Tclin TOP2B DNA topoisomerase 2-beta

Protein Summary

Description

Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. 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]

Uniprot Accession IDs

• Q02880
• Q13600
• Q9UMG8
• Q9UQP8

Gene Name

• TOP2B

Ensembl ID

• ENST00000264331
• ENSP00000264331
• ENSG00000077097
• ENST00000435706
• ENSP00000396704

Symbol

• TOPIIB
• top2beta

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
protein domain	1
drug perturbation	0.96
virus perturbation	0.95
hub protein	0.88

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 160.93   (req: < 5)

Gene RIFs: 52   (req: <= 3)

Antibodies: 250   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 160.93   (req: >= 5)

Gene RIFs: 52   (req: > 3)

Antibodies: 250   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 11

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Approved Drugs (2)

Explore Approved Drugs

1 – 2 of 2

aclarubicin

TOP2BTclin Enzyme

INHIBITOR :

etoposide

TOP2BTclin Enzyme

IC50 : 7.16

Active Ligands (11)

Explore Active Ligands

1 – 10 of 11

decernotinib

TOP2BTclin Enzyme

Kd : 6.83

AZD8186

TOP2BTclin Enzyme

Kd : 6.03

CHEMBL4161876

TOP2BTclin Enzyme

IC50 : 8.16

CHEMBL4174756

TOP2BTclin Enzyme

IC50 : 7.9

Ametantrone

TOP2BTclin Enzyme

IC50 : 7.52

CHEMBL4160802

TOP2BTclin Enzyme

IC50 : 7.5

CHEMBL4172196

TOP2BTclin Enzyme

IC50 : 7.09

CHEMBL4169404

TOP2BTclin Enzyme

IC50 : 6.96

CHEMBL4213218

TOP2BTclin Enzyme

IC50 : 6.24

CHEMBL4205327

TOP2BTclin Enzyme

IC50 : 6.07

GWAS Traits (7)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
smoking status measurement	EFO_0006527	2	2	2		61.3
heel bone mineral density	EFO_0009270	2	1	2		56.4
mean corpuscular volume	EFO_0004526	1	1	1		31.4
intraocular pressure measurement	EFO_0004695	1	1	1		29
carotid artery intima media thickness	EFO_0007117	1	1	1		21.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
smoking status measurement	EFO_0006527	2		61.3
heel bone mineral density	EFO_0009270	2		56.4
mean corpuscular volume	EFO_0004526	1		31.4
intraocular pressure measurement	EFO_0004695	1		29
carotid artery intima media thickness	EFO_0007117	1		21.5

Reset Zoom  Beta Count   Odds Ratio

Orthologs (16)

1 – 5 of 16

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	DNA topoisomerase II beta	VGNC:8848	460232
Macaque	DNA topoisomerase II beta		677709
Mouse	topoisomerase (DNA) II beta	MGI:98791	21974
Dog	DNA topoisomerase II beta	VGNC:49632	477044
Horse	DNA topoisomerase II beta	VGNC:50517	100059572

Species	Name	OMA	EggNOG	Inparanoid
Chimp	DNA topoisomerase II beta
Macaque	DNA topoisomerase II beta
Mouse	topoisomerase (DNA) II beta
Dog	DNA topoisomerase II beta
Horse	DNA topoisomerase II beta

Protein Structure (10 Structures, 1 AlphaFold Model)

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Representation

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Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

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More information can be found at RCSB PDB

AF-Q02880-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 10

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (7)

Reactome (5)

KEGG (1)

PathwayCommons (1)

Metabolism of proteins (R-HSA-392499)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499
Reactome	Post-translational protein modification	1450 targets	R-HSA-597592
Reactome	SUMO E3 ligases SUMOylate target proteins	170 targets	R-HSA-3108232
Reactome	SUMOylation	176 targets	R-HSA-2990846
Reactome	SUMOylation of DNA replication proteins	46 targets	R-HSA-4615885

Name	Explore in Pharos	Explore in Source
Metabolism of proteins	2050 targets	R-HSA-392499
Post-translational protein modification	1450 targets	R-HSA-597592
SUMO E3 ligases SUMOylate target proteins	170 targets	R-HSA-3108232
SUMOylation	176 targets	R-HSA-2990846
SUMOylation of DNA replication proteins	46 targets	R-HSA-4615885

Gene Ontology Terms (23)

Functions (10)

Components (5)

Processes (8)

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Items per page:

10

1 – 10 of 10

GO Term	Evidence	Assigned by
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA topoisomerase type II (ATP-hydrolyzing) activity	Inferred from Direct Assay (IDA)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
histone deacetylase binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein C-terminus binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein heterodimerization activity	Inferred from Physical Interaction (IPI)	UniProtKB
protein kinase C binding	Inferred from Physical Interaction (IPI)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
DNA binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (198)

Explore Interacting Targets

1 – 10 of 198

• See Interactions on String-DB

CUL5

Tbio

Novelty:  0.00792494

p_int:  0.999999938

p_ni:  2.2e-8

p_wrong:  4e-8

Score:  0.32

Data Source:  BioPlex,STRINGDB

ASB3

Tbio

Novelty:  0.15921018

p_int:  0.999999925

p_ni:  5.1e-8

p_wrong:  2.4e-8

Score:  0.695

Data Source:  BioPlex,STRINGDB

HSD3B2

Tclin

Family:  Enzyme

Novelty:  0.00711552

p_int:  0.999977552

p_ni:  0.000022381

p_wrong:  6.7e-8

Score:  0.195

Data Source:  BioPlex,STRINGDB

PLAUR

Tchem

Family:  Enzyme

Novelty:  0.00087642

p_int:  0.994778883

p_ni:  0.001392415

p_wrong:  0.003828702

Data Source:  BioPlex

GPATCH4

Tdark

Novelty:  1.13040547

p_int:  0.919926828

p_ni:  0.00020309

p_wrong:  0.079870083

Data Source:  BioPlex

SMARCA4

Tchem

Family:  Epigenetic

Novelty:  0.00112496

Score:  0.99

Data Source:  STRINGDB

SUPT16H

Tbio

Family:  Enzyme

Novelty:  0.01026868

Score:  0.989

Data Source:  STRINGDB

BAZ1B

Tbio

Family:  Epigenetic

Novelty:  0.02374034

Score:  0.984

Data Source:  STRINGDB

SMARCE1

Tbio

Family:  TF

Novelty:  0.01748089

Score:  0.983

Data Source:  STRINGDB

SMARCC1

Tbio

Family:  TF; Epigenetic

Novelty:  0.00961765

Score:  0.983

Data Source:  STRINGDB

Publication Statistics

PubMed Score  160.93

PubMed score by year

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PubTator Score  224.13

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
ATP-binding
Autism spectrum disorder
Complete proteome
Cytoplasm
Disease mutation
DNA-binding
Isomerase

GWAS Trait Find Similar Targets

No Header	No Header
age at first sexual intercourse measurement
carotid artery intima media thickness
heel bone mineral density
intraocular pressure measurement
mean corpuscular volume
open-angle glaucoma
smoking status measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
mortality/aging
nervous system phenotype
respiratory system phenotype
skeleton phenotype