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 PRKCA
Gene summary
Basic gene Info.Gene symbolPRKCA
Gene nameprotein kinase C, alpha
SynonymsAAG6|PKC-alpha|PKCA|PRKACA
CytomapUCSC genome browser: 17q22-q23.2
Type of geneprotein-coding
RefGenesNM_002737.2,
DescriptionPKC-Aaging-associated gene 6protein kinase C alpha type
Modification date20141222
dbXrefs MIM : 176960
HGNC : HGNC
Ensembl : ENSG00000154229
HPRD : 01498
Vega : OTTHUMG00000179533
ProteinUniProt: P17252
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PRKCA
BioGPS: 5578
PathwayNCI Pathway Interaction Database: PRKCA
KEGG: PRKCA
REACTOME: PRKCA
Pathway Commons: PRKCA
ContextiHOP: PRKCA
ligand binding site mutation search in PubMed: PRKCA
UCL Cancer Institute: PRKCA
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:0006468protein phosphorylation10770950
GO:0035408histone H3-T6 phosphorylation20228790
GO:0043536positive regulation of blood vessel endothelial cell migration20011604
GO:0090330regulation of platelet aggregation12724315


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Ligand binding site mutations for PRKCA

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
D481D481ECOAD1
C115D116NCOAD1
N468N468KLUSC1
T134,C132D133NLUSC1
D424L425FSKCM1
C115D116NSKCM1
C151G152RSKCM1
C151G152RSTAD1
E387R389QUCEC1
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 PRKCA
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
C132D133N-1.0602042
T134D133N-1.0602042
C115D116N-1.0189324
D481D481E-0.93492989
N468N468K-0.87795264
D424L425F-0.82919993
C151G152R-0.55964941
E387R389Q-0.53304676
(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 PRKCA from PDB

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Differential gene expression and gene-gene network for PRKCA
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 PRKCA and the right PPI network was created from samples without mutations in the LBS of PRKCA. 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 PRKCA
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0018800Cardiomegaly2Biomarker
umls:C0011853Diabetes Mellitus, Experimental1Biomarker
umls:C0021841Intestinal Neoplasms1Biomarker

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

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Pharmacological information for PRKCA
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
Approved|nutraceuticalDB00144Phosphatidyl serineSmall molecule
Approved|nutraceutical|vet_approvedDB00163Vitamin ESmall molecule
ApprovedDB00675TamoxifenSmall molecule
ApprovedDB05013Ingenol MebutateSmall molecule
InvestigationalDB08846Ellagic AcidSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PRKCA go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
LW43-(1H-INDOL-3-YL)-4-[2-(4-METHYLPIPERAZIN-1-YL)QUINAZOLIN-4-YL]-1H-PYRROLE-2,5-DIONE3iw4BE387 D424 N468 D481
LW43-(1H-INDOL-3-YL)-4-[2-(4-METHYLPIPERAZIN-1-YL)QUINAZOLIN-4-YL]-1H-PYRROLE-2,5-DIONE3iw4AE387 D481
LW43-(1H-INDOL-3-YL)-4-[2-(4-METHYLPIPERAZIN-1-YL)QUINAZOLIN-4-YL]-1H-PYRROLE-2,5-DIONE3iw4CE387 N468 D481


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Conservation information for LBS of PRKCA
Multiple alignments for P17252 in multiple species
LBSAA sequence# speciesSpecies
A366TEELYAIKILK3Homo sapiens, Bos taurus, Mus musculus
A366TKELFAIKVLK1Caenorhabditis elegans
A366SEELYAIKILK1Drosophila melanogaster
A480GHIKIADFGMC3Homo sapiens, Bos taurus, Mus musculus
A480GHIKITDFGMC1Caenorhabditis elegans
A480GHVKIADFGMC1Drosophila melanogaster
C115GSPTFCDHCGS3Homo sapiens, Bos taurus, Mus musculus
C115SSPTFCDHCGS1Caenorhabditis elegans
C115AGPTFCDHCGS1Drosophila melanogaster
C118TFCDHCGSLLY5Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Bos taurus, Mus musculus
C132HQGMKCDTCDM3Homo sapiens, Bos taurus, Mus musculus
C132HQGMKCQSCDT1Caenorhabditis elegans
C132HQGLKCSACDM1Drosophila melanogaster
C135MKCDTCDMNVH3Homo sapiens, Bos taurus, Mus musculus
C135MKCQSCDTNVH1Caenorhabditis elegans
C135LKCSACDMNVH1Drosophila melanogaster
C143NVHKQCVINVP2Homo sapiens, Bos taurus
C143NVHHRCVKNVP1Caenorhabditis elegans
C143NVHARCKENVP1Drosophila melanogaster
C143NVHKQCVINDP1Mus musculus
C151NVPSLCGMDHT2Homo sapiens, Bos taurus
C151NVPNMCGTDNT1Caenorhabditis elegans
C151NVPSLCGCDHT1Drosophila melanogaster
C151NDPSLCGMDHT1Mus musculus
D424YVNGGDLMYHI3Homo sapiens, Bos taurus, Mus musculus
D424FVNGGDLMYQI1Caenorhabditis elegans
D424YVNGGDLMFQI1Drosophila melanogaster
D467RDLKLDNVMLD2Homo sapiens, Bos taurus
D467RDLKLDNVMLE1Caenorhabditis elegans
D467RDLKLDNVLLD1Drosophila melanogaster
D467RDLKLNNVMLN1Mus musculus
D481HIKIADFGMCK3Homo sapiens, Bos taurus, Mus musculus
D481HIKITDFGMCK1Caenorhabditis elegans
D481HVKIADFGMCK1Drosophila melanogaster
E387ECTMVEKRVLA3Homo sapiens, Bos taurus, Mus musculus
E387ECTMTEKRVLA1Caenorhabditis elegans
E387ECTMIEKRVLA1Drosophila melanogaster
E418LYFVMEYVNGG3Homo sapiens, Bos taurus, Mus musculus
E418LYFVMEFVNGG1Caenorhabditis elegans
E418LFFVMEYVNGG1Drosophila melanogaster
F350LGKGSFGKVML3Homo sapiens, Bos taurus, Mus musculus
F350LGKGSFGKVLL2Caenorhabditis elegans, Drosophila melanogaster
G346FLMVLGKGSFG3Homo sapiens, Bos taurus, Mus musculus
G346FLTVLGKGSFG1Caenorhabditis elegans
G346FIKVLGKGSFG1Drosophila melanogaster
H102DPRSKHKFKIH3Homo sapiens, Bos taurus, Mus musculus
H102DPRQQHKWKVQ1Caenorhabditis elegans
H102SPKTQHNFEPF1Drosophila melanogaster
H140CDMNVHKQCVI3Homo sapiens, Bos taurus, Mus musculus
H140CDTNVHHRCVK1Caenorhabditis elegans
H140CDMNVHARCKE1Drosophila melanogaster
K368ELYAIKILKKD4Homo sapiens, Drosophila melanogaster, Bos taurus, Mus musculus
K368ELFAIKVLKKD1Caenorhabditis elegans
L345NFLMVLGKGSF3Homo sapiens, Bos taurus, Mus musculus
L345NFLTVLGKGSF1Caenorhabditis elegans
L345NFIKVLGKGSF1Drosophila melanogaster
M417RLYFVMEYVNG3Homo sapiens, Bos taurus, Mus musculus
M417RLYFVMEFVNG1Caenorhabditis elegans
M417RLFFVMEYVNG1Drosophila melanogaster
M470KLDNVMLDSEG2Homo sapiens, Bos taurus
M470KLDNVMLERDG1Caenorhabditis elegans
M470KLDNVLLDADG1Drosophila melanogaster
M470KLNNVMLNSEG1Mus musculus
N468DLKLDNVMLDS2Homo sapiens, Bos taurus
N468DLKLDNVMLER1Caenorhabditis elegans
N468DLKLDNVLLDA1Drosophila melanogaster
N468DLKLNNVMLNS1Mus musculus
T134GMKCDTCDMNV3Homo sapiens, Bos taurus, Mus musculus
T134GMKCQSCDTNV1Caenorhabditis elegans
T134GLKCSACDMNV1Drosophila melanogaster
T401KPPFLTQLHSC3Homo sapiens, Bos taurus, Mus musculus
T401KPSFLVALHSC1Caenorhabditis elegans
T401KPPFLVQLHSC1Drosophila melanogaster
V353GSFGKVMLADR3Homo sapiens, Bos taurus, Mus musculus
V353GSFGKVLLGEQ1Caenorhabditis elegans
V353GSFGKVLLAER1Drosophila melanogaster
V420FVMEYVNGGDL4Homo sapiens, Drosophila melanogaster, Bos taurus, Mus musculus
V420FVMEFVNGGDL1Caenorhabditis elegans
Y419YFVMEYVNGGD3Homo sapiens, Bos taurus, Mus musculus
Y419YFVMEFVNGGD1Caenorhabditis elegans
Y419FFVMEYVNGGD1Drosophila melanogaster


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