Pallaoro M, Fejzo M S, Shayesteh L, Blount J L, Caughey G H
Cardiovascular Research Institute and Departments of Medicine and Laboratory Medicine, University of California, San Francisco, California 94143-0911, USA.
J Biol Chem. 1999 Feb 5;274(6):3355-62. doi: 10.1074/jbc.274.6.3355.
Tryptases are serine proteases implicated in asthma and are very highly expressed in human mast cells. They fall into two groups, alpha and beta. Although several related tryptase mRNAs are known, it is unclear which if any are transcripts of separate haploid genes. The studies described here investigated the nature and number of human tryptases and sought possibly novel members of the family. To this end, two human bacterial artificial chromosome (BAC) clones containing tryptase genes were identified and mapped to chromosome 16p13.3, of which approximately 2.2 megabases are syntenic with the part of mouse chromosome 17 containing tryptase genes mouse mast cell protease (mMCP)-6 and -7. Sequencing and restriction mapping suggest that the BACs may partially overlap. Sequenced BAC genes correspond to three known beta-tryptases (betaI, betaII, and betaIII), an alpha-like gene, and a pair of novel hybrid genes related partly to alpha/beta-tryptases and partly to orthologs of mMCP-7. betaII and betaIII, betaI and alphaII, as well as the two mMCP-7-like genes, may be alleles at single loci; in total, there are at least three nonallelic tryptase genes in the isolated BAC clones. DNA blotting and restriction analysis suggest that the BACs include most members of the immediate tryptase family. Thus, chromosome 16p13.3 harbors a cluster of known and previously undescribed members of the tryptase gene family.
类胰蛋白酶是与哮喘相关的丝氨酸蛋白酶，在人类肥大细胞中高度表达。它们分为α和β两组。虽然已知有几种相关的类胰蛋白酶mRNA，但尚不清楚哪些（如果有的话）是单独单倍体基因的转录本。本文所述的研究调查了人类类胰蛋白酶的性质和数量，并寻找该家族可能的新成员。为此，鉴定了两个包含类胰蛋白酶基因的人类细菌人工染色体（BAC）克隆，并将其定位到16号染色体短臂1区3带，其中约2.2兆碱基与小鼠17号染色体上包含类胰蛋白酶基因小鼠肥大细胞蛋白酶（mMCP）-6和-7的部分区域同线。测序和限制性图谱分析表明，这些BAC可能部分重叠。测序的BAC基因对应于三种已知的β-类胰蛋白酶（βI、βII和βIII）、一个α样基因以及一对新的杂交基因，它们部分与α/β-类胰蛋白酶相关，部分与mMCP-7的直系同源物相关。βII和βIII、βI和αII以及两个mMCP-7样基因可能是单个位点的等位基因；在分离的BAC克隆中，总共有至少三个非等位类胰蛋白酶基因。DNA印迹和限制性分析表明，这些BAC包含类胰蛋白酶家族的大多数成员。因此，16号染色体短臂1区3带含有一组已知的和以前未描述的类胰蛋白酶基因家族成员。
