Recombinant Human Serine/threonine-protein kinase ATR(ATR) ,partial

Code CSB-YP622666HU
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Source Yeast
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Code CSB-EP622666HU
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Source E.coli
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Code CSB-EP622666HU-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-BP622666HU
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Source Baculovirus
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Code CSB-MP622666HU
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Source Mammalian cell
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Product Details

Purity >85% (SDS-PAGE)
Target Names ATR
Uniprot No. Q13535
Alternative Names Ataxia telangiectasia and Rad3 related; Ataxia telangiectasia and Rad3-related protein; ATR; ATR_HUMAN; FCTCS; FRAP Related Protein 1; FRAP-related protein 1; FRP1; MEC1; MEC1 mitosis entry checkpoint 1 homolog; Protein kinase ATR; RAC3; Rad3 related protein; SCKL; SCKL1; Serine/threonine protein kinase ATR; Serine/threonine-protein kinase ATR
Species Homo sapiens (Human)
Protein Length Partial
Tag Info The following tags are available.
N-terminal His-tagged
Tag-Free
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
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
Protein FAQs
Storage Condition Store at -20°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
(From Uniprot)
Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication.
Gene References into Functions
  1. ATR inhibition synergizes with WEE1 inhibition in TNBC. PMID: 29605721
  2. Identification of novel ATR mutations in oropharyngeal squamous cell carcinoma patients who do not have Seckel syndrome and are HPV negative suggesting that functional loss of ATR may be an important step in the aetiology of oropharyngeal cancer. PMID: 28017652
  3. ATR couples DNA replication with mitosis and preserves genome integrity by enforcing an S/G2 checkpoint. PMID: 30139873
  4. Findings indicate that nuclear phosphoinositide lipids (PPIs) metabolism mediates an early damage response to specifically recruit ataxia telangiectasia and Rad3-related protein (ATR). PMID: 29242514
  5. Inhibition of FPR1 and/or NADPH oxidase functions prevents VEGFR2 transactivation and the triggering of the downstream signalling cascades. PMID: 29743977
  6. the sequence of administration of an ATR kinase inhibitor and a DNA damaging agent impacts the DNA damage induced by the combination. experiments identify competing ATR and Cdc7 kinase-dependent mechanisms at replication origins in human cells. PMID: 29123096
  7. The observations suggest a novel role of ATR kinase in mediating its own signal attenuation via PPM1D recruitment to chromatin as an essential mechanism for restarting the stalled forks, cell cycle re-entry and cellular recovery from replication stress. PMID: 29485113
  8. DNA alkylation damage leads to ATR-Chk1 activation in cancer cells and ATR-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage. PMID: 29378956
  9. The ATR kinase inhibitor VX-970 (NSC 780162) is in clinical development in combination with primary cytotoxic agents. PMID: 28888173
  10. a mitosis-specific and R loop-driven ATR pathway acts at centromeres to promote faithful chromosome segregation, revealing functions of R loops and ATR in suppressing chromosome instability. PMID: 29170278
  11. both ATR and Chk1 kinase activities are important for viral replication. The findings suggest that HSV-1 activates ATR and Chk1 during early stages of infection and utilizes the enzymes to promote its own replication. The observation may be exploitable for antiviral approaches. PMID: 29263259
  12. Following DNA damage, addition of the TLK1 inhibitor, THD, or overexpression of NEK1-T141A mutant impaired ATR and Chk1 activation, indicating the existence of a TLK1>NEK1>ATR>Chk1 pathway. Indeed, overexpression of the NEK1-T141A mutant resulted in an altered cell cycle response after exposure of cells to oxidative stress, including bypass of G1 arrest and implementation of an intra S-phase checkpoint. PMID: 28426283
  13. These findings suggest that inhibition of ATR is a promising strategy to enhance the antitumor activity of GEM for treating pancreatic cancer PMID: 28440428
  14. Suggest that activation of ATR/CHK1 signaling pathway is key for Epstein Barr virus-induced B-cell transformation. PMID: 28031537
  15. ATR plays a fundamental nuclear role in maintaining host genome integrity. RNAi-mediated inhibition of canonical ATR signaling suppresses genome replication. PMID: 28467896
  16. These our data suggest that ETAA1 is a new ATR activator involved in replication checkpoint control. PMID: 27818175
  17. ATR is a therapeutic target for synovial sarcoma treatment. PMID: 29038346
  18. Nucleotide biosynthesis in ATR-inhibited acute lymphoblastic leukemia (ALL) cells reveals substantial remaining de novo and salvage activities, and could not eliminate the disease in vivo. PMID: 28808226
  19. AZD7762 demonstrates synergy with regard to inhibition of AR-CDC6-ATR-Chk1 signaling. PMID: 28228262
  20. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. PMID: 28273450
  21. Rif1 can mediate MCM dephosphorylation at replication forks and that the stability of dephosphorylated replisomes strongly depends on Chk1 activity. PMID: 28273463
  22. the sequence ultraviolet-pyrimidine dimers-nucleotide excision repair pathway-ATR-RNAPII-Alternative splicing (AS) as a pathway linking DNA damage repair to the control of both RNAPII phosphorylation and AS regulation. PMID: 28329680
  23. Results from our analysis showed that Pak1 overexpression, knockdown and Pak1 knockout cell line models showed that Pak1 confers protection to keratinocytes from UV-B-induced apoptosis and DNA damage via ATR. PMID: 28692051
  24. PM2.5 exposure strongly induced the activation of the ATR (ATR serine/threonine kinase)-CHEK1/CHK1 (checkpoint kinase 1) axis, which subsequently triggered TP53-dependent autophagy and VEGFA production in Beas-2B cells. PMID: 27463284
  25. REV3/ATR knockdown enhances the cytotoxicity of cisplatin in non-small cell lung cells. PMID: 28075014
  26. ATR promotes homologous recombination after CDK-driven DNA end resection. PMID: 28089683
  27. Authors examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells. They discuss the multiple data that have revealed an elegant yet increasingly complex mechanism of ATR activation. [Review] PMID: 28811666
  28. results reveal a previously unknown role for transcription factor IIH in ATR kinase activation in non-replicating, non-cycling cells PMID: 28592488
  29. Our data reveal that BETi can potentiate the cell stress and death caused by ATR inhibitors. This suggests that ATRi can be used in combination therapies of lymphomas without the use of genotoxic drugs PMID: 26804177
  30. Small molecule ATR and Chk1 inhibitors potently sensitize lymphoma cells to UVA radiation and induce a prominent apoptotic response PMID: 27743911
  31. ATR inhibition potentiated Chk1 inhibitor induced replication stress and cytotoxicity via the abrogation of ATR-dependent feedback activation of Chk1 induced by Chk1 inhibitor generated replication stress in tumor cell lines. PMID: 27693461
  32. Our data suggests that total cellular b-catenin levels decrease in the presence of secreted frizzled-related protein 1 and Wnt inhibitory factor 1, and a significant increase in cell death after tyrosine kinase inhibitor treatment is observed. On the contrary, when secreted frizzled-related protein 1 is suppressed, total b-catenin levels increase in the cell and the cells become resistant to tyrosine kinase inhibitors. PMID: 28468589
  33. HPV31 regulates RRM2 levels through expression of E7 and activation of the ATR-Chk1-E2F1 DNA damage response, which is essential to combat replication stress upon entry into S-phase. PMID: 27764728
  34. disruption of IGF-1R signaling with small-molecule inhibitors or IGF-1 withdrawal partially abrogates both the phosphorylation and activation of CHK1 by ATR and the accompanying inhibition of chromosomal DNA synthesis in UVB-irradiated keratinocytes. PMID: 27979966
  35. that parallel TopBP1- and ETAA1-mediated pathways underlie ATR activation and that their combined action is essential for coping with replication stress PMID: 27723717
  36. It is proposed that ATR functions control cell plasticity by sensing structural deformations of different cellular components, including DNA and initiating appropriate repair responses. (Review) PMID: 27283761
  37. MMR proteins activate DNA toxicity by modulating ATR foci formation during convergent transcription PMID: 27131875
  38. High ATR expression is associated with colorectal cancer. PMID: 26755646
  39. High ATR expression correlates with urinary bladder cancer. PMID: 26657501
  40. ATRIP deacetylation by SIRT2 promotes ATR-ATRIP binding to replication protein A-single-stranded DNA to drive ATR activation and thus facilitate recovery from replication stress. PMID: 26854234
  41. Findings reveal a novel role for ATR in cilia signaling distinct from its canonical function during replication and strengthen emerging links between cilia function and development. PMID: 26908596
  42. In conclusion, this study exemplifies cancer-specific synthetic lethality between two proteins in the same pathway and raises the prospect of combining ATR and CHK1 inhibitors as promising cancer therapy. PMID: 26748709
  43. These results therefore suggest that whereas DNA polymerase stalling at DNA lesions activates ATR to protect cell viability and prevent apoptosis, the stalling of RNA polymerases instead activates ATR to induce an apoptotic form of cell death in non-cycling cells. PMID: 26940878
  44. ATR inhibition rewires cellular signaling networks induced by replication stress. PMID: 26572502
  45. RAD9 has a prominent role in the ATR-Chk1 pathway that is necessary for successful formation of the damage-sensing complex and DNA damage checkpoint signaling. PMID: 26667770
  46. Common cancer-associated imbalances in the DNA damage response confer sensitivity to single agent ATR inhibition. PMID: 26486089
  47. The innate immune regulator STAT-5 is shown to regulate transcription of the ATR binding factor TopBP1, and this is critical for the induction of the ATR pathway in human papillomavirus-infected keratinocytes. PMID: 26695634
  48. ATR is down-regulated by STAT3-regulated microRNA-383 in A431 cells. PMID: 26261078
  49. We suggest that MNNG-stimulated ATR/CHK1 signaling stabilizes E2F3 by S124 phosphorylation, and then E2F3 together with NFY co-transactivate RRM2 expression for DNA repair. PMID: 26921499
  50. ATR controls basal deoxycytidine kinase activity in response to replication stress. PMID: 26620371

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Involvement in disease Seckel syndrome 1 (SCKL1); Cutaneous telangiectasia and cancer syndrome, familial (FCTCS)
Subcellular Location Nucleus, Nucleus, PML body, Chromosome
Protein Families PI3/PI4-kinase family, ATM subfamily
Tissue Specificity Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary.
Database Links

HGNC: 882

OMIM: 210600

KEGG: hsa:545

STRING: 9606.ENSP00000343741

UniGene: Hs.271791

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