TOP2A DNA topoisomerase II alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: TOP2Aprovided by HGNC
Official Full Name: DNA topoisomerase II alphaprovided by HGNC
Primary source: HGNC:HGNC:11989
See related: Ensembl:ENSG00000131747 MIM:126430; AllianceGenome:HGNC:11989
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TOP2; TP2A; TOPIIA; TOP2alpha
Summary: 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]
Expression: Biased expression in testis (RPKM 34.8), lymph node (RPKM 21.9) and 13 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q21.2

Exon count:: 36

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (40388525..40417896, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (41252019..41281395, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (38544777..38574148, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis.
Title: Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis.
TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.
Title: TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.
HPV16 E6 promoting cervical cancer progression through down-regulation of miR-320a to increase TOP2A expression.
Title: HPV16 E6 promoting cervical cancer progression through down-regulation of miR-320a to increase TOP2A expression.
Association of TOP2A and ADH1B with lipid levels and prognosis in patients with lung adenocarcinoma and squamous cell carcinoma.
Title: Association of TOP2A and ADH1B with lipid levels and prognosis in patients with lung adenocarcinoma and squamous cell carcinoma.
ERK2-topoisomerase II regulatory axis is important for gene activation in immediate early genes.
Title: ERK2-topoisomerase II regulatory axis is important for gene activation in immediate early genes.
EZH2-H3K27me3-mediated silencing of mir-139-5p inhibits cellular senescence in hepatocellular carcinoma by activating TOP2A.
Title: EZH2-H3K27me3-mediated silencing of mir-139-5p inhibits cellular senescence in hepatocellular carcinoma by activating TOP2A.
Role of TOP2A and CDC6 in liver cancer.
Title: Role of TOP2A and CDC6 in liver cancer.
cDCBLD2 mediates sorafenib resistance in hepatocellular carcinoma by sponging miR-345-5p binding to the TOP2A coding sequence.
Title: cDCBLD2 mediates sorafenib resistance in hepatocellular carcinoma by sponging miR-345-5p binding to the TOP2A coding sequence.
Targeted sequencing of cancer-related genes reveals a recurrent TOP2A variant which affects DNA binding and coincides with global transcriptional changes in glioblastoma.
Title: Targeted sequencing of cancer-related genes reveals a recurrent TOP2A variant which affects DNA binding and coincides with global transcriptional changes in glioblastoma.
The abscission checkpoint senses chromatin bridges through Top2alpha recruitment to DNA knots.
Title: The abscission checkpoint senses chromatin bridges through Top2α recruitment to DNA knots.

Submit: New GeneRIF Correction See all GeneRIFs (390)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of TOP2A, TOP2B, or TOP2A/2B by siRNA significantly decreases HIV-1 replication in Sup T1 cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 is identified to have a physical interaction with topoisomerase (DNA) II alpha 170kDa (TOP2A) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed
Tat	tat	Interaction of HIV-1 Tat with TOP2A in T-cells is identified by a proteomic strategy based on affinity chromatography coupled with mass spectrometry	PubMed
capsid	gag	Knockdown of TOP2A, TOP2B, or TOP2A/2B by siRNA significantly decreases p24 levels in HIV-1 infected cell culture supernatants when compared to control	PubMed
reverse transcriptase	gag-pol	HIV-1 RT co-localizes with TOP2A and TOP2B in cytosol of HIV-1 infected Sup T1 and PBMC cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-31685 (e-PCR)
- UniSTS:70696

D17S1230 (e-PCR)
- UniSTS:149843

L17787 (e-PCR)
- UniSTS:26251

RH12872 (e-PCR)
- UniSTS:14479

SHGC-12497 (e-PCR)
- UniSTS:6329

RH17658 (e-PCR)
- UniSTS:7622

D17S1435E (e-PCR)
- UniSTS:150473

GDB:180937 (e-PCR)
- UniSTS:155131

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP-dependent activity, acting on DNA	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding, bending	IDA Inferred from Direct Assay more info	PubMed
enables DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables RNA binding	HDA more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase C binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA ligation	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA topological change	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA topological change	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in apoptotic chromosome condensation	IBA Inferred from Biological aspect of Ancestor more info
involved_in apoptotic chromosome condensation	IDA Inferred from Direct Assay more info	PubMed
involved_in chromosome segregation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic cleavage	IEA Inferred from Electronic Annotation more info
involved_in female meiotic nuclear division	IEA Inferred from Electronic Annotation more info
involved_in hematopoietic progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA duplex unwinding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of single stranded viral RNA replication via double stranded DNA intermediate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in resolution of meiotic recombination intermediates	IBA Inferred from Biological aspect of Ancestor more info
involved_in rhythmic process	IEA Inferred from Electronic Annotation more info
involved_in sister chromatid segregation	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with centriole	IDA Inferred from Direct Assay more info	PubMed
located_in chromosome, centromeric region	IEA Inferred from Electronic Annotation more info
located_in condensed chromosome	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in male germ cell nucleus	IEA Inferred from Electronic Annotation more info
colocalizes_with nuclear chromosome	IDA Inferred from Direct Assay more info	PubMed
NOT located_in nucleolus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of ribonucleoprotein complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DNA topoisomerase 2-alpha

Names: DNA gyrase; DNA topoisomerase (ATP-hydrolyzing); DNA topoisomerase II, 170 kD; DNA topoisomerase II, alpha isozyme; topoisomerase (DNA) II alpha 170kDa

NP_001058.2

EC 5.6.2.2

XP_005257689.1

EC 5.6.2.2

XP_011523467.1

EC 5.6.2.2

XP_054173009.1

EC 5.6.2.2

XP_054173010.1

EC 5.6.2.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027678.2 RefSeqGene

Range

5055..34426

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001067.4 → NP_001058.2 DNA topoisomerase 2-alpha

See identical proteins and their annotated locations for NP_001058.2

Status: REVIEWED

Source sequence(s)

AC080112, BC140791, DB069825

Consensus CDS

CCDS45672.1

UniProtKB/Swiss-Prot

B2RTS1, P11388, Q71UN1, Q71UQ5, Q9HB24, Q9HB25, Q9HB26, Q9UP44, Q9UQP9

Related

ENSP00000411532.1, ENST00000423485.6

Conserved Domains (1) summary

PTZ00108
Location:25 → 1497

PTZ00108; DNA topoisomerase 2-like protein; Provisional

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

40388525..40417896 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005257632.2 → XP_005257689.1 DNA topoisomerase 2-alpha isoform X1

Conserved Domains (8) summary

cd03365
Location:443 → 563

TOPRIM_TopoIIA; TOPRIM_TopoIIA: topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topoisomerase II. TopoIIA enzymes cut both strands of ...

cd00187
Location:699 → 1162

TOP4c; DNA Topoisomerase, subtype IIA; domain A'; bacterial DNA topoisomerase IV (C subunit, ParC), bacterial DNA gyrases (A subunit, GyrA),mammalian DNA toposiomerases II. DNA topoisomerases are essential enzymes that regulate the conformational changes in DNA ...

cd03481
Location:253 → 405

TopoIIA_Trans_ScTopoIIA; TopoIIA_Trans_ScTopoIIA: Transducer domain, having a ribosomal S5 domain 2-like fold, of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topo IIA. S. cerevisiae Topo IIA is a homodimer encoded ...

PTZ00108
Location:13 → 1485

PTZ00108; DNA topoisomerase 2-like protein; Provisional

pfam02518
Location:68 → 173

HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

pfam08070
Location:1423 → 1509

DTHCT; DTHCT (NUC029) region

pfam15323
Location:1345 → 1449

Ashwin; Developmental protein

pfam16898
Location:561 → 699

TOPRIM_C; C-terminal associated domain of TOPRIM
XM_011525165.3 → XP_011523467.1 DNA topoisomerase 2-alpha isoform X2

Conserved Domains (6) summary

cd03365
Location:455 → 575

TOPRIM_TopoIIA; TOPRIM_TopoIIA: topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topoisomerase II. TopoIIA enzymes cut both strands of ...

cd00187
Location:711 → 1174

TOP4c; DNA Topoisomerase, subtype IIA; domain A'; bacterial DNA topoisomerase IV (C subunit, ParC), bacterial DNA gyrases (A subunit, GyrA),mammalian DNA toposiomerases II. DNA topoisomerases are essential enzymes that regulate the conformational changes in DNA ...

cd03481
Location:265 → 417

TopoIIA_Trans_ScTopoIIA; TopoIIA_Trans_ScTopoIIA: Transducer domain, having a ribosomal S5 domain 2-like fold, of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topo IIA. S. cerevisiae Topo IIA is a homodimer encoded ...

PTZ00108
Location:25 → 1364

PTZ00108; DNA topoisomerase 2-like protein; Provisional

pfam02518
Location:80 → 185

HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

pfam16898
Location:573 → 711

TOPRIM_C; C-terminal associated domain of TOPRIM