Tosi M, Duponchel C, Meo T, Couture-Tosi E
Unité d'Immunogénétique, Institut Pasteur, INSERM U276.
J Mol Biol. 1989 Aug 20;208(4):709-14. doi: 10.1016/0022-2836(89)90161-7.
The exon-intron structure of the human complement C1s gene displays a striking similarity with that of the gene encoding haptoglobin, a peculiar transport protein distantly related to the serine proteases. While the protease regions of the serine zymogens are typically encoded by multiple exons, the protease domains of C1s and of its genetically linked and functionally interacting homolog C1r are encoded as intronless domains, not unlike a region of haptoglobin, which in fact is devoid of proteolytic activity. The close similarity of the C1s gene with haptoglobin includes the precise conservation of exon-intron junctions and it extends to upstream exons encoding the short repeats typical of several complement components, but found also in other functionally unrelated proteins. Additional evidence of the common ancestry of C1r, C1s and haptoglobin is the presence, within the protease domain, of a set of sequence markers that distinguish these three proteins from all known serine proteases. The finding of vertebrate serine protease genes with an uninterrupted protease-encoding exon supports the definition of a novel evolutionary branch of this gene family and rules out the hypothesis that regards this unusual exon as an irrelevant byproduct of the extravagant functional divergence of haptoglobin.
人类补体C1s基因的外显子-内含子结构与编码触珠蛋白的基因有着惊人的相似性，触珠蛋白是一种特殊的运输蛋白，与丝氨酸蛋白酶有较远的亲缘关系。虽然丝氨酸酶原的蛋白酶区域通常由多个外显子编码，但C1s及其基因连锁且功能相互作用的同源物C1r的蛋白酶结构域被编码为无内含子结构域，这与触珠蛋白的一个区域类似，事实上触珠蛋白缺乏蛋白水解活性。C1s基因与触珠蛋白的密切相似性包括外显子-内含子连接的精确保守性，并且这种相似性延伸到编码几种补体成分典型短重复序列的上游外显子，但在其他功能不相关的蛋白质中也有发现。C1r、C1s和触珠蛋白有共同祖先的额外证据是，在蛋白酶结构域内存在一组序列标记，这些标记将这三种蛋白质与所有已知的丝氨酸蛋白酶区分开来。发现具有不间断蛋白酶编码外显子的脊椎动物丝氨酸蛋白酶基因，支持了该基因家族一个新进化分支的定义，并排除了将这个不寻常的外显子视为触珠蛋白过度功能分化的无关副产物的假设。
