Phospho-Chk1 (Ser280) Antibody (YA9942)
(Synonyms: CHEK1; CHK1; Serine/threonine-protein kinase Chk1; CHK1 checkpoint homolog; Cell cycle checkpoint kinase; Checkpoint kinase-1)
Based on 1 Customer Validation
Phospho-Chk1 (Ser280) Antibody (YA9942) is a Rabbit-derived and non-conjugated IgG Recombinant, Monoclonal antibody, targeting to Phospho-Chk1 (Ser280).
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Host:
Rabbit
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Isotype:
IgG
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Application:
WB
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Reactivity :
Human, Mouse, Rat
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Formulation:
Supplied in TBS (pH7.4), 0.05% BSA, 40% Glycerol, 0.05% Sodium Azide.
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Conjugation:
Non-conjugated
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
Applications
| Application |
WB
WB: Western Blot
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|---|---|
| Dilution Ratio | 1:1000 |
Product Details
Phospho-Chk1 (Ser280) Antibody (YA9942) is a Rabbit-derived and non-conjugated IgG Recombinant, Monoclonal antibody, targeting to Phospho-Chk1 (Ser280).
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Host Rabbit
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Species ReactivityHuman, Mouse, Rat
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Observed Molecular WeightObserved band size: 54 kDa
Note: Due to possible protein modifications or aggregation, the molecular weight should be confirmed by actual measurement, and the predicted value is for reference only.
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Calculated Molecular Weight Predicted band size: 54 kDa
Synthetic phosphopeptide corresponding to residues surrounding Ser280 of human Chk1.
Endogenous
affinity purified
Non-conjugated
Phosphorylated
IgG
Product Properties
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Appearance
Solution
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Formulation
Supplied in TBS (pH7.4), 0.05% BSA, 40% Glycerol, 0.05% Sodium Azide.
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Concentration
Batch-dependent, Please check the COA for the concentration of each lot. Check Lot Concentration
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Storage & Stability
Stored at -20°C for 1 year. Avoid repeated freeze / thaw cycles.
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Shipping
Shipping with blue ice.
Background
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Function
Chk1 is a 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 (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). 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[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27].
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Subcellular Localization
Nucleus; Chromosome; Cytoplasm; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
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Expression
Tissue_Specificity: Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon. -
Isoforms & Post-Translational Modification
Phospho-Chk1 has 3 isoforms, O14757-1: amino acid length is 476, molecular weight is 54434 Da (predicted); O14757-2: amino acid length is 382, molecular weight is 43703 Da (predicted); O14757-3: amino acid length is 442, molecular weight is 50415 Da (predicted).
Phosphorylated by ATR in a RAD17-dependent manner in response to ultraviolet irradiation and inhibition of DNA replication. Phosphorylated by ATM in response to ionizing irradiation. ATM and ATR can both phosphorylate Ser-317 and Ser-345 and this results in enhanced kinase activity. Phosphorylation at Ser-345 induces a change in the conformation of the protein, activates the kinase activity and is a prerequisite for interaction with FBXO6 and subsequent ubiquitination at Lys-436. Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear retention. Conversely, dephosphorylation at Ser-345 by PPM1D may contribute to exit from checkpoint mediated cell cycle arrest. Phosphorylation at Ser-280 by AKT1/PKB, may promote mono and/or diubiquitination. -
Subunit
Interacts (phosphorylated by ATR) with RAD51.
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SwissProt ID
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Synonyms
CHEK1; CHK1; Serine/threonine-protein kinase Chk1; CHK1 checkpoint homolog; Cell cycle checkpoint kinase; Checkpoint kinase-1
Documentation
References
[1]. Feijoo C, et al. Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing. J Cell Biol. 2001 Sep 3;154(5):913-23. [Content Brief]
[2]. Zhao H, et al. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14795-800. [Content Brief]
[3]. Heffernan TP, et al. An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage. Mol Cell Biol. 2002 Dec;22(24):8552-61. [Content Brief]
[4]. Chen MS, et al. Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding. Mol Cell Biol. 2003 Nov;23(21):7488-97. [Content Brief]
[5]. Pichierri P, et al. The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways. EMBO J. 2004 Mar 10;23(5):1178-87. [Content Brief]
[6]. Krämer A, et al. Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase. Nat Cell Biol. 2004 Sep;6(9):884-91. [Content Brief]
[7]. Huang X, et al. DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint. Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1065-70. [Content Brief]
[8]. Sørensen CS, et al. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol. 2005 Feb;7(2):195-201. [Content Brief]
[9]. Yu X, et al. Ubiquitination of the DNA-damage checkpoint kinase CHK1 by TRAF4 is required for CHK1 activation. J Hematol Oncol. 2020 May 1;13(1):40. [Content Brief]
[10]. Sørensen CS, et al. Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer Cell. 2003 Mar;3(3):247-58. [Content Brief]
[11]. Xiao Z, et al. Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J Biol Chem. 2003 Jun 13;278(24):21767-73. [Content Brief]
[12]. Hassepass I, et al. Phosphorylation at serine 75 is required for UV-mediated degradation of human Cdc25A phosphatase at the S-phase checkpoint. J Biol Chem. 2003 Aug 8;278(32):29824-9. [Content Brief]
[13]. Jin J, et al. SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev. 2003 Dec 15;17(24):3062-74. [Content Brief]
[14]. Melixetian M, et al. NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint. Nat Cell Biol. 2009 Oct;11(10):1247-53. [Content Brief]
[15]. Sanchez Y, et al. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science. 1997 Sep 5;277(5331):1497-501. [Content Brief]
[16]. Sørensen CS, et al. NEK11: linking CHK1 and CDC25A in DNA damage checkpoint signaling. Cell Cycle. 2010 Feb 1;9(3):450-5. [Content Brief]
[17]. Lee MY, et al. Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced phosphorylation. Cell Cycle. 2008 Sep 1;7(17):2705-9. [Content Brief]
[18]. Shieh SY, et al. The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev. 2000 Feb 1;14(3):289-300. [Content Brief]
[19]. Ou YH, et al. p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the regulation of DNA-damage-induced C-terminal acetylation. Mol Biol Cell. 2005 Apr;16(4):1684-95. [Content Brief]
[20]. Jin Y, et al. 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J. 2006 Mar 22;25(6):1207-18. [Content Brief]
[21]. Wang X, et al. Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway. Mol Cell Biol. 2007 Apr;27(8):3098-108. [Content Brief]
[22]. Groth A, et al. Human Tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint. EMBO J. 2003 Apr 1;22(7):1676-87. [Content Brief]
[23]. Krause DR, et al. Suppression of Tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1. Oncogene. 2003 Sep 4;22(38):5927-37. [Content Brief]
[24]. Yang XH, et al. Chk1 and Claspin potentiate PCNA ubiquitination. Genes Dev. 2008 May 1;22(9):1147-52. [Content Brief]
[25]. Inoue Y, et al. Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage. EMBO J. 2007 Apr 18;26(8):2083-93. [Content Brief]
[26]. Halder S, et al. SPRTN protease and checkpoint kinase 1 cross-activation loop safeguards DNA replication. Nat Commun. 2019 Jul 17;10(1):3142. [Content Brief]
[27]. Li F, et al. CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress. Mol Cell. 2020 Nov 5;80(3):410-422.e6. [Content Brief]
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