAAAGE GDNGPGLQGP SREPPLADNL 130 140 150 160 170 180 YDEDDDDEGE EEEEAAAAAI GYRDNLLFGD EIITNGFHSC ESDEEDRASH ASSSDWTPRP 190 200 210 220 230 240 RIGPYTFVQQ HLMIGTDPRT ILKDLLPETI PPPELDDMTL WQIVINILSE PPKRKKRKDI 250 260 270 280 290 300 NTIEDAVKLL QECKKIIVLT GAGVSVSCGI PDFRSRDGIY ARLAVDFPDL PDPQAMFDIE 310 320 330 340 350 360 YFRKDPRPFF KFAKEIYPGQ FQPSLCHKFI ALSDKEGKLL RNYTQNIDTL EQVAGIQRII 370 380 390 400 410 420 QCHGSFATAS CLICKYKVDC EAVRGDIFNQ VVPRCPRCPA DEPLAIMKPE IVFFGENLPE 430 440 450 460 470 480 QFHRAMKYDK DEVDLLIVIG SSLKVRPVAL IPSSIPHEVP QILINREPLP HLHFDVELLG 490 500 510 520 530 540 DCDVIINELC HRLGGEYAKL CCNPVKLSEI TEKPPRTQKE LAYLSELPPT PLHVSEDSSS 550 560 570 580 590 600 PERTSPPDSS VIVTLLDQAA KSNDDLDVSE SKGCMEEKPQ EVQTSRNVES IAEQMENPDL 610 620 630 640 650 660 KNVGSSTGEK NERTSVAGTV RKCWPNRVAK EQISRRLDGN QYLFLPPNRY IFHGAEVYSD 670 680 690 700 710 720 SEDDVLSSSS CGSNSDSGTC QSPSLEEPME DESEIEEFYN GLEDEPDVPE RAGGAGFGTD 730 740 GDDQEAINEA ISVKQEVTDM NYPSNKS
	Isoform 2 (delta-exon8) [UniParc]. Checksum: BFD54C8E408F23BD	FASTA	561	61,066
	10 20 30 40 50 60 MADEAALALQ PGGSPSAAGA DREAASSPAG EPLRKRPRRD GPGLERSPGE PGGAAPEREV 70 80 90 100 110 120 PAAARGCPGA AAAALWREAE AEAAAAGGEQ EAQATAAAGE GDNGPGLQGP SREPPLADNL 130 140 150 160 170 180 YDEDDDDEGE EEEEAAAAAI GYRDNLLFGD EIITNGFHSC ESDEEDRASH ASSSDWTPRP 190 200 210 220 230 240 RIGPYTFVQQ HLMIGTDPRT ILKDLLPETI PPPELDDMTL WQIVINILSE PPKRKKRKDI 250 260 270 280 290 300 NTIEDAVKLL QECKKIIVLT GAGVSVSCGI PDFRSRDGIY ARLAVDFPDL PDPQAMFDIE 310 320 330 340 350 360 YFRKDPRPFF KFAKEIYPGQ FQPSLCHKFI ALSDKEGKLL RNYTQNIDTL EQVAGIQRII 370 380 390 400 410 420 QCHGSFATAS CLICKYKVDC EAVRGDIFNQ VVPRCPRCPA DEPLAIMKPE IVFFGENLPE 430 440 450 460 470 480 QFHRAMKYDK DEVDLLIVIG SSLKVRPVAL IPSNQYLFLP PNRYIFHGAE VYSDSEDDVL 490 500 510 520 530 540 SSSSCGSNSD SGTCQSPSLE EPMEDESEIE EFYNGLEDEP DVPERAGGAG FGTDGDDQEA 550 560 INEAISVKQE VTDMNYPSNK S

References

	« Hide 'large scale' referencesShow 'large scale' references »
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[2]	"Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression." Takata T., Ishikawa F. Biochem. Biophys. Res. Commun. 301:250-257(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH HES1 AND HEY2, MUTAGENESIS OF HIS-363.
[3]	NIEHS SNPs program Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-3.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 124-747. Tissue: Prostate.
[6]	"hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase." Vaziri H., Dessain S.K., Ng Eaton E., Imai S., Frye R.A., Pandita T.K., Guarente L., Weinberg R.A. Cell 107:149-159(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF TP53, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-363.
[7]	"Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence." Langley E., Pearson M., Faretta M., Bauer U.-M., Frye R.A., Minucci S., Pelicci P.G., Kouzarides T. EMBO J. 21:2383-2396(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH PML, MUTAGENESIS OF HIS-363.
[8]	"Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1." Bitterman K.J., Anderson R.M., Cohen H.Y., Latorre-Esteves M., Sinclair D.A. J. Biol. Chem. 277:45099-45107(2002) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[9]	"Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan." Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S., Wood J.G., Zipkin R.E., Chung P., Kisielewski A., Zhang L.-L., Scherer B., Sinclair D.A. Nature 425:191-196(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[10]	"Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase." Frye R.A., Mayo M.W. EMBO J. 23:2369-2380(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Mammalian SIRT1 represses forkhead transcription factors." Motta M.C., Divecha N., Lemieux M., Kamel C., Chen D., Gu W., Bultsma Y., McBurney M., Guarente L. Cell 116:551-563(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF FOXO3, FUNCTION IN REGULATION OF FOXO3.
[12]	"FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)." van der Horst A., Tertoolen L.G.J., de Vries-Smits L.M.M., Frye R.A., Medema R.H., Burgering B.M.T. J. Biol. Chem. 279:28873-28879(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF MLLT7.
[13]	"Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin." Vaquero A., Scher M., Lee D., Erdjument-Bromage H., Tempst P., Reinberg D. Mol. Cell 16:93-105(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]	"Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase." Brunet A., Sweeney L.B., Sturgill J.F., Chua K.F., Greer P.L., Lin Y., Tran H., Ross S.E., Mostoslavsky R., Cohen H.Y., Hu L.S., Cheng H.L., Jedrychowski M.P., Gygi S.P., Sinclair D.A., Alt F.W., Greenberg M.E. Science 303:2011-2015(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF FOXO3, FUNCTION IN REGULATION OF FOXO3.
[15]	"Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase." Cohen H.Y., Miller C., Bitterman K.J., Wall N.R., Hekking B., Kessler B., Howitz K.T., Gorospe M., de Cabo R., Sinclair D.A. Science 305:390-392(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF XRCC6, INDUCTION BY CR.
[16]	"Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation." Yang Y., Hou H., Haller E.M., Nicosia S.V., Bai W. EMBO J. 24:1021-1032(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FHL2, FUNCTION IN DEACETYLATION OF FOXO1, FUNCTION IN REGULATION OF FOXO1.
[17]	"Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins." Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I. Mol. Biol. Cell 16:4623-4635(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[18]	"Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications." Zhao X., Sternsdorf T., Bolger T.A., Evans R.M., Yao T.-P. Mol. Cell. Biol. 25:8456-8464(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF MEF2D, INTERACTION WITH HDAC4.
[19]	"SIRT1 regulates HIV transcription via Tat deacetylation." Pagans S., Pedal A., North B.J., Kaehlcke K., Marshall B.L., Dorr A., Hetzer-Egger C., Henklein P., Frye R., McBurney M.W., Hruby H., Jung M., Verdin E., Ott M. PLoS Biol. 3:210-220(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV-1 TAT.
[20]	"Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation." Kuzmichev A., Margueron R., Vaquero A., Preissner T.S., Scher M., Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P.J., Reinberg D. Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION WITH THE PRC4 COMPLEX, INTERACTION WITH SUZ12.
[21]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage." Wang C., Chen L., Hou X., Li Z., Kabra N., Ma Y., Nemoto S., Finkel T., Gu W., Cress W.D., Chen J. Nat. Cell Biol. 8:1025-1031(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH E2F1.
[23]	"Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1." Wong S., Weber J.D. Biochem. J. 407:451-460(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF RB1.
[24]	"Sirt1 interacts with transducin-like enhancer of split-1 to inhibit nuclear factor kappaB-mediated transcription." Ghosh H.S., Spencer J.V., Ng B., McBurney M.W., Robbins P.D. Biochem. J. 408:105-111(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TLE1.
[25]	"SIRT1 promotes DNA repair activity and deacetylation of Ku70." Jeong J., Juhn K., Lee H., Kim S.H., Min B.H., Lee K.M., Cho M.H., Park G.H., Lee K.H. Exp. Mol. Med. 39:8-13(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF XRCC6, FUNCTION IN DNA REPAIR.
[26]	"SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity." Dai J.M., Wang Z.Y., Sun D.C., Lin R.X., Wang S.Q. J. Cell. Physiol. 210:161-166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF TP73, FUNCTION IN REGULATION OF TP73.
[27]	"Sirtuin 1 is required for antagonist-induced transcriptional repression of androgen-responsive genes by the androgen receptor." Dai Y., Ngo D., Forman L.W., Qin D.C., Jacob J., Faller D.V. Mol. Endocrinol. 21:1807-1821(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN AR-DEPENDENT REPRESSION.
[28]	"Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity." Kim E.-J., Kho J.-H., Kang M.-R., Um S.-J. Mol. Cell 28:277-290(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RPS19BP1.
[29]	Erratum Kim E.-J., Kho J.-H., Kang M.-R., Um S.-J. Mol. Cell 28:513-513(2007)
[30]	"SIRT1 deacetylates and positively regulates the nuclear receptor LXR." Li X., Zhang S., Blander G., Tse J.G., Krieger M., Guarente L. Mol. Cell 28:91-106(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF NR1H3 AND NR1H2.
[31]	"SIRT1 regulates the function of the Nijmegen breakage syndrome protein." Yuan Z., Zhang X., Sengupta N., Lane W.S., Seto E. Mol. Cell 27:149-162(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF NBN, FUNCTION IN DNA REPAIR.
[32]	"An acetylation/deacetylation-SUMOylation switch through a phylogenetically conserved psiKXEP motif in the tumor suppressor HIC1 regulates transcriptional repression activity." Stankovic-Valentin N., Deltour S., Seeler J., Pinte S., Vergoten G., Guerardel C., Dejean A., Leprince D. Mol. Cell. Biol. 27:2661-2675(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF HIC1.
[33]	"SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation." Vaquero A., Scher M., Erdjument-Bromage H., Tempst P., Serrano L., Reinberg D. Nature 450:440-444(2007) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF HIS-363.
[34]	"Epigenetic control of rDNA loci in response to intracellular energy status." Murayama A., Ohmori K., Fujimura A., Minami H., Yasuzawa-Tanaka K., Kuroda T., Oie S., Daitoku H., Okuwaki M., Nagata K., Fukamizu A., Kimura K., Shimizu T., Yanagisawa J. Cell 133:627-639(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE ENOSC COMPLEX, FUNCTION, MUTAGENESIS OF HIS-363.
[35]	"JNK2-dependent regulation of SIRT1 protein stability." Ford J., Ahmed S., Allison S., Jiang M., Milner J. Cell Cycle 7:3091-3097(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-27 AND SER-47.
[36]	"Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation." Kwon H.S., Brent M.M., Getachew R., Jayakumar P., Chen L.F., Schnolzer M., McBurney M.W., Marmorstein R., Greene W.C., Ott M. Cell Host Microbe 3:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV-1 TAT, FUNCTION IN T-CELL ACTIVATION.
[37]	"Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation." Li K., Casta A., Wang R., Lozada E., Fan W., Kane S., Ge Q., Gu W., Orren D., Luo J. J. Biol. Chem. 283:7590-7598(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF WRN, FUNCTION IN DNA DAMAGE.
[38]	"SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activation." Lan F., Cacicedo J.M., Ruderman N., Ido Y. J. Biol. Chem. 283:27628-27635(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF STK11.
[39]	"DBC1 is a negative regulator of SIRT1." Kim J.-E., Chen J., Lou Z. Nature 451:583-586(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KIAA1967, ENZYME REGULATION, MUTAGENESIS OF HIS-363, MASS SPECTROMETRY.
[40]	"Negative regulation of the deacetylase SIRT1 by DBC1." Zhao W., Kruse J.-P., Tang Y., Jung S.Y., Qin J., Gu W. Nature 451:587-590(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KIAA1967, ENZYME REGULATION.
[41]	"Phosphorylation regulates SIRT1 function." Sasaki T., Maier B., Koclega K.D., Chruszcz M., Gluba W., Stukenberg P.T., Minor W., Scrable H. PLoS ONE 3:E4020-E4020(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-14; SER-26; SER-27; SER-47; SER-159; SER-162; SER-172; SER-173; THR-530; THR-544; SER-545; THR-719 AND SER-747, MUTAGENESIS OF THR-530 AND SER-540.
[42]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[43]	"A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy." Lee I.H., Cao L., Mostoslavsky R., Lombard D.B., Liu J., Bruns N.E., Tsokos M., Alt F.W., Finkel T. Proc. Natl. Acad. Sci. U.S.A. 105:3374-3379(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF ATG5; ATG7 AND MAP1LC3B, FUNCTION IN AUTOPHAGY.
[44]	"Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2." Zschoernig B., Mahlknecht U. Biochem. Biophys. Res. Commun. 381:372-377(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-659 AND SER-661, MUTAGENESIS OF SER-659; SER-661 AND SER-684.
[45]	"Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogues and 32P-NAD." Du J., Jiang H., Lin H. Biochemistry 48:2878-2890(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[46]	"Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation." Purushotham A., Schug T.T., Xu Q., Surapureddi S., Guo X., Li X. Cell Metab. 9:327-338(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPARA.
[47]	"Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear receptor estrogen receptor-related receptor gamma transactivation." Xie Y.B., Park J.H., Kim D.K., Hwang J.H., Oh S., Park S.B., Shong M., Lee I.K., Choi H.S. J. Biol. Chem. 284:28762-28774(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CREBZF.
[48]	"A c-Myc-SIRT1 feedback loop regulates cell growth and transformation." Yuan J., Minter-Dykhouse K., Lou Z. J. Cell Biol. 185:203-211(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF MYC, FUNCTION IN REGULATION OF MYC.
[49]	"hSirT1-dependent regulation of the PCAF-E2F1-p73 apoptotic pathway in response to DNA damage." Pediconi N., Guerrieri F., Vossio S., Bruno T., Belloni L., Schinzari V., Scisciani C., Fanciulli M., Levrero M. Mol. Cell. Biol. 29:1989-1998(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF PCAF, FUNCTION IN DNA REPAIR.
[50]	"JNK1 phosphorylates SIRT1 and promotes its enzymatic activity." Nasrin N., Kaushik V.K., Fortier E., Wall D., Pearson K.J., de Cabo R., Bordone L. PLoS ONE 4:E8414-E8414(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-27; SER-47 AND THR-530, MUTAGENESIS OF SER-27; SER-47 AND THR-530, SUBCELLULAR LOCATION.
[51]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-530; SER-535 AND THR-719, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[52]	"SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells." Zu Y., Liu L., Lee M.Y., Xu C., Liang Y., Man R.Y., Vanhoutte P.M., Wang Y. Circ. Res. 106:1384-1393(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN REGULATION OF STK11.
[53]	"Role of SIRT1 in homologous recombination." Uhl M., Csernok A., Aydin S., Kreienberg R., Wiesmuller L., Gatz S.A. DNA Repair 9:383-393(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DNA REPAIR HOMOLOGOUS RECOMBINATION.
[54]	"SIRT1 suppresses activator protein-1 transcriptional activity and cyclooxygenase-2 expression in macrophages." Zhang R., Chen H.Z., Liu J.J., Jia Y.Y., Zhang Z.Q., Yang R.F., Zhang Y., Xu J., Wei Y.S., Liu D.P., Liang C.C. J. Biol. Chem. 285:7097-7110(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FOS AND JUN.
[55]	"SIRT1 regulates autoacetylation and histone acetyltransferase activity of TIP60." Wang J., Chen J. J. Biol. Chem. 285:11458-11464(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF KAT5.
[56]	"SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism." Ponugoti B., Kim D.H., Xiao Z., Smith Z., Miao J., Zang M., Wu S.Y., Chiang C.M., Veenstra T.D., Kemper J.K. J. Biol. Chem. 285:33959-33970(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF SREBF1.
[57]	"Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha." Lim J.H., Lee Y.M., Chun Y.S., Chen J., Kim J.E., Park J.W. Mol. Cell 38:864-878(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF HIF1A, FUNCTION IN REGULATION OF HIF1A.
[58]	"SIRT1 regulates UV-induced DNA repair through deacetylating XPA." Fan W., Luo J. Mol. Cell 39:247-258(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF XPA.
[59]	"SIRT1 deacetylates APE1 and regulates cellular base excision repair." Yamamori T., DeRicco J., Naqvi A., Hoffman T.A., Mattagajasingh I., Kasuno K., Jung S.B., Kim C.S., Irani K. Nucleic Acids Res. 38:832-845(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF APEX1, FUNCTION IN DNA REPAIR, MUTAGENESIS OF HIS-363, INDUCTION, SUBCELLULAR LOCATION.
[60]	"Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation." Chanda D., Xie Y.B., Choi H.S. Nucleic Acids Res. 38:4607-4619(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NR0B2.
[61]	"SIRT1 negatively regulates the mammalian target of rapamycin." Ghosh H.S., McBurney M., Robbins P.D. PLoS ONE 5:E9199-E9199(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TSC2.
[62]	"SIRT1 undergoes alternative splicing in a novel auto-regulatory loop with p53." Lynch C.J., Shah Z.H., Allison S.J., Ahmed S.U., Ford J., Warnock L.J., Li H., Serrano M., Milner J. PLoS ONE 5:E13502-E13502(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION (ISOFORM 2), INDUCTION (ISOFORM 2), INTERACTION WITH TP53 AND RPS19BP1.
[63]	"Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C." Ming M., Shea C.R., Guo X., Li X., Soltani K., Han W., He Y.Y. Proc. Natl. Acad. Sci. U.S.A. 107:22623-22628(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DNA REPAIR, SUPPRESSION OF XPC.
[64]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-47, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE. Tissue: Cervix carcinoma.
[65]	"SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2." Hirschey M.D., Shimazu T., Capra J.A., Pollard K.S., Verdin E. Aging (Albany NY) 3:635-642(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF HMGCS1.
[66]	"Tumor necrosis factor alpha-mediated cleavage and inactivation of SirT1 in human osteoarthritic chondrocytes." Dvir-Ginzberg M., Gagarina V., Lee E.J., Booth R., Gabay O., Hall D.J. Arthritis Rheum. 63:2363-2373(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PROCESSING.
[67]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[68]	"EVI1 up-regulates the stress responsive gene SIRT1 which triggers deacetylation and degradation of EVI1." Pradhan A.K., Kuila N., Singh S., Chakraborty S. Biochim. Biophys. Acta 1809:269-275(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF MECOM.
[69]	"Energy sensing factors PGC-1alpha and SIRT1 modulate PXR expression and function." Buler M., Aatsinki S.M., Skoumal R., Hakkola J. Biochem. Pharmacol. 82:2008-2015(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NR1I2.
[70]	"Sirt1 deacetylates c-Myc and promotes c-Myc/Max association." Mao B., Zhao G., Lv X., Chen H.Z., Xue Z., Yang B., Liu D.P., Liang C.C. Int. J. Biochem. Cell Biol. 43:1573-1581(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF MYC, FUNCTION IN REGULATION OF MYC.
[71]	"MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation." Yuan F., Xie Q., Wu J., Bai Y., Mao B., Dong Y., Bi W., Ji G., Tao W., Wang Y., Yuan Z. J. Biol. Chem. 286:6940-6945(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY STK4/MST1.
[72]	"Cancer cell survival following DNA damage-mediated premature senescence is regulated by mammalian target of rapamycin (mTOR)-dependent Inhibition of sirtuin 1." Back J.H., Rezvani H.R., Zhu Y., Guyonnet-Duperat V., Athar M., Ratner D., Kim A.L. J. Biol. Chem. 286:19100-19108(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS, PHOSPHORYLATION AT SER-47, MUTAGENESIS OF SER-47 AND PHE-474.
[73]	"Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and ensures genome protection." Bosch-Presegue L., Raurell-Vila H., Marazuela-Duque A., Kane-Goldsmith N., Valle A., Oliver J., Serrano L., Vaquero A. Mol. Cell 42:210-223(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN STABILIZATION OF SUV39H1.
[74]	"SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities." Peng L., Yuan Z., Ling H., Fukasawa K., Robertson K., Olashaw N., Koomen J., Chen J., Lane W.S., Seto E. Mol. Cell. Biol. 31:4720-4734(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF DNMT1, FUNCTION IN REGULATION OF DNMT1.
[75]	"SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability." Marshall G.M., Liu P.Y., Gherardi S., Scarlett C.J., Bedalov A., Xu N., Iraci N., Valli E., Ling D., Thomas W., van Bekkum M., Sekyere E., Jankowski K., Trahair T., Mackenzie K.L., Haber M., Norris M.D., Biankin A.V., Perini G., Liu T. PLoS Genet. 7:E1002135-E1002135(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN REGULATION OF MYCN, INTERACTION WITH MYCN.
[76]	"The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO." Rizki G., Iwata T.N., Li J., Riedel C.G., Picard C.L., Jan M., Murphy C.T., Lee S.S. PLoS Genet. 7:E1002235-E1002235(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCFC1.
[77]	"Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1)." Liu X., Wang D., Zhao Y., Tu B., Zheng Z., Wang L., Wang H., Gu W., Roeder R.G., Zhu W.G. Proc. Natl. Acad. Sci. U.S.A. 108:1925-1930(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SETD7, MUTAGENESIS OF LYS-233; LYS-235; LYS-236 AND LYS-238.
[78]	"The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy." Sundaresan N.R., Pillai V.B., Wolfgeher D., Samant S., Vasudevan P., Parekh V., Raghuraman H., Cunningham J.M., Gupta M., Gupta M.P. Sci. Signal. 4:RA46-RA46(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF AKT1, FUNCTION IN REGULATION OF AKT1.
[79]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-47 AND THR-719, MASS SPECTROMETRY.
[80]	"75kDa SirT1 blocks TNFalpha-mediated apoptosis in human osteoarthritic chondrocytes." Oppenheimer H., Gabay O., Meir H., Haze A., Kandel L., Liebergall M., Gagarina V., Lee E.J., Dvir-Ginzberg M. Arthritis Rheum. 64:718-728(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (SIRTT1 75 KDA FRAGMENT), SUBCELLULAR LOCATION (75SIRT1).
[81]	"SIRT1 links CIITA deacetylation to MHC II activation." Wu X., Kong X., Chen D., Li H., Zhao Y., Xia M., Fang M., Li P., Fang F., Sun L., Tian W., Xu H., Yang Y., Qi X., Gao Y., Sha J., Chen Q., Xu Y. Nucleic Acids Res. 39:9549-9558(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF CIITA.
[82]	"PML regulates PER2 nuclear localization and circadian function." Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A., Rea M.A., Zhao Z., Lee C.C., Chang K.S. EMBO J. 31:1427-1439(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF PML.
[83]	"Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation." Wang F., Chan C.H., Chen K., Guan X., Lin H.K., Tong Q. Oncogene 31:1546-1557(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF FOXO3, FUNCTION IN REGULATION OF FOXO3.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF083106 mRNA. Translation: AAD40849.2.
AF235040 mRNA. Translation: AAG38486.1.
DQ278604 Genomic DNA. Translation: ABB72675.1.
AL133551 Genomic DNA. Translation: CAI16036.1.
BC012499 mRNA. Translation: AAH12499.1. Different initiation.

IPI

IPI00016802.

RefSeq

NP_001135970.1. NM_001142498.1.
NP_036370.2. NM_012238.4.

UniGene

Hs.369779.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4I5I	X-ray	2.50	A/B	241-516	[»]

ProteinModelPortal

Q96EB6.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29757N.

IntAct

Q96EB6. 109 interactions.

STRING

9606.ENSP00000212015.

PTM databases

PhosphoSite

Q96EB6.

Polymorphism databases

DMDM

38258633.

Proteomic databases

PaxDb

Q96EB6.

PeptideAtlas

Q96EB6.

PRIDE

Q96EB6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000212015; ENSP00000212015; ENSG00000096717.

GeneID

23411.

KEGG

hsa:23411.

UCSC

uc001jnd.3. human.

Organism-specific databases

CTD

23411.

GeneCards

GC10P069644.

HGNC

HGNC:14929. SIRT1.

HPA

CAB003855.
HPA006295.

MIM

604479. gene.

neXtProt

NX_Q96EB6.

PharmGKB

PA37935.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0846.

HOGENOM

HOG000038016.

HOVERGEN

HBG054192.

InParanoid

Q96EB6.

KO

K11411.

OMA

DQEAINE.

OrthoDB

EOG4RNB8G.

PhylomeDB

Q96EB6.

Enzyme and pathway databases

Pathway_Interaction_DB

foxopathway. FoxO family signaling.
ar_tf_pathway. Regulation of Androgen receptor activity.
hdac_classi_pathway. Signaling events mediated by HDAC Class I.
hdac_classiii_pathway. Signaling events mediated by HDAC Class III.

Gene expression databases

ArrayExpress

Q96EB6.

Bgee

Q96EB6.

CleanEx

HS_SIRT1.

Genevestigator

Q96EB6.

GermOnline

ENSG00000096717. Homo sapiens.

Family and domain databases

Gene3D

3.30.1600.10. 2 hits.

InterPro

IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]

PANTHER

PTHR11085. PTHR11085. 1 hit.

Pfam

PF02146. SIR2. 1 hit.
[Graphical view]

PROSITE

PS50305. SIRTUIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q96EB6.

ChEMBL

CHEMBL4506.

GenomeRNAi

23411.

NextBio

45603.

SOURCE

Search...

Entry information

Entry name

SIR1_HUMAN

Accession

Primary (citable) accession number: Q96EB6
Secondary accession number(s): Q2XNF6 , Q5JVQ0, Q9GZR9, Q9Y6F0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2003
Last sequence update:	October 31, 2003
Last modified:	May 1, 2013
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.