Names & Taxonomy
- Uniprot ID:
- P11387
- Entry Name:
- TOP1_HUMAN
- Status:
- reviewed
- Protein Names:
- DNA topoisomerase 1 (EC 5.99.1.2) (DNA topoisomerase I)
- Gene Names:
- TOP1
- Gene Names Primary:
- TOP1
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 765
- Sequence:
- MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKKHKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEPEDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKDKDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPENVKFYYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNEEKNIITNLSKCDFTQMSQYFKAQTEARKQMSKEEKLKIKEENEKLLKEYGFCIMDNHKERIANFKIEPPGLFRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENIQGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALYFIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFLGKDSIRYYNKVPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQQLKELTAPDENIPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLADARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMADEDYEF
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Nucleus, nucleolus
Function
- 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.
- Catalytic Activity:
- ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.
- Enzyme Regulation:
- ENZYME REGULATION: Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.
- Active Site:
- ACT_SITE 723 723 O-(3'-phospho-DNA)-tyrosine intermediate.
- Cross Reference Drug Bank:
- DB00762 DB04967 DB05630 DB01030
- Gene Ontology Go:
- cytoplasmic mRNA processing body
nucleolus
nucleoplasm
nucleus
perikaryon
replication fork protection complex
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
cellular protein metabolic process
chromatin remodeling
chromosome segregation
circadian regulation of gene expression
circadian rhythm
DNA replication
DNA topological change
embryonic cleavage
phosphorylation
post-translational protein modification
programmed cell death
protein sumoylation
response to drug
viral process - Gene Ontology Biological Process:
- cellular protein metabolic process
chromatin remodeling
chromosome segregation
circadian regulation of gene expression
circadian rhythm
DNA replication
DNA topological change
embryonic cleavage
phosphorylation
post-translational protein modification
programmed cell death
protein sumoylation
response to drug
viral process - Gene Ontology Molecular Function:
- 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 - Gene Ontology Cellular Component:
- cytoplasmic mRNA processing body
nucleolus
nucleoplasm
nucleus
perikaryon
replication fork protection complex - Keywords:
- 3D-structure
Acetylation
Biological rhythms
Chromosomal rearrangement
Complete proteome
DNA-binding
Direct protein sequencing
Host-virus interaction
Isomerase
Isopeptide bond
Nucleus
Phosphoprotein
Polymorphism
Proto-oncogene
Reference proteome
Topoisomerase
Ubl conjugation - Interacts With:
- P00519; P01106; Q99801
Publication
- PubMed ID:
- 2833744 1851751 14702039 11780052 2176592 7882333 2461859 2544263 2479024 10556215 12149243 17081983 18003733 18669648 19413330 19168442 19608861 20068231 21269460 21406692 22904072 23185622 24275569 25218447 25772364 25755297 9488644 9488652 10841763 12209008 12426403 12533542 14594810 15165849 15801827 16033260 1849260 1332703 16959974