Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TOP2A contributors: mct/npt - updated : 29-04-2016
HGNC name topoisomerase (DNA) II alpha 170kDa
HGNC id 11989
Location 17q21.2      Physical location : 38.544.773 - 38.574.202
Synonym name DNA topoisomerase II, alpha isozyme
Synonym symbol(s) TOP2, TP2A
EC.number 5.99.1.3
DNA
TYPE functioning gene
STRUCTURE 29.37 kb     35 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Physical map
ZPBP2 17q21.2 zona pellucida binding protein 2 GSDML 17q21.2 gasdermin-like ORMDL3 17q12 ORM1-like 3 (S. cerevisiae) LOC342669 17q21.2 similar to leucine-rich repeat domain-containing protein GSDM 17q21.2 gasdermin PSMD3 17q21.1 proteasome (prosome, macropain) 26S subunit, non-ATPase, 3 CSF3 17q11.2-q12 colony stimulating factor 3 (granulocyte) TRAP100 THRA 17q11.2 thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian) NR1D1 17q11.2 nuclear receptor subfamily 1, group D, member 1 MLN51 17q12-q21.3 nuclear receptor subfamily 1, group D, member 1 LOC339287 17q21.2 hypothetical protein LOC339287 Link-GEFII 17q21.2 Link guanine nucleotide exchange factor II WIRE 17q21.2 WIRE protein CDC6 17q21.3 CDC6 cell division cycle 6 homolog (S. cerevisiae) RARA 17q12 retinoic acid receptor, alpha GJC1 17q21.1 gap junction protein, chi 1, 31.9kDa (connexin 31.9) LOC390791 17 similar to peptidyl-Pro cis trans isomerase TOP2A 17q21.31 topoisomerase (DNA) II alpha 170kDa IGFBP4 17q12 insulin-like growth factor binding protein 4 CTEN 17q21.2 C-terminal tensin-like LOC284134 17q21.2 hypothetical LOC284134 CCR7 17q21.1 chemokine (C-C motif) receptor 7 SMARCE1 17q21.1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1 MGC45562 17q21.2 hypothetical protein MGC45562 KRT24 17q11.2 keratin 24 KRT25B 17q21.2 keratin 25B KRT25A 17q21.2 keratin 25A KRT25C 17q21.2 keratin 25C KRT25D 17q21.2 keratin 25C MGC21518 17q21.2 hypothetical protein MGC21518 KRT12 17q21.1 keratin 12 (Meesmann corneal dystrophy) KRT20 17q21.2 keratin 20 KRT23 17q21.2 keratin 23 (histone deacetylase inducible) LOC390792 17 similar to type I hair keratin 6
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
  • 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)
  • 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