Clements J, Hooper J, Dong Y, Harvey T
Centre for Molecular Biotechnology, School of Life Sciences, Queensland University of Technology, Brisbane, Australia.
Biol Chem. 2001 Jan;382(1):5-14. doi: 10.1515/BC.2001.002.
The tissue kallikreins are serine proteases encoded by highly conserved multi-gene families. The rodent kallikrein (KLK) families are particularly large, consisting of 13-26 genes clustered in one chromosomal locus. It has been recently recognised that the human KLK gene family is of a similar size (15 genes) with the identification of another 12 related genes (KLK4-KLK15) within and adjacent to the original human KLK locus (KLK1-3) on chromosome 19q13.4. The structural organisation and size of these new genes is similar to that of other KLK genes except for additional exons encoding 5' or 3' untranslated regions. Moreover, many of these genes have multiple mRNA transcripts, a trait not observed with rodent genes. Unlike all other kallikreins, the KLK4-KLK15 encoded proteases are less related (25-44%) and do not contain a conventional kallikrein loop. Clusters of genes exhibit high prostatic (KLK2-4, KLK15) or pancreatic (KLK6-13) expression, suggesting evolutionary conservation of elements conferring tissue specificity. These genes are also expressed, to varying degrees, in a wider range of tissues suggesting a functional involvement of these newer human kallikrein proteases in a diverse range of physiological processes.
组织激肽释放酶是由高度保守的多基因家族编码的丝氨酸蛋白酶。啮齿动物激肽释放酶（KLK）家族特别庞大，由聚集在一个染色体位点的13 - 26个基因组成。最近人们认识到，人类KLK基因家族大小相似（15个基因），在19号染色体13.4区的原始人类KLK位点（KLK1 - 3）内及相邻区域又鉴定出另外12个相关基因（KLK4 - KLK15）。这些新基因的结构组织和大小与其他KLK基因相似，只是额外含有编码5'或3'非翻译区的外显子。此外，这些基因中有许多具有多个mRNA转录本，这是啮齿动物基因所没有的特征。与所有其他激肽释放酶不同，KLK4 - KLK15编码的蛋白酶相关性较低（25 - 44%），且不包含传统的激肽释放酶环。基因簇表现出高前列腺（KLK2 - 4、KLK15）或胰腺（KLK6 - 13）表达，表明赋予组织特异性的元件具有进化保守性。这些基因也在更广泛的组织中不同程度地表达，表明这些新的人类激肽释放酶蛋白酶在多种生理过程中发挥功能作用。
