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 PDK2
Gene summary
Basic gene Info.Gene symbolPDK2
Gene namepyruvate dehydrogenase kinase, isozyme 2
SynonymsPDHK2|PDKII
CytomapUCSC genome browser: 17q21.33
Type of geneprotein-coding
RefGenesNM_001199898.1,
NM_001199899.1,NM_001199900.1,NM_002611.4,
DescriptionPDH kinase 2[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrialpyruvate dehydrogenase kinase, isoenzyme 2pyruvate dehydrogenase, lipoamide, kinase isozyme 2, mitochondrial
Modification date20141207
dbXrefs MIM : 602525
HGNC : HGNC
Ensembl : ENSG00000005882
HPRD : 03955
Vega : OTTHUMG00000161948
ProteinUniProt: Q15119
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PDK2
BioGPS: 5164
PathwayNCI Pathway Interaction Database: PDK2
KEGG: PDK2
REACTOME: PDK2
Pathway Commons: PDK2
ContextiHOP: PDK2
ligand binding site mutation search in PubMed: PDK2
UCL Cancer Institute: PDK2
Assigned class in mutLBSgeneDBC: This gene just belongs to mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0006468protein phosphorylation19833728


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Ligand binding site mutations for PDK2
Lollipop-style diagram of mutations at LBS in amino-acid sequence.
We represented ligand binding site mutations only. (You can see big image via clicking.)
 
: non-synonymous mutation on LBS, Circle size denotes number of samples.

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
R74R74QBRCA1
A259A259VCOAD1
M130M130IKIRC1
R162R162SLUSC1
V81P79LSKCM1
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 PDK2
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
R74R74Q-1.1841045
R162R162S-0.97468287
M130M130I-0.66688305
V81P79L-0.48079363
A259A259V-0.190975
(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 PDK2 from PDB

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Differential gene expression and gene-gene network for PDK2
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 PDK2 and the right PPI network was created from samples without mutations in the LBS of PDK2. 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 PDK2
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0878544Cardiomyopathies1Biomarker

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

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Pharmacological information for PDK2
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
ExperimentalDB086084-({(2R,5S)-2,5-DIMETHYL-4-[(2R)-3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANOYL]PIPERAZIN-1-YL}CARBONYL)BENZONITRILESmall molecule
ExperimentalDB08609(N-{4-[(ETHYLANILINO)SULFONYL]-2-METHYLPHENYL}-3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANAMIDESmall molecule
ExperimentalDB08610N-(2-AMINOETHYL)-2-{3-CHLORO-4-[(4-ISOPROPYLBENZYL)OXY]PHENYL} ACETAMIDESmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PDK2 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
PV1(5-BROMO-2,4-DIHYDROXYPHENYL)(1,3-DIHYDRO-2H-ISOINDOL- 2-YL)METHANONE4mp2AA259
PFT4-(1,3-DIHYDRO-2H-ISOINDOL-2-YLCARBONYL)BENZENE-1,3-DIOL4mp7AA259
PV24-(ISOINDOLIN-2-YLSULFONYL)BENZENE-1,3-DIOL4mpcAA259
PV84-[(5-HYDROXY-1,3-DIHYDRO-2H-ISOINDOL-2-YL) SULFONYL]BENZENE-1,3-DIOL4mpeAA259
PV02-[(2,4-DIHYDROXYPHENYL)SULFONYL]-2,3-DIHYDRO-1H- ISOINDOLE-4,6-DIOL4mpnAA259


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Conservation information for LBS of PDK2
Multiple alignments for Q15119 in multiple species
LBSAA sequence# speciesSpecies
A259KNAMRATVESH3Homo sapiens, Mus musculus, Rattus norvegicus
A324GGTPLAGFGYG3Homo sapiens, Mus musculus, Rattus norvegicus
D290SIKMSDRGGGV3Homo sapiens, Mus musculus, Rattus norvegicus
E251YHMLFELFKNA3Homo sapiens, Mus musculus, Rattus norvegicus
E262MRATVESHESS3Homo sapiens, Mus musculus, Rattus norvegicus
F326TPLAGFGYGLP3Homo sapiens, Mus musculus, Rattus norvegicus
F52KTSFTFLRQEL3Homo sapiens, Mus musculus, Rattus norvegicus
G133PTMAQGVLEYK3Homo sapiens, Mus musculus, Rattus norvegicus
G294SDRGGGVPLRK3Homo sapiens, Mus musculus, Rattus norvegicus
G325GTPLAGFGYGL3Homo sapiens, Mus musculus, Rattus norvegicus
G327PLAGFGYGLPI3Homo sapiens, Mus musculus, Rattus norvegicus
G329AGFGYGLPISR3Homo sapiens, Mus musculus, Rattus norvegicus
H123TIRNRHNDVVP3Homo sapiens, Mus musculus, Rattus norvegicus
I119DALVTIRNRHN3Homo sapiens, Mus musculus, Rattus norvegicus
I151VSNQNIQYFLD3Homo sapiens, Mus musculus, Rattus norvegicus
I165LSRISIRMLIN3Homo sapiens, Mus musculus, Rattus norvegicus
I169SIRMLINQHTL3Homo sapiens, Mus musculus, Rattus norvegicus
L155NIQYFLDRFYL3Homo sapiens, Mus musculus, Rattus norvegicus
L168ISIRMLINQHT3Homo sapiens, Mus musculus, Rattus norvegicus
L252HMLFELFKNAM3Homo sapiens, Mus musculus, Rattus norvegicus
L303RKIERLFSYMY3Homo sapiens, Mus musculus, Rattus norvegicus
L31FSPSPLSMKQF3Homo sapiens, Mus musculus, Rattus norvegicus
L323TGGTPLAGFGY3Homo sapiens, Mus musculus, Rattus norvegicus
L330GFGYGLPISRL3Homo sapiens, Mus musculus, Rattus norvegicus
L346QGDLQLFSMEG3Homo sapiens, Mus musculus, Rattus norvegicus
L53TSFTFLRQELP3Homo sapiens, Mus musculus, Rattus norvegicus
L61ELPVRLANIMK3Homo sapiens, Mus musculus, Rattus norvegicus
L71KEINLLPDRVL3Homo sapiens, Mus musculus, Rattus norvegicus
M130DVVPTMAQGVL3Homo sapiens, Mus musculus, Rattus norvegicus
N150PVSNQNIQYFL3Homo sapiens, Mus musculus, Rattus norvegicus
N255FELFKNAMRAT3Homo sapiens, Mus musculus, Rattus norvegicus
P331FGYGLPISRLY3Homo sapiens, Mus musculus, Rattus norvegicus
P72EINLLPDRVLS2Homo sapiens, Rattus norvegicus
P72EINLLPDRVLG1Mus musculus
Q171RMLINQHTLIF3Homo sapiens, Mus musculus, Rattus norvegicus
Q35PLSMKQFLDFG3Homo sapiens, Mus musculus, Rattus norvegicus
R120ALVTIRNRHND3Homo sapiens, Mus musculus, Rattus norvegicus
R162RFYLSRISIRM3Homo sapiens, Mus musculus, Rattus norvegicus
R166SRISIRMLINQ3Homo sapiens, Mus musculus, Rattus norvegicus
R258FKNAMRATVES3Homo sapiens, Mus musculus, Rattus norvegicus
R74NLLPDRVLSTP2Homo sapiens, Rattus norvegicus
R74NLLPDRVLGTP1Mus musculus
S49ACEKTSFTFLR3Homo sapiens, Mus musculus, Rattus norvegicus
T354MEGFGTDAVIY3Homo sapiens, Mus musculus, Rattus norvegicus
V134TMAQGVLEYKD3Homo sapiens, Mus musculus, Rattus norvegicus
V295DRGGGVPLRKI3Homo sapiens, Mus musculus, Rattus norvegicus
V75LLPDRVLSTPS2Homo sapiens, Rattus norvegicus
V75LLPDRVLGTPS1Mus musculus
V81LSTPSVQLVQS2Homo sapiens, Rattus norvegicus
V81LGTPSVQLVQS1Mus musculus
Y137QGVLEYKDTYG3Homo sapiens, Mus musculus, Rattus norvegicus
Y328LAGFGYGLPIS3Homo sapiens, Mus musculus, Rattus norvegicus
Y382SAWRHYQTIQE3Homo sapiens, Mus musculus, Rattus norvegicus
Y88LVQSWYVQSLL3Homo sapiens, Mus musculus, Rattus norvegicus


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