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Aliases for TOP2A Gene

Aliases for TOP2A Gene

  • Topoisomerase (DNA) II Alpha 2 3
  • Topoisomerase (DNA) II Alpha 170kDa 2 3
  • DNA Topoisomerase II, Alpha Isozyme 3 4
  • EC 5.99.1.3 4 63
  • TOP2 3 4
  • DNA Topoisomerase (ATP-Hydrolyzing) 3
  • DNA Topoisomerase II, 170 KD 3
  • DNA Gyrase 3
  • TP2A 3

External Ids for TOP2A Gene

Previous HGNC Symbols for TOP2A Gene

  • TOP2

Previous GeneCards Identifiers for TOP2A Gene

  • GC17M038044
  • GC17M040720
  • GC17M038453
  • GC17M038919
  • GC17M038920
  • GC17M035798
  • GC17M038544
  • GC17M034337

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) is a Protein Coding gene. Diseases associated with TOP2A include breast adenoid cystic carcinoma and cervix endometriosis. Among its related pathways are Cell Cycle, Mitotic and Integrated Pancreatic Cancer Pathway. GO annotations related to this gene include poly(A) RNA binding and protein heterodimerization activity. 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 knots and tangles are often resolved by topoisomerases.

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

Regulatory Elements for TOP2A Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for TOP2A Gene

Chromosome:
17
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

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.
  • Ubiquitination at Lys 123, Lys 207, Lys 227, Lys 233, Lys 251, Lys 287, Lys 321, Lys 336, Lys 386, Lys 397, Lys 466, Lys 480, Lys 529, Lys 614, Lys 632, Lys 676, Lys 723, Lys 821, Lys 827, Lys 1011, Lys 1028, and Lys 1075
  • Modification sites at PhosphoSitePlus

Other Protein References for TOP2A Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for TOP2A Gene

Gene Families for TOP2A Gene

Suggested Antigen Peptide Sequences for TOP2A Gene

Graphical View of Domain Structure for InterPro Entry

P11388

UniProtKB/Swiss-Prot:

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

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 9049244
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

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TOP2A

In Situ Assay Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targets 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
cytoskeleton 1
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 10788521
GO:0005654 nucleoplasm TAS --
GO:0005730 NOT nucleolus IDA 9049244
genes like me logo Genes that share ontologies with TOP2A: view

Pathways & Interactions for TOP2A Gene

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

PCR Array Products

SIGNOR curated interactions for TOP2A Gene

Is activated by:
Other effect:

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:0006265 DNA topological change IDA 22323612
genes like me logo Genes that share ontologies with TOP2A: view

Drugs & Compounds for TOP2A Gene

(87) Drugs for TOP2A Gene - From: DGIdb, FDA Approved Drugs, NovoSeek, HMDB, DrugBank, ApexBio, ClinicalTrials, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Etoposide Approved Pharma Biomarker, inhibitor, Target Topo II inhibitor, Topoisomerase 2 Inhibitors, Topoisomerase II inhibitor 1127
Doxorubicin Approved, Investigational Pharma inhibitor, Target Topo II inhibitor,immunosuppresive antineoplastic antibiotic 1525
Teniposide Approved Pharma inhibitor, Target 19
Epirubicin Approved Pharma inhibitor, Target 343
Mitoxantrone Approved, Investigational Pharma inhibitor, Target 246

(20) Additional Compounds for TOP2A Gene - From: NovoSeek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Doxorubicin hydrochloride
25316-40-9
(Glc)4
5fluorouracil
Actinomycin D
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Antagonist, Gating inhibitor 58-64-0
genes like me logo Genes that share compounds with TOP2A: view

Drug Products

Transcripts for TOP2A Gene

Unigene Clusters for TOP2A Gene

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

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TOP2A

Flow Cytometry Products

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 differential expression in normal tissues according to GTEx for TOP2A Gene

This gene is overexpressed in Testis (x8.6).

Protein differential expression in normal tissues from HIPED for TOP2A Gene

This gene is overexpressed in Testis (22.3), Ovary (21.2), Nasal epithelium (8.3), and Lung (7.4).

Integrated Proteomics: protein expression in normal tissues and cell lines 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 expression patterns with TOP2A: view

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Protein tissue co-expression partners for TOP2A Gene

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
cow
(Bos Taurus)
Mammalia TOP2A 35
  • 92.11 (n)
  • 92.94 (a)
TOP2A 36
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TOP2A 35
  • 92.09 (n)
  • 93.86 (a)
TOP2A 36
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Top2a 35
  • 87.14 (n)
  • 90.01 (a)
Top2a 16
Top2a 36
  • 89 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TOP2A 35
  • 99 (n)
  • 98.6 (a)
TOP2A 36
  • 91 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Top2a 35
  • 86.34 (n)
  • 89.05 (a)
oppossum
(Monodelphis domestica)
Mammalia TOP2A 36
  • 84 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TOP2A 36
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves TOP2A 35
  • 72.54 (n)
  • 77.34 (a)
TOP2A 36
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TOP2A 36
  • 72 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia topoii 35
  • 69.8 (n)
  • 75.64 (a)
African clawed frog
(Xenopus laevis)
Amphibia LOC398512 35
zebrafish
(Danio rerio)
Actinopterygii top2a 35
  • 66.05 (n)
  • 69.58 (a)
wufc08c07 35
top2a 36
  • 53 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Top2 37
  • 60 (a)
Top2 35
  • 59.99 (n)
  • 63.1 (a)
Top2 36
  • 54 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008917 35
  • 58.92 (n)
  • 64.94 (a)
worm
(Caenorhabditis elegans)
Secernentea F31E8.6 37
  • 41 (a)
F32A11.4 37
  • 59 (a)
F32A11.5 37
  • 54 (a)
R05D3.1 37
  • 40 (a)
Y46H3C.4 37
  • 35 (a)
ZK1127.7 37
  • 54 (a)
top-2 35
  • 59.67 (n)
  • 61.24 (a)
cin-4 36
  • 52 (a)
ManyToMany
top-2 36
  • 51 (a)
ManyToMany
Y46H3C.4 36
  • 44 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes TOP2 36
  • 43 (a)
OneToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.13260 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 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

(2) 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/T)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

Variation tolerance for TOP2A Gene

Residual Variation Intolerance Score: 13.32% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.13; 61.35% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TOP2A Gene

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

PCR Panel Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TOP2A Gene

Disorders for TOP2A Gene

MalaCards: The human disease database

(8) MalaCards diseases for TOP2A Gene - From: Orphanet, DISEASES, NovoSeek, and GeneCards

Disorder Aliases PubMed IDs
breast adenoid cystic carcinoma
  • mammary adenocystic carcinoma
cervix endometriosis
  • cervical endometriosis
adenosquamous pancreas carcinoma
  • adenosquamous carcinoma of pancreas
malignant peripheral nerve sheath tumor
  • neurofibrosarcoma
adenocarcinoma in situ
- elite association
Search TOP2A in MalaCards View complete list of genes associated with diseases

Relevant External Links for TOP2A

Genetic Association Database (GAD)
TOP2A
Human Genome Epidemiology (HuGE) Navigator
TOP2A
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TOP2A
genes like me logo Genes that share disorders with TOP2A: view

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

Publications for TOP2A Gene

  1. Solamargine upregulation of Fas, downregulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells. (PMID: 17639997) Liang C.H. … Kuo K.W. (Mol Nutr Food Res 2007) 23 25 26 67
  2. Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. (PMID: 17578914) Azarova A.M. … Liu L.F. (Proc. Natl. Acad. Sci. U.S.A. 2007) 23 25 26 67
  3. Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. (PMID: 17010609) Rody A. … Kaufmann M. (Breast 2007) 23 25 26 67
  4. DNA topoisomerase IIalpha (TOP2A) inhibitors up-regulate fatty acid synthase gene expression in SK-Br3 breast cancer cells: in vitro evidence for a 'functional amplicon' involving FAS, Her-2/neu and TOP2A genes. (PMID: 17089011) Menendez J.A. … Lupu R. (Int. J. Mol. Med. 2006) 23 25 26 67
  5. 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. (PMID: 16234514) Knoop A.S. … Ejlertsen B. (J. Clin. Oncol. 2005) 23 25 26 67

Products for TOP2A Gene

Sources for TOP2A Gene

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