PSMD14 (D18C7) Rabbit mAb

• 产品编号：CST-4197S      品牌：CST       原厂货号：4197S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

PSMD14 (D18C7) Rabbit mAb兔单抗识别内源性的总PSMD14蛋白。该抗体与COPS5/JAB1并无交叉反应性。该单克隆抗体经合成与人PSMD14蛋白氨基末端的邻近氨基酸残基序列一致的肽段，免疫动物产生。26S蛋白酶体是一种高丰度，大小约2 MDa的复合物，它具有泛素蛋白酶体途径的蛋白水解臂。它主要由两种亚型复合物组成，19S调节颗粒(RP)和20S催化核心颗粒(CP)，在许多情况下RPs会覆盖CP的任一末端。CP由包含催化位点的2种堆积β-环组成，每一种β-环由7种亚基组成(β_1-7)，且两侧包含两个分别由七个亚基构成的α环 (α_1-7).。因此，20S CP 的结构为α_1-7β_1-7β_1-7α_1-7。RP包括了一个底部和一个盖子。部分底部由ATPases的六角环组成，功能为打开底物蛋白和打开α-亚基交错的N-末端片段的闸门，从而使得未折叠的底物进入催化部位。盖子主要起特异性识别泛素信号的作用(1)。除了19S帽子之外，其他的蛋白和复合物，例如蛋白酶体活化因子28 (PA28/11S)，与20S的筒状末端结合，从而促进闸门的开放和激活。此外，蛋白酶体相关的DUBs和E3s能够改变底物嵌合的多泛素链，这可能调节了它们对降解的敏感性(2)。组成19S RP盖子的亚基中，只有PSMD14 (POH1)有确定的功能。PSMD14分为金属酶DUB，并且它的活性对于酵母和人的蛋白酶体的功能具有重要作用(3-6)。确实，PSMD14包括一种Mpr1-Pad1氨基末端(MPN)结构域，该结构域具有高度保守的、嵌入的标记模序，该模序从Jab1/Pad1/MPN结构域金属酶拷贝有金属依赖的异构肽JAMM。PSMD14的JAMM模序由4种带电荷的氨基酸组成：两个组氨酸残基和一个天冬氨酸残基后有一个谷氨酸残基(EXnHXHX10D)。组氨酸残基，与天冬氨酸残基一样，与锌离子结合，并与谷氨酸一起形成PSMD14的催化位点(3,4)。PSMD14被认为可以裂解临近的相对底物特异的泛素链，从而移除总的泛素链(3)。最近的研究表明PSMD14是ErbB2 (7)和c-Jun (8)蛋白水平重要的调节因子。

1. Finley, D. (2009) Annu Rev Biochem 78, 477-513.
2. Lee, M.J. et al. (2011) Mol Cell Proteomics 10, R110.003871.
3. Verma, R. et al. (2002) Science 298, 611-5.
4. Yao, T. and Cohen, R.E. (2002) Nature 419, 403-7.
5. Maytal-Kivity, V. et al. (2002) BMC Biochem 3, 28.
6. Gallery, M. et al. (2007) Mol Cancer Ther 6, 262-8.
7. Liu, H. et al. (2009) PLoS One 4, e5544.
8. Nabhan, J.F. and Ribeiro, P. (2006) J Biol Chem 281, 16099-107.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Xenopus, Dog

Specificity / Sensitivity

PSMD14 (D18C7) Rabbit mAb recognizes endogenous levels of total PSMD14 protein. This antibody does not cross-react with COPS5/JAB1.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues near the amino terminus of human PSMD14 protein.

Background

The 26S proteasome is a highly abundant, ~2 MDa complex that serves as the proteolytic arm of the ubiquitin-proteasome system. It consists largely of two sub-complexes, the 19S regulatory particle (RP) and the 20S catalytic core particle (CP); in many cases two RPs cap either end of a CP. The CP is made of two stacked β-rings that contain the catalytic sites, each of which is made of seven subunits (β_1-7), flanked on either side by two α-rings, which are also made of seven subunits each (α_1-7). Thus, the structure of the 20S CP is α_1-7β_1-7β_1-7α_1-7. The RP includes a base and a lid. The base, in part, is composed of a hexametric ring of ATPases that function to unfold the substrate and open the gate of the interlacing amino-terminal segments of the α-subunits, thus allowing entry of the unfolded substrate into the catalytic chamber. The lid is predominantly involved in specific recognition of the ubiquitin signal (1). In addition to the 19S cap, other proteins and complexes, such as proteasome activator 28 (PA28/11S), bind to the end of the 20S cylinder and activate it by facilitating opening of the gate. Furthermore, proteasome-associated DUBs and E3s can remodel substrate-anchored polyubiquitin chains, which may modulate their susceptibility to degradation (2).Of the subunits that comprise the 19S RP lid, only PSMD14 (POH1) has a known function. PSMD14 is classified as a metalloenzyme DUB and its activity has been shown to be critical for proteasome function in both yeast and humans (3-6). Indeed, PSMD14 harbors an Mpr1-Pad1-N-terminal (MPN) domain with an embedded, highly conserved signature motif for metal-dependent isopeptidases that has been dubbed JAMM, from Jab1/Pad1/MPN domain metalloenzyme. The JAMM motif of PSMD14 consists of a pattern of four charged amino acids: a glutamate residue followed by two histidines and an aspartate (EXnHXHX10D). It has been proposed that the histidine residues, in concert with the aspartate, bind to a zinc ion that, together with the preceding glutamate, forms the catalytic site of PSMD14 (3,4). PSMD14 is thought to cleave ubiquitin chains with proximal specificity relative to the substrate, thus removing whole ubiquitin chains en bloc (3). Recent studies have implicated PSMD14 as an important regulator of ErbB2 (7) and c-Jun (8) protein levels.

1. Finley, D. (2009) Annu Rev Biochem 78, 477-513.
2. Lee, M.J. et al. (2011) Mol Cell Proteomics 10, R110.003871.
3. Verma, R. et al. (2002) Science 298, 611-5.
4. Yao, T. and Cohen, R.E. (2002) Nature 419, 403-7.
5. Maytal-Kivity, V. et al. (2002) BMC Biochem 3, 28.
6. Gallery, M. et al. (2007) Mol Cancer Ther 6, 262-8.
7. Liu, H. et al. (2009) PLoS One 4, e5544.
8. Nabhan, J.F. and Ribeiro, P. (2006) J Biol Chem 281, 16099-107.

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.