TOP2B
DNA topoisomerase 2-beta
Also known as: TOP2B_HUMAN, top2beta, TOPIIB
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q02880
- Gene
- TOP2B
- Ensembl
- ENSG00000077097
- Chromosome
- 3
- Canonical length
- 1626 aa
- Protein class
- Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
- Quaternary structure
- Homodimer
OverviewNCBI 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, 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]
Canonical amino-acid sequenceUniProt
1626 residues, UniProt reviewed canonical sequence.
>Q02880|TOP2B
1 MAKSGGCGAG AGVGGGNGAL TWVTLFDQNN AAKKEESETA NKNDSSKKLS VERVYQKKTQ
61 LEHILLRPDT YIGSVEPLTQ FMWVYDEDVG MNCREVTFVP GLYKIFDEIL VNAADNKQRD
121 KNMTCIKVSI DPESNIISIW NNGKGIPVVE HKVEKVYVPA LIFGQLLTSS NYDDDEKKVT
181 GGRNGYGAKL CNIFSTKFTV ETACKEYKHS FKQTWMNNMM KTSEAKIKHF DGEDYTCITF
241 QPDLSKFKME KLDKDIVALM TRRAYDLAGS CRGVKVMFNG KKLPVNGFRS YVDLYVKDKL
301 DETGVALKVI HELANERWDV CLTLSEKGFQ QISFVNSIAT TKGGRHVDYV VDQVVGKLIE
361 VVKKKNKAGV SVKPFQVKNH IWVFINCLIE NPTFDSQTKE NMTLQPKSFG SKCQLSEKFF
421 KAASNCGIVE SILNWVKFKA QTQLNKKCSS VKYSKIKGIP KLDDANDAGG KHSLECTLIL
481 TEGDSAKSLA VSGLGVIGRD RYGVFPLRGK ILNVREASHK QIMENAEINN IIKIVGLQYK
541 KSYDDAESLK TLRYGKIMIM TDQDQDGSHI KGLLINFIHH NWPSLLKHGF LEEFITPIVK
601 ASKNKQELSF YSIPEFDEWK KHIENQKAWK IKYYKGLGTS TAKEAKEYFA DMERHRILFR
661 YAGPEDDAAI TLAFSKKKID DRKEWLTNFM EDRRQRRLHG LPEQFLYGTA TKHLTYNDFI
721 NKELILFSNS DNERSIPSLV DGFKPGQRKV LFTCFKRNDK REVKVAQLAG SVAEMSAYHH
781 GEQALMMTIV NLAQNFVGSN NINLLQPIGQ FGTRLHGGKD AASPRYIFTM LSTLARLLFP
841 AVDDNLLKFL YDDNQRVEPE WYIPIIPMVL INGAEGIGTG WACKLPNYDA REIVNNVRRM
901 LDGLDPHPML PNYKNFKGTI QELGQNQYAV SGEIFVVDRN TVEITELPVR TWTQVYKEQV
961 LEPMLNGTDK TPALISDYKE YHTDTTVKFV VKMTEEKLAQ AEAAGLHKVF KLQTTLTCNS
1021 MVLFDHMGCL KKYETVQDIL KEFFDLRLSY YGLRKEWLVG MLGAESTKLN NQARFILEKI
1081 QGKITIENRS KKDLIQMLVQ RGYESDPVKA WKEAQEKAAE EDETQNQHDD SSSDSGTPSG
1141 PDFNYILNMS LWSLTKEKVE ELIKQRDAKG REVNDLKRKS PSDLWKEDLA AFVEELDKVE
1201 SQEREDVLAG MSGKAIKGKV GKPKVKKLQL EETMPSPYGR RIIPEITAMK ADASKKLLKK
1261 KKGDLDTAAV KVEFDEEFSG APVEGAGEEA LTPSVPINKG PKPKREKKEP GTRVRKTPTS
1321 SGKPSAKKVK KRNPWSDDES KSESDLEETE PVVIPRDSLL RRAAAERPKY TFDFSEEEDD
1381 DADDDDDDNN DLEELKVKAS PITNDGEDEF VPSDGLDKDE YTFSPGKSKA TPEKSLHDKK
1441 SQDFGNLFSF PSYSQKSEDD SAKFDSNEED SASVFSPSFG LKQTDKVPSK TVAAKKGKPS
1501 SDTVPKPKRA PKQKKVVEAV NSDSDSEFGI PKKTTTPKGK GRGAKKRKAS GSENEGDYNP
1561 GRKTSKTTSK KPKKTSFDQD SDVDIFPSDF PTEPPSLPRT GRARKEVKYF AESDEEEDDV
1621 DFAMFNLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TOP2B can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.37
- Highest tissue expression
- 65 nTPM
Expression across tissuesHPA
Tissue
- retina: 65 nTPM
- thymus: 63 nTPM
- parathyroid gland: 42 nTPM
- tonsil: 39 nTPM
- lymph node: 37 nTPM
- thyroid gland: 36 nTPM
Single-cell type
- rod photoreceptor cells: 322 nCPM
- neutrophil progenitors: 258 nCPM
- megakaryocyte progenitors: 254 nCPM
- monocyte progenitors: 252 nCPM
- megakaryocyte-erythroid progenitors: 243 nCPM
- prostatic glandular cells: 172 nCPM
Immune cell
- NK-cell: 3 nTPM
- MAIT T-cell: 2.3 nTPM
- gdT-cell: 2 nTPM
- memory CD8 T-cell: 2 nTPM
- memory CD4 T-cell: 1.9 nTPM
- naive CD4 T-cell: 1.9 nTPM
Brain region
- white matter: 62 nTPM
- cerebellum: 58 nTPM
- hypothalamus: 51 nTPM
- basal ganglia: 51 nTPM
- spinal cord: 51 nTPM
- cerebral cortex: 51 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about TOP2B.
Disease | AllUniProt
Conditions TOP2B is implicated in, by any mechanism.
- B-cell immunodeficiency, distal limb anomalies, and urogenital malformations (BILU) MIM:609296
Disease | GeneticClinVar
4 pathogenic / likely-pathogenic of 1,184 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- B-cell immunodeficiency, distal limb anomalies, and urogenital malformations
- Autism spectrum disorder
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.25
- gnomAD pLI
- 1
- gnomAD missense Z
- 3.86
- DepMap mean gene effect
- -0.01
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- axonogenesis
- B cell differentiation
- cellular response to ATP
- cellular response to hydrogen peroxide
- cellular senescence
- DNA topological change
- forebrain development
- neuron migration
- positive regulation of double-strand break repair via nonhomologous end joining
- positive regulation of single stranded viral RNA replication via double stranded DNA intermediate
- resolution of meiotic recombination intermediates
- sister chromatid segregation
Molecular functions
- ATP binding
- chromatin binding
- DNA binding
- DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity
- metal ion binding
- ribonucleoprotein complex binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- DNA topoisomerase II, eukaryotic-type
- DNA topoisomerase, type IIA
- DNA topoisomerase, type IIA, domain A
- Histidine kinase/HSP90-like ATPase domain
- TOPRIM domain
- DTHCT
- DNA topoisomerase, type IIA, subunit B, domain 2
- DNA topoisomerase, type IIA, alpha-helical domain superfamily
- DNA topoisomerase, type IIA, domain A, alpha-beta
- DNA topoisomerase, type IIA, subunit B, C-terminal
- DNA topoisomerase, type IIA-like domain superfamily
- Small ribosomal subunit protein uS5 domain 2-type fold, subgroup
- DNA topoisomerase, type IIA, conserved site
- Ribosomal protein uS5 domain 2-type superfamily
- C-terminal associated domain of TOPRIM
- DNA topoisomerase 2, TOPRIM domain
- Histidine kinase/HSP90-like ATPase superfamily
- DNA Topoisomerase II
- DNA gyrase B
- DNA gyrase/topoisomerase IV, subunit A
- Toprim domain
- Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
- DTHCT (NUC029) region
- C-terminal associated domain of TOPRIM
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of TOP2B in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads TOP2B as an antibody target. Whether an autoantibody or antibody against TOP2B could matter depends on whether native TOP2B is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TOP2B is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label TOP2B as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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