Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system.
Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system.
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DOI：
10.1016/s0021-9258(19)39298-1
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发表时间：
1990-04
期刊：
影响因子：
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通讯作者：
T. Petersen;M. Martzen;A. Ichinose;E. Davie
中科院分区：
文献类型：
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作者：
T. Petersen;M. Martzen;A. Ichinose;E. Davie
纤溶酶原编码基因的组织和结构是通过体外扩增正常人的白细胞DNA和从三个不同的人类基因组文库中分离出独特的克隆来确定的。用限制性内切酶图谱、Southern杂交和DNA测序对这些克隆进行了鉴定。人纤溶酶原基因全长约52.5kb，由18个内含子隔开的19个外显子组成。DNA序列分析表明，纤溶酶原的5个kringle结构由两个外显子编码。内含子-外显子交界处的内含子中的核苷酸与其他真核基因中发现的核苷酸类似。还鉴定了纤溶酶原基因的三个多聚腺苷酸化位点。从纤溶酶原基因组DNA和cDNA推导的氨基酸序列与氨基酸序列分析所确定的血浆蛋白的氨基酸序列进行比较，发现在多肽链的几个位置存在明显的氨基酸多态性。对扩增的基因组DNA和基因组克隆的核苷酸序列分析也表明，纤溶酶原基因与包括载脂蛋白(A)在内的其他几种蛋白关系密切。这种蛋白可能是通过纤溶酶原基因的复制和外显子改组而进化的。在人类基因组文库中还观察到另一个纤溶酶原相关基因(S)的存在。
The organization and structure of the gene coding for plasminogen has been determined by a combination of in vitro amplification of leukocyte DNA from normal individuals and isolation of unique clones from three different human genomic libraries. These clones were characterized by restriction mapping, Southern blotting, and DNA sequencing. The gene for human plasminogen spanned about 52.5 kilobases of DNA and consisted of 19 exons separated by 18 introns. DNA sequence analysis revealed that the five kringle structures in plasminogen were coded by two exons. The nucleotides in the introns at the intron-exon boundaries were GT-AG analogous to those found in other eukaryotic genes. Three polyadenylation sites for plasminogen mRNA were also identified. When the amino acid sequences deduced from the genomic DNA and cDNAs of plasminogen were compared with that of the plasma protein determined by amino acid sequence analysis, an apparent amino acid polymorphism was observed in several positions of the polypeptide chain. Nucleotide sequence analysis of the amplified genomic DNAs and genomic clones also revealed that the plasminogen gene was very closely related to several other proteins, including apolipoprotein(a). This protein may have evolved via duplication and exon shuffling of the plasminogen gene. The presence of another plasminogen-related gene(s) in the human genomic library was also observed.