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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of two novel transmembrane γ-carboxyglutamic acid proteins expressed broadly in fetal and adult tissues
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Identification of two novel transmembrane γ-carboxyglutamic acid proteins expressed broadly in fetal and adult tissues

机译：鉴定两种在胎儿和成人组织中广泛表达的跨膜γ-羧基谷氨酸蛋白

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摘要

The proline-rich γ-carboxyglutamic acid (GIa) proteins (PRGPs) 1 and 2 are the founding members of a family of vitamin K- dependent single-pass integral membrane proteins character- ized by an extracellular amino terminal domain of approxi- mately 45 amino acids that is rich in Gla. The intracellular carboxyl terminal region of these two proteins contains one or two copies of the sequence PPXY, a motif present in a variety of proteins involved in such diverse cellular functions as signal transduction, cell cycle progression, and protein turnover. In this report, we describe the cloning of the cDNAs for two additional human transmembrane Gla proteins (TMG) of 20--24 kDa named TMG3 and TMG4. These two proteins possess extracellular Gla domains with 13 or 9 potential Gla residues, respectively, followed by membrane-spanning hydrophobic regions and cytoplasmic carboxyl terminal regions that contain PPXY motifs. This emerg- ing family of integral membrane Gla proteins includes proline- rich Gla protein (PRGP) 1, PRGP2, TMG3, and TMG4, all of which are characterized by broad and variable distribution in both fetal and adult tissues. Members of this family can be grouped into two subclasses on the basis of their gene organization and amino acid sequence. These observations suggest novel physi- ological functions for vitamin K beyond its known role in the biosynthesis of proteins involved in blood coagulation and bone development. The identification and characterization of these proteins may allow a more complete understanding of the teratogenic consequences of exposure in utero to vitamin K antagonists. such as warfarin-based anticoagulants.
机译：富含脯氨酸的γ-羧基谷氨酸（GIa）蛋白（PRGPs）1和2是依赖维生素K的单程整合膜蛋白家族的创始成员，其特征是约45的细胞外氨基末端结构域富含Gla的氨基酸。这两种蛋白质的细胞内羧基末端区域包含一个或两个序列PPXY，这是存在于多种蛋白质中的基序，这些蛋白质参与多种细胞功能，例如信号转导，细胞周期进程和蛋白质更新。在此报告中，我们描述了另外两个20--24 kDa的人类跨膜Gla蛋白（TMG）的cDNA克隆，分别命名为TMG3和TMG4。这两种蛋白质具有分别带有13个或9个潜在Gla残基的胞外Gla结构域，其后是跨膜的疏水区域和含有PPXY图案的细胞质羧基末端区域。这个新兴的完整膜Gla蛋白家族包括富含脯氨酸的Gla蛋白（PRGP）1，PRGP2，TMG3和TMG4，所有这些蛋白的特征都是在胎儿和成人组织中分布广泛且可变。根据其基因组织和氨基酸序列，该家族的成员可以分为两个亚类。这些观察结果表明，维生素K在其参与血液凝固和骨骼发育的蛋白质的生物合成中的已知作用之外，还具有新颖的生理功能。这些蛋白质的鉴定和表征可以更全面地了解子宫内暴露于维生素K拮抗剂的致畸后果。如基于华法林的抗凝剂。

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