TOP2B DNA topoisomerase II beta [Homo sapiens (human)] - Gene

Summary

Official Symbol: TOP2Bprovided by HGNC
Official Full Name: DNA topoisomerase II betaprovided by HGNC
Primary source: HGNC:HGNC:11990
See related: Ensembl:ENSG00000077097 MIM:126431; AllianceGenome:HGNC:11990
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: BILU; TOPIIB; top2beta
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, beta, is localized to chromosome 3 and the alpha form is localized to chromosome 17. 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]
Expression: Ubiquitous expression in urinary bladder (RPKM 32.3), brain (RPKM 31.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p24.2

Exon count:: 36

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (25597905..25664907, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (25600752..25667754, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (25639396..25706398, complement)

Chromosome 3 - NC_000003.12 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?

MDM2 provides TOP2 poison resistance by promoting proteolysis of TOP2betacc in a p53-independent manner.
Title: MDM2 provides TOP2 poison resistance by promoting proteolysis of TOP2βcc in a p53-independent manner.
DNA-PKcs-mediated transcriptional regulation of TOP2B drives chemoresistance in acute myeloid leukemia.
Title: DNA-PKcs-mediated transcriptional regulation of TOP2B drives chemoresistance in acute myeloid leukemia.
Using energy to go downhill-a genoprotective role for ATPase activity in DNA topoisomerase II.
Title: Using energy to go downhill-a genoprotective role for ATPase activity in DNA topoisomerase II.
To Break or Not to Break: The Role of TOP2B in Transcription.
Title: To Break or Not to Break: The Role of TOP2B in Transcription.
Revisiting TOP2B-related phenotypes: Three new cases and literature review.
Title: Revisiting TOP2B-related phenotypes: Three new cases and literature review.
Taspase1 Facilitates Topoisomerase IIbeta-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription.
Title: Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription.
Effects of hsa-miR-9-3p and hsa-miR-9-5p on Topoisomerase IIbeta Expression in Human Leukemia K562 Cells with Acquired Resistance to Etoposide.
Title: Effects of hsa-miR-9-3p and hsa-miR-9-5p on Topoisomerase IIβ Expression in Human Leukemia K562 Cells with Acquired Resistance to Etoposide.
TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells.
Title: TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells.
A comprehensive structural analysis of the ATPase domain of human DNA topoisomerase II beta bound to AMPPNP, ADP, and the bisdioxopiperazine, ICRF193.
Title: A comprehensive structural analysis of the ATPase domain of human DNA topoisomerase II beta bound to AMPPNP, ADP, and the bisdioxopiperazine, ICRF193.
BRCA1-BARD1 regulates transcription through modulating topoisomerase IIbeta.
Title: BRCA1-BARD1 regulates transcription through modulating topoisomerase IIβ.

Submit: New GeneRIF Correction See all GeneRIFs (74)

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

Associated conditions

Description	Tests
B-cell immunodeficiency, distal limb anomalies, and urogenital malformations MedGen: C1836437 OMIM: 609296 GeneReviews: Not available	Compare labs

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
HIV-1 replication is enhanced by over-expression of TOP2B (TopoisomeraseIIb)	PubMed
HIV-1 replication requires TOP2B (TopoisomeraseIIb) as shown through inhibition by ICRF-193 or merbarone treatment or siRNA knockdown	PubMed
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
Tat	tat	HIV-1 Tat binds TOP2B (topoisomeraseIIb), XRCC6 (Ku70), and PARP1 during transactivation and viral replication	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

MARC_23644-23645:1029443453:1 (e-PCR)
- UniSTS:268732

D3S3335 (e-PCR)
- UniSTS:36064

SGC31578 (e-PCR)
- UniSTS:48625

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA binding	IEA Inferred from Electronic Annotation more info
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 chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ribonucleoprotein complex binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in B cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA topological change	IDA Inferred from Direct Assay more info	PubMed
involved_in axonogenesis	IEA Inferred from Electronic Annotation more info
involved_in cellular response to ATP	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
involved_in cellular senescence	IEA Inferred from Electronic Annotation more info
involved_in forebrain development	IEA Inferred from Electronic Annotation more info
involved_in neuron migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of double-strand break repair via nonhomologous end joining	IEA Inferred from Electronic Annotation more info
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 resolution of meiotic recombination intermediates	IBA Inferred from Biological aspect of Ancestor more info
involved_in sister chromatid segregation	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
part_of heterochromatin	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 ribonucleoprotein complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: DNA topoisomerase 2-beta

Names: DNA topoisomerase II, 180 kD; DNA topoisomerase II, beta isozyme; U937 associated antigen; antigen MLAA-44; topo II beta; topoisomerase (DNA) II beta 180kDa; topoisomerase II beta; topoisomerase IIb

NP_001059.2

EC 5.6.2.2

NP_001317629.1

EC 5.6.2.2

XP_011532359.1

EC 5.6.2.2

XP_047304777.1

EC 5.6.2.2

XP_047304778.1

EC 5.6.2.2

XP_054203683.1

EC 5.6.2.2

XP_054203684.1

EC 5.6.2.2

XP_054203685.1

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_052961.1 RefSeqGene

Range

4466..71389

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001068.3 → NP_001059.2 DNA topoisomerase 2-beta isoform 2

See identical proteins and their annotated locations for NP_001059.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate in-frame splice site in the 5' coding region, compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.

Source sequence(s)

AB208879, BF514624, BM150930, X68060

Consensus CDS

CCDS46776.1

UniProtKB/TrEMBL

Q71UH4

Related

ENSP00000396704.2, ENST00000435706.6

Conserved Domains (7) summary

cd03365
Location:471 → 591

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:727 → 1187

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:281 → 433

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:41 → 1466

PTZ00108; DNA topoisomerase 2-like protein; Provisional

pfam02518
Location:96 → 193

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

pfam08070
Location:1503 → 1604

DTHCT; DTHCT (NUC029) region

pfam16898
Location:589 → 727

TOPRIM_C; C-terminal associated domain of TOPRIM
NM_001330700.2 → NP_001317629.1 DNA topoisomerase 2-beta isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC093416

Consensus CDS

CCDS82746.1

UniProtKB/Swiss-Prot

Q02880, Q13600, Q9UMG8, Q9UQP8

UniProtKB/TrEMBL

Q71UH4

Related

ENSP00000264331.4, ENST00000264331.9

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_000003.12 Reference GRCh38.p14 Primary Assembly

Range

25597905..25664907 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047448821.1 → XP_047304777.1 DNA topoisomerase 2-beta isoform X2

Related

ENSP00000514098.1, ENST00000699043.1
XM_011534057.4 → XP_011532359.1 DNA topoisomerase 2-beta isoform X1

UniProtKB/TrEMBL

Q71UH4

Conserved Domains (7) summary

cd03365
Location:476 → 596

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:732 → 1192

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:286 → 438

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:46 → 1466

PTZ00108; DNA topoisomerase 2-like protein; Provisional

pfam02518
Location:101 → 198

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

pfam08070
Location:1471 → 1572

DTHCT; DTHCT (NUC029) region

pfam16898
Location:594 → 732

TOPRIM_C; C-terminal associated domain of TOPRIM
XM_047448822.1 → XP_047304778.1 DNA topoisomerase 2-beta isoform X3

Related

ENSP00000391112.1, ENST00000424225.1