Protein: DNA topoisomerase 1 (EC 5.6.2.1) (DNA topoisomerase I) (Q04750)
Organism: Mus musculus (Mouse)
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 rotates around the intact phosphodiester bond on the opposing 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. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter.
Subcellular location: Nucleus, nucleolus {ECO:0000250|UniProtKB:P11387}. Nucleus, nucleoplasm {ECO:0000250|UniProtKB:P11387}. Note=Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumoylated forms found in both nucleoplasm and nucleoli. {ECO:0000250|UniProtKB:P11387}.
Sequence: MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKDKDKDREKSKHSNSEHKDSEKKHKEKEKTKHKDGSSEKHKDKHKDRDKERRKEEKIRAAGDAKIKKEKENGFSSPPRIKDEPEDDGYFAPPKEDIKPLKRLRDEDDADYKPKKIKTEDIKKEKKRKSEEEEDGKLKKPKNKDKDKKVAEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPESVKFYYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNDEKNTITNLSKCDFTQMSQYFKAQSEARKQMSKEEKLKIKEENEKLLKEYGFCVMDNHRERIANFKIEPPGLFRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENIQGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALYFIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFPGKDSIRYYNKVPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQQLKELTAPDENVPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQSKIDAKKDQLADARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMTDEDYEF
InterPro domains: - IPR013499: DNA topoisomerase I, eukaryotic-type (domain) [362-739]
- IPR036202: DNA topoisomerase I, DNA binding, eukaryotic-type, N-terminal domain superfamily (homologous_superfamily) [204-432]
- IPR001631: DNA topoisomerase I (family) [362-730]
- IPR013034: DNA topoisomerase I, DNA binding, N-terminal domain 1 (homologous_superfamily) [234-321]
- IPR011010: DNA breaking-rejoining enzyme, catalytic core (homologous_superfamily) [434-766]
- IPR008336: DNA topoisomerase I, DNA binding, eukaryotic-type (domain) [217-431]
- IPR013500: DNA topoisomerase I, catalytic core, eukaryotic-type (domain) [434-666]
- IPR051062: DNA topoisomerase IB (family) [14-767]
- IPR014727: DNA topoisomerase I, catalytic core, alpha/beta subdomain (homologous_superfamily) [589-767]
- IPR048045: DNA topoisomerase I, DNA-binding domain (domain) [218-432]
- IPR025834: Topoisomerase I C-terminal domain (domain) [697-767]
- IPR014711: DNA topoisomerase I, catalytic core, alpha-helical subdomain, eukaryotic-type (homologous_superfamily) [434-588]
- IPR013030: DNA topoisomerase I, DNA binding, N-terminal domain 2 (homologous_superfamily) [206-431]
- IPR018521: DNA topoisomerase IB, active site (active_site) [712-730]
Interaction partners: - DNA topoisomerase 2-beta
- DNA topoisomerase 2-alpha
- Tyrosyl-DNA phosphodiesterase 1
- Poly [ADP-ribose] polymerase 1
- RNA-binding motif protein, X chromosome
- RNA binding motif protein, X-linked-like-1
- Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN
- Ribonuclease H2 subunit A
- Cell division cycle and apoptosis regulator protein 1
- DNA topoisomerase 3-alpha
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016853 (isomerase activity), GO:1901363 (heterocyclic compound binding), GO:0140640 (catalytic activity, acting on a nucleic acid), GO:0097159 (organic cyclic compound binding), GO:0003682 (chromatin binding), GO:0003676 (nucleic acid binding), GO:0003916 (DNA topoisomerase activity), GO:0140097 (catalytic activity, acting on DNA), GO:0003677 (DNA binding), GO:0003917 (DNA topoisomerase type I (single strand cut, ATP-independent) activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0048511 (rhythmic process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0044237 (cellular metabolic process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0007623 (circadian rhythm), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0009410 (response to xenobiotic stimulus), GO:0046483 (heterocycle metabolic process), GO:0019538 (protein metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0016043 (cellular component organization), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0032922 (circadian regulation of gene expression), GO:0006793 (phosphorus metabolic process), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0090304 (nucleic acid metabolic process), GO:0006259 (DNA metabolic process), GO:0006325 (chromatin organization), GO:0006796 (phosphate-containing compound metabolic process), GO:0006996 (organelle organization), GO:0010468 (regulation of gene expression), GO:0006265 (DNA topological change), GO:0006338 (chromatin remodeling), GO:0006468 (protein phosphorylation), GO:0018193 (peptidyl-amino acid modification), GO:0051276 (chromosome organization), GO:0016310 (phosphorylation), GO:0071103 (DNA conformation change), GO:0018105 (peptidyl-serine phosphorylation), GO:0018209 (peptidyl-serine modification)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)