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FLASH GENE
Symbol TOP2A contributors: mct/npt - updated : 29-04-2018
HGNC name topoisomerase (DNA) II alpha 170kDa
HGNC id 11989
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
35 - 5698 170 1531 - 2009 19223331
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunelymph node   highly
Reproductivemale systemtestis  highly
Urinarybladder   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • GRDD (glucose-regulated destruction domain), mapped to the N-terminal 70-170 amino acid sequence
  • three functional domains associated with energy transduction, DNA-breakage reunion activity
  • a C terminal nuclear localization signal (NLS), that appears to play significant roles in modulating the DNA cleavage/ligation reaction of the enzyme and its response to anticancer agents, and that determine its isoform-specific functions in proliferating cells
  • mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • type II topoisomerase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • catalyzing the ATP dependent breakage passage and rejoining of double strand of DNA
  • relaxing both positively and negatively supercoiled DNA
  • target of several drugs widely used in the treatment of cancers
  • playing a vital role in the removal of topological complexities left on DNA during S phase
  • removes supercoils and catenanes generated during DNA metabolic processes such as transcription and replication
  • TOP2A is essential for cell proliferation, whereas TOP2B is required only for aspects of nerve growth and brain development
  • involvement of TOP2A in the formation of radiation-induced chromatid breaks
  • acts in the same pathway of telomere protection as TERF2 and DCLRE1B
  • ENDOG and TOP2A may actively participate in apoptotic chromatin degradation
  • adopts a global conformation in which the second of its two inter-protomer contact points, one at the C-terminus, has separated
  • TOP1, TOP2A are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
  • ZNF148 and TOP2A regulate each other through Competing endogenous RNA (ceRNA) regulatory mechanism in colorectal cancer (CRC), which has biological effects on cell proliferation.
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction between its glucose-regulated destruction domain (GRDD) and MPN domain of CSN5
  • SETMAR physically interacts and co-localizes with TOP2A (Topo IIalpha), the key chromosome decatenating enzyme
  • SETMAR interacts with TOP2A and enhances its decatenation activity
  • functional relationship between BLM, ERCC6L and TOP2A in the centromere decatenation process
  • TDP2 is not only specific but also efficient in recognizing and processing trapped TOP2A cleavage complexes even in the form of a longer peptide
  • TDP2 having preferential action at abortive TOP2A and possibly TOP3A cleavage complexes
  • bends its DNA substrate using a bipartite, nucleolytic center formed at an N-terminal dimerization interface of the cleavage core
  • KIF4A and condensin work in parallel to promote mitotic chromosome morphology, acting in apparent opposition to TOP2A
  • both KIF4A and TOP2A depend on SMC2 for their localization on the chromatid axis and that SMC2 exhibits a reciprocal dependency on KIF4A for localization on the chromatid axes
  • TOP2A, TOP1 are involved in initiating aphidicolin-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
  • active role of TDP1 in the repair of TOP2A-induced DNA damage
  • PTEN is physically associated with a decatenation enzyme TOP2A and PTEN influences its stability through OTUD3 deubiquitinase
  • MAPK6, an atypical MAPK, phosphorylates TDP2 at S60 and regulates TDP2 phosphodiesterase activity, thereby cooperatively protecting lung cancer cells against TOP2A inhibitors-induced DNA damage and growth inhibition
  • SMC5/SMC6 complex physically interacts with TOP2A, and the SMC5/6 complex functions in resolving TOP2A-mediated DSB-repair intermediates generated during replication
  • AIRE promote DNA breaks via its interaction with topoisomerase 2 (TOP2A)
  • CTDNEP1 post-translationally modulates the activities of key regulators for chromosome segregation and mitotic checkpoint regulators including topoisomerase TOP2A and checkpoint kinase CHEK1
  • cell & other
    REGULATION
    activated by HMGB1, HMGB2 (could significantly up-regulate TOP2A gene promoter only in cells lacking functional retinoblastoma protein pRb) (Stros 2009)
    inhibited by Rb during cell cycle
    Other markely upregulated in proliferating cells
    phosphorylated by aurora B kinase AURKB
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    or amplified simultaneously with ERBB2 in breast cancers
    tumoral     --over  
    in gastric cancer
    Susceptibility
    Variant & Polymorphism including a variant associated with drug resistance
    Candidate gene
    Marker
  • its expression is a valuable prognostic indicator for colorectal cancer (useful in treatment selection for early colorectal cancer and malignant colorectal polyps resected under endoscopy)
  • independent prognostic biomarker of disease free survival in postoperative non-small cell lung cancer patients who received adjuvant chemotherapy (
  • TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer
  • Therapy target
    ANIMAL & CELL MODELS