mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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Bioinformatics and Systems Medicine Laboratory Bioinformatics and Systems Medicine Laboratory

Gene Summary

Ligand Binding Site Mutation Information

Protein Structure Related Information

Gene Expression and Gene-Gene Network

Phenotype Information

Pharmacological Information

Conservation Information for LBS

Gene summary for SIRT1
Gene summary
Basic gene Info.Gene symbolSIRT1
Gene namesirtuin 1
SynonymsSIR2L1
CytomapUCSC genome browser: 10q21.3
Type of geneprotein-coding
RefGenesNM_001142498.1,
NM_012238.4,
DescriptionNAD-dependent deacetylase sirtuin-1NAD-dependent protein deacetylase sirtuin-1SIR2-like protein 1SIR2alphahSIR2hSIRT1regulatory protein SIR2 homolog 1sir2-like 1sirtuin type 1
Modification date20141222
dbXrefs MIM : 604479
HGNC : HGNC
Ensembl : ENSG00000096717
HPRD : 08381
Vega : OTTHUMG00000018340
ProteinUniProt: Q96EB6
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_SIRT1
BioGPS: 23411
PathwayNCI Pathway Interaction Database: SIRT1
KEGG: SIRT1
REACTOME: SIRT1
Pathway Commons: SIRT1
ContextiHOP: SIRT1
ligand binding site mutation search in PubMed: SIRT1
UCL Cancer Institute: SIRT1
Assigned class in mutLBSgeneDBB: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0000122negative regulation of transcription from RNA polymerase II promoter12535671
GO:0000183chromatin silencing at rDNA18485871
GO:0001525angiogenesis20620956
GO:0002821positive regulation of adaptive immune response21890893
GO:0006343establishment of chromatin silencing15469825
GO:0006476protein deacetylation18203716
GO:0006974cellular response to DNA damage stimulus18203716
GO:0006979response to oxidative stress14976264
GO:0007346regulation of mitotic cell cycle15692560
GO:0016239positive regulation of macroautophagy18296641
GO:0016567protein ubiquitination21841822
GO:0016575histone deacetylation12006491
GO:0032088negative regulation of NF-kappaB transcription factor activity15152190
GO:0034983peptidyl-lysine deacetylation15469825
GO:0042542response to hydrogen peroxide19934257
GO:0043065positive regulation of apoptotic process15152190
GO:0043124negative regulation of I-kappaB kinase/NF-kappaB signaling17680780
GO:0043433negative regulation of sequence-specific DNA binding transcription factor activity11672523
GO:0043518negative regulation of DNA damage response, signal transduction by p53 class mediator11672523
GO:0045348positive regulation of MHC class II biosynthetic process21890893
GO:0045892negative regulation of transcription, DNA-templated11672523
GO:0045944positive regulation of transcription from RNA polymerase II promoter21807113
GO:0046628positive regulation of insulin receptor signaling pathway21241768
GO:0051097negative regulation of helicase activity18203716
GO:0070301cellular response to hydrogen peroxide20027304
GO:0070932histone H3 deacetylation20027304
GO:0071356cellular response to tumor necrosis factor15152190
GO:2000480negative regulation of cAMP-dependent protein kinase activity20203304
GO:2000757negative regulation of peptidyl-lysine acetylation20100829
GO:2000773negative regulation of cellular senescence20203304
GO:2000774positive regulation of cellular senescence18687677


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Ligand binding site mutations for SIRT1

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
C371A369TCOAD1
D292D292EKIRC1
Q294,D292P293SKIRC1
D298D298HLUAD1
Y280R282SLUSC1
Y280R282HUCEC1
D475D475YUCEC1
cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma.


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Protein structure related information for SIRT1
Relative protein structure stability change (ΔΔE) using Mupro 1.1
Mupro score denotes assessment of the effect of mutations on thermodynamic stability.
  (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability)
: nsSNV at non-LBS: nsSNV at LBS

nsSNVs sorted by the relative stability change of protein structure by each mutation
Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene.
LBSAAchange of nsSNVRelative stability change
Y280R282H-1.4734913
Y280R282S-1.4257312
Q294P293S-1.3080088
D292P293S-1.3080088
D298D298H-0.68512452
D475D475Y-0.59450614
C371A369T-0.44183214
D292D292E-0.27528256
(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132)

Structure image for SIRT1 from PDB

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Differential gene expression and gene-gene network for SIRT1
Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

Differential co-expressed gene network based on protein-protein interaction data (CePIN)
* Left PPI network was created from samples with mutations in the LBS of SIRT1 and the right PPI network was created from samples without mutations in the LBS of SIRT1. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


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Phenotype information for SIRT1
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0028754Obesity28Biomarker, GeneticVariation, Therapeutic
umls:C0524851Neurodegenerative Diseases15Biomarker, Therapeutic
umls:C0004153Atherosclerosis12AlteredExpression, Biomarker
umls:C0524620Metabolic Syndrome X8Biomarker, GeneticVariation, Therapeutic
umls:C0015695Fatty Liver8Biomarker, Therapeutic
umls:C1458155Breast Neoplasms7Biomarker
umls:C0021655Insulin Resistance6Biomarker, GeneticVariation, Therapeutic
umls:C0004364Autoimmune Diseases6Biomarker
umls:C0033578Prostatic Neoplasms5AlteredExpression, Biomarker
umls:C0014072Encephalomyelitis, Autoimmune, Experimental3Biomarker, Therapeutic
umls:C0018799Heart Diseases3Biomarker
umls:C0035309Retinal Diseases3Biomarker
umls:C0011853Diabetes Mellitus, Experimental2Biomarker, Therapeutic
umls:C0019693HIV Infections2Biomarker
umls:C2609414Acute Kidney Injury1Biomarker
umls:C0751955Brain Infarction1Biomarker
umls:C0006118Brain Neoplasms1Biomarker
umls:C2931673Ceroid lipofuscinosis, neuronal 1, infantile1Biomarker
umls:C0009319Colitis1Biomarker
umls:C0011303Demyelinating Diseases1Therapeutic
umls:C0016059Fibrosis1Biomarker
umls:C0919532Genomic Instability1Biomarker
umls:C0271650Glucose Intolerance1Therapeutic
umls:C0020564Hypertrophy1Therapeutic
umls:C0027055Myocardial Reperfusion Injury1Therapeutic
umls:C0522224Paralysis1Therapeutic
umls:C0155862Pneumonia, Pneumococcal1Biomarker

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

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Pharmacological information for SIRT1
Gene expression profile of anticancer drug treated cell-lines (CCLE)
Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient.

Gene-centered drug-gene interaction network
Drug information targeting mutLBSgene (Approved drugs only)
Drug statusDrugBank IDNameTypeDrug structure
InvestigationalDB05073SRT501Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of SIRT1 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
ZNZINC(2+)4i5iAC371
ZNZINC(2+)4i5iBC371
ZNZINC(2+)4if6AC371
ZNZINC(2+)4kxqAC371
ZNZINC(2+)4ig9AC371
ZNZINC(2+)4ig9CC371
ZNZINC(2+)4ig9EC371
ZNZINC(2+)4ig9GC371
ZNZINC(2+)5btrAC371
ZNZINC(2+)5btrBC371
ZNZINC(2+)5btrCC371
ZNZINC(2+)4zzhAC371
ZNZINC(2+)4zziAC371
ZNZINC(2+)4zzjAC371
STLRESVERATROL5btrAD292 Q294 D298
STLRESVERATROL5btrBD292 Q294 D298
STLRESVERATROL5btrCD292 Q294 D298
STLRESVERATROL5btrAD298
STLRESVERATROL5btrBD298
IIIPeptide ligand (GLY,PRO,HIS,MET,GLY,SER,GLN,TYR,LEU,PHE,LEU,PRO,PRO,ASN,ARG,TYR,ILE,PHE,HIS,GLY,ALA,GLU,VAL,TYR,SER,ASP)4if6AD475
IIIPeptide ligand (GLY,PRO,HIS,MET,GLY,SER,GLN,TYR,LEU,PHE,LEU,PRO,PRO,ASN,ARG,TYR,ILE,PHE,HIS,GLY,ALA,GLU,VAL,TYR,SER,ASP)4kxqAD475
IIIPeptide ligand (GLY,SER,GLN,TYR,LEU,PHE,LEU,PRO,PRO,ASN,ARG,TYR,ILE,PHE,HIS,GLY,ALA,GLU,VAL,TYR,SER)4ig9AD475
IIIPeptide ligand (MET,GLY,SER,GLN,TYR,LEU,PHE,LEU,PRO,PRO,ASN,ARG,TYR,ILE,PHE,HIS)4ig9CD475
IIIPeptide ligand (PRO,HIS,MET,GLY,SER,GLN,TYR,LEU,PHE,LEU,PRO,PRO,ASN,ARG,TYR,ILE,PHE,HIS)4ig9ED475
IIIPeptide ligand (MET,GLY,SER,GLN,TYR,LEU,PHE,LEU,PRO,PRO,ASN,ARG,TYR,ILE,PHE,HIS,GLY,ALA,GLU,VAL,TYR,SER)4ig9GD475
IIIPeptide ligand (ARG,HIS,LYS,ALY,LEU,NLE,PHE)4zzjAQ294
APRADP-RIBOSE4if6AY280
APRADP-RIBOSE4kxqAY280
NADNAD ZWITTERION4i5iAY280 Q294
NADNAD ZWITTERION4i5iBY280 Q294


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Conservation information for LBS of SIRT1
Multiple alignments for Q96EB6 in multiple species
LBSAA sequence# speciesSpecies


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