mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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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 PPP3CA
Gene summary
Basic gene Info.Gene symbolPPP3CA
Gene nameprotein phosphatase 3, catalytic subunit, alpha isozyme
SynonymsCALN|CALNA|CALNA1|CCN1|CNA1|PPP2B
CytomapUCSC genome browser: 4q24
Type of geneprotein-coding
RefGenesNM_000944.4,
NM_001130691.1,NM_001130692.1,
DescriptionCAM-PRP catalytic subunitcalcineurin A alphacalmodulin-dependent calcineurin A subunit alpha isoformprotein phosphatase 2B, catalytic subunit, alpha isoformprotein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoformserine/threonine-protein
Modification date20141207
dbXrefs MIM : 114105
HGNC : HGNC
Ensembl : ENSG00000138814
HPRD : 00234
Vega : OTTHUMG00000133839
ProteinUniProt: Q08209
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PPP3CA
BioGPS: 5530
PathwayNCI Pathway Interaction Database: PPP3CA
KEGG: PPP3CA
REACTOME: PPP3CA
Pathway Commons: PPP3CA
ContextiHOP: PPP3CA
ligand binding site mutation search in PubMed: PPP3CA
UCL Cancer Institute: PPP3CA
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:0006470protein dephosphorylation18815128
GO:0033173calcineurin-NFAT signaling cascade22688515
GO:0035690cellular response to drug11005320
GO:0045944positive regulation of transcription from RNA polymerase II promoter22688515
GO:0051533positive regulation of NFAT protein import into nucleus22688515
GO:0051592response to calcium ion18815128


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Ligand binding site mutations for PPP3CA

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
M329M329VBLCA1
H281E282DBRCA1
D118G117WCOAD1
H199V198LLUSC1
Y341P340SSKCM1
N150H151YSKCM1
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 PPP3CA
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
N150H151Y0.06075911
Y341P340S-1.2314566
H199V198L-1.0232237
M329M329V-1.022648
D118G117W-0.61056167
H281E282D-0.31248807
(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 PPP3CA from PDB

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Differential gene expression and gene-gene network for PPP3CA
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 PPP3CA and the right PPI network was created from samples without mutations in the LBS of PPP3CA. 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 PPP3CA
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0270611Brain Injuries2Biomarker
umls:C0149721Hypertrophy, Left Ventricular1Biomarker
umls:C0030305Pancreatitis1Biomarker
umls:C0031117Peripheral Nervous System Diseases1Biomarker
umls:C0033578Prostatic Neoplasms1Biomarker
umls:C0039584Testicular Diseases1Biomarker

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

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Pharmacological information for PPP3CA
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
ExperimentalDB08231MYRISTIC ACIDSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PPP3CA go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
FEIRON(3+)2p6bAD118
FEIRON(3+)2p6bCD118
FEIRON(3+)3ll8AD118
FEIRON(3+)3ll8CD118
FEIRON(3+)1auiAD118 H281
FEIRON(3+)1m63AD118 H281
FEIRON(3+)1m63ED118 H281
ZNZINC(2+)1auiAD118 N150 H199 H281
ZNZINC(2+)1m63AD118 N150 H199 H281
ZNZINC(2+)1m63ED118 N150 H199 H281
ZNZINC(2+)2p6bAD118 N150 H199 H281
ZNZINC(2+)2p6bCD118 N150 H199 H281
ZNZINC(2+)3ll8AD118 N150 H199 H281
ZNZINC(2+)3ll8CD118 N150 H199 H281
IIIPeptide ligand (GLY,PRO,HIS,PRO,VAL,ILE,VAL,ILE,THR,GLY,PRO,HIS,GLU,GLU,LEU,GLU)2jogAM329
IIIPeptide ligand (PRO,HIS,PRO,VAL,ILE,VAL,ILE,THR,GLY,PRO,HIS,GLU,GLU,NH2)2p6bAM329
IIIPeptide ligand (PRO,HIS,PRO,VAL,ILE,VAL,ILE,THR,GLY,PRO,HIS,GLU,GLU,NH2)2p6bCM329
IIIPeptide ligand (GLU,PRO,ILE,ALA,ILE,ILE,ILE,THR,ASP,THR,GLU)3ll8AM329
IIIPeptide ligand (DAL,MLE,MLE,MVA,BMT,ABA,SAR,MLE,VAL,MLE,ALA)1m63AY341
IIIPeptide ligand (DAL,MLE,MLE,MVA,BMT,ABA,SAR,MLE,VAL,MLE,ALA)1m63EY341
IIIPeptide ligand (DAL,MLE,MLE,MVA,BMT,ABA,SAR,MLE,VAL,MLE,ALA)1mf8AY341


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Conservation information for LBS of PPP3CA
Multiple alignments for Q08209 in multiple species
LBSAA sequence# speciesSpecies
D118YLFLGDYVDRG8Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
D90VTVCGDIHGQF6Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
D90ITICGDIHGQY1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D90VTVCGDIHGQY1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
E103LMKLFEVGGSP5Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster
E103LLKLFEVGGDP1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
E103LMKLFEVGGNP1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
E103LMKLFEIGGSP1Drosophila melanogaster
F299SQTTGFPSLIT6Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
F299NKVTGFPSLIT1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
F299TKTTGFPSLMT1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F356TWSLPFVGEKV8Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
G298KSQTTGFPSLI6Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
G298NNKVTGFPSLI1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G298KTKTTGFPSLM1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
H199QFLCVHGGLSP7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
H199QYFCVHGGISP1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
H281SILRAHEAQDA4Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
H281SIIRAHEAQDA3Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Drosophila melanogaster, Drosophila melanogaster
H281SVIRAHEAQDV1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
H92VCGDIHGQFFD4Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
H92VCGDIHGQFYD2Drosophila melanogaster, Drosophila melanogaster
H92ICGDIHGQYYD1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
H92VCGDIHGQYYD1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
I331NNVMNIRQFNC7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
I331ENVMNIRQFHM1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K100FFDLMKLFEVG4Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
K100YYDLLKLFEVG1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K100YYDLMKLFEVG1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K100FYDLMKLFEIG1Drosophila melanogaster
K100FYDLMKLFEVG1Drosophila melanogaster
K318DVYNNKAAVLK7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
K318DTYHNKAAVLK1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L275QHNNLLSILRA4Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
L275QNNNLLSIIRA2Drosophila melanogaster, Drosophila melanogaster
L275KANGLLSIIRA1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L275ENNNLLSVIRA1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L312SAPNYLDVYNN7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
L312SAPNYLDTYHN1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L343PHPYWLPNFMD7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
L343PHPYWLPDFMD1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
M290DAGYRMYRKSQ6Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
M290DAGYRMYKNNK1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
M290DVGYRMYRKTK1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
M329YENNVMNIRQF7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
M329YEENVMNIRQF1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N150FLLRGNHECRH6Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
N150WMLRGNHECKH1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N150WLLRGNHECAH1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
N316YLDVYNNKAAV7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
N316YLDTYHNKAAV1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N327LKYENNVMNIR7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
N327LKYEENVMNIR1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N330ENNVMNIRQFN7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
N330EENVMNIRQFH1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N335NIRQFNCSPHP7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
N335NIRQFHMSPHP1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
P300QTTGFPSLITI6Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
P300KVTGFPSLITM1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
P300KTTGFPSLMTI1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
P344HPYWLPNFMDV7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
P344HPYWLPDFMDV1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Q333VMNIRQFNCSP7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
Q333VMNIRQFHMSP1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
R122GDYVDRGYFSI7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
R122GDYVDRGAFSF1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
R332NVMNIRQFNCS7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
R332NVMNIRQFHMS1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
T297RKSQTTGFPSL6Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
T297KNNKVTGFPSL1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
T297RKTKTTGFPSL1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V104MKLFEVGGSPA5Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster
V104LKLFEVGGDPA1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V104MKLFEVGGNPA1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V104MKLFEIGGSPA1Drosophila melanogaster
V314PNYLDVYNNKA7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
V314PNYLDTYHNKA1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V328KYENNVMNIRQ7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
V328KYEENVMNIRQ1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
W342SPHPYWLPNFM7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
W342SPHPYWLPDFM1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
W352MDVFTWSLPFV8Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
Y288AQDAGYRMYRK6Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
Y288AQDAGYRMYKN1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Y288AQDVGYRMYRK1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y324AAVLKYENNVM7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
Y324AAVLKYEENVM1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Y341CSPHPYWLPNF7Homo sapiens, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Bos taurus, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Drosophila melanogaster
Y341MSPHPYWLPDF1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)


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