STRUCTURE & MOLECULAR BIOLOGY OF THE PROTEIN S GENE

S蛋白是调节止血作用的关键成分。 S蛋白是活性蛋白C的辅因子，C是一种酶 对两种蛋白质成分的降解负责 凝血途径。因此，蛋白质S通过 蛋白C的作用是下调血液凝结过程。 功能蛋白缺乏的个体S，要么是因为 遗传或环境获得性原因具有更高的风险 经历血栓性疾病。常见症状 与S蛋白缺乏有关的有血栓性静脉炎、 深静脉血栓形成和肺血栓。就目前而言 蛋白质S缺乏症的遗传基础及其与疾病的关系 血栓形成是未知的。建议的长远目标 研究旨在了解蛋白质S缺乏症的遗传基础 和血栓形成。这将在一定程度上通过 建议的研究，旨在更好地了解 S基因的正常和异常蛋白及其功能 S蛋白制品的性质。的具体方法。 实现这些目标包括：a)克隆和定性(通过 限制性内切酶和DNA测序) 人蛋白S基因及其与遗传学的比较 蛋白质S缺陷者，b)染色体定位 S蛋白基因与S蛋白基因的特异性杂交 缺乏不同人类染色体的人鼠细胞杂交， C)细胞内S蛋白信使核糖核酸水平的定量 相信或怀疑参与止血并根据 止血调节因素的影响，以及d)部位定向 针对结构/功能的S蛋白的诱变 相互关系，包括β-羟基天冬氨酸和 γ-羧基谷氨酸、凝血酶裂解和表皮 蛋白质中的生长因子、前肽和GLA结构域 结果可能最终导致诊断和治疗方法的改进 S蛋白缺乏症和/或病症的治疗 血栓性疾病。

Protein S is a key component for the regulation of hemostasis. Protein S serves as a cofactor for activated protein C, an enzyme responsible for the degradation of two protein elements of the blood coagulation pathway. Consequently, protein S through the action of protein C down-regulates the blood clotting process. Individuals deficient in functional protein S, either because of genetic or environmentally-acquired reasons, are at a higher risk of experiencing thrombotic disorders. Symptoms commonly associated with Protein S deficiency include thrombophlebitis, deep vein thrombosis, and pulmonary emboli. At the present time the genetic basis of protein S deficiency and its relationship to thrombosis are unknown. The long-term objective of the proposed research is to understand the genetic basis of protein S deficiency and thrombosis. This will be accomplished, in part, through the proposed studies, designed to provide a better understanding of the normal and abnormal protein S genes and the functional properties of the protein S products. Specific methods for achieving these goals include: a) cloning and characterization (by restriction endonuclease and DNA sequencing) of the normal human protein S gene and comparison to that from genetically protein S deficient individuals, b) chromosomal localization of the protein S gene by specific hybridization of protein S cDNA to mouse-human cell hybrids lacking different human chromosomes, c) quantitation of protein S messenger RNA levels in cells believed or suspected of participating in hemostasis and under the influence of hemostatic regulatory factors, and d) site-directed mutagenesis of protein S to address structure/function relationships, including the role of beta-hydroxyaspartic and gamma-carboxyglutamic acids, thrombin cleavage, and epidermal growth factor, propeptide and "Gla" domains in proteins S. The results may eventually lead to improved methods of diagnosis and therapy for patients having protein S deficiency and/or suffering from thrombotic disorders.