hERG1a (D1Y2J) Rabbit mAb

• 产品编号：CST-12889S      品牌：CST       原厂货号：12889S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

hERG1a (D1Y2J) Rabbit mAb兔单抗可以识别内源性成熟和未成熟的hERG1a蛋白水平。该抗体会在某些细胞系与未知源性的蛋白在65和42kDa处产生条带。抗体不识别hERG1b蛋白。单克隆抗体由合成肽段免疫动物产生，该肽段与人hERG1a蛋白Ala223附近氨基酸一致。hERG1(human ether-a-go-go-related gene potassium channel 1)是一个电压门控钾通道alpha-亚蛋白，介导了心脏延迟整流钾电流的快速激活元件(IKr) (1,2)。hERG通道由两个亚基组成，1a和1b，是由可变剪接导致的氨基端序列不同。原生hERG通道由hERG1a和 hERG1b异聚体形成。两个亚基都会有助于IKr电流(3-6)。化合物或hERG编码基因KCNH2突变诱导的hERG阻断会导致室性心律失常伴随遗传性和获得性长QT综合征和心肌细胞凋亡(7-10)。因此，hERG通道是发展III型抗心律失常药物的原始靶点(11,12)。hERG通道也被多种非抗心律失常化合物抑制，并导致副作用。因此，在为多种疾病选择治疗药物时hERG通道阻断是一种常见的衡量标准(11,13,14)。研究表明hERG参与了癌细胞存活(15)。在正常成年人组织中，hERG表达在心脏，脑，子宫肌层，胰腺和造血祖细胞(16,17)。hERG也表达在上皮细胞，神经细胞，白血病，结缔组织起源的多种肿瘤细胞系，但不在正常细胞中表达(18-22)。此外，hERG的表达与增强癌细胞的增殖，侵袭，较差预后相关联(23,24)。

1. Warmke, J.W. and Ganetzky, B. (1994) Proc Natl Acad Sci U S A 91, 3438-42.
2. Sanguinetti, M.C. and Tristani-Firouzi, M. (2006) Nature 440, 463-9.
3. Lees-Miller, J.P. et al. (1997) Circ Res 81, 719-26.
4. London, B. et al. (1997) Circ Res 81, 870-8.
5. Lees-Miller, J.P. et al. (2003) Mol Cell Biol 23, 1856-62.
6. Sale, H. et al. (2008) Circ Res 103, e81-95.
7. Curran, M.E. et al. (1995) Cell 80, 795-803.
8. Itoh, T. et al. (1998) Hum Genet 102, 435-9.
9. González-Juanatey, J.R. et al. (2003) Circulation 107, 127-31.
10. Gong, Q. et al. (2006) J Biol Chem 281, 4069-74.
11. Thomas, D. et al. (2006) Curr Pharm Des 12, 2271-83.
12. Staudacher, I. et al. (2010) Curr Opin Drug Discov Devel 13, 23-30.
13. Wible, B.A. et al. (2005) J Pharmacol Toxicol Methods 52, 136-45.
14. Yang, B.F. et al. (2004) Acta Pharmacol Sin 25, 554-60.
15. Jehle, J. et al. (2011) Cell Death Dis 2, e193.
16. Pond, A.L. et al. (2000) J Biol Chem 275, 5997-6006.
17. Rosati, B. et al. (2000) FASEB J 14, 2601-10.
18. Smith, G.A. et al. (2002) J Biol Chem 277, 18528-34.
19. Lastraioli, E. et al. (2004) Cancer Res 64, 606-11.
20. Masi, A. et al. (2005) Br J Cancer 93, 781-92.
21. Lin, H. et al. (2007) J Cell Physiol 212, 137-47.
22. Gong, J.H. et al. (2010) Oncol Rep 23, 1747-56.
23. Ding, X.W. et al. (2008) J Surg Oncol 97, 57-62.
24. Shao, X.D. et al. (2008) Cancer Biol Ther 7, 45-50.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Monkey

Specificity / Sensitivity

hERG1a (D1Y2J) Rabbit mAb recognizes endogenous levels of both mature and immature hERG1a protein. This antibody cross-reacts with proteins of unknown origin at 65 and 42 kDa in some cell lines. This antibody does not recognize hERG1b protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ala223 of human hERG1a protein.

Background

hERG1(human ether-a-go-go-related gene potassium channel 1) is a voltage gated potassium channel alpha-subunit which mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (1,2). The hERG channel is composed of two subunits, 1a and 1b, which differ at amino terminus due to alternative splicing. Native hERG channels are heteromers of hERG1a with hERG1b. Both subunits contribute to IKr current (3-6).

Blockade of hERG currents induced by compounds or mutation of hERG encoding gene-KCNH2 causes ventricular arrhythmias associated with inherited and acquired long QT syndrome and cardiomyocyte apoptosis (7-10). Therefore, hERG channel is a primary target for the development of class III antiarrhythmic agents (11,12). The hERG channel is also inhibited by a variety of non-antiarrhythmic compounds, which result in side effects. Consequently, hERG channel blockage is a common counter screen when selecting therapeutic agents for various diseases (11,13,14).

Research studies have implicated hERG in cancer cell survival (15). In normal human adult tissue, hERG is expressed in heart, brain, myometrium, pancreas, and hematopoietic progenitors (16,17). hERG is expressed in various cancer cell lines of epithelial, neuronal, leukemic, and connective tissue origin but not in corresponding normal cells (18-22). Furthermore, hERG expression is associated with enhanced cancer cell proliferation, invasiveness, and poor prognosis (23,24).

1. Warmke, J.W. and Ganetzky, B. (1994) Proc Natl Acad Sci U S A 91, 3438-42.
2. Sanguinetti, M.C. and Tristani-Firouzi, M. (2006) Nature 440, 463-9.
3. Lees-Miller, J.P. et al. (1997) Circ Res 81, 719-26.
4. London, B. et al. (1997) Circ Res 81, 870-8.
5. Lees-Miller, J.P. et al. (2003) Mol Cell Biol 23, 1856-62.
6. Sale, H. et al. (2008) Circ Res 103, e81-95.
7. Curran, M.E. et al. (1995) Cell 80, 795-803.
8. Itoh, T. et al. (1998) Hum Genet 102, 435-9.
9. González-Juanatey, J.R. et al. (2003) Circulation 107, 127-31.
10. Gong, Q. et al. (2006) J Biol Chem 281, 4069-74.
11. Thomas, D. et al. (2006) Curr Pharm Des 12, 2271-83.
12. Staudacher, I. et al. (2010) Curr Opin Drug Discov Devel 13, 23-30.
13. Wible, B.A. et al. (2005) J Pharmacol Toxicol Methods 52, 136-45.
14. Yang, B.F. et al. (2004) Acta Pharmacol Sin 25, 554-60.
15. Jehle, J. et al. (2011) Cell Death Dis 2, e193.
16. Pond, A.L. et al. (2000) J Biol Chem 275, 5997-6006.
17. Rosati, B. et al. (2000) FASEB J 14, 2601-10.
18. Smith, G.A. et al. (2002) J Biol Chem 277, 18528-34.
19. Lastraioli, E. et al. (2004) Cancer Res 64, 606-11.
20. Masi, A. et al. (2005) Br J Cancer 93, 781-92.
21. Lin, H. et al. (2007) J Cell Physiol 212, 137-47.
22. Gong, J.H. et al. (2010) Oncol Rep 23, 1747-56.
23. Ding, X.W. et al. (2008) J Surg Oncol 97, 57-62.
24. Shao, X.D. et al. (2008) Cancer Biol Ther 7, 45-50.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150
mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02%
sodium azide. Store at –20°C. Do not aliquot the antibody.
*Species cross-reactivity is determined by western blot.
** Anti-rabbit secondary antibodies must be used to
detect this antibody.