Rabbit CHEK2 Polyclonal Antibody | anti-CHEK2 antibody

CHEK2, NT (CHEK2, CDS1, CHK2, RAD53, Rad53 homolog, Checkpoint kinase 2)

Cat. Num. AAA646355

• Gene Names: CHEK2; CDS1; CHK2; LFS2; RAD53; hCds1; HuCds1; PP1425
• Reactivity: Human, Mouse, Rat
• Applications: ELISA, Western Blot, Immunohistochemistry
• Purity: Affinity Purified; Purified by immunoaffinity chromatography
• Synonyms: CHEK2; Polyclonal Antibody; NT (CHEK2; CDS1; CHK2; RAD53; Rad53 homolog; Checkpoint kinase 2); Anti -CHEK2; anti-CHEK2 antibody

• Host: Rabbit
• Reactivity: Human, Mouse, Rat
• Clonality: Polyclonal
• Isotype: IgG
• Specificity: Recognizes human CHEK2/CHK2. Species Crossreactivity: Mouse, rat.
• Purity/Purification: Affinity Purified; Purified by immunoaffinity chromatography
• Form/Format: Supplied as a liquid in PBS, (without Mg2+, Ca2+), pH 7.4, 150mM sodium chloride, 0.02% sodium azide, 50% glycerol.

• Applicable Applications for anti-CHEK2 antibody: ELISA (EL/EIA), Western Blot (WB), Immunohistochemistry (IHC)
• Application Notes: Suitable for use in ELISA, Western Blot, Immunohistochemistry.; Dilution: ELISA: 1:10,000; Western Blot: 1:500-1:1000; Immunohistochemistry (Paraffin): 10ug/ml
• Immunogen: Synthetic peptide corresponding to human CHEK2/CHK2 at N-Terminal.
• Preparation and Storage: May be stored at 4 degree C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20 degree C. Aliquots are stable for at least 12 months. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.

Immunohistochemistry (IHC)

(Human Testis: Formalin-Fixed, Paraffin-Embedded (FFPE))

Western Blot (WB)

(Western blot analysis of extracts from Jurkat and HeLa cells treated with etoposide 25uM 24 hours, using Chk2 (Ab-68). The lane on the right is treated with the synthesized peptide.)

Related Product Information for anti-CHEK2 antibody

CHK2 is a serine/threonine kinase in the CDS subfamily that is activated in response to DNA damage and may regulate cell cycle arrest. It is the human homolog of RAD53 in S. cerevisiae and CDS1 in S. pombe. The protein has a FHA domain, which means it is located in the nucleus. Its kinase activity is up regulated by autophosphorylation in response to DNA damage and to replication blocks. It controls cell cycle checkpoint and may participate in transduction of the DNA damage and replicational stress signals. It also inhibits CDC25 phosphatase to prevent the cell entry into mitosis. Studies show that the deficiency of CHK2 may cause Li-Fraumeni syndrome and other human cancers, such as breast cancer via other gene's function.

Product Categories/Family for anti-CHEK2 antibody

Antibodies; Abs to Protein Kinases

NCBI and Uniprot Product Information

• NCBI GI #: 47678367
• NCBI GeneID: 11200
• UniProt Accession #: O96017; Q6QA03; Q6QA04; Q6QA05; Q6QA06; Q6QA07; Q6QA08; Q6QA10; A8K3Y9; B7ZBF3; B7ZBF4; B7ZBF5
• Molecular Weight: 60,915 Da
• NCBI Official Full Name: CHEK2
• NCBI Official Synonym Full Names: checkpoint kinase 2
• NCBI Official Symbol: CHEK2
• NCBI Official Synonym Symbols: CDS1; CHK2; LFS2; RAD53; hCds1; HuCds1; PP1425
• NCBI Protein Information: serine/threonine-protein kinase Chk2; cds1 homolog; CHK2 checkpoint homolog; checkpoint-like protein CHK2
• UniProt Protein Name: Serine/threonine-protein kinase Chk2
• Protein Family: Serine/threonine-protein kinase
• UniProt Gene Name: CHEK2
• UniProt Synonym Gene Names: CDS1; CHK2; RAD53; Hucds1; hCds1
• UniProt Entry Name: CHK2_HUMAN

NCBI Description

In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

Uniprot Description

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. Ref.1 Ref.2 Ref.3 Ref.14 Ref.17 Ref.20 Ref.22 Ref.23 Ref.24 Ref.27 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.37

Catalytic activity: ATP + a protein = ADP + a phosphoprotein.

Cofactor: Magnesium.

Enzyme regulation: Activated through phosphorylation at Thr-68 by ATM in response to DNA double-strand breaks. Activation is modulated by several mediators including MDC1 and TP53BP1. Induces homodimerization with exchange of the T-loop/activation segment between protomers and transphosphorylation of the protomers. The autophosphorylated kinase dimer is fully active. Negatively regulated by PPM1D through dephosphorylation of Thr-68. Ref.26

Subunit structure: Homodimer. Homodimerization is part of the activation process but the dimer may dissociate following activation. Interacts with PML. Interacts with TP53. Interacts with RB1; phosphorylates RB1. Interacts with BRCA1. Interacts (phosphorylated at Thr-68) with MDC1; requires ATM-mediated phosphorylation of CHEK2. Interacts with TP53BP1; modulates CHEK2 phosphorylation at Thr-68 in response to ionizing radiation. Interacts with CDC25A; phosphorylates CDC25A and mediates its degradation in response to ionizing radiation. Interacts with CUL1; mediates CHEK2 ubiquitination and regulation. Ref.14 Ref.17 Ref.19 Ref.21 Ref.22 Ref.24 Ref.34 Ref.42

Subcellular location: Isoform 2: Nucleus Ref.4 Ref.20 Ref.22. Note: Isoform 10 is present throughout the cell. Ref.4 Ref.20 Ref.22Isoform 4: Nucleus Ref.4 Ref.20 Ref.22. Isoform 7: Nucleus Ref.4 Ref.20 Ref.22. Isoform 9: Nucleus Ref.4 Ref.20 Ref.22. Isoform 12: Nucleus Ref.4 Ref.20 Ref.22. Nucleus › PML body. Nucleus › nucleoplasm. Note: Recruited into PML bodies together with TP53. Ref.4 Ref.20 Ref.22

Tissue specificity: High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues.

Post-translational modification: Phosphorylated. Phosphorylated at Ser-73 by PLK3 in response to DNA damage, promoting phosphorylation at Thr-68 by ATM and the G2/M transition checkpoint. Phosphorylation at Thr-68 induces homodimerization. Autophosphorylates at Thr-383 and Thr-387 in the T-loop/activation segment upon dimerization to become fully active and phosphorylate its substrates like for instance CDC25C. DNA damage-induced autophosphorylation at Ser-379 induces CUL1-mediated ubiquitination and regulates the pro-apoptotic function. Phosphorylation at Ser-456 also regulates ubiquitination. Phosphorylated by PLK4. Ref.15 Ref.16 Ref.19 Ref.26 Ref.28 Ref.29 Ref.31 Ref.34 Ref.36 Ref.42Ubiquitinated. CUL1-mediated ubiquitination regulates the pro-apoptotic function. Ubiquitination may also regulate protein stability. Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination. Ref.31 Ref.34 Ref.40

Involvement in disease: Li-Fraumeni syndrome 2 (LFS2) [MIM:609265]: A highly penetrant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.46Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.Osteogenic sarcoma (OSRC) [MIM:259500]: A sarcoma originating in bone-forming cells, affecting the ends of long bones.Note: The gene represented in this entry may be involved in disease pathogenesis.Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry (Ref.18). Ref.18 Ref.39

Sequence similarities: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CHK2 subfamily.Contains 1 FHA domain.Contains 1 protein kinase domain.