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  4. Recombinant Mouse Serine/threonine-protein kinase Chk1 (Chek1)

Recombinant Mouse Serine/threonine-protein kinase Chk1 (Chek1)

  • 货号：
    CSB-YP005338MO
  • 规格：
  • 来源：
    Yeast
  • 其他：
  • 货号：
    CSB-EP005338MO
  • 规格：
  • 来源：
    E.coli
  • 其他：
  • 货号：
    CSB-EP005338MO-B
  • 规格：
  • 来源：
    E.coli
  • 共轭：
    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.

  • 其他：
  • 货号：
    CSB-BP005338MO
  • 规格：
  • 来源：
    Baculovirus
  • 其他：
  • 货号：
    CSB-MP005338MO
  • 规格：
  • 来源：
    Mammalian cell
  • 其他：

产品详情

  • 纯度：
    >85% (SDS-PAGE)
  • 基因名：
  • Uniprot No.：
  • 别名：
    Chek1; Chk1Serine/threonine-protein kinase Chk1; EC 2.7.11.1; CHK1 checkpoint homolog; Checkpoint kinase-1
  • 种属：
    Mus musculus (Mouse)
  • 蛋白长度：
    Full length protein
  • 表达区域：
    1-476
  • 氨基酸序列
    MAVPFVEDWD LVQTLGEGAY GEVQLAVNRI TEEAVAVKIV DMKRAIDCPE NIKKEICINK MLSHENVVKF YGHRREGHIQ YLFLEYCSGG ELFDRIEPDI GMPEQDAQRF FHQLMAGVVY LHGIGITHRD IKPENLLLDE RDNLKISDFG LATVFRHNNR ERLLNKMCGT LPYVAPELLK RKEFHAEPVD VWSCGIVLTA MLAGELPWDQ PSDSCQEYSD WKEKKTYLNP WKKIDSAPLA LLHKILVETP SARITIPDIK KDRWYNKPLN RGAKRPRATS GGMSESSSGF SKHIHSNLDF SPVNNGSSEE TVKFSSSQPE PRTGLSLWDT GPSNVDKLVQ GISFSQPTCP EHMLVNSQLL GTPGSSQNPW QRLVKRMTRF FTKLDADKSY QCLKETFEKL GYQWKKSCMN QVTVSTTDRR NNKLIFKINL VEMDEKILVD FRLSKGDGLE FKRHFLKIKG KLSDVVSSQK VWFPVT
  • 蛋白标签：
    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.
  • 产品提供形式：
    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.
  • 复溶：
    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.
  • 储存条件：
    Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
  • 保质期：
    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.
  • 货期：
    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.
  • 注意事项：
    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.

产品评价

靶点详情

  • 功能：
    Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest. Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin. Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity.
  • 基因功能参考文献：
    1. CHK1 expression levels control the timing of lymphomagenesis PMID: 29167438
    2. During neurogenesis, cortical neurons became protected from S-phase Chk1 pathway activation by the DNA methyltransferase Dnmt1, and underwent cell death after S-phase progression. PMID: 28928282
    3. Chk1(-/-) MEFs exhibited the absence of double-strand breaks, yet cells showed delayed DNA damage recovery with pan-nuclear immunostaining pattern of Histone H2AX. PMID: 28349497
    4. 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
    5. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis PMID: 25843721
    6. Altogether, our results classify E4F1 as a master regulator of CHK1 activity that ensures high fidelity of DNA replication, thus safeguarding genome stability. PMID: 25843717
    7. Heterozygous loss of Chk1 in a Wnt-driven background resulted in an increase in DNA damage and apoptosis and accelerated both tumour development and progression. PMID: 24037525
    8. PAR, supplied by PARP1, interacts with Chk1 via a novel PAR-binding regulatory (PbR) motif in Chk1, independent of ATR and its activity PMID: 24356582
    9. High level of phospho-Chk1 is associated with skin tumors. PMID: 24184701
    10. Chk1 is essential for the developmental formation of murine epidermal melanocytes but hemizygosity has little permanent developmental consequence in this cell type PMID: 23557358
    11. activated Akt1 in Brca1-deficient cells impairs Chk1 nuclear localization and subsequently disrupts interaction of Chk1 and Rad51 leading to homologous recombination defects. PMID: 22665067
    12. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition PMID: 22430210
    13. The stress kinases p38 and JNK are activated when DNA replication is blocked and their activity allows S/M, but not G 2/M, checkpoint maintenance when Chk1 is inhibited. PMID: 22935704
    14. Chk1 is indispensable for prophase I arrest and functions in G 2/M checkpoint regulation in meiotic oocytes. PMID: 22544319
    15. hypoxia can activate p53 through inactivation of MDMX by the ATR-Chk1-MDMX-14-3-3gamma pathway. PMID: 22556425
    16. complete loss of Chk1 is incompatible with epithelial tumorigenesis, whereas partial loss of function (haploinsufficiency) fosters benign malignant tumor progression. PMID: 21804609
    17. an extra Chk1 allele prolongs the survival of ATR-Seckel mice, which suffer from high levels of replicative stress, but not that of ATM-deficient mice, which accumulate DNA breaks PMID: 22370720
    18. genetic disruption of PP5 is associated with enhanced and prolonged phosphorylation of a single serine (Ser-345) on Chk1 PMID: 21921034
    19. nuclear but not centrosomal Chk1 contributes to correct timing of mitotic entry. PMID: 21628425
    20. Data show that checkpoint kinase-1 functions as a mitogen-dependent protein kinase that prevents premature differentiation of trophoblast stem cells by suppressing expression of p21 and p57, but not p27. PMID: 21791608
    21. VIP blockade induces microcephaly through Mcph1 signaling; VIP/Mcph1/Chk1 signaling is key for normal cortical development PMID: 21737879
    22. TAp73 induction by nitric oxide: regulation by checkpoint kinase 1 (CHK1) and protection against apoptosis. PMID: 21212274
    23. Results suggest that the Chk1/2 double mutation leads to a high level of spontaneous DNA damage, but fails to eliminate cells with damaged DNA, which may ultimately increase cancer susceptibility independently of senescence. PMID: 20834228
    24. data show that Chk1 is critical for maintaining genome integrity and serves as a double-edged sword for cancer: although its inhibition kills cancer cells, it also triggers tumorigenesis when favorable mutations are accumulated for cell growth PMID: 20473325
    25. results support a role for Chk1 in maintaining the balance between erythroid progenitors and enucleated erythroid cells during differentiation PMID: 20052416
    26. CHEK1 protein interacts with XIAP during mitosis. PMID: 14759516
    27. Association of Fhit gene inactivation with increased survival after DNA damage, related to over-active checkpoints regulated by ATR/CHK1 pathway. Potential effects of Fhit-dependent DNA damage response on tumor progression. PMID: 15389587
    28. Erythropoietin or IL-3 significantly enhanced etoposide-induced activation-specific phosphorylation of Chk1. PMID: 15674326
    29. loss of PTEN and subsequent activation of AKT impair CHK1 through phosphorylation, ubiquitination, and reduced nuclear localization to promote genomic instability in tumor cells PMID: 15710331
    30. These data demonstrate that lack of PTEN generates DNA damage due to inappropriate inactivation of CHK1.DNA damage due to the loss of PTEN is likely to stimulate tumor development. PMID: 15970699
    31. Inhibition of PARP1 activity signals via a Chk1-dependent pathway for cell death by apoptosis. PMID: 16002346
    32. inhibition of ataxia telangiectasia and Rad3 related and ataxia-telangiectasia mutated kinases with caffeine or Chk1 with UCN-01, results in activation of a p38-dependent intra-S-phase checkpoint and activation of apoptosis in ES cells PMID: 16138010
    33. DSB repair from the complementary NHEJ pathway of PARP-1, but not SSB repair from the BER function of PARP-1, may play an essential role in the over-activated CHK1 regulated G2 checkpoint response and radiosensitivity in PARP-1-/- cells PMID: 17102615
    34. Two-step phosphorylation of Chk1 at S317 and S345 appeared to be required for proper localization of Chk1 to centrosomes. PMID: 17242188
    35. Chk1 is both critical for the survival of proliferating cells and engages in cross-talk with the Chk2 checkpoint kinase pathway PMID: 17360434
    36. These findings show, for the first time, that TLR9 engagement on CD4 T cells reduces IR-induced apoptosis by influencing cell-cycle checkpoint activity. PMID: 18086870
    37. Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression. PMID: 18243098
    38. Chk1 appears to help defend genomic integrity through effects on several other pathways, including Fanconi anemia proteins, the mitotic spindle, and transcription of cell cycle-related genes [review] PMID: 18424430
    39. Chk1 is required for DNA replication at least through regulating RNR2 gene transcription. PMID: 18616928
    40. Chk1 deficiency in the mouse small intestine results in p53-independent crypt death and subsequent intestinal compensation. PMID: 19169280
    41. Chk1 is a multifunctional kinase that serves as a nexus between the DNA damage response and the mitotic exit pathways during cell-cycle progression to prevent genomic instability and cancer PMID: 19289837
    42. Data show that Chk1 inhibitor PF-00477736 offers a therapeutic potential for the enhancement of taxane therapy. PMID: 19584159

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  • 亚细胞定位：
    Nucleus. Chromosome. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome.
  • 蛋白家族：
    Protein kinase superfamily, CAMK Ser/Thr protein kinase family, NIM1 subfamily
  • 组织特异性：
    Found in all adult tissues tested. Elevated expression in testis, lung and spleen. 15.5 day old embryos show ubiquitous expression with strong expression in brain, liver, kidney, pancreas, intestine, thymus and lung.
  • 数据库链接：

    KEGG: mmu:12649

    STRING: 10090.ENSMUSP00000034625

    UniGene: Mm.16753