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人类6号染色体p25区域与小鼠13号染色体的比较显示,小鼠中的卵清蛋白丝氨酸蛋白酶抑制剂基因库大幅扩展。

Comparison of human chromosome 6p25 with mouse chromosome 13 reveals a greatly expanded ov-serpin gene repertoire in the mouse.

作者信息

Kaiserman Dion, Knaggs Susan, Scarff Katrina L, Gillard Anneliese, Mirza Ghazala, Cadman Matthew, McKeone Richard, Denny Paul, Cooley Jessica, Benarafa Charaf, Remold-O'Donnell Eileen, Ragoussis Jiannis, Bird Phillip I

机构信息

Department of Biochemistry and Molecular Biology, Monash University, 3800, Australia.

出版信息

Genomics. 2002 Mar;79(3):349-62. doi: 10.1006/geno.2002.6716.

DOI:10.1006/geno.2002.6716
PMID:11863365
Abstract

Ov-serpins are intracellular proteinase inhibitors implicated in the regulation of tumor progression, inflammation, and cell death. The 13 human ov-serpin genes are clustered at 6p25 (3 genes) and 18q21 (10 genes), and share common structures. We show here that a 1-Mb region on mouse chromosome 13 contains at least 15 ov-serpin genes compared with the three ov-serpin genes within 0.35 Mb at human 6p25 (SERPINB1 (MNEI), SERPINB6 (PI-6), SER-PINB9 (PI-9)). The mouse serpins have characteristics of functional inhibitors and fall into three groups on the basis of similarity to MNEI, PI-6, or PI-9. The genes map between the mouse orthologs of the Werner helicase interacting protein and NAD(P)H menadioine oxidoreductase 2 genes, in a region that contains the markers D13Mit136 and D13Mit116. They have the seven-exon structure typical of human 6p25 ov-serpin genes, with identical intron phasing. Most show restricted patterns of expression, with common sites of synthesis being the placenta and immune tissue. Compared with human, this larger mouse serpin repertoire probably reflects the need to regulate a larger proteinase repertoire arising from differing evolutionary pressures on the reproductive and immune systems.

摘要

卵清蛋白丝氨酸蛋白酶抑制剂(Ov-serpins)是细胞内蛋白酶抑制剂,与肿瘤进展、炎症和细胞死亡的调节有关。13个人类Ov-serpin基因聚集在6p25(3个基因)和18q21(10个基因),并具有共同的结构。我们在此表明,小鼠13号染色体上一个1兆碱基(Mb)的区域至少包含15个Ov-serpin基因,而人类6p25上0.35 Mb范围内只有3个Ov-serpin基因(丝氨酸蛋白酶抑制剂B1(MNEI)、丝氨酸蛋白酶抑制剂B6(PI-6)、丝氨酸蛋白酶抑制剂B9(PI-9))。小鼠丝氨酸蛋白酶抑制剂具有功能抑制剂的特征,并根据与MNEI、PI-6或PI-9的相似性分为三组。这些基因定位于Werner解旋酶相互作用蛋白和NAD(P)H甲萘醌氧化还原酶2基因的小鼠直系同源基因之间,该区域包含标记D13Mit136和D13Mit116。它们具有人类6p25卵清蛋白丝氨酸蛋白酶抑制剂基因典型的七外显子结构,内含子相位相同。大多数呈现出受限的表达模式,常见的合成部位是胎盘和免疫组织。与人类相比,这种更大的小鼠丝氨酸蛋白酶抑制剂库可能反映了由于生殖和免疫系统面临不同的进化压力而需要调节更大的蛋白酶库。

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