TOP3A
DNA topoisomerase 3-alpha
Also known as: TOP3, TOP3A_HUMAN, ZGRF7
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q13472
- Gene
- TOP3A
- Ensembl
- ENSG00000177302
- Chromosome
- 17
- Canonical length
- 1001 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins
OverviewNCBI Gene
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
Canonical amino-acid sequenceUniProt
1001 residues, UniProt reviewed canonical sequence.
>Q13472|TOP3A
1 MIFPVARYAL RWLRRPEDRA FSRAAMEMAL RGVRKVLCVA EKNDAAKGIA DLLSNGRMRR
61 REGLSKFNKI YEFDYHLYGQ NVTMVMTSVS GHLLAHDFQM QFRKWQSCNP LVLFEAEIEK
121 YCPENFVDIK KTLERETRQC QALVIWTDCD REGENIGFEI IHVCKAVKPN LQVLRARFSE
181 ITPHAVRTAC ENLTEPDQRV SDAVDVRQEL DLRIGAAFTR FQTLRLQRIF PEVLAEQLIS
241 YGSCQFPTLG FVVERFKAIQ AFVPEIFHRI KVTHDHKDGI VEFNWKRHRL FNHTACLVLY
301 QLCVEDPMAT VVEVRSKPKS KWRPQALDTV ELEKLASRKL RINAKETMRI AEKLYTQGYI
361 SYPRTETNIF PRDLNLTVLV EQQTPDPRWG AFAQSILERG GPTPRNGNKS DQAHPPIHPT
421 KYTNNLQGDE QRLYEFIVRH FLACCSQDAQ GQETTVEIDI AQERFVAHGL MILARNYLDV
481 YPYDHWSDKI LPVYEQGSHF QPSTVEMVDG ETSPPKLLTE ADLIALMEKH GIGTDATHAE
541 HIETIKARMY VGLTPDKRFL PGHLGMGLVE GYDSMGYEMS KPDLRAELEA DLKLICDGKK
601 DKFVVLRQQV QKYKQVFIEA VAKAKKLDEA LAQYFGNGTE LAQQEDIYPA MPEPIRKCPQ
661 CNKDMVLKTK KNGGFYLSCM GFPECRSAVW LPDSVLEASR DSSVCPVCQP HPVYRLKLKF
721 KRGSLPPTMP LEFVCCIGGC DDTLREILDL RFSGGPPRAS QPSGRLQANQ SLNRMDNSQH
781 PQPADSRQTG SSKALAQTLP PPTAAGESNS VTCNCGQEAV LLTVRKEGPN RGRQFFKCNG
841 GSCNFFLWAD SPNPGAGGPP ALAYRPLGAS LGCPPGPGIH LGGFGNPGDG SGSGTSCLCS
901 QPSVTRTVQK DGPNKGRQFH TCAKPREQQC GFFQWVDENT APGTSGAPSW TGDRGRTLES
961 EARSKRPRAS SSDMGSTAKK PRKCSLCHQP GHTRPFCPQN RLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TOP3A 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)
- 0.34
- Highest tissue expression
- 6.4 nTPM
Expression across tissuesHPA
Tissue
- cerebellum: 6.4 nTPM
- liver: 6.2 nTPM
- testis: 6.2 nTPM
- skin: 5.8 nTPM
- spleen: 5.8 nTPM
- skeletal muscle: 5.5 nTPM
Single-cell type
- choroid plexus epithelial cells: 32 nCPM
- brain inhibitory neurons: 28 nCPM
- brain excitatory neurons: 28 nCPM
- renal collecting duct intercalated cells: 28 nCPM
- other brain neurons: 25 nCPM
- distal convoluted tubule cells: 24 nCPM
Immune cell
- neutrophil: 4.1 nTPM
- eosinophil: 3.4 nTPM
- classical monocyte: 3 nTPM
- intermediate monocyte: 2.7 nTPM
- NK-cell: 2.2 nTPM
- total PBMC: 2 nTPM
Brain region
- cerebellum: 6.6 nTPM
- choroid plexus: 4.8 nTPM
- cerebral cortex: 4.4 nTPM
- hypothalamus: 4.4 nTPM
- white matter: 4.3 nTPM
- basal ganglia: 4.2 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about TOP3A.
Disease | AllUniProt
Conditions TOP3A is implicated in, by any mechanism.
- Microcephaly, growth restriction, and increased sister chromatid exchange 2 (MGRISCE2) MIM:618097
- Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5 (PEOB5) MIM:618098
Disease | GeneticClinVar
37 pathogenic / likely-pathogenic of 514 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Microcephaly, growth restriction, and increased sister chromatid exchange 2
- Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5
- Mitochondrial disease
- Inborn genetic diseases
- Monogenic short statue
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)
- 0.68
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.31
- DepMap mean gene effect
- -1.18
- DepMap dependency class
- common
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
- chromosome separation
- DNA recombination
- DNA repair
- DNA topological change
- double-strand break repair via homologous recombination
- meiotic cell cycle
- mitochondrial DNA metabolic process
- resolution of DNA recombination intermediates
Molecular functions
- DNA binding
- DNA topoisomerase type I (single strand cut, ATP-independent) activity
- single-stranded DNA binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- DNA topoisomerase, type IA
- DNA topoisomerase, type IA, domain 2
- DNA topoisomerase, type IA, DNA-binding domain
- TOPRIM domain
- Zinc finger, GRF-type
- DNA topoisomerase, type IA, central
- DNA topoisomerase, type IA, central region, subdomain 1
- DNA topoisomerase, type IA, central region, subdomain 2
- DNA topoisomerase, type IA, central region, subdomain 3
- DNA topoisomerase, type IA, core domain
- DNA topoisomerase, type IA, active site
- DNA topoisomerase 3-like, TOPRIM domain
- DNA topoisomerase
- Toprim domain
- GRF zinc finger
- DNA topoisomerase, type IA, zn finger
- Topoisomerase DNA binding C4 zinc finger
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of TOP3A 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 TOP3A as an antibody target. Whether an autoantibody or antibody against TOP3A could matter depends on whether native TOP3A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TOP3A 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 TOP3A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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