Genomic structure and chromosomal localization of the human hepatocyte growth factor activator inhibitor type 1 and 2 genes
Genomic structure and chromosomal localization of the human hepatocyte growth factor activator inhibitor type 1 and 2 genes
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DOI：
10.1046/j.1432-1327.2000.01368.x
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发表时间：
2000-06-01
期刊：
影响因子：
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通讯作者：
Koono, M
中科院分区：
文献类型：
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作者：
Itoh, M;Yamauchi, M;Koono, M
肝细胞生长因子激活物抑制物1(HAI-1)和肝细胞生长因子激活物抑制物2(HAI-2)是新近发现的可从人胃癌细胞系MKN45中纯化和克隆的特异性抑制肝细胞生长因子激活物(HGFA)的昆尼茨型丝氨酸蛋白酶抑制剂。HAI-2与最初报道的胎盘bikunin蛋白相同。这两种蛋白都含有两个Kuritz抑制域(KDS)，其中第一个域(Kd1)主要负责对HGFA的抑制活性，并且在各种组织中广泛表达。本研究通过对人类基因组细菌人工染色体(BAC)文库的筛选，克隆了这两种结构相似蛋白的编码基因，并对其基因组结构进行了比较。HAI-1和HAI-2基因分别由11个外显子和8个外显子组成，其跨度分别为12kbp和12.5kbp。在每个基因的Kd1和Kd2之间插入3个外显子，其中中间的外显子为低密度脂蛋白受体样区(HAI-1)和睾丸特异性外显子(HAI-2)。HAI-1和HAI-2在5‘-侧翼区没有发现同源区，也没有TATA和CAAT盒。基因定位于染色体15q15(HAI-1)和19q13.11(HAI-2)。这些结果表明，虽然HAI-1和HAI-2基因可能来源于同一个祖先基因，但它们在进化过程中获得了不同的体内作用。
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) are recently discovered Kunitz-type serine protease inhibitors which can be purified and cloned from human stomach cancer cell line MKN45 as specific inhibitors against hepatocyte growth factor activator (HGFA). HAI-2 was identical with the protein originally reported as placental bikunin. Both proteins contain two Kunitz inhibitor domains (KDs), of which the first domain (KD1) is mainly responsible for the inhibitory activity against HGFA, and are expressed ubiquitously in various tissues. In this study, we cloned the genes coding for these two structurally similar proteins by screening of human genomic bacterial artificial chromosome (BAC) library and their genomic structures were compared. HAI-1 and -2 genes consist of 11 and 8 exons spanning 12 kbp and 12.5 kbp, respectively. Three exons were inserted between KD1 and KD2 of each gene, of which the middle one was the low-density lipoprotein (LDL) receptor-like domain (HAI-1) and the testis specific exon (HAI-2). Apparently homologous regions between HAI-1 and -2 were not found in 5'-flanking region and neither TATA nor CAAT box was present. The genes were mapped to chromosome 15q15 (HAI-1) and 19q13.11 (HAI-2). These results suggested that although HAI-1 and -2 genes might be derived from same ancestor gene, they acquired distinctive in vivo roles during their evolution.