Miyazawa K, Wang Y, Minoshima S, Shimizu N, Kitamura N
Department of Life Science, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Eur J Biochem. 1998 Dec 1;258(2):355-61. doi: 10.1046/j.1432-1327.1998.2580355.x.
The organization and structure of the gene coding for hepatocyte growth factor activator (HGFA) have been determined by isolation of unique clones from a human genomic library. These clones were characterized by restriction mapping, Southern blotting and DNA sequencing. The complete sequence of the gene was determined and found to span about 7.5 kilobases of DNA and consist of 14 exons separated by 13 introns. The coding region of HGFA consists of multiple putative domains that are homologous to those observed in blood coagulation factor XII (FXII). These regions were found as separate exons in the gene, and the exon/intron arrangement was similar to that of FXII, suggesting that the genes for HGFA and FXII have arisen through gene duplication events from a common ancestral gene. The major transcription initiation site is located 75 bp upstream of the translational start codon. The gene was mapped to chromosome 4p16, using spot-blot hybridization on sorted chromosomes and fluorescence in situ hybridization on metaphase chromosome spreads. The phylogenetic and functional relationships between HGFA and FXII as well as urokinase and tissue-type plasminogen activator are discussed.
通过从人类基因组文库中分离出独特的克隆，已确定了肝细胞生长因子激活剂（HGFA）编码基因的组织和结构。这些克隆通过限制性图谱分析、Southern印迹分析和DNA测序进行了表征。确定了该基因的完整序列，发现其跨越约7.5千碱基的DNA，由14个外显子和13个内含子分隔组成。HGFA的编码区由多个与凝血因子XII（FXII）中观察到的结构域同源的推定结构域组成。这些区域在基因中作为单独的外显子被发现，并且外显子/内含子排列与FXII相似，这表明HGFA和FXII的基因是通过基因复制事件从一个共同的祖先基因产生的。主要转录起始位点位于翻译起始密码子上游75 bp处。使用分选染色体上的斑点杂交和中期染色体铺展上的荧光原位杂交，将该基因定位到染色体4p16。讨论了HGFA与FXII以及尿激酶和组织型纤溶酶原激活剂之间的系统发育和功能关系。
