ID:TOP1_HUMAN DESCRIPTION: RecName: Full=DNA topoisomerase 1; EC=5.99.1.2; AltName: Full=DNA topoisomerase I; 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 than 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. CATALYTIC ACTIVITY: ATP-independent breakage of single-stranded DNA, followed by passage and rejoining. ENZYME REGULATION: Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity. SUBUNIT: Monomer. Interacts with SV40 Large T antigen; this interactions allows viral DNA replication. INTERACTION: P01106:MYC; NbExp=2; IntAct=EBI-876302, EBI-447544; Q99801:NKX3-1; NbExp=6; IntAct=EBI-876302, EBI-1385894; SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus, nucleoplasm. 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. TISSUE SPECIFICITY: Endothelial cells. PTM: Sumoylated. 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. DISEASE: Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98. MISCELLANEOUS: Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils. SIMILARITY: Belongs to the type IB topoisomerase family. SEQUENCE CAUTION: Sequence=CAA36834.1; Type=Erroneous gene model prediction; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TOP1ID320ch20q11.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF01028 - Eukaryotic DNA topoisomerase I, catalytic core PF02919 - Eukaryotic DNA topoisomerase I, DNA binding fragment PF14370 - C-terminal topoisomerase domain
SCOP Domains: 46596 - Eukaryotic DNA topoisomerase I, dispensable insert domain 56349 - DNA breaking-rejoining enzymes 56741 - Eukaryotic DNA topoisomerase I, N-terminal DNA-binding fragment
ModBase Predicted Comparative 3D Structure on P11387
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
