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MGP003171

UniProt Annotations

Entry Information
Gene Nametopoisomerase (DNA) I
Protein EntryTOP1_HUMAN
UniProt IDP11387
SpeciesHuman
Comments
Comment typeDescription
Catalytic ActivityATP-independent breakage of single-stranded DNA, followed by passage and rejoining. {ECO:0000255|PROSITE- ProRule:PRU10130, ECO:0000269|PubMed:14594810, ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:2833744}.
DiseaseNote=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.
Enzyme RegulationSpecifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.
FunctionReleases 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. {ECO:0000250|UniProtKB:Q13472, ECO:0000269|PubMed:14594810, ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:22904072, ECO:0000269|PubMed:2833744}.
InteractionP00519:ABL1; NbExp=7; IntAct=EBI-876302, EBI-375543; P01106:MYC; NbExp=2; IntAct=EBI-876302, EBI-447544; Q99801:NKX3-1; NbExp=6; IntAct=EBI-876302, EBI-1385894;
MiscellaneousEukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.
PtmPhosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin. {ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:23185622}.
PtmSumoylated. Lys-117 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment. {ECO:0000269|PubMed:12149243}.
Sequence CautionSequence=CAA36834.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
SimilarityBelongs to the type IB topoisomerase family. {ECO:0000305}.
Subcellular LocationNucleus, nucleolus {ECO:0000269|PubMed:12149243}. Nucleus, nucleoplasm {ECO:0000269|PubMed:12149243}. Note=Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumolyated forms found in both nucleoplasm and nucleoli.
SubunitMonomer. Interacts with SV40 Large T antigen; this interactions allows viral DNA replication. {ECO:0000269|PubMed:10841763, ECO:0000269|PubMed:12209008, ECO:0000269|PubMed:12533542, ECO:0000269|PubMed:15165849, ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:18003733, ECO:0000269|PubMed:9488644, ECO:0000269|PubMed:9488652}.
Tissue SpecificityEndothelial cells. {ECO:0000269|PubMed:19168442}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TOP1ID320ch20q11.html";
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