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 PDE2A
Gene summary
Basic gene Info.Gene symbolPDE2A
Gene namephosphodiesterase 2A, cGMP-stimulated
SynonymsCGS-PDE|PDE2A1|PED2A4|cGSPDE
CytomapUCSC genome browser: 11q13.4
Type of geneprotein-coding
RefGenesNM_001143839.3,
NM_001146209.2,NM_001243784.1,NM_002599.4,
DescriptioncGMP-dependent 3',5'-cyclic phosphodiesterasecGMP-stimulated phosphodiesterase 1cGMP-stimulated phosphodiesterase 4cyclic GMP-stimulated phosphodiesterase
Modification date20141207
dbXrefs MIM : 602658
HGNC : HGNC
Ensembl : ENSG00000186642
HPRD : 04041
Vega : OTTHUMG00000102045
ProteinUniProt: O00408
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PDE2A
BioGPS: 5138
PathwayNCI Pathway Interaction Database: PDE2A
KEGG: PDE2A
REACTOME: PDE2A
Pathway Commons: PDE2A
ContextiHOP: PDE2A
ligand binding site mutation search in PubMed: PDE2A
UCL Cancer Institute: PDE2A
Assigned class in mutLBSgeneDBA: This gene has a literature evidence and it belongs to targetable_mutLBSgenes.
References showing study about ligand binding site mutation for PDE2A.1. Heikaus, C. C., Stout, J. R., Sekharan, M. R., Eakin, C. M., Rajagopal, P., Brzovic, P. S., ... & Klevit, R. E. (2008). Solution Structure of the cGMP Binding GAF Domain from Phosphodiesterase 5 INSIGHTS INTO NUCLEOTIDE SPECIFICITY, DIMERIZATION, AND cGMP-DEPENDENT CONFORMATIONAL CHANGE. Journal of Biological Chemistry, 283(33), 22749-22759. 18534985

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 promoter17329248
GO:0006198cAMP catabolic process14687666
GO:0008152metabolic process17329248
GO:0033159negative regulation of protein import into nucleus, translocation17329248
GO:0036006cellular response to macrophage colony-stimulating factor stimulus14687666
GO:0046069cGMP catabolic process14687666
GO:0071321cellular response to cGMP17704206
GO:0097011cellular response to granulocyte macrophage colony-stimulating factor stimulus14687666


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Ligand binding site mutations for PDE2A
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
I866A867VCOAD1
I822K821RKIRC1
N704T703RLUAD1
N704N704SLUAD1
L774I776MLUSC1
Y655P653TLUSC1
I866A867VOV1
M847,M845E846KSKCM1
N704N704YSTAD1
N704,H700G702CUCEC1
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 PDE2A
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
N704N704Y0.21625259
N704N704S0.008137558
L774I776M-1.5330969
M845E846K-1.2817133
M847E846K-1.2817133
I866A867V-1.1876784
N704T703R-1.0810062
Y655P653T-1.0619263
N704G702C-0.48538548
H700G702C-0.48538548
I822K821R-0.38224486
(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 PDE2A from PDB

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Differential gene expression and gene-gene network for PDE2A
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 PDE2A and the right PPI network was created from samples without mutations in the LBS of PDE2A. 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 PDE2A
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C1458155Breast Neoplasms1Biomarker

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

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Pharmacological information for PDE2A
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
ExperimentalDB02315Cyclic Guanosine MonophosphateSmall molecule
InvestigationalDB05142ND7001Small molecule
ExperimentalDB079543-isobutyl-1-methyl-7H-xanthineSmall molecule
ApprovedDB08811TofisopamSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PDE2A go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
MGMAGNESIUM(2+)4d09CH700
MGMAGNESIUM(2+)4d09DH700
EH9(2S,3R)-EHNA4c1iDI866
788N-BENZYL-4-METHYL-1-PHENYL[1,2,4]TRIAZOLO[4, 3-A]QUINOXALINE-8-CARBOXAMIDE4d09DL774 I822 M847
788N-BENZYL-4-METHYL-1-PHENYL[1,2,4]TRIAZOLO[4, 3-A]QUINOXALINE-8-CARBOXAMIDE4d09AL774 M847
Q2T1-(5-BUTOXYPYRIDIN-3-YL)-4-METHYL-8- (MORPHOLIN-4-YLMETHYL)[1,2,4]TRIAZOLO[4,3-A] QUINOXALINE4d08CM845 M847
788N-BENZYL-4-METHYL-1-PHENYL[1,2,4]TRIAZOLO[4, 3-A]QUINOXALINE-8-CARBOXAMIDE4d09BM847
Q2T1-(5-BUTOXYPYRIDIN-3-YL)-4-METHYL-8- (MORPHOLIN-4-YLMETHYL)[1,2,4]TRIAZOLO[4,3-A] QUINOXALINE4d08DN704 M845 M847
Q2T1-(5-BUTOXYPYRIDIN-3-YL)-4-METHYL-8- (MORPHOLIN-4-YLMETHYL)[1,2,4]TRIAZOLO[4,3-A] QUINOXALINE4d08AN704 M847
Q2T1-(5-BUTOXYPYRIDIN-3-YL)-4-METHYL-8- (MORPHOLIN-4-YLMETHYL)[1,2,4]TRIAZOLO[4,3-A] QUINOXALINE4d08BN704 M847
IBM3-ISOBUTYL-1-METHYL-9H-XANTHINE3ituBY655
IBM3-ISOBUTYL-1-METHYL-9H-XANTHINE3ituCY655
IBM3-ISOBUTYL-1-METHYL-9H-XANTHINE3ituDY655
EH9(2S,3R)-EHNA4c1iAY655
EH9(2S,3R)-EHNA4c1iCY655
1L61-(2-HYDROXYETHYL)-3-(2-METHYLBUTAN-2-YL)-5-[4-(2- METHYL-1H-IMIDAZOL-1-YL)PHENYL]-6,7-DIHYDROPYRAZOLO[4, 3-E][1,4]DIAZEPIN-8(1H)-ONE4jibBY655 I822 M847 I866
EH9(2S,3R)-EHNA4c1iBY655 I866
788N-BENZYL-4-METHYL-1-PHENYL[1,2,4]TRIAZOLO[4, 3-A]QUINOXALINE-8-CARBOXAMIDE4d09CY655 L774 M847 I866
IBM3-ISOBUTYL-1-METHYL-9H-XANTHINE3ituAY655 M847
1L61-(2-HYDROXYETHYL)-3-(2-METHYLBUTAN-2-YL)-5-[4-(2- METHYL-1H-IMIDAZOL-1-YL)PHENYL]-6,7-DIHYDROPYRAZOLO[4, 3-E][1,4]DIAZEPIN-8(1H)-ONE4jibAY655 M847
1L61-(2-HYDROXYETHYL)-3-(2-METHYLBUTAN-2-YL)-5-[4-(2- METHYL-1H-IMIDAZOL-1-YL)PHENYL]-6,7-DIHYDROPYRAZOLO[4, 3-E][1,4]DIAZEPIN-8(1H)-ONE4jibCY655 M847
1L61-(2-HYDROXYETHYL)-3-(2-METHYLBUTAN-2-YL)-5-[4-(2- METHYL-1H-IMIDAZOL-1-YL)PHENYL]-6,7-DIHYDROPYRAZOLO[4, 3-E][1,4]DIAZEPIN-8(1H)-ONE4jibDY655 M847
19FBAY60-75502-(3,4-DIMETHOXYBENZYL)-7-[(2R,3R)-2-HYDROXY-6- PHENYLHEXAN-3-YL]-5-METHYLIMIDAZO[5,1-F][1,2, 4]TRIAZIN-4(3H)-ONE4htxAY655 M847 I866
19FBAY60-75502-(3,4-DIMETHOXYBENZYL)-7-[(2R,3R)-2-HYDROXY-6- PHENYLHEXAN-3-YL]-5-METHYLIMIDAZO[5,1-F][1,2, 4]TRIAZIN-4(3H)-ONE4htxBY655 M847 I866
19FBAY60-75502-(3,4-DIMETHOXYBENZYL)-7-[(2R,3R)-2-HYDROXY-6- PHENYLHEXAN-3-YL]-5-METHYLIMIDAZO[5,1-F][1,2, 4]TRIAZIN-4(3H)-ONE4htxCY655 M847 I866
19FBAY60-75502-(3,4-DIMETHOXYBENZYL)-7-[(2R,3R)-2-HYDROXY-6- PHENYLHEXAN-3-YL]-5-METHYLIMIDAZO[5,1-F][1,2, 4]TRIAZIN-4(3H)-ONE4htxDY655 M847 I866


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Conservation information for LBS of PDE2A
Multiple alignments for O00408 in multiple species
LBSAA sequence# speciesSpecies
D697SCMCHDLDHRG3Homo sapiens, Rattus norvegicus, Bos taurus
D808LMTSCDLSDQT3Homo sapiens, Rattus norvegicus, Bos taurus
D811SCDLSDQTKGW3Homo sapiens, Rattus norvegicus, Bos taurus
E727EGSVMERHHFA3Homo sapiens, Rattus norvegicus, Bos taurus
F830LIYKEFFSQGD3Homo sapiens, Rattus norvegicus, Bos taurus
F862ELQISFMEHIA3Homo sapiens, Rattus norvegicus, Bos taurus
H656RDPPYHNWMHA3Homo sapiens, Rattus norvegicus, Bos taurus
H660YHNWMHAFSVS3Homo sapiens, Rattus norvegicus, Bos taurus
H696ISCMCHDLDHR3Homo sapiens, Rattus norvegicus, Bos taurus
H700CHDLDHRGTNN3Homo sapiens, Rattus norvegicus, Bos taurus
H730VMERHHFAQAI3Homo sapiens, Rattus norvegicus, Bos taurus
H773TDLAHHLRIFK3Homo sapiens, Rattus norvegicus, Bos taurus
I822KTTRKIAELIY3Homo sapiens, Rattus norvegicus, Bos taurus
I826KIAELIYKEFF3Homo sapiens, Rattus norvegicus, Bos taurus
I866SFMEHIAMPIY3Homo sapiens, Rattus norvegicus, Bos taurus
I870HIAMPIYKLLQ3Homo sapiens, Rattus norvegicus, Bos taurus
L770ILATDLAHHLR3Homo sapiens, Rattus norvegicus, Bos taurus
L774DLAHHLRIFKD3Homo sapiens, Rattus norvegicus, Bos taurus
L809MTSCDLSDQTK3Homo sapiens, Rattus norvegicus, Bos taurus
L858AYIPELQISFM3Homo sapiens, Rattus norvegicus, Bos taurus
M845MGNRPMEMMDR3Homo sapiens, Rattus norvegicus, Bos taurus
M847NRPMEMMDREK3Homo sapiens, Rattus norvegicus, Bos taurus
M848RPMEMMDREKA3Homo sapiens, Rattus norvegicus, Bos taurus
N704DHRGTNNSFQV3Homo sapiens, Rattus norvegicus, Bos taurus
Q812CDLSDQTKGWK3Homo sapiens, Rattus norvegicus, Bos taurus
Q859YIPELQISFME3Homo sapiens, Rattus norvegicus, Bos taurus
S721AALYSSEGSVM3Homo sapiens, Rattus norvegicus, Bos taurus
S861PELQISFMEHI3Homo sapiens, Rattus norvegicus, Bos taurus
T768DIILATDLAHH3Homo sapiens, Rattus norvegicus, Bos taurus
T805LCLLMTSCDLS3Homo sapiens, Rattus norvegicus, Bos taurus
Y655YRDPPYHNWMH3Homo sapiens, Rattus norvegicus, Bos taurus
Y827IAELIYKEFFS3Homo sapiens, Rattus norvegicus, Bos taurus


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