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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]
TOP2A (DNA Topoisomerase II Alpha) is a Protein Coding gene. Diseases associated with TOP2A include Malignant Peripheral Nerve Sheath Tumor and Female Breast Cancer. Among its related pathways are Gastric Cancer Network 2 and Cell cycle Cell cycle (generic schema). Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity. An important paralog of this gene is TOP2B.
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.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0000287 | magnesium ion binding | IDA | 22323612 |
GO:0003677 | DNA binding | IDA | 9049244 |
GO:0003682 | chromatin binding | IDA | 9049244 |
GO:0003723 | RNA binding | HDA | 22681889 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000228 | colocalizes_with nuclear chromosome | IDA | 9049244 |
GO:0000793 | condensed chromosome | IEA | -- |
GO:0005634 | nucleus | IBA,IDA | 10788521 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005730 | NOT nucleolus | IDA | 9049244 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Cell Cycle, Mitotic |
.83
|
|
2 | Metabolism of proteins | ||
3 | SUMOylation |
.95
|
|
4 | Chromatin Regulation / Acetylation | ||
5 | DNA Damage |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000712 | resolution of meiotic recombination intermediates | IBA | 21873635 |
GO:0000819 | sister chromatid segregation | IBA | 21873635 |
GO:0002244 | hematopoietic progenitor cell differentiation | IEA | -- |
GO:0006259 | DNA metabolic process | IEA | -- |
GO:0006265 | DNA topological change | IMP | 12711669 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Epirubicin | Approved | Pharma | Target, inhibitor | 483 | ||
Doxorubicin | Approved, Investigational | Pharma | Target, inhibitor | Topo II inhibitor,immunosuppresive antineoplastic antibiotic | 2029 | |
Etoposide | Approved | Pharma | Target, inhibitor, Biomarker | Topo II inhibitor, Topoisomerase 2 Inhibitors | 1461 | |
Teniposide | Approved | Pharma | Target, inhibitor | 20 | ||
Daunorubicin | Approved | Pharma | Target, inhibitor | DNA topoisomerase II inhibitor | 383 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
Dexrazoxane hydrochloride |
|
1263283-43-7 |
|
|
||
Doxorubicin hydrochloride |
|
25316-40-9 |
|
|
||
Mitoxantrone dihydrochloride |
|
70476-82-3 |
|
|
Compound | Action | Cas Number |
---|---|---|
Dexrazoxane hydrochloride | Topoisomerase II inhibitor | 1263283-43-7 |
Doxorubicin hydrochloride | Antitumor antibiotic agent. Inhibits DNA topoisomerase II | 25316-40-9 |
Ellipticine | Antitumor and intercalating agent; inhibits DNA topoisomerase II | 519-23-3 |
Mitoxantrone dihydrochloride | Topoisomerase II inhibitor; immunosuppressive and antineoplastic agent | 70476-82-3 |
Compound | Action | Cas Number |
---|---|---|
(S)-10-Hydroxycamptothecin | 19685-09-7 | |
Amonafide | DNA intercalator,Topo II inhibitor | 69408-81-7 |
Amrubicin | Topoisomerase II inhibitor, anthracycline agent | 110267-81-7 |
Amsacrine | Topoisomerase 2 inhibitor | 51264-14-3 |
Amsacrine hydrochloride | Topoisomerase 2 inhibitor | 54301-15-4 |
Beta-Lapachone | DNA topoisomerase I inhibitor,selective | 4707-32-8 |
Camptothecin | Topoisomerase I inhibitor,prototypic | 7689-03-4 |
Ciprofloxacin | 85721-33-1 | |
Daunorubicin | DNA topoisomerase II inhibitor | 20830-81-3 |
Dexrazoxane HCl (ICRF-187, ADR-529) | Topoisomerase II inhibitor,intracellular ion chelator,cardioprotective agent | 149003-01-0 |
Doxorubicin | Topo II inhibitor,immunosuppresive antineoplastic antibiotic | 23214-92-8 |
Doxorubicin (Adriamycin) HCl | Antitumour antibiotic,inhibits TOPO II. | 25316-40-9 |
Ellipticine | DNA topoisomerase II inhibitor | 519-23-3 |
Epirubicin HCl | Antibiotic antitumor agent | 56390-09-1 |
Etoposide | Topo II inhibitor | 33419-42-0 |
Flumequine | 42835-25-6 | |
Gatifloxacin | Fluoroquinolone antibiotic,inhibits bacterial TOPO II | 112811-59-3 |
Idarubicin HCl | Anthracycline and daunorubicin analog,topoisomerase inhibitor | 57852-57-0 |
Irinotecan | Topoisomerase I inhibitor | 97682-44-5 |
Mitoxantrone HCl | Topoisomerase II inhibitor, anti-neoplastic drug | 70476-82-3 |
Moxifloxacin HCl | Fluoroquinolone antibiotic | 186826-86-8 |
Novobiocin Sodium | 1476-53-5 | |
Ofloxacin | Fluoroquinolones,antibiotics | 82419-36-1 |
Pirarubicin | Topo II inhibitor;antineoplastic;analogue of doxorubicin | 72496-41-4 |
Podophyllotoxin | 518-28-5 | |
Teniposide | 29767-20-2 | |
Topotecan HCl | Topoisomerase 1 inhibitor | 119413-54-6 |
Voreloxin | Topo II inhibitor | 175414-77-4 |
Voreloxin Hydrochloride | Antineoplastic naphthyridine analogue | 175519-16-1 |
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: |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | TOP2A 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | TOP2A 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | TOP2A 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Top2a 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Top2a 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | TOP2A 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | TOP2A 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | TOP2A 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | TOP2A 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | topoii 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | LOC398512 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | top2a 30 31 |
|
OneToOne | |
wufc08c07 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | Top2 30 31 32 |
|
OneToMany | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP008917 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | top-2 30 31 |
|
ManyToMany | |
F32A11.4 32 |
|
|
|||
F32A11.5 32 |
|
|
|||
ZK1127.7 32 |
|
|
|||
cin-4 31 |
|
ManyToMany | |||
Y46H3C.4 31 32 |
|
ManyToMany | |||
F31E8.6 32 |
|
|
|||
R05D3.1 32 |
|
|
|||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | TOP2 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany | |
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.13260 30 |
|
SNP ID | Clinical significance and condition | Chr 17 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
714415 | Likely Benign: not provided | 40,396,413(-) | C/G | MISSENSE_VARIANT | |
714733 | Benign: not provided | 40,412,819(-) | T/C | SYNONYMOUS_VARIANT | |
715084 | Likely Benign: not provided | 40,411,699(-) | C/T | MISSENSE_VARIANT | |
715785 | Benign: not provided | 40,392,210(-) | A/G | INTRON_VARIANT | |
717511 | Likely Benign: not provided | 40,400,650(-) | T/C | MISSENSE_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
nsv1146669 | OTHER | inversion | 26484159 |
nsv833445 | CNV | loss | 17160897 |
Disorder | Aliases | PubMed IDs |
---|---|---|
malignant peripheral nerve sheath tumor |
|
|
female breast cancer |
|
|
neuroblastoma |
|
|
ataxia-telangiectasia |
|
|
breast cancer |
|