Sirt1 - sirtuin 1 Gene

Also Known as Sir2; Sir2a; SIR2L1; Sir2alpha

Species: Mus musculus

Gene Type: protein coding

Gene ID: 93759

About Sirt1

Chromosome 10: 63,154,784-63,217,483 reverse strand.GRCm39:CM001003.3

This gene has 7 transcripts (splice variants), 156 orthologues, 6 paralogues and is associated with 145 phenotypes. Ubiquitous expression in CNS E11.5 (RPKM 7.7), limb E14.5 (RPKM 5.8) and 26 other tissues.

Summary

This gene encodes a member of the Sirtuin family of proteins, characterized by their deacetylase activity and proposed role in longevity. The encoded protein regulates gene expression in a wide range of cell and tissue types through its NAD+-dependent deacetylation of histones, transcription factors and transcriptional coactivators. Brain-specific overexpression of this gene has been shown to result in increased median lifespan. Viability of homozygous knockout mice for this gene varies with strain background. Homozygous knockout mice of strains that do not exhibit embryonic lethality are sterile and have a reduced lifespan. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

Sirt1 Products (2)

mRNA	Protein	Name
NM_001159589.2	NP_001153061.1	NAD-dependent protein deacetylase sirtuin-1 isoform 2
NM_019812.3	NP_062786.1	NAD-dependent protein deacetylase sirtuin-1 isoform 1

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables NAD-dependent histone H3K9 deacetylase activity	IDA IDA: Inferred from direct assay	20972425	MGI
enables NAD-dependent histone deacetylase activity	IDA IDA: Inferred from direct assay	10693811	MGI
enables NAD-dependent protein lysine deacetylase activity	EXP EXP: Inferred from Experiment	11250901	MGI
enables NAD-dependent protein lysine deacetylase activity	IDA IDA: Inferred from direct assay	11672523	MGI
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA IDA: Inferred from direct assay	19299583	MGI
enables deacetylase activity	IMP IMP: Inferred from mutant phenotype	18004385	MGI
enables enzyme binding	IPI IPI: Inferred from physical interaction	19578370	MGI
enables p53 binding	IPI IPI: Inferred from physical interaction	11672522	MGI
enables promoter-specific chromatin binding	IDA IDA: Inferred from direct assay	22514318	MGI
enables protein binding	IPI IPI: Inferred from physical interaction	11672523	MGI
enables protein domain specific binding	IPI IPI: Inferred from physical interaction	15175761	MGI
enables protein lysine deacetylase activity	IDA IDA: Inferred from direct assay	19578370	MGI
enables protein lysine deacetylase activity	IMP IMP: Inferred from mutant phenotype	17521387	MGI
enables protein-propionyllysine depropionylase activity	IMP IMP: Inferred from mutant phenotype	30026585	MGI
enables transcription coactivator activity	IDA IDA: Inferred from direct assay	25526086	MGI
enables transcription corepressor activity	IMP IMP: Inferred from mutant phenotype	15175761	MGI

Biological Process GO Annotation	Evidence	References	Source
involved in DNA synthesis involved in DNA repair	IMP IMP: Inferred from mutant phenotype	17612497	MGI
involved in angiogenesis	IMP IMP: Inferred from mutant phenotype	22315447	MGI
acts upstream of or within behavioral response to starvation	IMP IMP: Inferred from mutant phenotype	20668205	MGI
involved in cellular response to ionizing radiation	IMP IMP: Inferred from mutant phenotype	17612497	MGI
acts upstream of or within cellular response to leukemia inhibitory factor	IEP IEP: Inferred from expression pattern	20439489	MGI
involved in cellular response to starvation	IMP IMP: Inferred from mutant phenotype	15175761	MGI
involved in cholesterol homeostasis	IMP IMP: Inferred from mutant phenotype	17936707	MGI
involved in circadian regulation of gene expression	IMP IMP: Inferred from mutant phenotype	18662546	MGI
involved in circadian rhythm	IEP IEP: Inferred from expression pattern	18662546	MGI
involved in fatty acid homeostasis	IMP IMP: Inferred from mutant phenotype	17347648	MGI
acts upstream of or within heterochromatin formation	IGI IGI: Inferred from genetic interaction	23160044	MGI
involved in intracellular glucose homeostasis	IMP IMP: Inferred from mutant phenotype	15744310	MGI
involved in intracellular triglyceride homeostasis	IMP IMP: Inferred from mutant phenotype	17936707	MGI
involved in intrinsic apoptotic signaling pathway in response to DNA damage	IDA IDA: Inferred from direct assay	16269335	MGI
involved in leptin-mediated signaling pathway	IMP IMP: Inferred from mutant phenotype	20620997	MGI
involved in macrophage differentiation	IMP IMP: Inferred from mutant phenotype	22315447	MGI
involved in negative regulation of DNA-binding transcription factor activity	IMP IMP: Inferred from mutant phenotype	20955178	MGI
acts upstream of or within negative regulation of DNA-templated transcription	IDA IDA: Inferred from direct assay	15381699	MGI
involved in negative regulation of TOR signaling	IMP IMP: Inferred from mutant phenotype	20169165	MGI
involved in negative regulation of fat cell differentiation	IMP IMP: Inferred from mutant phenotype	15175761	MGI
involved in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IMP IMP: Inferred from mutant phenotype	11672522	MGI
acts upstream of or within negative regulation of neuron apoptotic process	IGI IGI: Inferred from genetic interaction	22956852	MGI
involved in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP IMP: Inferred from mutant phenotype	21149730	MGI
involved in negative regulation of phosphorylation	IMP IMP: Inferred from mutant phenotype	17612497	MGI
involved in negative regulation of prostaglandin biosynthetic process	IMP IMP: Inferred from mutant phenotype	20042607	MGI
involved in negative regulation of transcription by RNA polymerase II	IDA IDA: Inferred from direct assay	19470756	MGI
involved in negative regulation of transcription by RNA polymerase II	IMP IMP: Inferred from mutant phenotype	20955178	MGI
involved in negative regulation of transforming growth factor beta receptor signaling pathway	IDA IDA: Inferred from direct assay	17098745	MGI
acts upstream of or within ovulation from ovarian follicle	IMP IMP: Inferred from mutant phenotype	12482959	MGI
involved in positive regulation of adipose tissue development	IMP IMP: Inferred from mutant phenotype	22315447	MGI
involved in positive regulation of apoptotic process	IMP IMP: Inferred from mutant phenotype	20167603	MGI
involved in positive regulation of cAMP-dependent protein kinase activity	IDA IDA: Inferred from direct assay	18687677	MGI
involved in positive regulation of cholesterol efflux	IMP IMP: Inferred from mutant phenotype	17936707	MGI
involved in positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IMP IMP: Inferred from mutant phenotype	20955178	MGI
involved in positive regulation of gluconeogenesis	IMP IMP: Inferred from mutant phenotype	26168293	MGI
involved in positive regulation of macroautophagy	IDA IDA: Inferred from direct assay	18296641	MGI
involved in positive regulation of macrophage apoptotic process	IMP IMP: Inferred from mutant phenotype	20042607	MGI
involved in positive regulation of macrophage cytokine production	IMP IMP: Inferred from mutant phenotype	22315447	MGI
involved in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP IMP: Inferred from mutant phenotype	20620997	MGI
involved in positive regulation of protein phosphorylation	IMP IMP: Inferred from mutant phenotype	17901049	MGI
involved in positive regulation of smooth muscle cell differentiation	IMP IMP: Inferred from mutant phenotype	25526086	MGI
involved in positive regulation of transcription by RNA polymerase II	IDA IDA: Inferred from direct assay	15220471	MGI
acts upstream of or within protein deacetylation	IDA IDA: Inferred from direct assay	22514318	MGI
involved in protein deacetylation	IDA IDA: Inferred from direct assay	11672523	MGI
involved in protein deacetylation	IMP IMP: Inferred from mutant phenotype	17521387	MGI
involved in protein depropionylation	IDA IDA: Inferred from direct assay	30026585	MGI
involved in protein destabilization	IDA IDA: Inferred from direct assay	17936707	MGI
involved in pyrimidine dimer repair by nucleotide-excision repair	IMP IMP: Inferred from mutant phenotype	21149730	MGI
involved in regulation of bile acid biosynthetic process	IMP IMP: Inferred from mutant phenotype	20375098	MGI
involved in regulation of brown fat cell differentiation	IMP IMP: Inferred from mutant phenotype	20620997	MGI
involved in regulation of glucose metabolic process	IMP IMP: Inferred from mutant phenotype	17347648	MGI
involved in regulation of lipid storage	IMP IMP: Inferred from mutant phenotype	22315447	MGI
involved in regulation of peroxisome proliferator activated receptor signaling pathway	IMP IMP: Inferred from mutant phenotype	15175761	MGI
involved in regulation of smooth muscle cell apoptotic process	IDA IDA: Inferred from direct assay	17098745	MGI
involved in response to insulin	IDA IDA: Inferred from direct assay	17901049	MGI
involved in response to leptin	IMP IMP: Inferred from mutant phenotype	20620997	MGI
acts upstream of or within spermatogenesis	IMP IMP: Inferred from mutant phenotype	12482959	MGI
involved in triglyceride mobilization	IMP IMP: Inferred from mutant phenotype	15175761	MGI
involved in white fat cell differentiation	IMP IMP: Inferred from mutant phenotype	15175761	MGI

Cellular Component GO Annotation	Evidence	References	Source
located in chromatin	IDA IDA: Inferred from direct assay	16269335	MGI
located in cytoplasm	IDA IDA: Inferred from direct assay	17197703	MGI
located in heterochromatin	IDA IDA: Inferred from direct assay	18004385	MGI
located in mitochondrion	IDA IDA: Inferred from direct assay	26767982	MGI
located in nucleus	IDA IDA: Inferred from direct assay	12482959	MGI
part of protein-containing complex	IDA IDA: Inferred from direct assay	22514318	MGI

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

Sirt1 Protein Structure

SIRT1

0
200
400
600
737 a.a.

Protein Preferred Names	Protein Names
NAD-dependent protein deacetylase sirtuin-1	NAD-dependent protein deacylase sirtuin-1 SIR2-like protein 1 regulatory protein SIR2 homolog 1 sirtuin 1 ((silent mating type information regulation 2, homolog) 1

Sirt1 Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	Sirt1	Q923E4	Ppargc1a	Mus musculus	O70343	Anti Bait CoIP	15744310
Intra	Sirt1	Q923E4	Ppargc1a	Mus musculus	O70343	Anti Tag CoIP	15716268
Intra	Sirt1	Q923E4	Ppargc1a	Mus musculus	O70343	Deacetylase Assay	15744310
Intra	Sirt1	Q923E4	Ncor1	Mus musculus	Q60974	Anti Bait CoIP	18829436
Intra	Sirt1	Q923E4	Ncor1	Mus musculus	Q60974	Pull Down	18829436
Cross	Sirt1	Q923E4	TP53	Homo sapiens	P04637	Pull Down	19680552
Cross	Sirt1	Q923E4	TP53	Homo sapiens	P04637	Deacetylase Assay	20167603
Cross	Sirt1	Q923E4	TP53	Homo sapiens	P04637	Deacetylase Assay	11672523
Cross	Sirt1	Q923E4	TP53	Homo sapiens	P04637	Deacetylase Assay	19680552
Intra	Sirt1	Q923E4	Nr0b2	Mus musculus	Q62227	Anti Bait CoIP	20375098
Cross	Sirt1	Q923E4	RB1	Homo sapiens	P06400	Anti Tag CoIP	17620057
Cross	Sirt1	Q923E4	RB1	Homo sapiens	P06400	Anti Bait CoIP	17620057
Intra	Sirt1	Q923E4	Hic1	Mus musculus	Q9R1Y5	Anti Bait CoIP	16269335
Intra	Sirt1	Q923E4	Dyrk3	Mus musculus	Q922Y0	Pull Down	20167603
Intra	Sirt1	Q923E4	Dyrk3	Mus musculus	Q922Y0	Anti Bait CoIP	20167603
Intra	Sirt1	Q923E4	Dyrk3	Mus musculus	Q922Y0	Y2H	20167603
Intra	Sirt1	Q923E4	Pparg	Mus musculus	P37238	Anti Bait CoIP	15175761
Intra	Sirt1	Q923E4	Hnf1a	Mus musculus	P22361	Anti Bait CoIP	21176092
Intra	Sirt1	Q923E4	Hnf1a	Mus musculus	P22361	Anti Tag CoIP	21176092
Intra	Sirt1	Q923E4	Hnf1a	Mus musculus	P22361	Pull Down	21176092
Intra	Sirt1	Q923E4	Smad7	Mus musculus	O35253	Anti Tag CoIP	17098745
Intra	Sirt1	Q923E4	Clock	Mus musculus	O08785	Anti Bait CoIP	18662546
Intra	Sirt1	Q923E4	Clock	Mus musculus	O08785	Pull Down	18662547
Intra	Sirt1	Q923E4	Clock	Mus musculus	O08785	Anti Tag CoIP	18662547
Intra	Sirt1	Q923E4	Clock	Mus musculus	O08785	Anti Bait CoIP	18662547
Intra	Sirt1	Q923E4	Clock	Mus musculus	O08785	Confocal	18662546
Intra	Sirt1	Q923E4	Dyrk1a	Mus musculus	Q61214	Anti Bait CoIP	20167603
Intra	Sirt1	Q923E4	Dyrk1a	Mus musculus	Q61214	Protein Kinase Assay	20167603
Intra	Sirt1	Q923E4	Dyrk1a	Mus musculus	Q61214	IF	20167603
Cross	Sirt1	Q923E4	RBL1	Homo sapiens	P28749	Anti Bait CoIP	17620057
Cross	Sirt1	Q923E4	RBL1	Homo sapiens	P28749	Anti Tag CoIP	17620057
Cross	Sirt1	Q923E4	RBL2	Homo sapiens	Q08999	Anti Bait CoIP	17620057

Cross: Cross-species interaction Intra: Intraspecies interaction

Related Agents

Approval
Clinical Phase
Pre-clinical Phase

Approval

Bioactive Molecules (4)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-B0150	Nicotinamide	Inhibitor	99.98%	Unkown
HY-B0879A	Suramin sodium salt	Inhibitor	99.98%	Yes
HY-B0879	Suramin	Inhibitor	/	Unkown
HY-B0150A	Nicotinamide hydrochloride	Inhibitor	/	Unkown

Clinical Phase

Bioactive Molecules (5)

Cat. No.	Product Name	Effect	Purity	Phase
HY-123033A	Nicotinamide riboside chloride	Activator	99.90%	Phase 4
HY-123033C	Nicotinamide riboside malate	Activator	98.04%	Phase 4
HY-123033B	Nicotinamide riboside tartrate	Activator	98.07%	Phase 4
HY-123033	Nicotinamide riboside	Activator	/	Phase 4
HY-15262	SRT 2104	Activator	99.27%	Phase 2

Pre-clinical Phase

Bioactive Molecules (83)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-10532	SRT 1720	Activator	99.90%	Unkown
HY-113402	Gamma-glutamylcysteine	Activator	98.53%	Unkown
HY-100578	AGK2	Inhibitor	99.43%	Unkown
HY-107454	OSS_128167	Inhibitor	98.92%	Unkown
HY-13515	Sirtinol	Inhibitor	98.0%	Unkown
HY-N0806	Sweroside	Activator	99.76%	Unkown
HY-N0704	Agrimol B	Activator	99.75%	Unkown
HY-15145A	SRT 1720 dihydrochloride	Activator	99.60%	Unkown
HY-124037	SRT 1460	Activator	98.16%	Unkown
HY-15510	Tenovin-6	Inhibitor	98.00%	Unkown
HY-100732	Cambinol	Inhibitor	99.89%	Unkown
HY-101278	Thiomyristoyl	Inhibitor	98.23%	Unkown
HY-15145	SRT 1720 monohydrochloride	Activator	99.92%	Unkown
HY-N0526	2"-O-Galloylhyperin	Inhibitor	99.57%	Unkown
HY-N0341	Scopolin	Activator	99.65%	Unkown
HY-15869	Inauhzin	Inhibitor	98.46%	Unkown
HY-101073	Salermide	Inhibitor	98.0%	Unkown
HY-16616	SIRT-IN-2	Inhibitor	98.08%	Unkown
HY-136199	SIRT1-IN-1	Inhibitor	98.15%	Unkown
HY-19759	SRT 2183	Activator	98.06%	Unkown
HY-103721	SIRT6-IN-2	Inhibitor	99.92%	Unkown
HY-P5247	Palmitoyl tetrapeptide-20	Activator	99.21%	Unkown
HY-118020A	Loliolide	Activator	99.92%	Unkown
HY-107245	Segetalin B	Activator	99.9%	Unkown
HY-114557	NSC 90469	Inhibitor	99.41%	Unkown
HY-104073	CAY10602	Activator	98.69%	Unkown
HY-16605	SIRT6-IN-6	Inhibitor	98.59%	Unkown
HY-N2787	8-Prenylnaringenin	Activator	99.63%	Unkown
HY-N0859	Schisanhenol	Inhibitor	99.99%	Unkown
HY-N1926	Dihydrocoumarin	Inhibitor	99.81%	Unkown
HY-15510B	Tenovin-6 Hydrochloride	Inhibitor	98.88%	Unkown
HY-W009300	4-Hydroxyestrone		≥99.0%	Unkown
HY-E70008	Lumbokinase	Activator	/	Unkown
HY-169934	SIRT1-IN-4	Inhibitor	98.62%	Unkown
HY-124113	4'-Bromo-resveratrol	Inhibitor	99.94%	Unkown
HY-19758A	Sirtuin modulator 1	Modulator	99.85%	Unkown
HY-15452A	(S)-Selisistat	Inhibitor	99.39%	Unkown
HY-117006	E1231	Activator	98.46%	Unkown
HY-N3504	Ophiopogonin D'	Activator	99.94%	Unkown
HY-156027	SIRT6-IN-3	Inhibitor	98.19%	Unkown
HY-16615	SIRT-IN-1	Inhibitor	98.14%	Unkown
HY-111329	JGB1741	Inhibitor	99.37%	Unkown
HY-N3225	Myricanol	Activator	98.93%	Unkown
HY-146689	SIRT1-IN-2	Inhibitor	98.31%	Unkown
HY-146690	SIRT1-IN-3	Inhibitor	99.12%	Unkown
HY-150727	SIRT5 inhibitor 4	Inhibitor	98.37%	Unkown
HY-122936	Tanshindiol C	Activator	98.47%	Unkown
HY-156781	Sirtuin-1 inhibitor 1	Inhibitor	98.09%	Unkown
HY-118343	AC-93253	Inhibitor	99.3%	Unkown
HY-19634	YK-3-237	Activator	99.54%	Unkown
HY-P5247A	Palmitoyl tetrapeptide-20 TFA	Activator	/	Unkown
HY-151519	SIRT2-IN-9	Inhibitor	99.45%	Unkown
HY-N12378	β-Patchoulene	Activator	96.88%	Unkown
HY-156023	SIRT1 activator 2	Activator	99.28%	Unkown
HY-148408	SIRT2-IN-11	Inhibitor	99.94%	Unkown
HY-P3364A	Ac-QPKK(Ac)-AMC acetate	Substrate	99.38%	Unkown
HY-111303	CHIC35	Inhibitor	/	Unkown
HY-148322	Sirtuin modulator 5	Modulator	/	Unkown
HY-148312	Sirtuin modulator 4	Inhibitor	/	Unkown
HY-114906	SIRT1/2/3-IN-2	Inhibitor	/	Unkown
HY-153509	Sirtuin-IN-1	Inhibitor	/	Unkown
HY-183044	SIRT1 activator 4	Activator	/	Unkown
HY-146013	Sirt1/2-IN-1	Inhibitor	/	Unkown
HY-139125	DCHC	Activator	/	Unkown
HY-182412	NH4-6	Inhibitor	/	Unkown
HY-114510	PRMT/HKMT-IN-1		/	Unkown
HY-169809	SIRT1-IN-5	Inhibitor	/	Unkown
HY-N18386	Altissimacoumarin F	Activator	/	Unkown
HY-N17821	Butrin	Inhibitor	/	Unkown
HY-136713	Sirt1/2-IN-5	Inhibitor	/	Unkown
HY-123241	ZINC08792229	Inhibitor	/	Unkown
HY-N10009	Cudraflavone B	Activator	/	Unkown
HY-138443A	BF-175	Agonist	/	Unkown
HY-184372	SIRT1-IN-7	Inhibitor	/	Unkown
HY-155784	SPC-180002	Inhibitor	/	Unkown
HY-N18048	Gypenoside CII	Control	/	Unkown
HY-160944	hsa62	Inhibitor	/	Unkown
HY-160617	SIRT2-IN-14	Inhibitor	/	Unkown
HY-170402	SIRT6-IN-4	Inhibitor	/	Unkown
HY-N9398	3β,6α,12β-Dammar-E-20(22)-ene-3,6,12,25-tetraol	Activator	/	Unkown
HY-183853	Arecaidine-propargyl ester	Activator	/	Unkown
HY-N11262	Sudachitin	Activator	/	Unkown
HY-W109401	SIRT-IN-6	Inhibitor	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Homo sapiens	Sirt1	NCBI	NCBI:23411