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Aliases for TOP2A Gene

Aliases for TOP2A Gene

  • Topoisomerase (DNA) II Alpha 170kDa 2 3
  • TOP2 3 4 6
  • DNA Topoisomerase II, Alpha Isozyme 3 4
  • EC 5.99.1.3 4 64
  • Topoisomerase (DNA) II Alpha (170kD) 2
  • DNA Topoisomerase (ATP-Hydrolyzing) 3
  • DNA Topoisomerase II, 170 KD 3
  • DNA Topoisomerase 2-Alpha 3
  • DNA Gyrase 3
  • TP2A 3

External Ids for TOP2A Gene

Previous Symbols for TOP2A Gene

  • TOP2

Summaries for TOP2A Gene

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 neuroblastoma and cervix endometriosis. Among its related pathways are Cell Cycle, Mitotic and Cell Cycle, Mitotic. GO annotations related to this gene include protein homodimerization activity and chromatin binding. An important paralog of this gene is TOP2B.

UniProtKB/Swiss-Prot for TOP2A Gene

  • 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. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).

Tocris 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

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TOP2A Gene

Genomics for TOP2A Gene

Genomic Location for TOP2A Gene

Start:
40,388,516 bp from pter
End:
40,417,950 bp from pter
Size:
29,435 bases
Orientation:
Minus strand

Genomic View for TOP2A Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for TOP2A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TOP2A Gene

Regulatory Elements for TOP2A Gene

Proteins for TOP2A Gene

  • Protein details for TOP2A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P11388-TOP2A_HUMAN
    Recommended name:
    DNA topoisomerase 2-alpha
    Protein Accession:
    P11388
    Secondary Accessions:
    • B2RTS1
    • Q71UN1
    • Q71UQ5
    • Q9HB24
    • Q9HB25
    • Q9HB26
    • Q9UP44
    • Q9UQP9

    Protein attributes for TOP2A Gene

    Size:
    1531 amino acids
    Molecular mass:
    174385 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Note=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+) or Ca(2+).;
    Quaternary structure:
    • Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation. Interacts with SETMAR; stimulates the topoisomerase activity (PubMed:18790802, PubMed:20457750).
    Miscellaneous:
    • Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils

    Three dimensional structures from OCA and Proteopedia for TOP2A Gene

    Alternative splice isoforms for TOP2A Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TOP2A Gene

Proteomics data for TOP2A Gene at MOPED

Post-translational modifications for TOP2A Gene

  • Phosphorylation has no effect on catalytic activity. However, phosphorylation at Ser-1106 by CSNK1D/CK1 promotes DNA cleavable complex formation.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys96, Lys123, Lys207, Lys227, Lys233, Lys251, Lys287, Lys321, Lys336, Lys386, Lys397, Lys466, Lys480, Lys489, Lys499, Lys520, Lys529, Lys535, Lys614, Lys632, Lys662, Lys676, Lys723, Lys821, Lys827, Lys967, Lys1011, Lys1028, Lys1075, and Lys1204

Other Protein References for TOP2A Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for TOP2A Gene

UniProtKB/Swiss-Prot:

TOP2A_HUMAN
Domain:
  • Contains 1 Toprim domain.:
    • P11388
Family:
  • Belongs to the type II topoisomerase family.:
    • P11388
genes like me logo Genes that share domains with TOP2A: view

No data available for Gene Families for TOP2A Gene

Function for TOP2A Gene

Molecular function for TOP2A Gene

GENATLAS Biochemistry: 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
UniProtKB/Swiss-Prot CatalyticActivity: ATP-dependent breakage, passage and rejoining of double-stranded DNA.
UniProtKB/Swiss-Prot EnzymeRegulation: Specifically inhibited by the intercalating agent amsacrine
UniProtKB/Swiss-Prot 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. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).

Enzyme Numbers (IUBMB) for TOP2A Gene

Gene Ontology (GO) - Molecular Function for TOP2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IDA 22323612
GO:0003677 DNA binding IDA 10788521
GO:0003682 chromatin binding IDA 9049244
GO:0003918 DNA topoisomerase type II (ATP-hydrolyzing) activity IDA 16611985
GO:0005080 protein kinase C binding IPI 16611985
genes like me logo Genes that share ontologies with TOP2A: view
genes like me logo Genes that share phenotypes with TOP2A: view

No data available for Animal Models , Transcription Factor Targeting and HOMER Transcription for TOP2A Gene

Localization for TOP2A Gene

Subcellular locations from UniProtKB/Swiss-Prot for TOP2A Gene

Cytoplasm. Nucleus, nucleoplasm. Note=Generally located in the nucleoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TOP2A Gene COMPARTMENTS Subcellular localization image for TOP2A gene
Compartment Confidence
nucleus 5
cytosol 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for TOP2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000228 colocalizes_with nuclear chromosome IDA 9049244
GO:0000793 condensed chromosome IEA --
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm TAS --
GO:0005730 NOT nucleolus IDA 9049244
genes like me logo Genes that share ontologies with TOP2A: view

Pathways for TOP2A Gene

genes like me logo Genes that share pathways with TOP2A: view

Gene Ontology (GO) - Biological Process for TOP2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000278 mitotic cell cycle TAS --
GO:0000712 resolution of meiotic recombination intermediates IBA --
GO:0000819 sister chromatid segregation IBA --
GO:0002244 hematopoietic progenitor cell differentiation IEA --
GO:0006200 obsolete ATP catabolic process --
genes like me logo Genes that share ontologies with TOP2A: view

Compounds for TOP2A Gene

(20) ApexBio Compounds for TOP2A Gene

Compound Action Cas Number
4-Demethylepipodophyllotoxin key intermediate compound for the preparation of podophyllotoxin-type anti-cancer drugs [6559-91-7]
Amonafide DNA intercalator and Topo II (topoisomerase II) inhibitor [69408-81-7]
Amrubicin Topoisomerase II inhibitor, anthracycline agent [110267-81-7]
Camptothecin prototypic DNA topoisomerase I inhibitor. [7689-3-4]
Deferasirox Fe3+ chelate rationally-designed oral iron chelator. [554435-83-5]
Dexrazoxane HCl (ICRF-187, ADR-529) cardioprotective agent. [149003-01-0]
Doxorubicin DNA topoisomerase I inhibitor [23214-92-8]
Doxorubicin (Adriamycin) HCl Antitumor antibiotic agent, inhibits DNA topoisomerase II. [25316-40-9]
Ellagic acid ATP-competitive inhibitor of casein kinase 2 (CK2) [476-66-4]
Epirubicin HCl Antibiotic antitumor agent. [56390-09-1]
Etoposide Topoisomerase II inhibitor [33419-42-0]
Gatifloxacin Fluoroquinolone antibiotic. [112811-59-3]
Genistein Phytoestrogen with a wide range of biological actions. [446-72-0]
Genz-644282 non-camptothecin inhibitor of topoisomerase I [529488-28-6]
Idarubicin HCl anthracycline and an analog of daunorubicin [57852-57-0]
Irinotecan isomer of the Topo I inhibitor Irinotecan [97682-44-5]
Ofloxacin fluorinated quinolone antibacterial. [82419-36-1]
Teniposide glycoside-derivative of podophyllotoxin. [29767-20-2]
TH-302 newly developed antineoplastic drug [918633-87-1]
Voreloxin Hydrochloride inhibitor of Topo II. [175519-16-1]

(5) Tocris Compounds for TOP2A Gene

Compound Action Cas Number
Camptothecin DNA topoisomerase inhibitor [7689-03-4]
CPT 11 DNA topoisomerase I inhibitor; antitumor [100286-90-6]
Doxorubicin hydrochloride Antitumor antibiotic agent. Inhibits DNA topoisomerase II [25316-40-9]
Etoposide Topoisomerase II inhibitor [33419-42-0]
SN 38 DNA topoisomerase I inhibitor; antitumor [86639-52-3]

(1) HMDB Compounds for TOP2A Gene

Compound Synonyms Cas Number PubMed IDs
Levofloxacin
  • Floxin
100986-85-4

(24) Drugbank Compounds for TOP2A Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Amsacrine
  • Acridinyl Anisidide
51264-14-3 target inhibitor
Ciprofloxacin
  • Ciprofloxacin dihydrochloride
85721-33-1 target inhibitor
Daunorubicin
20830-81-3 target inhibitor
Dexrazoxane
  • Desrazoxane
24584-09-6 target inhibitor
Doxorubicin
  • Adria
23214-92-8 target inhibitor

(49) Novoseek inferred chemical compound relationships for TOP2A Gene

Compound -log(P) Hits PubMed IDs
amsacrine 86 14
etoposide 78.4 37
azatoxin 78.2 2
mitoxantrone 72.7 8
doxorubicin 68.2 24
genes like me logo Genes that share compounds with TOP2A: view

Transcripts for TOP2A Gene

Unigene Clusters for TOP2A Gene

Topoisomerase (DNA) II alpha 170kDa:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TOP2A Gene

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:

Relevant External Links for TOP2A Gene

GeneLoc Exon Structure for
TOP2A
ECgene alternative splicing isoforms for
TOP2A

Expression for TOP2A Gene

mRNA expression in normal human tissues for TOP2A Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TOP2A Gene

This gene is overexpressed in Testis (8.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for TOP2A Gene

SOURCE GeneReport for Unigene cluster for TOP2A Gene Hs.156346

genes like me logo Genes that share expressions with TOP2A: view

Orthologs for TOP2A Gene

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

Orthologs for TOP2A Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TOP2A 36
  • 99 (n)
  • 98.6 (a)
TOP2A 37
  • 91 (a)
OneToOne
cow
(Bos Taurus)
Mammalia TOP2A 36
  • 92.11 (n)
  • 92.94 (a)
TOP2A 37
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TOP2A 36
  • 92.09 (n)
  • 93.86 (a)
TOP2A 37
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Top2a 36
  • 87.14 (n)
  • 90.01 (a)
Top2a 16
Top2a 37
  • 89 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia TOP2A 37
  • 84 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TOP2A 37
  • 79 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Top2a 36
  • 86.34 (n)
  • 89.05 (a)
chicken
(Gallus gallus)
Aves TOP2A 36
  • 72.54 (n)
  • 77.34 (a)
TOP2A 37
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TOP2A 37
  • 72 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia LOC398512 36
tropical clawed frog
(Silurana tropicalis)
Amphibia topoii 36
  • 69.8 (n)
  • 75.64 (a)
zebrafish
(Danio rerio)
Actinopterygii top2a 36
  • 66.05 (n)
  • 69.58 (a)
top2a 37
  • 53 (a)
OneToOne
wufc08c07 36
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008917 36
  • 58.92 (n)
  • 64.94 (a)
fruit fly
(Drosophila melanogaster)
Insecta Top2 36
  • 59.99 (n)
  • 63.1 (a)
Top2 37
  • 54 (a)
OneToMany
Top2 38
  • 60 (a)
worm
(Caenorhabditis elegans)
Secernentea cin-4 37
  • 52 (a)
ManyToMany
top-2 36
  • 59.67 (n)
  • 61.24 (a)
top-2 37
  • 51 (a)
ManyToMany
Y46H3C.4 37
  • 44 (a)
ManyToMany
ZK1127.7 38
  • 54 (a)
F32A11.4 38
  • 59 (a)
F31E8.6 38
  • 41 (a)
R05D3.1 38
  • 40 (a)
Y46H3C.4 38
  • 35 (a)
F32A11.5 38
  • 54 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes TOP2 37
  • 43 (a)
OneToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.13260 36
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 63 (a)
OneToMany
Species with no ortholog for TOP2A:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TOP2A Gene

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

Paralogs for TOP2A Gene

Paralogs for TOP2A Gene

Selected SIMAP similar genes for TOP2A Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with TOP2A: view

Variants for TOP2A Gene

Sequence variations from dbSNP and Humsavar for TOP2A Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs13695 -- 40,388,941(-) AGGCC(A/G)AAGAA utr-variant-3-prime
rs471692 -- 40,400,518(-) TAATT(A/G)TGGAT intron-variant
rs505633 -- 40,401,662(-) gcgca(A/T)tttcg intron-variant
rs520630 -- 40,405,114(-) ggctc(A/G)ggagg intron-variant
rs525812 -- 40,419,040(-) CAAAA(C/G)TAGCC upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for TOP2A Gene

Variant ID Type Subtype PubMed ID
nsv833445 CNV Loss 17160897
nsv908223 CNV Gain 21882294

Relevant External Links for TOP2A Gene

HapMap Linkage Disequilibrium report
TOP2A
Human Gene Mutation Database (HGMD)
TOP2A

Disorders for TOP2A Gene

(2) University of Copenhagen DISEASES for TOP2A Gene

(75) Novoseek inferred disease relationships for TOP2A Gene

Disease -log(P) Hits PubMed IDs
breast cancer 63.8 90
tumors 57.1 118
mpnst 46.3 7
small cell lung cancer 45.2 4
breast carcinoma 44.7 17

Relevant External Links for TOP2A

Genetic Association Database (GAD)
TOP2A
Human Genome Epidemiology (HuGE) Navigator
TOP2A
genes like me logo Genes that share disorders with TOP2A: view

No data available for UniProtKB/Swiss-Prot for TOP2A Gene

Publications for TOP2A Gene

  1. Structural organization of the human TOP2A and TOP2B genes. (PMID: 9795238) Lang A.J. … Cole S.P. (Gene 1998) 3 4 23
  2. Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469. (PMID: 10942766) Escargueil A.E. … Larsen A.K. (J. Biol. Chem. 2000) 3 4 23
  3. Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast. (PMID: 8393377) Wasserman R.A. … Wang J.C. (Cancer Res. 1993) 3 4 23
  4. Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia. (PMID: 16507781) Monzo M. … Sierra J. (Blood 2006) 3 23 49
  5. Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. (PMID: 19401546) O'Malley F.P. … Pritchard K.I. (J. Natl. Cancer Inst. 2009) 3 23 49

Products for TOP2A Gene

Sources for TOP2A Gene

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