Current perspectives on the molecular biology of the renal tissue kallikrein gene and the related tissue kallikrein gene family.

Renal tissue kallikrein is a member of the multigene family of serine proteases called the tissue kallikrein (KLK) gene family. This is a highly conserved family of genes, with a genomic structural organization that is identical for all these genes and other genes in the larger serine protease family, such as trypsin and chymotrypsin. These genes exhibit high sequence similarity both within and between species. However, there are clearly areas of sequence variability, which is most apparent in regions that form the substrate binding pocket of each enzyme and confers the substrate specificity of each individual enzyme. These genes are also often expressed in the same tissue, although each gene can have an individual tissue-specific pattern of expression. Similar patterns of diversity yet identity are also apparent in the regulation of kallikrein gene expression or enzyme activity. These similarities, and the fact that several of these gene families are located in tight clusters in the genome, support the notion that they have arisen by gene duplication. In this review, an overview of the molecular biology of the renal tissue kallikrein (KLK1) gene and the larger KLK gene family is given, highlighting the similarities yet diversity that is the hallmark of this family of genes, and how this knowledge has, and will, impact on our understanding of the role these enzymes play in normal physiological events and disease.