Cloning of a kallikrein pseudogene

Kallikreins are a group of serine proteases clustered together on a small region of chromosome 19q13.4. Recent reports suggest that kallikreins are differentially expressed in malignancy and have potential as cancer biomarkers. The human kallikrein gene locus has now been fully characterized and 15 functional kallikreins were identified. Although many kallikrein pseudogenes have already been characterized in rodents, none have been identified in humans. In the current study, we identified the first human kallikrein pseudogene named ΨKLK1 and mapped it between the KLK2 and KLK4 genes. This pseudogene shares a moderate degree of similarity with the adjacent functional kallikreins. It has a conserved histidine residue of the catalytic triad of serine proteases and its surrounding motif, but lacks the aspartate and serine residues. Positions of some cysteine residues are also conserved in the pseudogene. This pseudogene lacks intronic sequences and should thus be classified as a processed pseudogene. EST and PCR analyses indicate that this pseudogene may be transcriptionally active, because mRNA was detected in many tissues including the prostate, testis, pituitary, and adrenal glands, as well as in tissues of the female genital organs. The mRNA sequence of the gene is, however, defective and is not predicted to code for a protein. Highly conserved sequences were found in the flanking region of the pseudogene, thus supporting the view that it evolved by retrotransposition. We also identified another serine protease fragment that has only the conserved histidine residue. The functional significance of the pseudogene and the other fragment is yet to be identified.