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 TOP2A
Gene summary
Basic gene Info.Gene symbolTOP2A
Gene nametopoisomerase (DNA) II alpha 170kDa
SynonymsTOP2|TP2A
CytomapUCSC genome browser: 17q21-q22
Type of geneprotein-coding
RefGenesNM_001067.3,
DescriptionDNA gyraseDNA topoisomerase (ATP-hydrolyzing)DNA topoisomerase 2-alphaDNA topoisomerase II, 170 kDDNA topoisomerase II, alpha isozyme
Modification date20141222
dbXrefs MIM : 126430
HGNC : HGNC
Ensembl : ENSG00000131747
HPRD : 00536
Vega : OTTHUMG00000155008
ProteinUniProt: P11388
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_TOP2A
BioGPS: 7153
PathwayNCI Pathway Interaction Database: TOP2A
KEGG: TOP2A
REACTOME: TOP2A
Pathway Commons: TOP2A
ContextiHOP: TOP2A
ligand binding site mutation search in PubMed: TOP2A
UCL Cancer Institute: TOP2A
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:0006200ATP catabolic process12079377
GO:0006265DNA topological change22323612
GO:0006266DNA ligation15491148
GO:0006974cellular response to DNA damage stimulus16611985
GO:0030263apoptotic chromosome condensation10959840
GO:0043065positive regulation of apoptotic process16611985


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Ligand binding site mutations for TOP2A
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
K949E948GBRCA1
N492R494LHNSC1
R929V928IKIRC1
R713E712VLUAD1
Y757S756FSKCM1
N91,E87L89IUCEC1
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 TOP2A
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
K949E948G-1.1345693
R929V928I-1.0536911
E87L89I-0.92339062
N91L89I-0.92339062
R713E712V-0.79339596
Y757S756F-0.51943682
N492R494L-0.45349653
(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 TOP2A from PDB

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Differential gene expression and gene-gene network for TOP2A
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 TOP2A and the right PPI network was created from samples without mutations in the LBS of TOP2A. 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 TOP2A
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C1458155Breast Neoplasms16AlteredExpression, Biomarker, GeneticVariation
umls:C0023418Leukemia4Biomarker
umls:C0017638Glioma3AlteredExpression, Biomarker
umls:C0206686Adrenocortical Carcinoma1Biomarker
umls:C0010606Carcinoma, Adenoid Cystic1Biomarker
umls:C0017661Glomerulonephritis, IGA1Biomarker
umls:C0032460Polycystic Ovary Syndrome1Biomarker
umls:C0033578Prostatic Neoplasms1Biomarker
umls:C0036095Salivary Gland Neoplasms1Biomarker

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

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Pharmacological information for TOP2A
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|investigationalDB00218MoxifloxacinSmall molecule
ApprovedDB00276AmsacrineSmall molecule
Approved|withdrawnDB00380DexrazoxaneSmall molecule
ApprovedDB00385ValrubicinSmall molecule
ApprovedDB00444TeniposideSmall molecule
ApprovedDB00445EpirubicinSmall molecule
ApprovedDB00467EnoxacinSmall molecule
ApprovedDB00487PefloxacinSmall molecule
Approved|investigationalDB00537CiprofloxacinSmall molecule
Approved|withdrawnDB00685TrovafloxacinSmall molecule
ApprovedDB00694DaunorubicinSmall molecule
ApprovedDB00773EtoposideSmall molecule
ApprovedDB00970DactinomycinSmall molecule
ApprovedDB00978LomefloxacinSmall molecule
Approved|investigationalDB00997DoxorubicinSmall molecule
ApprovedDB01059NorfloxacinSmall molecule
Approved|investigationalDB01137LevofloxacinSmall molecule
ApprovedDB01165OfloxacinSmall molecule
ApprovedDB01177IdarubicinSmall molecule
ApprovedDB01179PodofiloxSmall molecule
Approved|investigationalDB01204MitoxantroneSmall molecule
ApprovedDB01208SparfloxacinSmall molecule
InvestigationalDB01645GenisteinSmall molecule
ApprovedDB04576FleroxacinSmall molecule
Approved|investigationalDB04967LucanthoneSmall molecule
InvestigationalDB04975BanoxantroneSmall molecule
InvestigationalDB04978SP1049CSmall molecule
InvestigationalDB05022AmonafideSmall molecule
InvestigationalDB05129ElsamitrucinSmall molecule
InvestigationalDB05920RTA 744Small molecule
InvestigationalDB06042ZEN-012Small molecule
ApprovedDB09047FinafloxacinSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of TOP2A go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
ANPAMP-PNP1zxmBE87 N91
NUCNucleic Acids4fm9AN492 K949
ANPAMP-PNP1zxmAN91
ADPADP1zxnAN91
ADPADP1zxnBN91
ADPADP1zxnCN91
ADPADP1zxnDN91
ADPADP4r1fAN91
ADPADP4r1fBN91
ADPADP4r1fCN91
MGMAGNESIUM(2+)4r1fDN91
ADPADP4r1fDN91
NUCNucleic Acids4fm9AR713 Y757 R929


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Conservation information for LBS of TOP2A
Multiple alignments for P11388 in multiple species
LBSAA sequence# speciesSpecies
A167RNGYGAKLCNI6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
D541IMIMTDQDQDG4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
D541LMVMADQDQDG1Caenorhabditis elegans
D541VMIMTDQDQDG1Drosophila melanogaster
D543IMTDQDQDGSH5Homo sapiens, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
D543VMADQDQDGSH1Caenorhabditis elegans
D545TDQDQDGSHIK5Homo sapiens, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
D545ADQDQDGSHIK1Caenorhabditis elegans
E461TLILTEGDSAK6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
E854LINGAEGIGTG4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
E854LVNGAQGIGTG1Caenorhabditis elegans
E854LVNGAEGIGTG1Drosophila melanogaster
E87YKIFDEILVNA5Homo sapiens, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
E87YKIYDEILVNA1Caenorhabditis elegans
F142VPALIFGQLLT4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
F142VPELIFGTLLT1Caenorhabditis elegans
F142VPTMIFGHLLT1Drosophila melanogaster
F653AISLAFSKKQV2Mus musculus, Rattus norvegicus
F653AISLAFSKKQI1Homo sapiens
F653AVDMAFSKKKI1Caenorhabditis elegans
F653SIVMAFSKKHI1Drosophila melanogaster
F653AITLAFSKKKV1Gallus gallus
G161KKVTGGRNGYG6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
G164TGGRNGYGAKL6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
G166GRNGYGAKLCN6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
G488VFPLRGKILNV3Homo sapiens, Mus musculus, Rattus norvegicus
G488VFPLRGKLLNV2Caenorhabditis elegans, Drosophila melanogaster
G488VFPLRGKMLNV1Gallus gallus
G857GAEGIGTGWSC4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
G857GAQGIGTGWST1Caenorhabditis elegans
G857GAEGIGTGWST1Drosophila melanogaster
G859EGIGTGWSCKI4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
G859QGIGTGWSTNI1Caenorhabditis elegans
G859EGIGTGWSTKI1Drosophila melanogaster
H548DQDGSHIKGLL5Homo sapiens, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
H548DQDGSHIKGLV1Caenorhabditis elegans
I125NNGKGIPVVEH4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
I125NNGKGIPVTQH1Caenorhabditis elegans
I125NNGQGIPVTMH1Drosophila melanogaster
I141YVPALIFGQLL4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
I141YVPELIFGTLL1Caenorhabditis elegans
I141YVPTMIFGHLL1Drosophila melanogaster
I490PLRGKILNVRE3Homo sapiens, Mus musculus, Rattus norvegicus
I490PLRGKLLNVRE2Caenorhabditis elegans, Drosophila melanogaster
I490PLRGKMLNVRE1Gallus gallus
I658FSKKQVDDRKE2Mus musculus, Rattus norvegicus
I658FSKKQIDDRKE1Homo sapiens
I658FSKKKIEERKD1Caenorhabditis elegans
I658FSKKHIESRKV1Drosophila melanogaster
I658FSKKKVEERKE1Gallus gallus
I856NGAEGIGTGWS5Homo sapiens, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
I856NGAQGIGTGWS1Caenorhabditis elegans
K168NGYGAKLCNIF6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
K378FDSQTKENMTL5Homo sapiens, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
K378FDSQTKETMTL1Caenorhabditis elegans
K489FPLRGKILNVR3Homo sapiens, Mus musculus, Rattus norvegicus
K489FPLRGKLLNVR2Caenorhabditis elegans, Drosophila melanogaster
K489FPLRGKMLNVR1Gallus gallus
K614KVKYYKGLGTS3Homo sapiens, Mus musculus, Rattus norvegicus
K614KIKYYKGLGTS2Caenorhabditis elegans, Gallus gallus
K614NIKYYKGLGTS1Drosophila melanogaster
K662QVDDRKEWLTN2Mus musculus, Rattus norvegicus
K662QIDDRKEWLTN1Homo sapiens
K662KIEERKDWLSK1Caenorhabditis elegans
K662HIESRKVWLTN1Drosophila melanogaster
K662KVEERKEWLTN1Gallus gallus
K723MVDGLKPGQRK3Homo sapiens, Mus musculus, Rattus norvegicus
K723LVDGLKPGQRK2Drosophila melanogaster, Gallus gallus
K723LVDGFKPGQRK1Caenorhabditis elegans
K798RLHGGKDSASP4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
K798RLQGGKDSASA1Caenorhabditis elegans
K798RLSGGKDCASA1Drosophila melanogaster
K949LNGTEKTPPLI3Homo sapiens, Gallus gallus, Rattus norvegicus
K949MESSDKKSPVI1Caenorhabditis elegans
K949SNGTEKVKGII1Drosophila melanogaster
K949LNGTEKTPSLI1Mus musculus
K990LHKVFKLQTSL2Homo sapiens, Rattus norvegicus
K990LHQVFKLQAVI1Caenorhabditis elegans
K990FYRVFKLTTTL1Drosophila melanogaster
K990LHKVFKLQTNL1Gallus gallus
K990LHKVFKLQSSL1Mus musculus
L491LRGKILNVREA3Homo sapiens, Mus musculus, Rattus norvegicus
L491LRGKLLNVREG1Caenorhabditis elegans
L491LRGKLLNVREA1Drosophila melanogaster
L491LRGKMLNVREA1Gallus gallus
L552SHIKGLLINFI5Homo sapiens, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
L552SHIKGLVINFI1Caenorhabditis elegans
N120LISIWNNGKGI2Homo sapiens, Rattus norvegicus
N120EISVYNNGKGI1Caenorhabditis elegans
N120MVSVWNNGQGI1Drosophila melanogaster
N120TISVWNNGKGI1Gallus gallus
N120VISIWNNGKGI1Mus musculus
N150LLTSSNYDDDE4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
N150LLTSSNYNDDE2Caenorhabditis elegans, Drosophila melanogaster
N163VTGGRNGYGAK6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
N492RGKILNVREAS3Homo sapiens, Mus musculus, Rattus norvegicus
N492RGKLLNVREGN1Caenorhabditis elegans
N492RGKLLNVREAN1Drosophila melanogaster
N492RGKMLNVREAS1Gallus gallus
N91DEILVNAADNK6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
N95VNAADNKQRDP4Homo sapiens, Caenorhabditis elegans, Mus musculus, Rattus norvegicus
N95VNAADNKQRDK2Drosophila melanogaster, Gallus gallus
N998TSLTCNSMVLF2Homo sapiens, Rattus norvegicus
N998AVINTTCMVLF1Caenorhabditis elegans
N998TTLSTNQMHAF1Drosophila melanogaster
N998TNLTCNSMVLF1Gallus gallus
N998SSLTCNSMVLF1Mus musculus
Q376PTFDSQTKENM5Homo sapiens, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
Q376PTFDSQTKETM1Caenorhabditis elegans
Q500EASHKQIMENA4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
Q500EGNMKQIADNA1Caenorhabditis elegans
Q500EANFKQLSENA1Drosophila melanogaster
R162KVTGGRNGYGA6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
R661KQVDDRKEWLT2Mus musculus, Rattus norvegicus
R661KQIDDRKEWLT1Homo sapiens
R661KKIEERKDWLS1Caenorhabditis elegans
R661KHIESRKVWLT1Drosophila melanogaster
R661KKVEERKEWLT1Gallus gallus
R713NSDNERSIPSM3Homo sapiens, Mus musculus, Rattus norvegicus
R713NLDNERSIPCL1Caenorhabditis elegans
R713NADNERSIPSL1Drosophila melanogaster
R713NSDNERSIPSL1Gallus gallus
R929SELPVRTWTQT1Homo sapiens
R929TELPIKQWTQD1Caenorhabditis elegans
R929SELPVGVWTQN1Drosophila melanogaster
R929TELPVRTWTQT1Gallus gallus
R929SELPIRTWTQT1Mus musculus
R929TELPIRTWTQT1Rattus norvegicus
R98ADNKQRDPKMS3Homo sapiens, Mus musculus, Rattus norvegicus
R98ADNKQRDPKMN1Caenorhabditis elegans
R98ADNKQRDKSMN1Drosophila melanogaster
R98ADNKQRDKSMS1Gallus gallus
S148GQLLTSSNYDD4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
S148GTLLTSSNYND1Caenorhabditis elegans
S148GHLLTSSNYND1Drosophila melanogaster
S149QLLTSSNYDDD4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
S149TLLTSSNYNDD1Caenorhabditis elegans
S149HLLTSSNYNDD1Drosophila melanogaster
S497NVREASHKQIM4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
S497NVREGNMKQIA1Caenorhabditis elegans
S497NVREANFKQLS1Drosophila melanogaster
S763HHGEMSLMMTI3Homo sapiens, Mus musculus, Rattus norvegicus
S763HHGEQSLMGTI1Caenorhabditis elegans
S763HHGEVSLQMTI1Drosophila melanogaster
S763HHGEASLMMTI1Gallus gallus
S861IGTGWSCKIPN4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
S861IGTGWSTNIPN1Caenorhabditis elegans
S861IGTGWSTKISN1Drosophila melanogaster
S994FKLQTSLTCNS2Homo sapiens, Rattus norvegicus
S994FKLQAVINTTC1Caenorhabditis elegans
S994FKLTTTLSTNQ1Drosophila melanogaster
S994FKLQTNLTCNS1Gallus gallus
S994FKLQSSLTCNS1Mus musculus
S999SLTCNSMVLFD3Homo sapiens, Mus musculus, Rattus norvegicus
S999VINTTCMVLFD1Caenorhabditis elegans
S999TLSTNQMHAFD1Drosophila melanogaster
S999NLTCNSMVLFD1Gallus gallus
T147FGQLLTSSNYD4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
T147FGTLLTSSNYN1Caenorhabditis elegans
T147FGHLLTSSNYN1Drosophila melanogaster
T215SGEDYTCITFQ2Mus musculus, Rattus norvegicus
T215NGEDYTCITFQ1Homo sapiens
T215TDEDFTKITFS1Caenorhabditis elegans
T215NGTDYTRITFS1Drosophila melanogaster
T215DGEDYTCVTFQ1Gallus gallus
T858AEGIGTGWSCK4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
T858AQGIGTGWSTN1Caenorhabditis elegans
T858AEGIGTGWSTK1Drosophila melanogaster
T996LQTSLTCNSMV2Homo sapiens, Rattus norvegicus
T996LQAVINTTCMV1Caenorhabditis elegans
T996LTTTLSTNQMH1Drosophila melanogaster
T996LQTNLTCNSMV1Gallus gallus
T996LQSSLTCNSMV1Mus musculus
W860GIGTGWSCKIP4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
W860GIGTGWSTNIP1Caenorhabditis elegans
W860GIGTGWSTKIS1Drosophila melanogaster
W931LPVRTWTQTYK2Homo sapiens, Gallus gallus
W931LPIRTWTQTYK2Mus musculus, Rattus norvegicus
W931LPIKQWTQDYK1Caenorhabditis elegans
W931LPVGVWTQNYK1Drosophila melanogaster
Y165GGRNGYGAKLC6Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Gallus gallus, Mus musculus, Rattus norvegicus
Y757AEMSSYHHGEM3Homo sapiens, Mus musculus, Rattus norvegicus
Y757AEISAYHHGEQ1Caenorhabditis elegans
Y757AEMSAYHHGEV1Drosophila melanogaster
Y757AEMSSYHHGEA1Gallus gallus


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