The expanded human kallikrein (KLK) gene family: Genomic organisation, tissue-specific expression and potential functions

The tissue kallikreins are serine proteases encoded by highly conserved mul ti-gene families. The rodent kallikrein (KLK) families are particularly lar ge, consisting of 13-26 genes clustered in one chromosomal locus. It has be en 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 simila r to that of other KLK genes except for additional exons encoding 5' or 3' untranslated regions. Moreover, many of these genes have multiple mRNA tran scripts, a trait not observed with rodent genes. Unlike all other kallikrei ns, the KLK4-KLK15 encoded proteases are less related (25-44%) and do not c ontain a conventional kallikrein loop. Clusters of genes exhibit high prost atic (KLK2-4, KLK15) or pancreatic (KLK6-13) expression, suggesting evoluti onary conservation of elements conferring tissue specificity. These genes a re also expressed, to varying degrees, in a wider range of tissues suggesti ng a functional involvement of these newer human kallikrein proteases in a diverse range of physiological processes.