- Catalog number
- PB9692
- Size / count
- 100 µg/Vial
- Dry ice
- No
- Hazardous
- No
- Discontinued
- No
- Background
- CHK2, a protein kinase that is activated in response to DNA damage, is involved in cell cycle arrest. Mapped on 22q12.1, CHK2 has a potential regulatory region rich in SQ and TQ amino acid pairs. It regulates BRCA1 function after DNA damage by phosphorylating serine-988 of BRCA1. Additionally, CHK2 can be modified by phosphorylation and activated in response to ionizing radiation, and can be also modified in response to hydroxyurea treatment. Furthermore, oligomerization of CHEK2 increases the efficiency of transautophosphorylation, resulting in the release of active CHEK2 monomers that proceed to enforce checkpoint control in irradiated cells. Moreover, CHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and that their observations provided a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast. There is a wide expression of small amounts of CHK2 mRNA with larger amounts in human testis, spleen, colon, and peripheral blood leukocytes.
- Synonyms
- Serine/threonine-protein kinase Chk2;2.7.11.1; CHK2 checkpoint homolog; Cds1 homolog; Hucds1; hCds1; Checkpoint kinase 2; CHEK2; CDS1, CHK2, RAD53
- Gene Name
- CHEK2
- Gene ID
- 11200
- UniProt
- O96017
- Host
- Rabbit
- Reactivity
- Human, Mouse, Rat
- Cross Reactivity
- No cross-reactivity with other proteins
- Immunogen
- A synthetic peptide corresponding to a sequence at the C-terminus of human Chk2, different from the related mouse sequence by four amino acids.
- Clonality
- Polyclonal
- Tissue Specificity
- High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues.
- Applications
- IHC, WB
- Field of Research
- Cancer, Cell Cycle, DNA/RNA, DNA Damage & Repair, DNA Damage Response, Epigenetics and Nuclear Signaling, Kinases/Phosphatases
- Purification
- Immunogen affinity purified.
- Concentration
- Adding 0.2 ml of distilled water will yield a concentration of 500 μg/ml.
- Form
- Lyophilized
- Reconstitution
- Add 0.2ml of distilled water will yield a concentration of 500ug/ml.
- Function
- Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X- R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978) . .
- References & Citations
- 1. Ahn, J.-Y.; Li, X.; Davis, H. L.; Canman, C. E. : Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain. J. Biol. Chem. 277: 19389-19395, 2002. 2. Bell, D. W.; Varley, J. M.; Szydlo, T. E.; Kang, D. H.; Wahrer, D. C. R.; Shannon, K. E.; Lubratovich, M.; Verselis, S. J.; Isselbacher, K. J.; Fraumeni, J. F.; Birch, J. M.; Li, F. P.; Garber, J. E.; Haber, D. A. : Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286: 2528-2531, 1999. 3. Brown, A. L.; Lee, C.-H.; Schwarz, J. K.; Mitiku, N.; Piwnica-Worms, H.; Chung, J. H. : A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage. Proc. Nat. Acad. Sci. 96: 3745-3750, 1999. 4. Lee, J.-S.; Collins, K. M.; Brown, A. L.; Lee, C.-H.; Chung, J. H. : hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 404: 201-204, 2000.
- Storage Conditions
- Store at -20°C for one year from date of receipt. After reconstitution, at 4°C for one month. It can also be aliquotted and stored frozen at -20°C for six months. Avoid repeated freeze-thaw cycles.
- Calculated Molecular Weight
- 60915 MW
- Observed Molecular Weight
- 65 kDa
- Specificity
- No cross reactivity with other proteins.
- Gene Name Synonym
- Serine/threonine-protein kinase Chk2
- Subcellular Location
- Isoform 2: Nucleus. Isoform 10 is present throughout the cell.
- Protein Name
- Serine/threonine-protein kinase Chk2
- Isotype
- Rabbit IgG
- Contents
- Each vial contains 5mg BSA, 0.9mg NaCl, 0.2mg Na2HPO4, 0.05mg NaN3.
