TOP2A
DNA topoisomerase 2-alpha
Also known as: TOP2, TOP2A_HUMAN, TOP2alpha, TOPIIA
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P11388
- Gene
- TOP2A
- Ensembl
- ENSG00000131747
- Chromosome
- 17
- Canonical length
- 1531 aa
- Protein class
- Cancer-related genes, Enzymes, FDA approved drug targets, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nucleoli
- 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, 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]
Canonical amino-acid sequenceUniProt
1531 residues, UniProt reviewed canonical sequence.
>P11388|TOP2A
1 MEVSPLQPVN ENMQVNKIKK NEDAKKRLSV ERIYQKKTQL EHILLRPDTY IGSVELVTQQ
61 MWVYDEDVGI NYREVTFVPG LYKIFDEILV NAADNKQRDP KMSCIRVTID PENNLISIWN
121 NGKGIPVVEH KVEKMYVPAL IFGQLLTSSN YDDDEKKVTG GRNGYGAKLC NIFSTKFTVE
181 TASREYKKMF KQTWMDNMGR AGEMELKPFN GEDYTCITFQ PDLSKFKMQS LDKDIVALMV
241 RRAYDIAGST KDVKVFLNGN KLPVKGFRSY VDMYLKDKLD ETGNSLKVIH EQVNHRWEVC
301 LTMSEKGFQQ ISFVNSIATS KGGRHVDYVA DQIVTKLVDV VKKKNKGGVA VKAHQVKNHM
361 WIFVNALIEN PTFDSQTKEN MTLQPKSFGS TCQLSEKFIK AAIGCGIVES ILNWVKFKAQ
421 VQLNKKCSAV KHNRIKGIPK LDDANDAGGR NSTECTLILT EGDSAKTLAV SGLGVVGRDK
481 YGVFPLRGKI LNVREASHKQ IMENAEINNI IKIVGLQYKK NYEDEDSLKT LRYGKIMIMT
541 DQDQDGSHIK GLLINFIHHN WPSLLRHRFL EEFITPIVKV SKNKQEMAFY SLPEFEEWKS
601 STPNHKKWKV KYYKGLGTST SKEAKEYFAD MKRHRIQFKY SGPEDDAAIS LAFSKKQIDD
661 RKEWLTNFME DRRQRKLLGL PEDYLYGQTT TYLTYNDFIN KELILFSNSD NERSIPSMVD
721 GLKPGQRKVL FTCFKRNDKR EVKVAQLAGS VAEMSSYHHG EMSLMMTIIN LAQNFVGSNN
781 LNLLQPIGQF GTRLHGGKDS ASPRYIFTML SSLARLLFPP KDDHTLKFLY DDNQRVEPEW
841 YIPIIPMVLI NGAEGIGTGW SCKIPNFDVR EIVNNIRRLM DGEEPLPMLP SYKNFKGTIE
901 ELAPNQYVIS GEVAILNSTT IEISELPVRT WTQTYKEQVL EPMLNGTEKT PPLITDYREY
961 HTDTTVKFVV KMTEEKLAEA ERVGLHKVFK LQTSLTCNSM VLFDHVGCLK KYDTVLDILR
1021 DFFELRLKYY GLRKEWLLGM LGAESAKLNN QARFILEKID GKIIIENKPK KELIKVLIQR
1081 GYDSDPVKAW KEAQQKVPDE EENEESDNEK ETEKSDSVTD SGPTFNYLLD MPLWYLTKEK
1141 KDELCRLRNE KEQELDTLKR KSPSDLWKED LATFIEELEA VEAKEKQDEQ VGLPGKGGKA
1201 KGKKTQMAEV LPSPRGQRVI PRITIEMKAE AEKKNKKKIK NENTEGSPQE DGVELEGLKQ
1261 RLEKKQKREP GTKTKKQTTL AFKPIKKGKK RNPWSDSESD RSSDESNFDV PPRETEPRRA
1321 ATKTKFTMDL DSDEDFSDFD EKTDDEDFVP SDASPPKTKT SPKLSNKELK PQKSVVSDLE
1381 ADDVKGSVPL SSSPPATHFP DETEITNPVP KKNVTVKKTA AKSQSSTSTT GAKKRAAPKG
1441 TKRDPALNSG VSQKPDPAKT KNRRKRKPST SDDSDSNFEK IVSKAVTSKK SKGESDDFHM
1501 DFDSAVAPRA KSVRAKKPIK YLEESDEDDL FLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TOP2A 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)
- 0.35
- Highest tissue expression
- 119 nTPM
Expression across tissuesHPA
Tissue
- thymus: 119 nTPM
- testis: 62 nTPM
- tonsil: 40 nTPM
- bone marrow: 40 nTPM
- lymph node: 38 nTPM
- esophagus: 27 nTPM
Single-cell type
- early primary spermatocytes: 818 nCPM
- monocyte progenitors: 686 nCPM
- erythrocyte progenitors: 501 nCPM
- megakaryocyte progenitors: 335 nCPM
- differentiating spermatogonia: 211 nCPM
- neutrophil progenitors: 176 nCPM
Immune cell
- T-reg: 2.4 nTPM
- NK-cell: 1.4 nTPM
- memory B-cell: 0.6 nTPM
- total PBMC: 0.4 nTPM
- memory CD4 T-cell: 0.3 nTPM
- memory CD8 T-cell: 0.3 nTPM
Brain region
- choroid plexus: 2.3 nTPM
- thalamus: 2.3 nTPM
- pons: 1.6 nTPM
- white matter: 0.7 nTPM
- amygdala: 0.3 nTPM
- cerebral cortex: 0.3 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about TOP2A.
Disease | ImmuneIEDB
Conditions an epitope on TOP2A was assayed in.
- colon cancer B cell
- gallbladder disease B cell
- ovarian cancer T cell
- carbamazepine allergy T cell
- breast cancer T cell
- prostate cancer T cell
- skin melanoma T cell
ReferencesPubMed · IEDB
Publications for TOP2A from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
2 publications
- Discovering novel lung cancer associated antigens and the utilization of their autoantibodies in detection of lung cancer.
2020 · Immunobiology · RCR 1.2 · 24 citations - Identification of tumor-associated antigens of lung cancer: SEREX combined with bioinformatics analysis.
2021 · J Immunol Methods · RCR 0.5 · 7 citations
Reference: B cellIEDB
1 publication
Reference: T cellIEDB
3 publications
- Direct interaction between HLA-B and carbamazepine activates T cells in patients with Stevens-Johnson syndrome.
2012 · J Allergy Clin Immunol · RCR 7.7 · 226 citations - First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients.
2012 · J Transl Med · RCR 1.9 · 74 citations - Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade.
2022 · Front Immunol · RCR 0.2 · 3 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
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)
- 0.29
- gnomAD pLI
- 0.99
- gnomAD missense Z
- 4.04
- DepMap mean gene effect
- -2.25
- DepMap dependency class
- pan
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic chromosome condensation
- chromatin organization
- chromosome segregation
- DNA damage response
- DNA topological change
- embryonic cleavage
- female meiotic nuclear division
- hematopoietic progenitor cell differentiation
- positive regulation of apoptotic process
- positive regulation of single stranded viral RNA replication via double stranded DNA intermediate
- positive regulation of transcription by RNA polymerase II
- regulation of circadian rhythm
- resolution of meiotic recombination intermediates
- rhythmic process
- sister chromatid segregation
Molecular functions
- ATP binding
- ATP-dependent activity, acting on DNA
- chromatin binding
- DNA binding
- DNA binding, bending
- DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity
- magnesium ion binding
- protein heterodimerization activity
- protein homodimerization activity
- protein kinase C binding
- RNA binding
- ubiquitin binding
Cellular components
- chromosome, centromeric region
- condensed chromosome
- cytoplasm
- male germ cell nucleus
- nucleolus
- nucleoplasm
- nucleus
- protein-containing complex
- ribonucleoprotein complex
- DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex
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 TOP2A 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 TOP2A as an antibody target. Whether an autoantibody or antibody against TOP2A could matter depends on whether native TOP2A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TOP2A 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 TOP2A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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