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    TOP2A DNA topoisomerase II alpha [ Homo sapiens (human) ]

    Gene ID: 7153, updated on 10-Sep-2017
    Official Symbol
    TOP2Aprovided by HGNC
    Official Full Name
    DNA topoisomerase II alphaprovided by HGNC
    Primary source
    HGNC:HGNC:11989
    See related
    Ensembl:ENSG00000131747 MIM:126430; Vega:OTTHUMG00000155008
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TOP2; TP2A
    Summary
    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]
    Orthologs
    Location:
    17q21.2
    Exon count:
    36
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 17 NC_000017.11 (40388521..40417950, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (38544773..38574202, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene RNA, 5S ribosomal pseudogene 441 Neighboring gene kelch repeat and BTB domain containing 2 pseudogene Neighboring gene ribosomal protein L23a pseudogene 75 Neighboring gene insulin like growth factor binding protein 4

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Replication interactions

    Interaction Pubs
    Knockdown of TOP2A, TOP2B, or TOP2A/2B by siRNA significantly decreases HIV-1 replication in Sup T1 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 is identified to have a physical interaction with topoisomerase (DNA) II alpha 170kDa (TOP2A) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    Tat tat Interaction of HIV-1 Tat with TOP2A in T-cells is identified by a proteomic strategy based on affinity chromatography coupled with mass spectrometry PubMed
    capsid gag Knockdown of TOP2A, TOP2B, or TOP2A/2B by siRNA significantly decreases p24 levels in HIV-1 infected cell culture supernatants when compared to control PubMed
    reverse transcriptase gag-pol HIV-1 RT co-localizes with TOP2A and TOP2B in cytosol of HIV-1 infected Sup T1 and PBMC cells PubMed

    Go to the HIV-1, Human Interaction Database

    • Cell Cycle, organism-specific biosystem (from REACTOME)
      Cell Cycle, organism-specific biosystem
      Cell Cycle
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      Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
    • Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
      Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
    • G0 and Early G1, organism-specific biosystem (from REACTOME)
      G0 and Early G1, organism-specific biosystemIn G0 and early G1 in quiescent cells, p130 (RBL2) bound to E2F4 or E2F5 and either DP1 or DP2, associates with the MuvB complex, forming an evolutionarily conserved DREAM complex, that represses tra...
    • Gastric Cancer Network 1, organism-specific biosystem (from WikiPathways)
      Gastric Cancer Network 1, organism-specific biosystemNetwork generated by mapping candidate oncogenes and tumor suppressor genes identified by integrated analysis of expression array and aCGH data. Networks generated by Ingenuity Pathway Analysis.
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    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • Mitotic G1-G1/S phases, organism-specific biosystem (from REACTOME)
      Mitotic G1-G1/S phases, organism-specific biosystem
      Mitotic G1-G1/S phases
    • Platinum drug resistance, organism-specific biosystem (from KEGG)
      Platinum drug resistance, organism-specific biosystemPlatinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. T...
    • Platinum drug resistance, conserved biosystem (from KEGG)
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    • Post-translational protein modification, organism-specific biosystem (from REACTOME)
      Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
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    • SUMO E3 ligases SUMOylate target proteins, organism-specific biosystem (from REACTOME)
      SUMO E3 ligases SUMOylate target proteins, organism-specific biosystemSUMO proteins are conjugated to lysine residues of target proteins via an isopeptide bond with the C-terminal glycine of SUMO (reviewed in Zhao 2007, Gareau and Lima 2010, Hannoun et al. 2010, Citro ...
    • SUMOylation, organism-specific biosystem (from REACTOME)
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    • SUMOylation of DNA replication proteins, organism-specific biosystem (from REACTOME)
      SUMOylation of DNA replication proteins, organism-specific biosystemThe sliding clamp protein PCNA, Aurora-A, Aurora-B, Borealin, and various topoisomerases can be SUMOylated (reviewed in Wan et al. 2012). SUMOylation of PCNA appears to reduce formation of double-str...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA binding, bending IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA topoisomerase type II (ATP-hydrolyzing) activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA topoisomerase type II (ATP-hydrolyzing) activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    DNA-dependent ATPase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    RNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    chromatin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    drug binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    histone deacetylase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein C-terminus binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein heterodimerization activity IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein kinase C binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    ubiquitin binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    DNA ligation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA topological change IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA topological change IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    apoptotic chromosome condensation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to DNA damage stimulus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    chromosome segregation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    embryonic cleavage IEA
    Inferred from Electronic Annotation
    more info
     
    hematopoietic progenitor cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    mitotic DNA integrity checkpoint IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    negative regulation of DNA duplex unwinding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of single stranded viral RNA replication via double stranded DNA intermediate IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase II promoter IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of viral genome replication IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein sumoylation TAS
    Traceable Author Statement
    more info
     
    regulation of circadian rhythm ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    resolution of meiotic recombination intermediates IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    rhythmic process IEA
    Inferred from Electronic Annotation
    more info
     
    sister chromatid segregation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Component Evidence Code Pubs
    DNA topoisomerase complex (ATP-hydrolyzing) IDA
    Inferred from Direct Assay
    more info
    PubMed 
    colocalizes_with centriole IDA
    Inferred from Direct Assay
    more info
    PubMed 
    condensed chromosome IEA
    Inferred from Electronic Annotation
    more info
     
    intracellular ribonucleoprotein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    colocalizes_with nuclear chromosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleolus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    NOT nucleolus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    colocalizes_with viral integration complex NAS
    Non-traceable Author Statement
    more info
    PubMed 
    Preferred Names
    DNA topoisomerase 2-alpha
    Names
    DNA gyrase
    DNA topoisomerase (ATP-hydrolyzing)
    DNA topoisomerase II, 170 kD
    DNA topoisomerase II, alpha isozyme
    topoisomerase (DNA) II alpha 170kDa
    NP_001058.2
    XP_005257689.1
    XP_011523467.1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_027678.1 RefSeqGene

      Range
      5001..34430
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001067.3NP_001058.2  DNA topoisomerase 2-alpha

      See identical proteins and their annotated locations for NP_001058.2

      Status: REVIEWED

      Source sequence(s)
      AC080112, BC140791, DB069825
      Consensus CDS
      CCDS45672.1
      UniProtKB/Swiss-Prot
      P11388
      Related
      ENSP00000411532.1, OTTHUMP00000207108, ENST00000423485.5, OTTHUMT00000338035
      Conserved Domains (8) summary
      cd03365
      Location:455575
      TOPRIM_TopoIIA; TOPRIM_TopoIIA: topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topoisomerase II. TopoIIA enzymes cut both strands of ...
      cd00187
      Location:7111174
      TOP4c; DNA Topoisomerase, subtype IIA; domain A'; bacterial DNA topoisomerase IV (C subunit, ParC), bacterial DNA gyrases (A subunit, GyrA),mammalian DNA toposiomerases II. DNA topoisomerases are essential enzymes that regulate the conformational changes in DNA ...
      cd03481
      Location:265417
      TopoIIA_Trans_ScTopoIIA; TopoIIA_Trans_ScTopoIIA: Transducer domain, having a ribosomal S5 domain 2-like fold, of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topo IIA. S. cerevisiae Topo IIA is a homodimer encoded ...
      PTZ00108
      Location:251497
      PTZ00108; DNA topoisomerase 2-like protein; Provisional
      pfam02518
      Location:80185
      HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
      pfam08070
      Location:14351521
      DTHCT; DTHCT (NUC029) region
      pfam15323
      Location:13571461
      Ashwin; Developmental protein
      pfam16898
      Location:573711
      TOPRIM_C; C-terminal associated domain of TOPRIM

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p7 Primary Assembly

      Range
      40388521..40417950 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005257632.1XP_005257689.1  DNA topoisomerase 2-alpha isoform X1

      Conserved Domains (8) summary
      cd03365
      Location:443563
      TOPRIM_TopoIIA; TOPRIM_TopoIIA: topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topoisomerase II. TopoIIA enzymes cut both strands of ...
      cd00187
      Location:6991162
      TOP4c; DNA Topoisomerase, subtype IIA; domain A'; bacterial DNA topoisomerase IV (C subunit, ParC), bacterial DNA gyrases (A subunit, GyrA),mammalian DNA toposiomerases II. DNA topoisomerases are essential enzymes that regulate the conformational changes in DNA ...
      cd03481
      Location:253405
      TopoIIA_Trans_ScTopoIIA; TopoIIA_Trans_ScTopoIIA: Transducer domain, having a ribosomal S5 domain 2-like fold, of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topo IIA. S. cerevisiae Topo IIA is a homodimer encoded ...
      PTZ00108
      Location:131485
      PTZ00108; DNA topoisomerase 2-like protein; Provisional
      pfam02518
      Location:68173
      HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
      pfam08070
      Location:14231509
      DTHCT; DTHCT (NUC029) region
      pfam15323
      Location:13451449
      Ashwin; Developmental protein
      pfam16898
      Location:561699
      TOPRIM_C; C-terminal associated domain of TOPRIM
    2. XM_011525165.1XP_011523467.1  DNA topoisomerase 2-alpha isoform X2

      Conserved Domains (6) summary
      cd03365
      Location:455575
      TOPRIM_TopoIIA; TOPRIM_TopoIIA: topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topoisomerase II. TopoIIA enzymes cut both strands of ...
      cd00187
      Location:7111174
      TOP4c; DNA Topoisomerase, subtype IIA; domain A'; bacterial DNA topoisomerase IV (C subunit, ParC), bacterial DNA gyrases (A subunit, GyrA),mammalian DNA toposiomerases II. DNA topoisomerases are essential enzymes that regulate the conformational changes in DNA ...
      cd03481
      Location:265417
      TopoIIA_Trans_ScTopoIIA; TopoIIA_Trans_ScTopoIIA: Transducer domain, having a ribosomal S5 domain 2-like fold, of the type found in proteins of the type IIA family of DNA topoisomerases similar to Saccharomyces cerevisiae Topo IIA. S. cerevisiae Topo IIA is a homodimer encoded ...
      PTZ00108
      Location:251364
      PTZ00108; DNA topoisomerase 2-like protein; Provisional
      pfam02518
      Location:80185
      HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
      pfam16898
      Location:573711
      TOPRIM_C; C-terminal associated domain of TOPRIM

    Alternate CHM1_1.1

    Genomic

    1. NC_018928.2 Alternate CHM1_1.1

      Range
      38780085..38809522 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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