Characterization of human γ-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families
Characterization of human γ-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families
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DOI：
10.4049/jimmunol.164.12.6566
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发表时间：
2000-06-15
影响因子：
4.4
通讯作者：
Verghese, GM
中科院分区：
文献类型：
--
作者：
Caughey, GH;Raymond, WW;Verghese, GM
在此之前，该实验室在人类染色体16p13.3上鉴定了α，β和肥大细胞蛋白酶-7样类胰蛋白酶基因簇。本工作描述了编码新的丝氨酸蛋白酶的相邻基因，称为γ-类胰蛋白酶，并产生了多类胰蛋白酶基因座的精细图谱。每个γ基因位于α 1H Ca 2+通道基因（CACNA 1H）和β II-或β III-类胰蛋白酶基因之间，并且与来自多态性小卫星MS 205的30 kb相似。类胰蛋白酶基因座还包含至少四个类胰蛋白酶样假基因，包括mastin，一种在狗身上表达但在人类身上不表达的基因基因组DNA印迹结果表明，γ I-和γ II-类胰蛋白酶是等位基因在同一网站，β II-和β III-类胰蛋白酶似乎是等位基因在相邻的网站，和α II-和β I-类胰蛋白酶似乎是等位基因在第三个网站。γ-类胰蛋白酶在肺、肠和几种其它组织中以及在也表达γ-类胰蛋白酶蛋白的肥大细胞系（HMC-1）中转录。免疫组化分析表明，γ-类胰蛋白酶表达的气道肥大细胞。γ-类胰蛋白酶催化结构域与已知的肥大细胞类胰蛋白酶的催化结构域相似至48%相同，并且具有小鼠同源物。我们预测γ-胰蛋白酶是具有胰蛋白酶底物特异性和独特激活模式的糖基化低聚物。在所描述的类胰蛋白酶中没有发现的特征是C-末端疏水结构域，其可能是膜锚。虽然催化结构域包含类胰蛋白酶样特征，但疏水片段和内含子外显子组织与另一种最近描述的蛋白酶前列腺素更密切相关。总之，这项工作描述了γ-类胰蛋白酶，其是染色体16 p类胰蛋白酶/前列腺素基因家族的新成员。其独特的功能可能意味着新的功能。
Previously, this laboratory identified clusters of alpha-, beta-, and mast cell protease-7-like tryptase genes on human chromosome 16p13.3. The present work characterizes adjacent genes encoding novel serine proteases, termed gamma-tryptases, and generates a refined map of the multitryptase locus, Each gamma gene lies between an alpha 1H Ca2+ channel gene (CACNA1H) and a beta II- or beta III-tryptase gene and is similar to 30 kb from polymorphic minisatellite MS205, The tryptase locus also contains at least four tryptase-like pseudogenes, including mastin, a gene expressed in dogs but not in humans. Genomic DNA blotting results suggest that gamma I- and gamma II-tryptases are alleles at the same site, beta II- and beta III-tryptases appear to be alleles at a neighboring site, and alpha II- and beta I-tryptases appear to be alleles at a third site. gamma-Tryptases are transcribed in lung, intestine, and in several other tissues and in a mast cell line (HMC-1) that also expresses gamma-tryptase protein. Immunohistochemical analysis suggests that gamma-tryptase is expressed by airway mast cells. gamma-Tryptase catalytic domains are similar to 48% identical with those of known mast cell tryptases and possess mouse homologues. We predict that gamma-tryptases are glycosylated oligomers with tryptic substrate specificity and a distinct mode of activation. A feature not found in described tryptases is a C-terminal hydrophobic domain, which may be a membrane anchor, Although the catalytic domains contain tryptase-like features, the hydrophobic segment and intron exon organization are more closely related to another recently described protease, prostasin, In summary, this work describes gamma-tryptases, which are novel members of chromosome 16p tryptase/prostasin gene families. Their unique features suggest possibly novel functions.