DNA topoisomerase 1

Details

Name
DNA topoisomerase 1
Synonyms
  • 5.99.1.2
  • DNA topoisomerase I
Gene Name
TOP1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001933|DNA topoisomerase 1
MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKK
HKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEP
EDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKD
KDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPENVKF
YYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNEEKNIITNLSKC
DFTQMSQYFKAQTEARKQMSKEEKLKIKEENEKLLKEYGFCIMDNHKERIANFKIEPPGL
FRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENI
QGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALY
FIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFLGKDSIRYYNK
VPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQ
QLKELTAPDENIPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLAD
ARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSK
LNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMADEDYEF
Number of residues
765
Molecular Weight
90725.19
Theoretical pI
9.95
GO Classification
Functions
chromatin binding / core promoter sequence-specific DNA binding / DNA binding / DNA topoisomerase type I activity / DNA topoisomerase type II (ATP-hydrolyzing) activity / poly(A) RNA binding
Processes
chromatin remodeling / chromosome segregation / circadian regulation of gene expression / circadian rhythm / DNA replication / DNA topological change / embryonic cleavage / phosphorylation / programmed cell death / response to drug / viral process
Components
cytoplasmic mRNA processing body / nucleolus / nucleoplasm / nucleus / perikaryon / replication fork protection complex
General Function
Poly(a) rna binding
Specific Function
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0016271|DNA topoisomerase 1 (TOP1)
ATGAGTGGGGACCACCTCCACAACGATTCCCAGATCGAAGCGGATTTCCGATTGAATGAT
TCTCATAAACACAAAGATAAACACAAAGATCGAGAACACCGGCACAAAGAACACAAGAAG
GAGAAGGACCGGGAAAAGTCCAAGCATAGCAACAGTGAACATAAAGATTCTGAAAAGAAA
CACAAAGAGAAGGAGAAGACCAAACACAAAGATGGAAGCTCAGAAAAGCATAAAGACAAA
CATAAAGACAGAGACAAGGAAAAACGAAAAGAGGAAAAGGTTCGAGCCTCTGGGGATGCA
AAAATAAAGAAGGAGAAGGAAAATGGCTTCTCTAGTCCACCACAAATTAAAGATGAACCT
GAAGATGATGGCTATTTTGTTCCTCCTAAAGAGGATATAAAGCCATTAAAGAGACCTCGA
GATGAGGATGATGCTGATTATAAACCTAAGAAAATTAAAACAGAAGATACCAAGAAGGAG
AAGAAAAGAAAACTAGAAGAAGAAGAGGATGGTAAATTGAAAAAACCCAAGAATAAAGAT
AAAGATAAAAAAGTTCCTGAGCCAGATAACAAGAAAAAGAAGCCGAAGAAAGAAGAGGAA
CAGAAGTGGAAATGGTGGGAAGAAGAGCGCTATCCTGAAGGCATCAAGTGGAAATTCCTA
GAACATAAAGGTCCAGTATTTGCCCCACCATATGAGCCTCTTCCAGAGAATGTCAAGTTT
TATTATGATGGTAAAGTCATGAAGCTGAGCCCCAAAGCAGAGGAAGTAGCTACGTTCTTT
GCAAAAATGCTCGACCATGAATATACTACCAAGGAAATATTTAGGAAAAATTTCTTTAAA
GACTGGAGAAAGGAAATGACTAATGAAGAGAAGAATATTATCACCAACCTAAGCAAATGT
GATTTTACCCAGATGAGCCAGTATTTCAAAGCCCAGACGGAAGCTCGGAAACAGATGAGC
AAGGAAGAGAAACTGAAAATCAAAGAGGAGAATGAAAAATTACTGAAAGAATATGGATTC
TGTATTATGGATAACCACAAAGAGAGGATTGCTAACTTCAAGATAGAGCCTCCTGGACTT
TTCCGTGGCCGCGGCAACCACCCCAAGATGGGCATGCTGAAGAGACGAATCATGCCCGAG
GATATAATCATCAACTGTAGCAAAGATGCCAAGGTTCCTTCTCCTCCTCCAGGACATAAG
TGGAAAGAAGTCCGGCATGATAACAAGGTTACTTGGCTGGTTTCCTGGACAGAGAACATC
CAAGGTTCCATTAAATACATCATGCTTAACCCTAGTTCACGAATCAAGGGTGAGAAGGAC
TGGCAGAAATACGAGACTGCTCGGCGGCTGAAAAAATGTGTGGACAAGATCCGGAACCAG
TATCGAGAAGACTGGAAGTCCAAAGAGATGAAAGTCCGGCAGAGAGCTGTAGCCCTGTAC
TTCATCGACAAGCTTGCTCTGAGAGCAGGCAATGAAAAGGAGGAAGGAGAAACAGCGGAC
ACTGTGGGCTGCTGCTCACTTCGTGTGGAGCACATCAATCTACACCCAGAGTTGGATGGT
CAGGAATATGTGGTAGAGTTTGACTTCCTCGGGAAGGACTCCATCAGATACTATAACAAG
GTCCCTGTTGAGAAACGAGTTTTTAAGAACCTACAACTATTTATGGAGAACAAGCAGCCC
GAGGATGATCTTTTTGATAGACTCAATACTGGTATTCTGAATAAGCATCTTCAGGATCTC
ATGGAGGGCTTGACAGCCAAGGTATTCCGTACATACAATGCCTCCATCACGCTACAGCAG
CAGCTAAAAGAACTGACAGCCCCGGATGAGAACATCCCAGCGAAGATCCTTTCTTATAAC
CGTGCCAATCGAGCTGTTGCAATTCTTTGTAACCATCAGAGGGCACCACCAAAAACTTTT
GAGAAGTCTATGATGAACTTGCAAACTAAGATTGATGCCAAGAAGGAACAGCTAGCAGAT
GCCCGGAGAGACCTGAAAAGTGCTAAGGCTGATGCCAAGGTCATGAAGGATGCAAAGACG
AAGAAGGTAGTAGAGTCAAAGAAGAAGGCTGTTCAGAGACTGGAGGAACAGTTGATGAAG
CTGGAAGTTCAAGCCACAGACCGAGAGGAAAATAAACAGATTGCCCTGGGAACCTCCAAA
CTCAATTATCTGGACCCTAGGATCACAGTGGCTTGGTGCAAGAAGTGGGGTGTCCCAATT
GAGAAGATTTACAACAAAACCCAGCGGGAGAAGTTTGCCTGGGCCATTGACATGGCTGAT
GAAGACTATGAGTTTTAG
Chromosome Location
20
Locus
20q12-q13.1
External Identifiers
ResourceLink
UniProtKB IDP11387
UniProtKB Entry NameTOP1_HUMAN
GenBank Protein ID339806
GenBank Gene IDJ03250
GenAtlas IDTOP1
HGNC IDHGNC:11986
General References
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  9. Maul GG, Jimenez SA, Riggs E, Ziemnicka-Kotula D: Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8492-6. [Article]
  10. Ahuja HG, Felix CA, Aplan PD: The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion. Blood. 1999 Nov 1;94(9):3258-61. [Article]
  11. Rallabhandi P, Hashimoto K, Mo YY, Beck WT, Moitra PK, D'Arpa P: Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecin. J Biol Chem. 2002 Oct 18;277(42):40020-6. Epub 2002 Jul 30. [Article]
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  13. Khopde S, Simmons DT: Simian virus 40 DNA replication is dependent on an interaction between topoisomerase I and the C-terminal end of T antigen. J Virol. 2008 Feb;82(3):1136-45. Epub 2007 Nov 14. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00762Irinotecanapproved, investigationalyesinhibitorDetails
DB01030Topotecanapproved, investigationalyesinhibitorDetails
DB04690CamptothecinexperimentalunknowninhibitorDetails
DB04882EdotecarininvestigationalunknownDetails
DB05129ElsamitrucininvestigationalunknownDetails
DB04967LucanthoneinvestigationalyesinhibitorDetails
DB05482SN-38investigationalunknownDetails
DB05806CositecaninvestigationalunknownDetails
DB06069XMT-1001investigationalunknownDetails
DB06159RubitecaninvestigationalunknownDetails
DB05630Sodium stibogluconateapproved, investigationalyesinhibitorDetails
DB073542,3-DIMETHOXY-12H-[1,3]DIOXOLO[5,6]INDENO[1,2-C]ISOQUINOLIN-6-IUMexperimentalunknownDetails
DB081594-(5,11-DIOXO-5H-INDENO[1,2-C]ISOQUINOLIN-6(11H)-YL)BUTANOATEexperimentalunknownDetails
DB11254HexylresorcinolapprovedunknowninhibitorDetails
DB14962Trastuzumab deruxtecanapproved, investigationalyesinhibitorDetails
DB14962Trastuzumab deruxtecanapproved, investigationalunknowninhibitorDetails
DB12893Sacituzumab govitecanapproved, investigationalyesinhibitorDetails
DB00997Doxorubicinapproved, investigationalyesinhibitorDetails
DB00970Dactinomycinapproved, investigationalunknowninhibitorDetails