Gene Report

Basic Information

Approved Symbol	SIRT1
Approved Name	sirtuin 1
Previous Name	sirtuin (silent mating type information regulation 2, S. cerevisiae, homolog) 1, "sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae)"
Symbol Alias	SIR2L1
Location	10q21
Position	chr10:69644427-69678147 (+)
External Links	Entrez Gene: 23411 Ensembl: ENSG00000096717 UCSC: uc001jnd.3 HGNC ID: 14929
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin; SNP mapped

Positive relationships between SIRT1 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
SIRT1	Kishi, 2010	patients and normal controls		We found an association between rs10997875 in SIRT1 gene and...... We found an association between rs10997875 in SIRT1 gene and MDD in the allele/genotype analysis. More...

Positive relationships between SIRT1 and other components at different levels (count: 0)

Positive relationship network of SIRT1 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between SIRT1 and MDD (count: 0)

Negative relationships between SIRT1 and other components at different levels (count: 0)

SIRT1 related SNPs in MK4MDD (count: 1)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs10997875	chr10:69679824(Forward)	downstream_gene_variant	1(1/0)

SIRT1 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
NAD-dependent protein deacetylase sirtuin-1	Q96EB6	0(0/0)	Gene mapped

SIRT1 related GO terms (count: 118)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0042393	histone binding	molecular function	IPI[15469825]
GO:0001934	positive regulation of protein phosphorylation	biological process	ISS
GO:0007517	muscle organ development	biological process	IEA
GO:0007346	regulation of mitotic cell cycle	biological process	IDA[15692560]
GO:0042981	regulation of apoptotic process	biological process	ISS[11672522]
GO:0004407	histone deacetylase activity	molecular function	IDA
GO:0043398	HLH domain binding	molecular function	IPI[12535671]
GO:0031648	protein destabilization	biological process	ISS
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway	biological process	ISS
GO:2000773	negative regulation of cellular senescence	biological process	IDA
GO:0005677	chromatin silencing complex	cellular component	IDA[18485871]
GO:0035358	regulation of peroxisome proliferator activated receptor signaling pathway	biological process	ISS
GO:0055089	fatty acid homeostasis	biological process	ISS
GO:0046628	positive regulation of insulin receptor signaling pathway	biological process	IDA
GO:0005719	nuclear euchromatin	cellular component	IDA[15469825]
GO:0070857	regulation of bile acid biosynthetic process	biological process	ISS
GO:0007283	spermatogenesis	biological process	IEA
GO:0042632	cholesterol homeostasis	biological process	ISS
GO:0043518	negative regulation of DNA damage response, signal transduction by p53 class mediator	biological process	IDA[11672523]
GO:0031937	positive regulation of chromatin silencing	biological process	IMP[15469825]
GO:0006974	response to DNA damage stimulus	biological process	IDA[18203716]
GO:0000183	chromatin silencing at rDNA	biological process	IDA[18485871]
GO:0006979	response to oxidative stress	biological process	IDA[14976264]
GO:0050872	white fat cell differentiation	biological process	ISS
GO:0000790	nuclear chromatin	cellular component	IDA[17505061]
GO:0006343	establishment of chromatin silencing	biological process	IDA[15469825]
GO:2000480	negative regulation of cAMP-dependent protein kinase activity	biological process	IDA
GO:0006342	chromatin silencing	biological process	TAS[10381378]
GO:0010875	positive regulation of cholesterol efflux	biological process	ISS
GO:2000111	positive regulation of macrophage apoptotic process	biological process	ISS
GO:0051019	mitogen-activated protein kinase binding	molecular function	IPI
GO:0042127	regulation of cell proliferation	biological process	IMP[12006491]
GO:0008284	positive regulation of cell proliferation	biological process	IMP
GO:0006642	triglyceride mobilization	biological process	ISS
GO:0032868	response to insulin stimulus	biological process	ISS
GO:0070403	NAD+ binding	molecular function	IEA
GO:0033158	regulation of protein import into nucleus, translocation	biological process	IMP[18203716]
GO:0071479	cellular response to ionizing radiation	biological process	ISS
GO:0003714	transcription corepressor activity	molecular function	IDA[12535671]; ISS
GO:0080134	regulation of response to stress	biological process	IDA[19934257]
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	IDA
GO:0045599	negative regulation of fat cell differentiation	biological process	ISS
GO:0016605	PML body	cellular component	IDA[12006491]
GO:0071356	cellular response to tumor necrosis factor	biological process	IDA[15152190]
GO:0051097	negative regulation of helicase activity	biological process	IDA[18203716]
GO:0000012	single strand break repair	biological process	IMP
GO:0070301	cellular response to hydrogen peroxide	biological process	IDA
GO:0033558	protein deacetylase activity	molecular function	IDA
GO:0008022	protein C-terminus binding	molecular function	IPI[18203716]
GO:0006260	DNA replication	biological process	TAS[17317627]
GO:0016567	protein ubiquitination	biological process	IDA
GO:0045348	positive regulation of MHC class II biosynthetic process	biological process	IDA
GO:2000655	negative regulation of cellular response to testosterone stimulus	biological process	IMP[17505061]
GO:0031393	negative regulation of prostaglandin biosynthetic process	biological process	ISS
GO:0001678	cellular glucose homeostasis	biological process	ISS
GO:0042326	negative regulation of phosphorylation	biological process	IMP[17612497]
GO:0005737	cytoplasm	cellular component	IDA; IDA[15469825]
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IDA[12535671]; IMP
GO:0000731	DNA synthesis involved in DNA repair	biological process	ISS
GO:0034979	NAD-dependent protein deacetylase activity	molecular function	IDA; IMP[11672523]
GO:0005635	nuclear envelope	cellular component	IDA[15469825]
GO:0034983	peptidyl-lysine deacetylation	biological process	IDA[15469825]
GO:0045739	positive regulation of DNA repair	biological process	IMP[19934257]
GO:0001525	angiogenesis	biological process	IDA
GO:0016239	positive regulation of macroautophagy	biological process	IDA[18296641]
GO:0005654	nucleoplasm	cellular component	IDA[16079181]
GO:0046872	metal ion binding	molecular function	IEA
GO:0002039	p53 binding	molecular function	IPI[11672523]
GO:0043065	positive regulation of apoptotic process	biological process	IDA[15152190]; IMP[19047049]
GO:0006351	transcription, DNA-dependent	biological process	IEA
GO:0045892	negative regulation of transcription, DNA-dependent	biological process	IDA[11672523]
GO:2000481	positive regulation of cAMP-dependent protein kinase activity	biological process	IMP[18687677]
GO:0043161	proteasomal ubiquitin-dependent protein catabolic process	biological process	IMP
GO:0006346	methylation-dependent chromatin silencing	biological process	TAS
GO:0035098	ESC/E(Z) complex	cellular component	IDA[15684044]
GO:0019213	deacetylase activity	molecular function	IDA[18203716]
GO:0001542	ovulation from ovarian follicle	biological process	IEA
GO:0017136	NAD-dependent histone deacetylase activity	molecular function	IDA[12006491]
GO:0043124	negative regulation of I-kappaB kinase/NF-kappaB cascade	biological process	IDA[17680780]
GO:0032007	negative regulation of TOR signaling cascade	biological process	IMP
GO:0003950	NAD+ ADP-ribosyltransferase activity	molecular function	TAS[17456799]
GO:0046969	NAD-dependent histone deacetylase activity (H3-K9 specific)	molecular function	ISS
GO:2000774	positive regulation of cellular senescence	biological process	IDA[18687677]
GO:0043280	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	biological process	IMP[19047049]
GO:0006344	maintenance of chromatin silencing	biological process	IMP[15469825]
GO:0034391	regulation of smooth muscle cell apoptotic process	biological process	ISS
GO:0033553	rDNA heterochromatin	cellular component	IDA[18485871]
GO:0005637	nuclear inner membrane	cellular component	IDA[15469825]
GO:0010906	regulation of glucose metabolic process	biological process	ISS
GO:0005634	nucleus	cellular component	IDA
GO:0005515	protein binding	molecular function	IPI[12006491]
GO:0051898	negative regulation of protein kinase B signaling cascade	biological process	IMP
GO:0000720	pyrimidine dimer repair by nucleotide-excision repair	biological process	IMP
GO:0071456	cellular response to hypoxia	biological process	IMP
GO:0060766	negative regulation of androgen receptor signaling pathway	biological process	IMP[17505061]
GO:0007569	cell aging	biological process	TAS[11672523]
GO:0006471	protein ADP-ribosylation	biological process	TAS[17456799]
GO:0006281	DNA repair	biological process	TAS[17317627]
GO:0030308	negative regulation of cell growth	biological process	IMP[17505061]
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	biological process	IMP
GO:0009267	cellular response to starvation	biological process	ISS
GO:0018394	peptidyl-lysine acetylation	biological process	IMP[18004385]
GO:0042802	identical protein binding	molecular function	IPI[15469825]
GO:0032071	regulation of endodeoxyribonuclease activity	biological process	IMP[19934257]
GO:0032088	negative regulation of NF-kappaB transcription factor activity	biological process	IDA[15152190]
GO:0002821	positive regulation of adaptive immune response	biological process	IDA
GO:0006364	rRNA processing	biological process	IEA
GO:0035356	cellular triglyceride homeostasis	biological process	ISS
GO:0043066	negative regulation of apoptotic process	biological process	IMP; TAS[17317627]
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity	biological process	IDA[11672523]; IMP[17505061]
GO:0005720	nuclear heterochromatin	cellular component	IDA[15469825]
GO:0019048	virus-host interaction	biological process	IEA
GO:0070932	histone H3 deacetylation	biological process	IDA; IMP[17505061]
GO:0016575	histone deacetylation	biological process	IDA[12006491]
GO:0006476	protein deacetylation	biological process	IDA; IMP[11672523]
GO:0005730	nucleolus	cellular component	IDA[15469825]; IDA[16079181]
GO:0043425	bHLH transcription factor binding	molecular function	IPI[12535671]
GO:2000757	negative regulation of peptidyl-lysine acetylation	biological process	IDA

SIRT1 related KEGG pathways (count: 0)

SIRT1 related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
PML_PATHWAY	pml pathway	Regulation of transcriptional activity by PML	The PML nuclear bodies are ring-shaped nuclear substructures...... The PML nuclear bodies are ring-shaped nuclear substructures associated with the regulation of transcription, transformation, cell growth, and apoptosis and are characterized by the presence of the protein PML. The activities of PML as a tumor suppressor and apoptosis inducing factor are exerted through the numerous proteins it interacts with in the PML-nuclear bodies including the tumor suppressor p53. DNA damage induced activation of p53-dependent apoptosis requires PML. PML acts as a coactivator for p53 and increases acetylation of p53 by the transcriptional coactivator CBP. This acetylation of p53 is reversed by the deacetylase SirT1, the human homolog of the yeast gene Sir2, and this deacetylation opposes the transcriptional activation of p53. The tumor suppressor Rb also interacts with the PML nuclear body, increasing transcriptional repression of genes involved in cell cycle progression, suggesting that PML may affect cellular transformation through more than one mechanism. PML interacts directly with Ubc9, which modifies PML through the attachment of the ubiquitin-like peptide Sumo-1. Sumo-1 modification of PML is not necessary for the nuclear bodies to form, but may affect the recruitment of proteins that interact with PML. PML is involved in non-p53 mediated apoptotic pathways, such as DAXX-mediated apoptosis induced by Fas and TNF and regulates the transcriptional repressor activity of Daxx. The sequestration of Daxx by the PML nuclear bodies relieves the repression of other transcription factors like Pax3 by Daxx. Tumor suppression by PML may in general involve the formation of specific regulatory transcription complexes, including those with DAXX, p53 and CBP. Factors that affect the assembly of PML into the PML nuclear bodies affect the proliferation and transformation of cells. Viral early proteins can interact with PML to disrupt the nuclear bodies, allowing increased proliferation of cells and reduced apoptosis, good conditions for DNA virus infection. Another factor that disrupts the formation of PML nuclear bodies is a translocation between the PML and RAR-alpha genes found in acute promyelocytic leukemia (APL) patients. Binding of retinoic acid to the RAR-alpha steroid hormone receptor activates transcription of retinoic-acid responsive genes. The translocation found in APL patients creates two chimeric proteins, RARalpha-PML and PML-RARalpha. Retinoic acid given to APL patients causes the reappearance of nuclear bodies, and the reversal of cellular transformation, effecting a cure for these patients. More...

SIRT1 related Reactome pathways (count: 0)

SIRT1 related interactors from protein-protein interaction data in HPRD (count: 14)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
SIRT1	TP53	No	in vitro;in vivo	11672523
SIRT1	HIC1	No	in vivo	16269335
SIRT1	HEY2	No	in vitro;in vivo	12535671
SIRT1	PPARGC1A	No	in vitro;in vivo	15744310
SIRT1	NR1H2	No	in vivo	17936707
SIRT1	FOXO3	No	in vitro;in vivo;yeast 2-hybrid	14976264
SIRT1	HES1	No	in vivo	12535671
SIRT1	NR1H3	No	in vivo	17936707
SIRT1	EP300	Yes	in vitro;in vivo	15632193
SIRT1	FOXO1	No	in vivo	15692560
SIRT1	HNF4A	No	in vivo	15744310
SIRT1	HIST1H1B	No	in vitro	15469825
SIRT1	RELA	No	in vivo	15152190
SIRT1	RRP8	No	in vivo	18485871

Gene Report

Gene mapped GO terms

Gene mapped BioCarta pathways