Multiple members of the plasminogen-apolipoprotein(a) gene family associated with thrombosis.
Multiple members of the plasminogen-apolipoprotein(a) gene family associated with thrombosis.
复制标题
纤溶酶原-载脂蛋白（a）基因家族的多个成员与血栓形成相关。
DOI：
10.1021/bi00127a011
复制
发表时间：
1992
期刊：
影响因子：
2.9
通讯作者：
Ichinose,A
中科院分区：
文献类型：
--
作者：
Ichinose,A
华盛顿大学生物化学系，SJ-70，西雅图，华盛顿98195,1991年10月24日收到；修订稿收到1992年1月6日摘要：纤溶酶原和载脂蛋白(A)[apo(A)]是与遗传性血栓形成密切相关的血浆蛋白。在一些发生静脉血栓的患者中发现低水平的纤溶酶原，而血浆载脂蛋白(A)浓度高的人群动脉血栓的发生率较高。为了研究和比较纤溶酶原-载脂蛋白(A)基因家族中其他四个密切相关的基因，人们已经分离和鉴定了两个不同的编码人载脂蛋白(A)的基因。这些基因包括纤溶酶原编码基因，两个独特的纤溶酶原相关基因，以及一个编码肝细胞生长因子的基因。对这些基因的核苷酸序列分析表明，纤溶酶原基因、载脂蛋白(A)基因和纤溶酶原相关基因的外显子及其边界的序列差异仅为1-5%。外显子/内含子的类型和内含子在分子中的位置也完全相同，这表明这些基因是通过复制和外显子改组从祖先的纤溶酶原基因进化而来的。利用这些结果，已经设计了基因特异性探针来分析该基因家族中的每一个基因。利用人-金黄地鼠杂交种的基因组DNA和基因特异性引物，将纤溶酶原基因和两个apo(A)基因都定位在6号染色体上。这些数据也使得通过体外扩增来鉴定个体的载脂蛋白(A)和纤溶酶原基因成为可能。它含有一个预激活肽、五个kringle结构域和一个丝氨酸蛋白酶结构域。载脂蛋白(A)[apo(A)]1是一种血浆糖蛋白，存在于一种类似低密度脂蛋白的颗粒中，称为脂蛋白-1。
Department of Biochemistry, University of Washington, SJ-70, Seattle, Washington 98195 Received October 24, 1991; Revised Manuscript Received January 6, 1992 abstract: Plasminogen and apolipoprotein (a)[apo (a)] are closely related plasma proteins that are associated with hereditary thrombophilia. Low plasminogen levels are found in some patients who developed venous thrombosis, while a population with high plasma concentrations of apo (a) have a higher incidence of arterial thrombosis. Twodifferent genes coding for human apo (a) have been isolated and characterized in order to study and compare these genes with four other closely related genes in the plasminogen-apo (a) gene family. These include the gene coding for plasminogen, two unique plasminogen-related genes, and a gene coding for hepatocyte growth factor. Nucleotide sequence analysis of these genes revealed that the exons and their boundaries of the genes for plasminogen and apo (a), and the plasminogen-related genes, differ only 1-5% in sequence. The types of exon/intronjunctions and positions of introns in the molecules are also exactly identical, suggesting that these genes have evolved from an ancestral plasminogen gene via duplication and exon shuffling. By utilizing these results, gene-specific probes have been designed for the analysis of each of the genes in this gene family. Theplasminogen and two apo (a) genes were all localizedto chromosome 6 by employing the gene-specific primers and genomic DNAs from human-hamstercell hybrids. These data also make it possible to characterize the apo (a) and plasminogen genes in individuals by in vitro amplification.^ Masminogen is a key proenzyme in the fibrinolytic and thrombolytic systems. It contains a preactivation peptide, five kringle domains, and a serine protease domain. Apolipoprotein (a)[apo (a)] 1 is a plasma glycoprotein which is present in a low-density lipoprotein (LDL)-like particle named lipo-