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TOP2A Gene

protein-coding   GIFtS: 72
GCID: GC17M038544

Topoisomerase (DNA) II Alpha 170kDa

(Previous name: topoisomerase (DNA) II alpha (170kD))
(Previous symbol: TOP2)
  See TOP2A-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Topoisomerase (DNA) II Alpha 170kDa1 2     TP2A2
TOP21 2 3 5     DNA Gyrase2
DNA Topoisomerase II, Alpha Isozyme2 3     DNA Topoisomerase (ATP-Hydrolyzing)2
EC 5.99.1.33 8     DNA Topoisomerase 2-Alpha2
Topoisomerase (DNA) II Alpha (170kD)1     DNA Topoisomerase II, 170 KD2

External Ids:    HGNC: 119891   Entrez Gene: 71532   Ensembl: ENSG000001317477   OMIM: 1264305   UniProtKB: P113883   

Export aliases for TOP2A gene to outside databases

Previous GC identifers: GC17M038044 GC17M040720 GC17M038453 GC17M038919 GC17M038920 GC17M035798 GC17M034337


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TOP2A Gene:
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during
transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid
separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes
the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one
another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene
duplication event. The gene encoding this form, alpha, is localized to chromosome 17 and the beta gene is
localized to chromosome 3. The gene encoding this enzyme functions as the target for several anticancer agents
and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced
activity of this enzyme may also play a role in ataxia-telangiectasia. (provided by RefSeq, Jul 2010)

GeneCards Summary for TOP2A Gene:
TOP2A (topoisomerase (DNA) II alpha 170kDa) is a protein-coding gene. Diseases associated with TOP2A include dna topoisomerase ii inhibition of, by amsacrine, and cervix endometriosis. GO annotations related to this gene include chromatin binding and protein homodimerization activity. An important paralog of this gene is TOP2B.

UniProtKB/Swiss-Prot: TOP2A_HUMAN, P11388
Function: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands.
Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of
daughter chromosomes

summary for TOP2A Gene:
Topoisomerases are ubiquitously expressed enzymes that overcome topological problems in genomic DNA, which
can result from DNA replication, transcription and repair. Common problems such as overwinding (positive
supercoiling), knots and tangles are resolved by topoisomerases by catalysing the breaking of one or two
strands of DNA. Topoisomerase type I enzymes cut just one strand of the DNA double helix, and hence relax
supercoiling of the DNA. Four genes encode Type I topoisomerases, which include nuclear topoisomerase I
(TOP1) and mitochondrial topoisomerase I (TOP1MT). Type I enzymes can also be sub-divided into Types A and B
based on their different catalytic mechanism for generating single DNA strand breaks. TOP1 and TOP1MT are
both type 1B since they form 3'-phosphotyrosyl bonds. Camptothecin is a natural product inhibitor of TOP1
that has led to the discovery of derivatives that are clinically used anti-cancer drugs. Such inhibitors
trap the enzyme in a cleavage complex with DNA. Type II topoisomerases (IIA and IIB) are particular
important for the disentanglement of DNA, which is overcome by generating double stranded DNA breaks.
Dysregulation of type II enzymes can therefore have a potentially significant genotoxic effect. There is a
broad range of topoisomerase II inhibitors that are used clinically as anticancer agents.

Gene Wiki entry for TOP2A Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000017.10  NT_010783.16  NC_018928.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the TOP2A gene promoter:
         GR   ATF-2   RelA   NF-kappaB   E47   CRE-BP1   Msx-1   Zic3   NF-kappaB1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidTOP2A promoter sequence
   Search Chromatin IP Primers for TOP2A

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TOP2A


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q21-q22   Ensembl cytogenetic band:  17q21.2   HGNC cytogenetic band: 17q21-q22

TOP2A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TOP2A gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17M038544:  view genomic region     (about GC identifiers)

Start:
38,544,768 bp from pter      End:
38,574,202 bp from pter
Size:
29,435 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: TOP2A_HUMAN, P11388 (See protein sequence)
Recommended Name: DNA topoisomerase 2-alpha  
Size: 1531 amino acids; 174385 Da
Cofactor: Magnesium. Binds two Mg(2+) per subunit. The magnesium ions form salt bridges with both the protein and
the DNA. Can also accept other divalent metal cations, such as Mn(2+) and Ca(2+) (Probable)
Subunit: Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation
Miscellaneous: Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas
prokaryotic enzymes relax only negative supercoils
4 PDB 3D structures from and Proteopedia for TOP2A:
1LWZ (3D)        1ZXM (3D)        1ZXN (3D)        4FM9 (3D)    
Secondary accessions: B2RTS1 Q71UN1 Q71UQ5 Q9HB24 Q9HB25 Q9HB26 Q9UP44 Q9UQP9
Alternative splicing: 4 isoforms:  P11388-1   P11388-2   P11388-3   P11388-4   

Explore the universe of human proteins at neXtProt for TOP2A: NX_P11388

Explore proteomics data for TOP2A at MOPED

Post-translational modifications: 

  • Phosphorylation has no effect on catalytic activity. However, phosphorylation at Ser-1106 by CSNK1D/CK1 promotes
    DNA cleavable complex formation1
  • Ubiquitination2 at Lys96, Lys123, Lys207, Lys227, Lys233, Lys251, Lys287, Lys321, Lys336, Lys386,
                                 Lys397, Lys466, Lys480, Lys489, Lys499, Lys520, Lys529, Lys535, Lys614, Lys632 (see all 30)
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for TOP2A (P11388) (see all 62)
     VVKKKNK  FDSQTKE  DDRKEWL  MIMTDQD 


    See TOP2A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_001058.2  
    ENSEMBL proteins: 
     ENSP00000411532   ENSP00000464055   ENSP00000462908  
    Reactome Protein details: P11388

    TOP2A Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for TOP2A
    OriGene Custom MassSpec
    OriGene Custom Protein Services for TOP2A
    GenScript Custom Purified and Recombinant Proteins Services for TOP2A
    Novus Biologicals TOP2A Protein
    Novus Biologicals TOP2A Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for TOP2A 

     
    antibodies-online proteins for TOP2A (2 products) 

     
    antibodies-online peptides for TOP2A

    TOP2A Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of TOP2A
    R&D Systems Antibodies for TOP2A
    Cell Signaling Technology (CST) Antibodies for TOP2A 
    OriGene Antibodies for TOP2A
    OriGene Custom Antibody Services for TOP2A
    Novus Biologicals TOP2A Antibodies
    Abcam antibodies for TOP2A
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for TOP2A
    antibodies-online antibodies for TOP2A (158 products) 

    TOP2A Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for TOP2A
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for TOP2A
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.
    Search eBioscience for ELISAs for TOP2A 
    antibodies-online kits for TOP2A (20 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 15):
     IPR028466 Top2a
     IPR002205 Topo_IIA_A/C
     IPR018522 TopoIIA_CS
     IPR013758 Topo_IIA_A/C_ab
     IPR012542 DTHCT

    Graphical View of Domain Structure for InterPro Entry P11388

    ProtoNet protein and cluster: P11388

    Selected Blocks protein domains (see all 6):
    IPB001154 Topoisomerase II signature
    IPB002205 DNA gyrase/topoisomerase IV
    IPB003594 ATP-binding region
    IPB003957 CCAAT-binding transcription factor subunit A signature
    IPB011558 DNA topoisomerase


    UniProtKB/Swiss-Prot: TOP2A_HUMAN, P11388
    Similarity: Belongs to the type II topoisomerase family
    Similarity: Contains 1 Toprim domain


    Find genes that share domains with TOP2A           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TOP2A_HUMAN, P11388
    Function: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands.
    Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of
    daughter chromosomes
    Catalytic activity: ATP-dependent breakage, passage and rejoining of double-stranded DNA
    Enzyme regulation: Specifically inhibited by the intercalating agent amsacrine

         Genatlas biochemistry entry for TOP2A:
    DNA topoisomerase II alpha (170kDa),ubiquitous,markely upregulated in proliferating cells,catalyzing the ATP
    dependent breakage and rejoining of double strand of DNA,relaxing both positively and negatively supercoiled
    DNA,inhibited by Rb during cell cycle,target of several drugs widely used in the treatment of human
    cancers,including a variant associated with drug resistance,deleted or amplified simultaneously with ERBB2 in
    breast cancers

         Enzyme Number (IUBMB): EC 5.99.1.31 2

         Gene Ontology (GO): Selected molecular function terms (see all 17):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000287magnesium ion binding IDA--
    GO:0003677DNA binding IDA10788521
    GO:0003682chromatin binding IDA9049244
    GO:0003918DNA topoisomerase type II (ATP-hydrolyzing) activity IDA16611985
    GO:0005080protein kinase C binding IPI16611985
         
    Find genes that share ontologies with TOP2A           About GenesLikeMe


    Phenotypes:
         4 GenomeRNAi human phenotypes for TOP2A:
     Increased cell death HMECs cel  Increased gamma-H2AX phosphory  Increased number of cells in m  Synthetic lethal with Ras 

    Animal Models:
       genOway: Develop your customized and physiologically relevant rodent model for TOP2A

    miRNA
    Products:
        
    miRTarBase miRNAs that target TOP2A:
    hsa-mir-21-5p (MIRT030914), hsa-mir-7-5p (MIRT047766), hsa-mir-186-5p (MIRT045191), hsa-mir-708-5p (MIRT037756), hsa-mir-1226-3p (MIRT036474), hsa-mir-193b-3p (MIRT016473)

    Block miRNA regulation of human, mouse, rat TOP2A using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TOP2A (see all 29):
    hsa-miR-548j hsa-miR-548i hsa-miR-520d-5p hsa-miR-548k hsa-miR-16-1* hsa-miR-548l hsa-miR-144 hsa-miR-548d-5p
    SwitchGear 3'UTR luciferase reporter plasmidTOP2A 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for TOP2A
    Predesigned siRNA for gene silencing in human, mouse, rat TOP2A

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for TOP2A

    Clone
    Products:
         
    OriGene clones in human, mouse for TOP2A (see all 7)
    OriGene ORF clones in mouse, rat for TOP2A
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: TOP2A (NM_001067)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TOP2A
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TOP2A

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for TOP2A
    Browse ESI BIO Cell Lines and PureStem Progenitors for TOP2A 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TOP2A


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TOP2A_HUMAN, P11388: Cytoplasm. Nucleus, nucleoplasm. Note=Generally located in the nucleoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol2
    mitochondrion1

    Gene Ontology (GO): Selected cellular component terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000228colocalizes with nuclear chromosome IDA9049244
    GO:0000793condensed chromosome ----
    GO:0000795synaptonemal complex IBA--
    GO:0005634nucleus IDA--
    GO:0005654nucleoplasm TAS--

    Find genes that share ontologies with TOP2A           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TOP2A About   (see all 14)  
    See pathways by source

    SuperPathContained pathways About
    1Cell Cycle, Mitotic
    Cell Cycle, Mitotic0.90
    Cell Cycle0.90
    2E2F mediated regulation of DNA replication
    Mitotic G1-G1/S phases0.81
    3Telomere C-strand (Lagging Strand) Synthesis
    Cell cycle Transition and termination of DNA replication0.43
    4Doxorubicin Pathway, Pharmacokinetics
    Doxorubicin Pathway (Cancer Cell), Pharmacodynamics0.43
    5Proteolysis Putative SUMO 1 pathway
    Proteolysis Putative SUMO 1 pathway0.33


    Find genes that share SuperPaths with TOP2A           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 Cell Signaling Technology (CST) Pathway for TOP2A
        Chromatin Regulation / Acetylation

    3 GeneGo (Thomson Reuters) Pathways for TOP2A
        Cell cycle Chromosome condensation in prometaphase
    Proteolysis Putative SUMO-1 pathway
    Cell cycle Transition and termination of DNA replication

    4 BioSystems Pathways for TOP2A
        Gastric cancer network 1
    Gastric cancer network 2
    Integrated Pancreatic Cancer Pathway
    RB in Cancer

    1 Reactome Pathway for TOP2A
        G0 and Early G1

    2 PharmGKB Pathways for TOP2A
        Doxorubicin Pathway (Cancer Cell), Pharmacodynamics
    Etoposide Pathway, Pharmacokinetics/Pharmacodynamics

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TOP2A: 
              Lung Cancer in human mouse rat
              Cancer Drug Targets in human mouse rat
              Cancer Drug Resistance in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TOP2A

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TOP2A (P113881, 2, 3 ENSP000004115324) via UniProtKB, MINT, STRING, and/or I2D (see all 273)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIST1H3EP684313, ENSP000003535814I2D: score=1 STRING: ENSP00000353581
    HIST1H3AP684313I2D: score=1 
    HIST1H3BP684313I2D: score=1 
    HIST1H3CP684313I2D: score=1 
    HIST1H3DP684313I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 20):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000278mitotic cell cycle TAS--
    GO:0000712resolution of meiotic recombination intermediates IBA--
    GO:0000819sister chromatid segregation IBA--
    GO:0006200ATP catabolic process IDA12079377
    GO:0006260DNA replication NAS15504738

    Find genes that share ontologies with TOP2A           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for TOP2A
    Selected ApexBio Compounds for TOP2A (see all 20)     About this table
    CompoundAction CAS #
    4'-Demethylepipodophyllotoxinkey intermediate compound for the preparation of podophyllotoxin-type anti-cancer drugs[6559-91-7]
    AmonafideDNA intercalator and Topo II (topoisomerase II) inhibitor[69408-81-7]
    AmrubicinTopoisomerase II inhibitor, anthracycline agent[110267-81-7]
    Camptothecinprototypic DNA topoisomerase I inhibitor[7689-3-4]
    Deferasirox Fe3+ chelaterationally-designed oral iron chelator[554435-83-5]
    Dexrazoxane HCl (ICRF-187, ADR-529)cardioprotective agent[149003-01-0]
    DoxorubicinDNA topoisomerase I inhibitor[23214-92-8]
    Doxorubicin (Adriamycin) HClAntitumor antibiotic agent, inhibits DNA topoisomerase II[25316-40-9]
    Ellagic acidATP-competitive inhibitor of casein kinase 2 (CK2)[476-66-4]
    Epirubicin HClAntibiotic antitumor agent[56390-09-1]

    Compounds for TOP2A available from Tocris Bioscience    About this table
    CompoundAction CAS #
    CPT 11DNA topoisomerase I inhibitor; antitumor[100286-90-6]
    Doxorubicin hydrochlorideAntitumor antibiotic agent. Inhibits DNA topoisomerase II[25316-40-9]
    EtoposideTopoisomerase II inhibitor[33419-42-0]
    SN 38DNA topoisomerase I inhibitor; antitumor[86639-52-3]
    CamptothecinDNA topoisomerase inhibitor[7689-03-4]

    1 HMDB Compound for TOP2A    About this table
    CompoundSynonyms CAS #PubMed Ids
    LevofloxacinFloxin (see all 5)100986-85-4--

    Selected DrugBank Compounds for TOP2A (see all 24)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    DexrazoxaneDesrazoxane (see all 7)24584-09-6targetinhibitor11984069 17652819 11332155 17115008 10194547 11752352 11179439 11046078 12911317
    AmsacrineAcridinyl Anisidide (see all 3)51264-14-3targetinhibitor1311390 11473732 11716434 10691026 11752352 11006484 1322791
    MitoxantroneMitoxanthrone (see all 2)65271-80-9targetinhibitor18687447 11278845 9631585 11752352 9494516 11004693 10451375
    DoxorubicinAdria (see all 4)23214-92-8targetinhibitor17016621 17351394 17578914 11752352 17010609 17089011
    EtoposideEPEG (see all 4)33419-42-0targetinhibitor17361331 17514873 16271071 11752352 16309315 16377807
    IdarubicinIdarubicin Hcl (see all 5)58957-92-9targetinhibitor10203104 11836027 11752352 10523799 12034365 8036155
    Podofilox-- 477-47-4targetinhibitor16061385 1331331 11752352 1334447 10783066 1845848
    TeniposideTeniposido [INN-Spanish] (see all 2)29767-20-2targetinhibitor16480143 17361331 17514873 8702194 16271071 11752352
    CiprofloxacinCiprofloxacin dihydrochloride (see all 5)85721-33-1targetinhibitor3015015 11752352 1323952
    Enoxacin-- 74011-58-8targetinhibitor18471102 11752352 10089819

    Selected Novoseek inferred chemical compound relationships for TOP2A gene (see all 49)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    amsacrine 86 19 8980384 (2), 8137294 (1), 8194167 (1), 8823806 (1) (see all 13)
    etoposide 78.4 43 7641205 (3), 8996519 (2), 10969596 (2), 18206427 (2) (see all 32)
    azatoxin 78.2 2 7763310 (2)
    mitoxantrone 72.7 10 8980384 (2), 18665175 (1), 17578914 (1), 11278845 (1) (see all 7)
    doxorubicin 68.2 29 8996519 (2), 15486187 (2), 19620488 (2), 8823806 (1) (see all 21)
    trastuzumab 63.4 6 18078328 (1), 19914538 (1), 15762277 (1), 17089011 (1) (see all 5)
    teniposide 61.4 9 7641205 (3), 8980384 (2), 8548781 (1), 9426516 (1) (see all 5)
    camptothecin 56.4 4 7961822 (1), 14973057 (1), 11205246 (1)
    (glc)4 51.2 12 8041119 (3), 8980384 (2)
    adriamycin 47.5 8 9494516 (2), 7805045 (2), 18401528 (1), 8615623 (1)



    Find genes that share compounds with TOP2A           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for TOP2A gene: 
    NM_001067.3  

    Unigene Cluster for TOP2A:

    Topoisomerase (DNA) II alpha 170kDa
    Hs.156346  [show with all ESTs]
    Unigene Representative Sequence: NM_001067
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000423485(uc002huq.3 uc002hur.1) ENST00000577541 ENST00000578412
    ENST00000577706 ENST00000581055
    miRNA
    Products:
         
    Block miRNA regulation of human, mouse, rat TOP2A using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TOP2A (see all 29):
    hsa-miR-548j hsa-miR-548i hsa-miR-520d-5p hsa-miR-548k hsa-miR-16-1* hsa-miR-548l hsa-miR-144 hsa-miR-548d-5p
    SwitchGear 3'UTR luciferase reporter plasmidTOP2A 3' UTR sequence
    Inhib. RNA
    Products:
         
    OriGene RNAi products in human, mouse, rat for TOP2A
    Predesigned siRNA for gene silencing in human, mouse, rat TOP2A
    Clone
    Products:
         
    OriGene clones in human, mouse for TOP2A (see all 7)
    OriGene ORF clones in mouse, rat for TOP2A
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    GenScript: all cDNA clones in your preferred vector: TOP2A (NM_001067)
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      QuantiFast Probe-based Assays in human, mouse, rat TOP2A

    Additional mRNA sequence: 

    AK024080.1 BC013429.1 BC062677.1 BC140791.1 J04088.1 L47276.1 L47277.1 

    21 DOTS entries:

    DT.99953788  DT.451782  DT.95300834  DT.99932666  DT.100683187  DT.100689464  DT.100825552  DT.100825545 
    DT.120991746  DT.91761832  DT.100038117  DT.100825557  DT.91761835  DT.95282052  DT.95300818  DT.100648081 
    DT.100825546  DT.102832750  DT.120991718  DT.40106389  DT.120991769 

    Selected AceView cDNA sequences (see all 471):

    CA488771 AI354911 AI613495 AA306247 BM559052 AK024080 AI457474 CB140758 
    AU142692 AI760467 BQ946184 AU117343 BQ773978 AL040877 AI446783 AA236734 
    AU130840 BC013429 BP369589 BM749174 BQ438926 AA731314 AA809450 CB217736 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for TOP2A    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25a ·
    SP1:                                                              -                                                                                         -   
    SP2:                                                                                                                                                            
    SP3:                                                                                                                                                            
    SP4:                                                                                                                                                            

    ExUns: 25b ^ 26 ^ 27 ^ 28a · 28b ^ 29 ^ 30 ^ 31 ^ 32 ^ 33 ^ 34a · 34b ^ 35
    SP1:                                                                              
    SP2:                                                                              
    SP3:                                                                              
    SP4:                                                                              


    ECgene alternative splicing isoforms for TOP2A

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    TOP2A expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CTCAGCAATG
    TOP2A Expression
    About this image


    TOP2A expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 18) fully expand
     
     Brain (Nervous System)    fully expand to see all 7 entries
             Endothelial Cells Blood Brain Barrier
             Cerebral Cortex
     
     Ovary (Reproductive System)    fully expand to see all 3 entries
             Secondary Oocyte Antral Follicle
     
     Thymus (Hematopoietic System)    fully expand to see all 2 entries
             Double Negative 2 Thymocytes Thymus
             Thymus
     
     Blood (Cardiovascular System)    fully expand to see all 2 entries
             Double Negative 2 Thymocytes Thymus
             Umbilical cord blood-derived mesenchymal stem cells
     
     Kidney (Urinary System)    fully expand to see all 2 entries
             Presumptive Podocytes Podocyte Layer
             Metanephros
    TOP2A Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TOP2A Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.156346
        Pathway & Disease-focused RT2 Profiler PCR Arrays including TOP2A: 
              Lung Cancer in human mouse rat
              Cancer Drug Targets in human mouse rat
              Cancer Drug Resistance in human mouse rat

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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TOP2A

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for TOP2A gene from Selected species (see all 18)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Top2a1 , 5 topoisomerase (DNA) II alpha1, 5 87.14(n)1
    90.01(a)1
      11 (62.91 cM)5
    219731  NM_011623.21  NP_035753.21 
     989929435 
    chicken
    (Gallus gallus)
    Aves TOP2A1 topoisomerase (DNA) II alpha 170kDa 72.54(n)
    77.34(a)
      395570  NM_204791.1  NP_990122.1 
    lizard
    (Anolis carolinensis)
    Reptilia TOP2A6
    topoisomerase (DNA) II alpha 170kDa
    72(a)
    1 ↔ 1
    6(70009033-70047926)
    African clawed frog
    (Xenopus laevis)
    Amphibia LOC3985122 hypothetical protein LOC398512 77.65(n)    BC044276.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufc08c072 Transcribed sequence with moderate similarity to protein more 76.55(n)    57055348 
    fruit fly
    (Drosophila melanogaster)
    Insecta Top21 , 3 meiosis DNA binding3
    Topoisomerase 21
    60(a)3
    59.99(n)1
    63.1(a)1
      37E13
    352251  NM_001273651.11  NP_001260580.11 
    worm
    (Caenorhabditis elegans)
    Secernentea F32A11.43
    top-21
    DNA topoisomerase II (N-terminal
    region)3
    top-21
    59(a)
    (best of 6)3
    59.67(n)1
    61.24(a)1
      II(13134927-13137287)3
    1748251  NM_064135.31  NP_496536.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes TOP26
    Topoisomerase II, relieves torsional strain in DNA...
    43(a)
    1 → many
    XIV(457704-461990) YNL088W


    ENSEMBL Gene Tree for TOP2A (if available)
    TreeFam Gene Tree for TOP2A (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TOP2A gene
    TOP2B2  
    2 SIMAP similar genes for TOP2A using alignment to 3 protein entries:     TOP2A_HUMAN (see all proteins):
    TOP2B    topIIb

    Find genes that share paralogs with TOP2A           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
    About This Section

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    Selected SNPs for TOP2A (see all 620)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs675609691,2
    C--38553556(-) CATCT-/A/AA  
            
    AAAAA
    1 -- int12NA 4
    rs346677331,2
    C,F--38554288(+) GCCTCA/CCAAAG 1 -- int12Minor allele frequency- C:0.25NA WA 4
    rs1123654941,2
    C,F--38554552(+) GGTTTC/TACCAT 1 -- int11Minor allele frequency- T:0.00CSA 1
    rs711526671,2
    C--38561709(-) GTCTCA/-AAAAA 1 -- int11Minor allele frequency- -:0.00NA 2
    rs681656621,2
    C,F--38565472(-) TACCC-/T/TT  
            
    TTTTT
    1 -- int12NA 4
    rs114565261,2
    C--38575393(+) TTTTT-/TGAGAT 1 -- us2k1 trp30--------
    rs1883916991,2
    --39331481(+) ACATGC/TATATT 1 -- ds50010--------
    rs1123796691,2
    C,F--39331491(+) TTACTG/AATCAA 1 -- ds50011Minor allele frequency- A:0.50NA 2
    rs27155551,2
    C,F,A,H--39331566(-) TAAGAC/TCTAAT 1 -- ds500116Minor allele frequency- T:0.06NS EA NA 1904
    rs129419741,2
    C,F,H--39331667(+) ATATTT/CTAGAA 1 -- ds500110Minor allele frequency- C:0.03NS EA NA WA 1210

    HapMap Linkage Disequilibrium report for TOP2A (38544768 - 38574202 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for TOP2A:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv833445CNV Loss17160897
    nsv908223CNV Gain21882294

    Site Specific Mutation Identification with PCR Assays
    2 Copy Number PCR Panels containing TOP2A:
    Oncogenes & Tumor Suppressor Genes 384HC
    Breast Cancer
    SeqTarget long-range PCR primers for resequencing TOP2A
    DNA2.0 Custom Variant and Variant Library Synthesis for TOP2A

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 126430    OMIM disorders: --

    4 diseases for TOP2A:    
    About MalaCards
    dna topoisomerase ii inhibition of, by amsacrine    cervix endometriosis    neuroblastoma    breast cancer

    2 diseases from the University of Copenhagen DISEASES database for TOP2A:
    Breast cancer     Cervix endometriosis

    Find genes that share disorders with TOP2A           About GenesLikeMe

    Selected Novoseek inferred disease relationships for TOP2A gene (see all 75)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    breast cancer 63.8 121 20130985 (4), 15891995 (4), 19945923 (4), 18465341 (3) (see all 55)
    tumors 57.1 162 14978790 (6), 19945923 (6), 14566826 (5), 10469452 (5) (see all 67)
    mpnst 46.3 8 14673046 (3), 16721726 (2), 14508395 (1), 18522746 (1)
    small cell lung cancer 45.2 4 8306338 (1), 9713494 (1), 8041119 (1), 12906927 (1)
    breast carcinoma 44.7 20 15628907 (2), 19886180 (2), 14632728 (2), 17013533 (2) (see all 13)
    carcinoma 42.8 14 10597187 (1), 9310953 (1), 12556100 (1), 15068318 (1) (see all 11)
    malignant peripheral nerve sheath tumors 41.4 1 14673046 (1)
    cancer 38.9 33 14632727 (2), 17363613 (2), 7641205 (2), 10652607 (2) (see all 23)
    leukemia 37.6 13 8914817 (2), 9494516 (2), 7643627 (1), 7873386 (1) (see all 11)
    ovarian carcinoma 36.8 6 15385105 (2), 8172796 (1), 14984957 (1), 9504690 (1) (see all 5)

    Genetic Association Database (GAD): TOP2A
    Human Genome Epidemiology (HuGE) Navigator: TOP2A (9 documents)

    Export disorders for TOP2A gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TOP2A gene, integrated from 10 sources (see all 701):
    (articles sorted by number of sources associating them with TOP2A)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer. (PubMed id 20130985)1, 4, 9 Konecny G.E....Slamon D.J. (Breast Cancer Res. Treat. 2010)
    2. Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. (PubMed id 19401546)1, 4, 9 O'Malley F.P....Pritchard K.I. (J. Natl. Cancer Inst. 2009)
    3. Structural organization of the human TOP2A and TOP2B genes. (PubMed id 9795238)1, 2, 9 Lang A.J.... Cole S.P. (Gene 1998)
    4. retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. (PubMed id 16234514)1, 7, 9 Knoop A.S....Ejlertsen B. (J. Clin. Oncol. 2005)
    5. Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469. (PubMed id 10942766)1, 2, 9 Escargueil A.E.... Larsen A.K. (J. Biol. Chem. 2000)
    6. Outcome of patients with early-stage breast cancer treated with doxorubicin-based adjuvant chemotherapy as a function of HER2 and TOP2A status. (PubMed id 19620488)1, 4, 9 Tubbs R....Hayes D.F. (J. Clin. Oncol. 2009)
    7. Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast. (PubMed id 8393377)1, 2, 9 Wasserman R.A.... Wang J.C. (Cancer Res. 1993)
    8. Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia. (PubMed id 16507781)1, 4, 9 Monzo M....Sierra J. (Blood 2006)
    9. Characterization of human NSCLC cell line with innate etoposide-resistance mediated by cytoplasmic localization of topoisomerase II alpha. (PubMed id 16271071)1, 7, 9 de Lucio B....Barrera-RodrA-guez R. (Cancer Sci. 2005)
    10. The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage. (PubMed id 22841979)1, 2 Wendorff T.J.... Berger J.M. (J. Mol. Biol. 2012)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 7153 HGNC: 11989 AceView: TOP2A Ensembl:ENSG00000131747 euGenes: HUgn7153
    ECgene: TOP2A H-InvDB: TOP2A

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for TOP2A Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TOP2A Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for TOP2A gene:
    Search GeneIP for patents involving TOP2A

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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