Gene: TOP1 - Homo sapiens
Last modified: Dec 09, 2014. Release 1 • Page created: May 19, 2024
Summary
Gene Symbol | : | TOP1 | ||||||||||||||||
NCBI Gene ID | : | 7150 | ||||||||||||||||
Species | : | Homo sapiens | ||||||||||||||||
Gene Synonyms | : | DNA topoisomerase 1 | RP3-511B24.1 | TOP1 | TOPI | topoisomerase (DNA) I | TOPOISOMERASE, DNA, I | type I DNA topoisomerase Source: GPSDB |
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Gene Homologs | : | AgaP_AGAP004078 (Anopheles gambiae) | AGOS_ACL008C (Eremothecium gossypii) | AT5G55310.1 (Arabidopsis thaliana) | KLLA0C06116g (Kluyveromyces lactis) | MGG_09917 (Magnaporthe oryzae) | NCU09118 (Neurospora crassa) | Os08g0154600 (Oryza sativa) | top-1 (Caenorhabditis elegans) | TOP1 (Arabidopsis thaliana) | TOP1 (Bos taurus) | TOP1 (Canis lupus familiaris) | Top1 (Drosophila melanogaster) | TOP1 (Gallus gallus) | TOP1 (Homo sapiens) | TOP1 (Macaca mulatta) | Top1 (Mus musculus) | TOP1 (Pan troglodytes) | Top1 (Rattus norvegicus) | TOP1 (Saccharomyces cerevisiae) | top1 (Schizosaccharomyces pombe) | top1l (Danio rerio) | ||||||||||||||||
Ageing Relevance Analysis | : |
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Ageing Factor Stable ID | : | AF_008543 | ||||||||||||||||
Download | : | XML |
Protein Information
Protein Name | Species | UniProt Accession Number | UniProt Entry Name | Protein Function | Sequence |
---|---|---|---|---|---|
DNA topoisomerase 1 | Homo sapiens | P11387 (UniProtKB/Swiss-Prot) | TOP1_HUMAN (UniProtKB/Swiss-Prot) | 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. | View |
Observations
Ageing Phenotype
Data Type 1
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
# | Observation Stable ID | Species | Gene | Other Ageing Factor | Description | PubMed | Source | ||||
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1 | OB_009795 | Homo sapiens |
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Topoisomerases regulate the topological states of DNA. Though no direct interaction has been reported, TOP1 has been indirectly linked to WRN [0487]. TOP1 may also be important in the regulation of various brain functions and its activity is age-dependent [1625]. Because TOP1 has been associated with several DNA metabolism proteins thought to play a role in ageing, it is possible that TOP1 is itself involved in human ageing, though further studies are necessary to confirm this hypothesis. | GenAge |
Data Type 2
no ageing phenotype observation—data type 2 available
Homology Analysis
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
Legend:
- #EGHG:
- Number of Experimentally Confirmed Ageing-related Genes In Homology Group
Sequences
TOP1_HUMAN | P11387 | DNA topoisomerase 1 (Homo sapiens) from UniProtKB/Swiss-Prot Length: 765 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380 390 400 410 420 430 440 450 460 470 480 490 500 510 520 530 540 550 560 570 580 590 600 610 620 630 640 650 660 670 680 690 700 710 720 730 740 750 760 TOP1_HUMAN 1 MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKKHKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEPEDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKDKDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPENVKFYYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNEEKNIITNLSKCDFTQMSQYFKAQTEARKQMSKEEKLKIKEENEKLLKEYGFCIMDNHKERIANFKIEPPGLFRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENIQGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALYFIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFLGKDSIRYYNKVPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQQLKELTAPDENIPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLADARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMADEDYEF 765
References
MeSH Terms: Only a subset of the Medical Subject Headings terms is shown: the Major Topics MeSH terms. They describe one of the main topics discussed in the article denoted by an asterisk on the MeSH term or MeSH/Subheading combination on the PubMed page. MeSH terms that belong to the Ageing MeSH are highlighted in green.
- Michishita E, Nakabayashi K, Ogino H, Suzuki T, Fujii M, Ayusawa D:
DNA topoisomerase inhibitors induce reversible senescence in normal human fibroblasts.
Biochem Biophys Res Commun. 1998; 253: 667-71.
PubMed (ID: 9918785), doi:10.1006/bbrc.1998.9832
MeSH Terms: Cell Aging; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors - Mao Y, Sun M, Desai SD, Liu LF:
SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage.
Proc Natl Acad Sci USA. 2000; 97: 4046-51.
PubMed (ID: 10759568), PubMed Central (ID: PMC18143), doi:10.1073/pnas.080536597
MeSH Terms: DNA Damage; DNA Repair; DNA Topoisomerases, Type I/metabolism; Saccharomyces cerevisiae Proteins; Ubiquitin-Conjugating Enzymes; Ubiquitins/metabolism - Pichierri P, Franchitto A, Mosesso P, Palitti F:
Werner's syndrome cell lines are hypersensitive to camptothecin-induced chromosomal damage.
Mutat Res. 2000; 456: 45-57.
PubMed (ID: 11087895)
MeSH Terms: Camptothecin/toxicity; Chromosome Aberrations; Enzyme Inhibitors/toxicity; Topoisomerase I Inhibitors; Werner Syndrome/genetics - Shen J, Loeb LA:
Unwinding the molecular basis of the Werner syndrome.
Mech Ageing Dev. 2001; 122: 921-44.
PubMed (ID: 11348659)
MeSH Terms: DNA Helicases/physiology; DNA-Binding Proteins; Werner Syndrome/enzymology - Wang JC:
Cellular roles of DNA topoisomerases: a molecular perspective.
Nat Rev Mol Cell Biol. 2002; 3: 430-40.
PubMed (ID: 12042765), doi:10.1038/nrm831
MeSH Terms: Chromosomes/genetics; DNA Topoisomerases, Type I/metabolism - Caldecott KW:
DNA single-strand break repair and spinocerebellar ataxia.
Cell. 2003; 112: 7-10.
PubMed (ID: 12526788)
MeSH Terms: DNA Damage/genetics; DNA Repair/genetics; DNA-Binding Proteins/genetics; Nuclear Proteins/genetics; Polynucleotide 5'-Hydroxyl-Kinase/genetics; Spinocerebellar Ataxias/genetics - Partridge JJ, Lopreiato JO, Latterich M, Indig FE:
DNA damage modulates nucleolar interaction of the Werner protein with the AAA ATPase p97/VCP.
Mol Biol Cell. 2003; 14: 4221-9.
PubMed (ID: 12937274), PubMed Central (ID: PMC207013), doi:10.1091/mbc.E03-02-0111
MeSH Terms: Cell Cycle Proteins/metabolism; Cell Nucleolus/metabolism; DNA Damage/physiology; DNA Helicases/metabolism; Werner Syndrome/metabolism - Laine JP, Opresko PL, Indig FE, Harrigan JA, von Kobbe C, Bohr VA:
Werner protein stimulates topoisomerase I DNA relaxation activity.
Cancer Res. 2003; 63: 7136-46.
PubMed (ID: 14612507)
MeSH Terms: DNA Helicases/metabolism; DNA Topoisomerases, Type I/metabolism - Plaschkes I, Silverman FW, Priel E:
DNA topoisomerase I in the mouse central nervous system: Age and sex dependence.
J Comp Neurol. 2005; 493: 357-69.
PubMed (ID: 16261531), doi:10.1002/cne.20793
MeSH Terms: Aging/metabolism; Brain/enzymology; DNA Topoisomerases, Type I/metabolism; Neurons/enzymology; Spinal Cord/enzymology
Sources
Ageing-related Data Sources
- AgeFactDB Homology Analysis
- GenAge
Additional Data Sources
- AgeFactDB Pipeline
- GPSDB
- HomoloGene
- NCBI Taxonomy
- PubMed
- UniProtKB/Swiss-Prot