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Rabbit Anti-Phospho-CHEK2 (Ser516)  antibody (bs-5257R)  
~~~促銷代碼KT202411~~~
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產(chǎn)品編號(hào) bs-5257R
英文名稱 Rabbit Anti-Phospho-CHEK2 (Ser516)  antibody
中文名稱 磷酸化細(xì)胞周期檢測(cè)點(diǎn)激酶2抗體
別    名 CHK2_HUMAN; Serine/threonine-protein kinase Chk2; EC:2.7.11.1; Serine/threonine-protein kinase Chk2; CDS1; CHK2; LFS2; RAD53; hCds1; HuCds1; PP1425; CHK2 checkpoint homolog; Cds1 homolog (Hucds1; hCds1); Checkpoint kinase 2;   
產(chǎn)品類型 磷酸化抗體 
研究領(lǐng)域 腫瘤  染色質(zhì)和核信號(hào)  激酶和磷酸酶  表觀遺傳學(xué)  
抗體來(lái)源 Rabbit
克隆類型 Polyclonal
交叉反應(yīng) Human (predicted: Mouse,Rat,Rabbit,Pig,Chicken,Dog)
產(chǎn)品應(yīng)用 WB=1:500-2000
not yet tested in other applications.
optimal dilutions/concentrations should be determined by the end user.
理論分子量 61kDa
細(xì)胞定位 細(xì)胞核 
性    狀 Liquid
濃    度 1mg/ml
免 疫 原 KLH conjugated Synthesised phosphopeptide derived from human CHEK2 around the phosphorylation site of Ser516: QP(p-S)TS 
亞    型 IgG
純化方法 affinity purified by Protein A
緩 沖 液 0.01M TBS (pH7.4) with 1% BSA, 0.02% Proclin300 and 50% Glycerol.
保存條件 Shipped at 4℃. Store at -20℃ for one year. Avoid repeated freeze/thaw cycles.
注意事項(xiàng) This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
PubMed PubMed
產(chǎn)品介紹 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]

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.

Subunit:
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.

Subcellular Location:
Isoform 2: Nucleus. Note=Isoform 10 is present throughout the cell.
Isoform 4: Nucleus.
Isoform 7: Nucleus.
Isoform 9: Nucleus.
Isoform 12: Nucleus.
Nucleus, PML body. Nucleus, nucleoplasm. Note=Recruited into PML bodies together with TP53.

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

Post-translational modifications:
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.
Ubiquitinated. CUL1-mediated ubiquitination regulates the pro-apoptotic function. Ubiquitination may also regulate protein stability (PubMed:17715138).

DISEASE:
Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:609265]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53.
Defects in CHEK2 may be a cause of susceptibility to prostate cancer (PC) [MIM:176807]. It is 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.
Defects in CHEK2 are found in some patients with osteogenic sarcoma (OSRC) [MIM:259500].
Defects in CHEK2 is a cause of susceptibility to 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=CHEK2 variants are associated with susceptibility to breast cancer and contribute to a substantial fraction of familial breast cancer (PubMed:12094328).

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

SWISS:
O96017

Gene ID:
11200

Database links:

Entrez Gene: 11200 Human

Entrez Gene: 50883 Mouse

Entrez Gene: 114212 Rat

SwissProt: O96017 Human

SwissProt: Q9Z265 Mouse

SwissProt: Q9R019 Rat



Chk2作為Cdks的調(diào)節(jié)參與細(xì)胞周期調(diào)節(jié)過(guò)程,是生物進(jìn)化過(guò)程中非常保守的蛋白激酶,在DNA損傷引起的細(xì)胞周期檢測(cè)點(diǎn)調(diào)節(jié)中有著非常重要的作用。
產(chǎn)品圖片
Sample: Hela(Human) Cell Lysate at 30 ug Primary: Anti-Phospho-CHK2 (Ser516) (bs-5257R) at 1/1000 dilution Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution Predicted band size: 61 kD Observed band size: 57 kD
Sample: 293T(Human) Cell Lysate at 30 ug Primary: Anti-Phospho-CHK2 (Ser516) (bs-5257R) at 1/1000 dilution Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution Predicted band size: 61 kD Observed band size: 57 kD
Sample: Hela UV(Human) Cell Lysate at 30 ug Hela (Human) Cell Lysate at 30 ug Primary: Anti-p-CHK2(Ser516)(bs-5257R) at 1/1000 dilution Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution Predicted band size: 61 kD Observed band size: 56 kD
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