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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

SIRT1 Gene

protein-coding GIFtS: 66
GCID: GC10P069644

sirtuin 1

(Previous names: sirtuin (silent mating type information regulation 2, S....)

Explore 58 diseases affiliated with
SIRT1 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Sirtuin 1¹ ²		Sirtuin (Silent Mating Type Information Regulation 2, S. Cerevisiae, Homolog) 1¹
SIR2L1¹ ² ³ ⁵		SIR2alpha²
Regulatory Protein SIR2 Homolog 1² ³		NAD-Dependent Deacetylase Sirtuin-1²
HSIR2¹		NAD-Dependent Protein Deacetylase Sirtuin-1²
HSIRT1¹		Sir2-Like 1²
SIR2-Like Protein 1² ³		Sirtuin Type 1²
Sirtuin (Silent Mating Type Information Regulation 2 Homolog) 1 (S. Cerevisiae)¹		EC 3.5.1.-³

External Ids:	HGNC: 14929¹	Entrez Gene: 23411²	Ensembl: ENSG00000096717⁷	OMIM: 604479⁵	UniProtKB: Q96EB6³

Export aliases for SIRT1 gene to outside databases

Previous GC identifers: GC10P068455 GC10P068731 GC10P069536 GC10P068989 GC10P069314 GC10P063643

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for SIRT1:

This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the

sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human

sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing

and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory

proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the

sirtuin family. Alternative splicing results in multiple transcript variants. (provided by RefSeq, Dec 2008)

UniProtKB/Swiss-Prot: SIR1_HUMAN, Q96EB6

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

Function: 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

summary for SIRT1:

Silent information regulator (Sir2)-like family deacetylases (also known as sirtuins) are a group of enzymes

closely related to histone deacetylases. These enzymes can be found in the cytoplasm, mitochondria or

nucleus and are ubiquitously expressed. Sir2-like family deacetylases catalyze the removal of acetyl groups

from lysine residues in histones and non-histone proteins, which is coupled to NAD+ hydrolysis. In general,

sirtuins do not act autonomously but as components of large multiprotein complexes, such as pRb-E2F and

mSin3A, that mediate important transcription regulatory pathways. Sirtuins have a role in regulation of

transcription and apoptosis leading to substantial interest in inhibitors of these enzymes as possible

antineoplastic agents. In addition, Sir2-like family deacteylases are involved in the normal ageing process

through their role in resistance to cellular stress.

Gene Wiki entry for SIRT1 (Sirtuin 1)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000010.10 NC_018921.1 NT_030059.13

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the SIRT1 gene promoter:
N-Myc MyoD C/EBPalpha
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): SIRT1 promoter sequence

Search SABiosciences Chromatin IP Primers for SIRT1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat SIRT1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 10q21.3 Ensembl cytogenetic band: 10q21.3 HGNC cytogenetic band: 10q21

SIRT1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SIRT1 gene location

GeneLoc information about chromosome 10 GeneLoc Exon Structure

GeneLoc location for GC10P069644: view genomic region (about GC identifiers)

Start:	69,644,427 bp from pter	End:	69,678,147 bp from pter
Size:	33,721 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: SIR1_HUMAN, Q96EB6 (See protein sequence)

Recommended Name: NAD-dependent protein deacetylase sirtuin-1

Size: 747 amino acids; 81681 Da

Cofactor: Binds 1 zinc ion per subunit (By similarity)

Subunit: 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

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

Subcellular location: SirtT1 75 kDa fragment: Cytoplasm. Mitochondrion

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

Miscellaneous: Calf histone H1 is used as substrate in the in vitro deacetylation assay (PubMed:15469825). As, in vivo,

interaction occurs between SIRT1 with HIST1H1E, deacetylation has been validated only for HIST1H1E

Miscellaneous: The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the

deacetylase activity and may not be physiologically relevant (PubMed:19220062)

Sequence caution: Sequence=AAH12499.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

1 PDB 3D structure from and Proteopedia for SIRT1:

4I5I (3D)

Secondary accessions: Q2XNF6 Q5JVQ0 Q9GZR9 Q9Y6F0

Alternative splicing: 2 isoforms: Q96EB6-1 Q96EB6-2

Explore the universe of human proteins at neXtProt for SIRT1: NX_Q96EB6

Post-translational modifications:

Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase

activity toward p53/TP53¹

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-545¹

Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa

fragment (75SirT1)¹

S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity (By similarity)¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q96EB6

SIRT1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001135970.1 NP_036370.2

ENSEMBL proteins:

ENSP00000212015 ENSP00000384508 ENSP00000384063 ENSP00000409208

Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant SIRT1 Protein
	R&D Systems Recombinant & Natural Proteins for SIRT1 (Sirtuin 1/SIRT1)
	Enzo Life Sciences proteins for SIRT1
	OriGene Purified Protein: SIRT1 OriGene Protein Over-expression Lysate: SIRT1 OriGene Custom Protein Services for SIRT1
	GenScript Custom Purified and Recombinant Proteins Services for SIRT1
	Novus Biologicals SIRT1 Proteins Novus Biologicals SIRT1 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for SIRT1

Gene Ontology (GO): 5/13 cellular component terms (GO ID links to tree view) (see all 13): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000790	nuclear chromatin	IDA	17505061
GO:0005634	nucleus	IDA	--
GO:0005635	nuclear envelope	IDA	15469825
GO:0005637	nuclear inner membrane	IDA	15469825
GO:0005654	nucleoplasm	IDA	16079181

SIRT1 for ontologies About GeneDecksing

SIRT1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of SIRT1
	R&D Systems Antibodies for SIRT1 (Sirtuin 1/SIRT1)
	OriGene Antibodies (see all 4): SIRT1 OriGene Custom Antibody Services for SIRT1
	GenScript Custom Superior Antibodies Services for SIRT1
	Novus Biologicals SIRT1 Antibodies
	Abcam antibodies for SIRT1
	Uscn Antibodies for SIRT1
	ThermoFisher Antibody for SIRT1

Assay Products for SIRT1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for SIRT1
	Enzo Life Sciences assays for SIRT1
	Uscn ELISAs and CLIAs for SIRT1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

SIRT1 for domains About GeneDecksing

3 InterPro domains/families:

IPR003000 Sirtuin

IPR026590 Ssirtuin_cat_dom

IPR026591 Sirtuin_cat_small_dom

Graphical View of Domain Structure for InterPro Entry Q96EB6

ProtoNet protein and cluster: Q96EB6

1 Blocks protein family: IPB003000 Silent information regulator protein Sir2

UniProtKB/Swiss-Prot: SIR1_HUMAN, Q96EB6

Similarity: Belongs to the sirtuin family. Class I subfamily

Similarity: Contains 1 deacetylase sirtuin-type domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: