Localization of a new prostate-specific antigen-related serine protease gene, KLK4, is evidence for an expanded human kallikrein gene family cluster on chromosome 19q13.3-13.4

The human tissue kallikrein (KLK) family of serine proteases, which is impo rtant in post-translational processing events, currently consists of just t hree genes-tissue kallikrein (KLK1), KLK2, and prostate-specific antigen (P SA) (KLK3)-clustered at chromosome 19q13.3-13.4. We identified an expressed sequence tag from an endometrial carcinoma cDNA library with 50% identity to the three known KLK genes. Primers designed to putative exon 2 and exon 3 regions from this novel kallikrein-related sequence were used to polymera se chain reaction-screen five cosmids spanning 130 kb around the KIK locus on chromosome 19. This new gene, which we have named KLK4, is 25 kb downstr eam of the KLK2 gene and follows a region that includes two other putative KLK-like gene fragments KLK4 spans 5.2 kb, has an identical genomic structu re-five exons and four introns-to the other KLK genes and is transcribed on the reverse strand, in the same direction as KLK1 but opposite to that of KLK2 and KLK3. It encodes a 254-amino acid prepro-serine protease that is m ost similar (78% identical) to pig enamel matrix serine protease but is als o 37% identical to PSA. These data suggest that the human kallikrein gene f amily locus on chromosome 19 is larger than previously thought and also ind icate a greater sequence divergence within this family compared with the hi ghly conserved rodent kallikrein genes.