Leytus S P, Foster D C, Kurachi K, Davie E W
Biochemistry. 1986 Sep 9;25(18):5098-102. doi: 10.1021/bi00366a018.
Factor X is one of six vitamin K dependent proteins known to be involved in blood coagulation, the others being factor VII, factor IX, prothrombin, protein S, and protein C. In the present studies, recombinant bacteriophage containing overlapping DNA inserts coding for the gene for human factor X have been isolated and characterized. These DNA inserts code for almost the entire gene for factor X, extending from the prepro leader peptide through the 3' noncoding region of the transcription product. The organization of the gene for factor X was established by DNA sequencing to identify the location of the introns and exons in the gene. Seven introns and eight exons were identified and their intron/exon boundaries established. The seven introns interrupt the coding sequence at essentially identical locations in the amino acid sequence as the introns in the genes for human factor IX and protein C. In addition, the introns in the gene for factor X divide the coding sequence into discrete exons that code for potential structural and functional domains of the protein. This information provides strong evidence to support the suggestion that the vitamin K dependent proteins present in plasma have evolved from a single, common gene and that this ancestral gene arose through a process that involved the assembly of small protein coding units of DNA into a single gene.
凝血因子X是已知参与血液凝固的六种维生素K依赖性蛋白质之一,其他五种是凝血因子VII、凝血因子IX、凝血酶原、蛋白S和蛋白C。在本研究中,已分离并鉴定了含有编码人凝血因子X基因的重叠DNA插入片段的重组噬菌体。这些DNA插入片段编码了几乎整个凝血因子X基因,从前原导肽延伸至转录产物的3'非编码区。通过DNA测序确定了凝血因子X基因的结构,以识别该基因中内含子和外显子的位置。鉴定出七个内含子和八个外显子,并确定了它们的内含子/外显子边界。这七个内含子在氨基酸序列中的位置与人类凝血因子IX和蛋白C基因中的内含子基本相同,从而中断了编码序列。此外,凝血因子X基因中的内含子将编码序列分成离散的外显子,这些外显子编码该蛋白质的潜在结构和功能域。这一信息为支持以下观点提供了有力证据:血浆中存在的维生素K依赖性蛋白质是从一个共同的单一基因进化而来的,并且这个祖先基因是通过一个涉及将小的DNA蛋白质编码单元组装成一个单一基因的过程产生的。