Recombinant Human DNA topoisomerase 1 (TOP1)

Code CSB-YP024056HU
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Source Yeast
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Code CSB-EP024056HU
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Source E.coli
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Code CSB-EP024056HU-B
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Source E.coli
Conjugate Avi-tag Biotinylated
E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.
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Code CSB-BP024056HU
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Source Baculovirus
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Code CSB-MP024056HU
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Source Mammalian cell
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Product Details

Purity
>85% (SDS-PAGE)
Target Names
TOP1
Uniprot No.
Alternative Names
DNA topoisomerase 1; DNA topoisomerase I; NUP98 fusion gene; TOP 1; TOP I; TOP1; TOP1_HUMAN; TOPI; Topoisomerase (DNA) I; Topoisomerase 1; Topoisomerase1; TopoisomeraseI; Type I DNA topoisomerase
Species
Homo sapiens (Human)
Expression Region
2-765
Target Protein Sequence
SGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK EKDREKSKHS NSEHKDSEKK HKEKEKTKHK DGSSEKHKDK HKDRDKEKRK EEKVRASGDA KIKKEKENGF SSPPQIKDEP EDDGYFVPPK EDIKPLKRPR DEDDADYKPK KIKTEDTKKE KKRKLEEEED GKLKKPKNKD KDKKVPEPDN KKKKPKKEEE QKWKWWEEER YPEGIKWKFL EHKGPVFAPP YEPLPENVKF YYDGKVMKLS PKAEEVATFF AKMLDHEYTT KEIFRKNFFK DWRKEMTNEE KNIITNLSKC DFTQMSQYFK AQTEARKQMS KEEKLKIKEE NEKLLKEYGF CIMDNHKERI ANFKIEPPGL FRGRGNHPKM GMLKRRIMPE DIIINCSKDA KVPSPPPGHK WKEVRHDNKV TWLVSWTENI QGSIKYIMLN PSSRIKGEKD WQKYETARRL KKCVDKIRNQ YREDWKSKEM KVRQRAVALY FIDKLALRAG NEKEEGETAD TVGCCSLRVE HINLHPELDG QEYVVEFDFL GKDSIRYYNK VPVEKRVFKN LQLFMENKQP EDDLFDRLNT GILNKHLQDL MEGLTAKVFR TYNASITLQQ QLKELTAPDE NIPAKILSYN RANRAVAILC NHQRAPPKTF EKSMMNLQTK IDAKKEQLAD ARRDLKSAKA DAKVMKDAKT KKVVESKKKA VQRLEEQLMK LEVQATDREE NKQIALGTSK LNYLDPRITV AWCKKWGVPI EKIYNKTQRE KFAWAIDMAD EDYEF
Protein Length
Full Length of Mature Protein
Tag Info
Tag type will be determined during the manufacturing process.
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Form
Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer before Lyophilization
Tris/PBS-based buffer, 6% Trehalose, pH 8.0
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet
Please contact us to get it.

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Target Background

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 ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.
Gene References into Functions
  1. TOP1 differentially modulates R-loops across the human genome. PMID: 30060749
  2. Results from a study on gene expression variability markers in early-stage human embryos shows that TOP1 is a putative expression variability marker for the 3-day, 8-cell embryo stage. PMID: 26288249
  3. High TOP1 expression is associated with aggressive tumor phenotype in breast cancer. PMID: 26959889
  4. Ru/Fe bimetallic complexes: Synthesis, characterization, cytotoxicity and study of their interactions with DNA/HSA and human topoisomerase IB. PMID: 29107586
  5. two regions of topoisomerase I, the N-terminal and the linker domains, were critical for subnuclear localization of the enzyme. The linker domain and the distal region of the N-terminal domain directed topoisomerase I to the nucleolus, whereas the remaining region of the N-terminal domain was responsible for the nucleoplasmic localization. PMID: 27428351
  6. High TOP1 expression is associated with Colorectal Cancers. PMID: 28870917
  7. HMGA2 potentiates the clinically important topoisomerase I inhibitor irinotecan/SN-38 in trapping the enzyme in covalent DNA-complexes, thereby attenuating transcription. PMID: 27587582
  8. IMMP2L transcription requires Topoisomerase I in human primary astrocytes PMID: 27932244
  9. This work identifies ADP-ribose polymers as key determinant for regulating Top1 subnuclear dynamics. PMID: 27466387
  10. copper(II) thiosemicarbazone complex may hit human topoisomerase IB and that metal coordination can be useful to improve cytotoxicity of this versatile class of compounds PMID: 27431056
  11. High prevalence of anti-topoisomerase I antibody positivity was found among Thai systemic sclerosis patients and this was associated with a high frequency of hand deformity, ACA negativity, a short duration of pulmonary fibrosis in diffuse cutaneous and a lower frequency of Raynaud's phenomenon in limited cutaneous subsets. PMID: 25293362
  12. These findings reveal BAZ1B as a key facilitator of topoisomerase I function during DNA replication that affects the response of cancer cells to topoisomerase I inhibitors. PMID: 27050524
  13. Results identified TOP1 gene copy gain, a loss of chromosome 20, and new yet unreported TOP1 mutations (R364K and G717R) in close proximity to the SN-38 binding site conferring colon cancer cells resistance to the drug. PMID: 27029323
  14. the highest expression of GGH and EGFR was noted in the left-sided colon; the highest expression of DHFR, FPGS, TOP1 and ERCC1 was noted in the rectosigmoid, whereas TYMP expression was approximately equivalent in the right-sided colon and rectum PMID: 26676887
  15. We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400 PMID: 26801902
  16. Data show that the single-molecule supercoil relaxation assay is a sensitive method to elucidate the detailed mechanisms of type IB topoisomerase (Top1) inhibitors and is relevant for the cellular efficacy of Top1 inhibitors. PMID: 26351326
  17. TOP1 bound at promoters was discovered to become fully active only after pause-release. This transition coupled the phosphorylation of the carboxyl-terminal-domain (CTD) of RNA polymerase II (RNAPII) with stimulation of TOP1 above its basal rate, enhancing its processivity. PMID: 27058666
  18. Data show that inhibition of DNA-dependent protein kinase catalytic subunit (DNA-PK) prevents type I DNA topoisomerase (Top1) degradation and proteasome activity in camptothecin (CPT)-treated quiescent WI38 cells. PMID: 26578593
  19. NO-induced down-regulation of topoisomerase I protein. PMID: 26540186
  20. b-ELE could inhibit the proliferation of HepG-2 cells and interfere with the expression and activity of TOPO I and TOPO IIa PMID: 26221582
  21. Acridine derivatives inhibited DNA topoisomerases I and II and prevented proliferation of HL-60 cells. PMID: 25960253
  22. Topoisomerase-1 and -2A gene copy numbers are elevated in mismatch repair-proficient colorectal cancers. PMID: 25777966
  23. Cinobufacini inhibited the proliferation of the HepG-2 cells induced apoptosis in a dose- and time-dependent manner and downregulated the mRNA and protein expression levels of TOPO I and TOPO II PMID: 25815590
  24. YB-1 serves as an intracellular promoter of TOPO1 catalytic activity that enhances camptothecin sensitivity through its direct interaction with TOPO1. PMID: 25539742
  25. We here report that a substantial number of patients with bile duct or pancreatic cancer have increased TOP1 copy number and increased TOP1/centromere-20 ratio. PMID: 25615400
  26. Results show that TOP1 gene is amplified in a subset of breast cancer patients suggesting the gene as a potential biomarker for response to treatment with Top1 inhibitors. PMID: 25855483
  27. Results show that camptothecin resistance status of colorectal cancer cells depend on the phosphorylation of TOP1 and the presence of CD44. PMID: 24960044
  28. varying expression levels of TOP1 and TDP1 polypeptides in multiple colorectal cancer cell lines and in clinical colorectal cancer samples, are reported. PMID: 25522766
  29. CCR6 SNPs are a risk factor for presence of anti-topoisomerase I antibodies in systemic sclerosis. PMID: 26314374
  30. ERCC1-XPF participates in DNA repair of the Top1-DNA damage complex. PMID: 26025908
  31. both TOP1 and TDP1 were upregulated in the tumor tissue compared to the adjacent non-tumor tissue in non-small cell lung cancer tissue PMID: 25987486
  32. mutations at the hydrophobic or charged residues of the putative polymer binding sites do not interfere with the ability of poly(ADP-ribose) to antagonize the antitumor activity of topoisomerase I poisons. PMID: 25227992
  33. No TOP1 copy number changes were found in patients with de novo diffuse large B-cell lymphoma or relapsed DLBCL treated with chemotherapy regimens including TOP2-targeting drugs. PMID: 25931012
  34. Mutation of Gly717Phe in human topoisomerase 1B has an effect on enzymatic function, reactivity to the camptothecin anticancer drug and on the linker domain orientation PMID: 25910424
  35. Top1 cleavage events generate short deletions; Top1 also promotes nick religation at rNMP sites PMID: 25887397
  36. analysis of how human and yeast DNA topoisomerase I domain interactions impact enzyme activity and sensitivity to camptothecin PMID: 25795777
  37. Study describes a molecular mechanism that operates at functional androgen-regulated enhancers and identify DNA topoisomerase I as a critical DNA-nicking enzyme involved in the process of cell-specific, ligand-driven enhancer activation. PMID: 25619691
  38. The combination of Top1 inhibitors with VE-821 inhibited the phosphorylation of ATR and Chk1. PMID: 25269479
  39. DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET PMID: 24040417
  40. Collectively, these findings suggest that the combinatorial inhibition of MET and Top1 is a potentially efficacious treatment strategy for Small cell lung cancer . PMID: 24327519
  41. our data show for the first time that HIF-1alpha is strongly correlated with resistance to topoisomerase I inhibitors in hepatocellular carcinoma. PMID: 24362462
  42. Analysis of the dynamical properties of DNA topoisomerase 1B bound to the more biologically relevant supercoiled substrate reveals an increased number of protein-DNA interactions and, most strikingly, the presence of a secondary protein-DNA binding site. PMID: 25056319
  43. homologous recombination seems relevant especially for Top1 and, to a lesser extent, for Top2 inhibitors. We also found and discuss differential pathways among Top1 inhibitors and Top2 inhibitors PMID: 24130054
  44. key factors in a molecular pathway connecting Top1 inhibition and human HIF-1alpha protein regulation and activity, widening the biologic and molecular activity of camptothecin PMID: 24252850
  45. [review] Telangiectasia and anti-CENP or anti-topo I antibodies in the presence of Raynaud's phenomenon and proximal skin thickening increase the sensitivity of a very early diagnosis of systemic sclerosis from 57% to 97%. PMID: 24461384
  46. This property facilitates the deprotonation of the 5' DNA end, suggesting that this is the limiting step in the topoisomerase religation mechanism. PMID: 23368812
  47. These results suggest that topo I is a novel target of erlotinib and a combination of TKIs with topo I inhibitors may be an effective treatment for breast cancer. PMID: 24399039
  48. Critical endogenous pathogenic lesions are associated with neurodegenerative syndromes arising from aberrant TOP-1 DNA. PMID: 24793032
  49. A fully functional linker is required to confer camptothecin sensitivity to topoisomerase I. PMID: 24004603
  50. MiR-23a could directly bind to 3'untranslated region of TOP1 mRNA, and suppress the corresponding protein expression. PMID: 24103454

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Involvement in disease
A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.
Subcellular Location
Nucleus, nucleolus. Nucleus, nucleoplasm. 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.
Protein Families
Type IB topoisomerase family
Tissue Specificity
Endothelial cells.
Database Links

HGNC: 11986

OMIM: 126420

KEGG: hsa:7150

STRING: 9606.ENSP00000354522

UniGene: Hs.472737

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