FertilityOnline | Spermatogenes

Detail Information of SG000040

General information

SG ID

SG000040

Gene Name

Sirt1

Gene Synonyms/Alias

AA673258, SIR2L1, Sir2, Sir2a, Sir2alpha

Organism

Mus musculus

NCBI Taxonomy ID

10090

Ensembl Gene ID

ENSMUSG00000020063

Ensembl Protein ID

ENSMUSP00000112595 ENSMUSP00000117819 ENSMUSP00000101082 ENSMUSP00000020257
ENSMUSP00000137565

Description

Sirtuin 1 [Mus musculus (house mouse)]

Orthology

Species	Uniprot	Gene stable ID	Gene Name
Rattus norvegicus	A0A0G2JZ79	RGD:1308542	Sirt1
Gallus gallus	F1N886	Ensembl:ENSGALG00000002761	SIRT1
Danio rerio	E7F8W3	ZFIN:ZDB-GENE-070801-2	sirt1

More Orthology >>

Status

Reviewed functional gene

Functional information

Function in Stage

premeiotic meiotic postmeiotic

Function in Cell Type

Elongated spermatid Leydig cell Sertoli cell

The information of related literature

1. Abstract
Sirt1 is a member of the sirtuin family of proteins and has important roles in numerous biological processes. Sirt1-/- mice display an increased frequency of abnormal spermatozoa, but the mechanism of Sirt1 ... PMID: [28003215]

2. Abstract
Sirtuins are NAD(+)-dependent deacylases that regulate numerous biological processes in response to the environment. SirT1 is the mammalian ortholog of yeast Sir2, and is involved in many metabolic pathways in somatic tissues. ... PMID: [25142464]

3. Abstract
Sirtuins (SIRTs) are class-III NAD-dependent histone deacetylases (HDACs) that regulate various physiological processes. Inactivation of SIRT1 in the mouse leads to male sterility, but the molecular mechanisms responsible for this phenotype have ... PMID: [18987333]

4. Abstract
In mammals, Sirt1, a member of the sirtuin family of proteins, functions as a nicotinamide adenine dinucleotide-dependent protein deactylase, and has important physiological roles, including the regulation of glucose metabolism, cell survival, ...

Figures for illustrating the function of this protein/gene

Liu, C., Song, Z., Wang, L., Yu, H., Liu, W., Shang, Y., Xu, Z., Zhao, H., Gao, F., Wen, J., Zhao, L., Gui, Y., Jiao, J. and Li, W. (2017) Sirt1 regulates acrosome biogenesis by modulating autophagic flux during spermiogenesis in mice. Development 144(3): 441-451. PMID: [28003215]

Bell, E. L., Nagamori, I., Williams, E. O., Del Rosario, A. M., Bryson, B. D., Watson, N., White, F. M., Sassone-Corsi, P. and Guarente, L. (2014) SirT1 is required in the male germ cell for differentiation and fecundity in mice. Development 141(18): 3495-504. PMID: [25142464]

U. Kolthur-Seetharam, K. Teerds, D. G. de Rooij, O. Wendling, M. McBurney, P. Sassone-Corsi and I. Davidson (2009) The histone deacetylase SIRT1 controls male fertility in mice through regulation of hypothalamic-pituitary gonadotropin signaling. Biol Reprod 80(2): 384-91. PMID: [18987333]

M. Coussens, J. G. Maresh, R. Yanagimachi, G. Maeda and R. Allsopp (2008) Sirt1 deficiency attenuates spermatogenesis and germ cell function. PLoS One 3(2): e1571. PMID: [18270565]

Functional description

Sirtuins (SIRTs) are class-III NAD-dependent histone deacetylases (HDACs) that regulate various physiological processes. In mammals, Sirt1, a member of the sirtuin family of proteins, functions as a nicotinamide adenine dinucleotide-dependent protein deactylase, and has important physiological roles, including the regulation of glucose metabolism, cell survival, and mitochondrial respiration.SIRT1 controls male fertility in mice through regulation of hypothalamic-pituitary gonadotropin signaling.

Protein complex

Complex name	Subunits(UniProt IDs)	Functional comment
SIRT1-HNF4-alpha-PGC-1-alpha complex, in response to fasting	P49698 O70343 Q923E4	Acetylation of PGC-1 alpha by SIRT1 decreases its ability to efficiently coactivate HNF4alpha. In general the results show that PGC-1 alpha and SIRT1 can function together to promote adaptation to nutrient deprivation by regulating the genetic programmes of gluconeogenesis and glycolysis. SIRT1 can act both positively and negatively to control gene expression as a cofactor for PGC-1 alpha.

Pathway

ReactomeID: R-MMU-427359
SIRT1 negatively regulates rRNA Expression

Human diseases

OMIM

Spermatogenesis failure

N/A

Expression and location

Tissue specificity (in Homo sapiens)	Expressed highest in testis
Testicular Cell specificity (in Mus musculus)	Expressed highest in spermatogonium
Testicular scRNA-seq (in Homo sapiens)	View detail
Testicular scRNA-seq (in Mus musculus)	View detail
Subcellular location	Nucleus, PML body

Mutation in human orthology

Variants founded in public databases

1000G (Phase 3): 1107 ESP6500 (SI-V2): 80 ExAC (r0.3.1): 511 dbSNP(Build 147): 2741

Variants founded in in-house datasets

Chinese health control (254): 4 European health control (283): 2 Chinese patients (168):

De novo Mutation Rate

Gene Name	DNMR-average	DNMR-SC
SIRT1	0.0000293075	0.0000213716

Other information

Click the right sign for more information

Sub-Ontologies	Accession	Term	Evidence
Biological Process	GO:0000012	single strand break repair	IEA
Biological Process	GO:0000122	negative regulation of transcription from RNA polymerase II promoter	IEA
Biological Process	GO:0000183	chromatin silencing at rDNA	IEA
Biological Process	GO:0000720	pyrimidine dimer repair by nucleotide-excision repair	IEA
Biological Process	GO:0000731	DNA synthesis involved in DNA repair	IMP
Biological Process	GO:0001525	angiogenesis	IEA
Biological Process	GO:0001542	ovulation from ovarian follicle	IMP
Biological Process	GO:0001678	cellular glucose homeostasis	IMP
Biological Process	GO:0001934	positive regulation of protein phosphorylation	IMP
Biological Process	GO:0001938	positive regulation of endothelial cell proliferation	IEA
Biological Process	GO:0002821	positive regulation of adaptive immune response	IEA
Biological Process	GO:0006325	chromatin organization	IEA
Biological Process	GO:0006343	establishment of chromatin silencing	IEA
Biological Process	GO:0006344	maintenance of chromatin silencing	IEA
Biological Process	GO:0006351	transcription, DNA-templated	IEA
Biological Process	GO:0006355	regulation of transcription, DNA-templated	IEA
Biological Process	GO:0006364	rRNA processing	IEA
Biological Process	GO:0006366	transcription from RNA polymerase II promoter	IEA
Biological Process	GO:0006476	protein deacetylation	IEA
Biological Process	GO:0006642	triglyceride mobilization	IMP
Biological Process	GO:0006915	apoptotic process	IEA
Biological Process	GO:0006974	cellular response to DNA damage stimulus	IEA
Biological Process	GO:0006979	response to oxidative stress	IEA
Biological Process	GO:0007275	multicellular organism development	IEA
Biological Process	GO:0007283	spermatogenesis	IMP
Biological Process	GO:0007346	regulation of mitotic cell cycle	IEA
Biological Process	GO:0007517	muscle organ development	IEA
Biological Process	GO:0007623	circadian rhythm	IEP
Biological Process	GO:0008284	positive regulation of cell proliferation	IEA
Biological Process	GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage	IDA
Biological Process	GO:0009267	cellular response to starvation	IMP
Biological Process	GO:0010629	negative regulation of gene expression	IEA
Biological Process	GO:0010875	positive regulation of cholesterol efflux	IMP
Biological Process	GO:0010883	regulation of lipid storage	IMP
Biological Process	GO:0010906	regulation of glucose metabolic process	IMP
Biological Process	GO:0010934	macrophage cytokine production	IMP
Biological Process	GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling	IMP
Biological Process	GO:0016239	positive regulation of macroautophagy	IEA
Biological Process	GO:0016567	protein ubiquitination	IEA
Biological Process	GO:0016575	histone deacetylation	IEA
Biological Process	GO:0018394	peptidyl-lysine acetylation	IEA
Biological Process	GO:0030154	cell differentiation	IEA
Biological Process	GO:0030225	macrophage differentiation	IMP
Biological Process	GO:0030308	negative regulation of cell growth	IEA
Biological Process	GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway	IDA
Biological Process	GO:0031393	negative regulation of prostaglandin biosynthetic process	IMP
Biological Process	GO:0031648	protein destabilization	IEA
Biological Process	GO:0031937	positive regulation of chromatin silencing	IEA
Biological Process	GO:0032007	negative regulation of TOR signaling	IEA
Biological Process	GO:0032071	regulation of endodeoxyribonuclease activity	IEA
Biological Process	GO:0032088	negative regulation of NF-kappaB transcription factor activity	IEA
Biological Process	GO:0032868	response to insulin	IDA
Biological Process	GO:0032922	circadian regulation of gene expression	IEA
Biological Process	GO:0033158	regulation of protein import into nucleus, translocation	IEA
Biological Process	GO:0033210	leptin-mediated signaling pathway	IMP
Biological Process	GO:0034391	regulation of smooth muscle cell apoptotic process	IDA
Biological Process	GO:0034983	peptidyl-lysine deacetylation	IEA
Biological Process	GO:0035356	cellular triglyceride homeostasis	IMP
Biological Process	GO:0035358	regulation of peroxisome proliferator activated receptor signaling pathway	IMP
Biological Process	GO:0042127	regulation of cell proliferation	IEA
Biological Process	GO:0042326	negative regulation of phosphorylation	IEA
Biological Process	GO:0042542	response to hydrogen peroxide	IEA
Biological Process	GO:0042595	behavioral response to starvation	IMP
Biological Process	GO:0042632	cholesterol homeostasis	IMP
Biological Process	GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IEA
Biological Process	GO:0043065	positive regulation of apoptotic process	IEA
Biological Process	GO:0043066	negative regulation of apoptotic process	IEA
Biological Process	GO:0043124	negative regulation of I-kappaB kinase/NF-kappaB signaling	IEA
Biological Process	GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	IEA
Biological Process	GO:0043280	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IEA
Biological Process	GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity	IEA
Biological Process	GO:0043518	negative regulation of DNA damage response, signal transduction by p53 class mediator	IEA
Biological Process	GO:0044321	response to leptin	IMP
Biological Process	GO:0045348	positive regulation of MHC class II biosynthetic process	IEA
Biological Process	GO:0045599	negative regulation of fat cell differentiation	IMP
Biological Process	GO:0045739	positive regulation of DNA repair	IEA
Biological Process	GO:0045766	positive regulation of angiogenesis	IEA
Biological Process	GO:0045892	negative regulation of transcription, DNA-templated	IEA
Biological Process	GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IEA
Biological Process	GO:0046628	positive regulation of insulin receptor signaling pathway	IEA
Biological Process	GO:0048511	rhythmic process	IEA
Biological Process	GO:0050872	white fat cell differentiation	IMP
Biological Process	GO:0051097	negative regulation of helicase activity	IEA
Biological Process	GO:0051152	positive regulation of smooth muscle cell differentiation	IMP
Biological Process	GO:0051574	positive regulation of histone H3-K9 methylation	IEA
Biological Process	GO:0051898	negative regulation of protein kinase B signaling	IEA
Biological Process	GO:0055089	fatty acid homeostasis	IMP
Biological Process	GO:0060766	negative regulation of androgen receptor signaling pathway	IEA
Biological Process	GO:0061647	histone H3-K9 modification	IEA
Biological Process	GO:0070301	cellular response to hydrogen peroxide	IEA
Biological Process	GO:0070857	regulation of bile acid biosynthetic process	IMP
Biological Process	GO:0070914	UV-damage excision repair	IEA
Biological Process	GO:0070932	histone H3 deacetylation	IEA
Biological Process	GO:0071356	cellular response to tumor necrosis factor	IEA
Biological Process	GO:0071441	negative regulation of histone H3-K14 acetylation	IEA
Biological Process	GO:0071456	cellular response to hypoxia	IEA
Biological Process	GO:0071479	cellular response to ionizing radiation	IMP
Biological Process	GO:0071900	regulation of protein serine/threonine kinase activity	IEA
Biological Process	GO:0090335	regulation of brown fat cell differentiation	IMP
Biological Process	GO:0090400	stress-induced premature senescence	IEA
Biological Process	GO:1900113	negative regulation of histone H3-K9 trimethylation	IDA
Biological Process	GO:1901215	negative regulation of neuron death	IGI
Biological Process	GO:1901984	negative regulation of protein acetylation	IEA
Biological Process	GO:1902166	negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IMP
Biological Process	GO:1902176	negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	IEA
Biological Process	GO:1902237	positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IMP
Biological Process	GO:1904179	positive regulation of adipose tissue development	IMP
Biological Process	GO:1990619	histone H3-K9 deacetylation	IEA
Biological Process	GO:2000111	positive regulation of macrophage apoptotic process	IMP
Biological Process	GO:2000480	negative regulation of cAMP-dependent protein kinase activity	IEA
Biological Process	GO:2000481	positive regulation of cAMP-dependent protein kinase activity	IEA
Biological Process	GO:2000619	negative regulation of histone H4-K16 acetylation	IEA
Biological Process	GO:2000655	negative regulation of cellular response to testosterone stimulus	IEA
Biological Process	GO:2000757	negative regulation of peptidyl-lysine acetylation	IEA
Biological Process	GO:2000773	negative regulation of cellular senescence	IEA
Biological Process	GO:2000774	positive regulation of cellular senescence	IEA
Cellular Component	GO:0000785	chromatin	IDA
Cellular Component	GO:0000790	nuclear chromatin	IEA
Cellular Component	GO:0005634	nucleus	IEA
Cellular Component	GO:0005635	nuclear envelope	IEA
Cellular Component	GO:0005637	nuclear inner membrane	IEA
Cellular Component	GO:0005654	nucleoplasm	IEA
Cellular Component	GO:0005677	chromatin silencing complex	IEA
Cellular Component	GO:0005719	nuclear euchromatin	IEA
Cellular Component	GO:0005720	nuclear heterochromatin	IEA
Cellular Component	GO:0005730	nucleolus	IEA
Cellular Component	GO:0005737	cytoplasm	IEA
Cellular Component	GO:0005739	mitochondrion	IEA
Cellular Component	GO:0005829	cytosol	IEA
Cellular Component	GO:0016605	PML body	IEA
Cellular Component	GO:0033553	rDNA heterochromatin	IEA
Cellular Component	GO:0035098	ESC/E(Z) complex	IEA
Molecular Function	GO:0001046	core promoter sequence-specific DNA binding	IDA
Molecular Function	GO:0001077	transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding	IDA
Molecular Function	GO:0002039	p53 binding	IEA
Molecular Function	GO:0003714	transcription corepressor activity	IEA
Molecular Function	GO:0004407	histone deacetylase activity	IEA
Molecular Function	GO:0005515	protein binding	IPI
Molecular Function	GO:0008022	protein C-terminus binding	IEA
Molecular Function	GO:0008134	transcription factor binding	IEA
Molecular Function	GO:0016787	hydrolase activity	IEA
Molecular Function	GO:0017136	NAD-dependent histone deacetylase activity	IEA
Molecular Function	GO:0019213	deacetylase activity	IEA
Molecular Function	GO:0019899	enzyme binding	IEA
Molecular Function	GO:0019904	protein domain specific binding	IPI
Molecular Function	GO:0033558	protein deacetylase activity	IEA
Molecular Function	GO:0034979	NAD-dependent protein deacetylase activity	IEA
Molecular Function	GO:0035257	nuclear hormone receptor binding	IEA
Molecular Function	GO:0042393	histone binding	IEA
Molecular Function	GO:0042802	identical protein binding	IEA
Molecular Function	GO:0043398	HLH domain binding	IEA
Molecular Function	GO:0043425	bHLH transcription factor binding	IEA
Molecular Function	GO:0046872	metal ion binding	IEA
Molecular Function	GO:0046969	NAD-dependent histone deacetylase activity (H3-K9 specific)	IDA
Molecular Function	GO:0051019	mitogen-activated protein kinase binding	IEA
Molecular Function	GO:0070403	NAD+ binding	IEA
Molecular Function	GO:1990254	keratin filament binding	IEA

Protein-Protein interaction information

Protein A	Gene name A	Protein B	Gene name B	Evidence
ENSMUSP00000020257	Sirt1	ENSMUSP00000020268	Ccar1	experimental
ENSMUSP00000020257	Sirt1	ENSMUSP00000020273	Supv3l1	experimental
ENSMUSP00000020257	Sirt1	ENSMUSP00000020283	H2afy2	experimental

More PPIs >>

Protein family and Domain

Q923E4