Vitamin K-Dependent Transmembrane Gla Proteins

超出所提供的空间。维生素K依赖性蛋白质在脊椎动物的血液凝固及其调节、骨吸收和组织矿化中发挥重要作用。维生素K依赖性蛋白含有γ羧基谷氨酸残基，其在内质网腔内的翻译后事件中产生。该反应由广泛分布在许多脊椎动物和非脊椎动物组织中的γ谷氨酰羧化酶催化。这项研究将集中在深入了解四种新的维生素K依赖性蛋白的生物学作用，这些蛋白是单跨膜蛋白。这些蛋白质的大小范围为17 kDa至25 kDa，并含有9至13个γ-羧基谷氨酸残基。它们被称为PRGP 1、PRGP 2、TMG 3和TMG 4。这些跨膜蛋白中的两种，PRGP 1和TMG 3的基因位于X染色体上，而PRGP 2和TMG 4的基因分别位于染色体19和11上。对转染的哺乳动物细胞的研究表明，它们需要维生素K进行翻译后修饰，而这种修饰反应可被华法林抑制。四个跨膜蛋白的羧基区域与Nedd 4 - 1样蛋白结合，表明它们可能在泛素循环中发挥作用。Nedd 4 - 1样蛋白具有C2结构域、2 - 4个WW结构域和HECT结构域，其在泛素循环中作为E3泛素连接酶起作用。这些反应的机制和特异性将在这些调查中详细检查。性能现场=

EXCEED THE SPACE PROVIDED. Vitamin K-dependent proteins have been shown to play a major role in vertebrates in blood coagulation and its regulation, as well as in bone resorption and tissue mineralization. The vitamin K-dependent proteins contain gamma carboxyglutamic acid residues that are generated in a post-translation event within the lumen of the endoplasmic reticulum. This reaction is catalyzed by a gamma glutamyl carboxylase that is widely distributed in numerous vertebrate and non-vertebrate tissues. This investigation will focus on gaining insight into the biological role of four novel vitamin K-dependent proteins that are single transmembrane proteins. These proteins range in size from 17 kDa to 25 kDa and contain from nine to thirteen gamma- carboxyglutamic acid residues. They have been called PRGP1, PRGP2, TMG3, and TMG4. Genes for two of these transmembrane proteins, PRGP1 and TMG3 are located on the X chromosome, while genes for PRGP2 and TMG4 are found on chromosome 19 and 11, respectively. Studies with transfected mammalian cells have now shown that they require vitamin K for their post-translational modification in a reaction that is inhibited by warfarin. The carboxyl region of the four transmembrane proteins bind to Nedd4-1ike proteins, suggesting that they may play a role in the ubiquitin cycle. Nedd4-1ike proteins have a C2 domain, two to four WW domains, and a HECT domain that functions as an E3 ubiquitin ligase in the ubiquitin cycle. The mechanism and specificity of these reactions will be examined in detail in these investigations. PERFORMANCE SITE ========================================Section End===========================================