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ATR (Ab-428) Antibody

  • 货号：
    CSB-PA267100
  • 规格：
    ￥2024
  • 图片：
    • Immunohistochemical analysis of paraffin-embedded human breast carcinoma tissue using ATR(Ab-428) Antiobdy(left) or the same antibody preincubated with blocking peptide(right).
  • 其他：

产品详情

  • 产品名称：
    Rabbit anti-Homo sapiens (Human) ATR Polyclonal antibody
  • Uniprot No.：
    Q13535
  • 基因名：
  • 宿主：
    Rabbit
  • 反应种属：
    Human
  • 免疫原：
    Peptide sequence around aa.426~430 (G-I-S-P-K) derived from Human ATR.
  • 免疫原种属：
    Homo sapiens (Human)
  • 克隆类型：
    Polyclonal
  • 纯化方式：
    Antibodies were produced by immunizing rabbits with synthetic peptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitope-specific peptide.
  • 浓度：
    It differs from different batches. Please contact us to confirm it.
  • 产品提供形式：
    Liquid
  • 应用范围：
    ELISA,IHC
  • 推荐稀释比：
    Application Recommended Dilution
    IHC 1:50-1:100
  • Protocols：
  • 储存条件：
    Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
  • 货期：
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.

产品评价

靶点详情

  • 功能：
    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 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. Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex.
  • 基因功能参考文献：
    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. s 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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  • 相关疾病：
    Seckel syndrome 1 (SCKL1); Cutaneous telangiectasia and cancer syndrome, familial (FCTCS)
  • 亚细胞定位：
    Nucleus. Chromosome. Note=Depending on the cell type, it can also be found in PML nuclear bodies. Recruited to chromatin during S-phase. Redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling.
  • 蛋白家族：
    PI3/PI4-kinase family, ATM subfamily
  • 组织特异性：
    Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary.
  • 数据库链接：

    HGNC: 882

    OMIM: 210600

    KEGG: hsa:545

    STRING: 9606.ENSP00000343741

    UniGene: Hs.271791