New Nomenclature for the Human Tissue Kallikrein Gene Family

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Abstract
The human kallikrein gene family is important to the discipline of clinical chemistry because it contains genes that encode for valuable cancer biomarkers, including the best tumor marker available today, prostate-specific antigen (PSA). Despite reports of numerous kallikrein-like genes in the mouse (1), until 2–3 years ago, only three human kallikrein genes were recognized: pancreatic/renal kallikrein (KLK1), human glandular kallikrein 2 (KLK2), and prostate-specific antigen (KLK3) (1)(2). The proteins encoded by the three kallikrein genes are now known as hK1, hK2, and hK3 (PSA). These three genes encode for serine proteases with either trypsin-like (hK1, hK2) or chymotrypsin-like (hK3) activity. Traditionally, kallikreins have been defined as enzymes that can act on high-molecular weight substrates and release bioactive peptides, known as kinins (3). Among the known kallikrein enzymes, only plasma kallikrein (encoded by a single gene localized on human chromosome 4q35; official symbol KLKB1) and pancreatic/renal kallikrein (hK1) have significant kininogenase activity. The proteins encoded by the KLK2 and the KLK3 genes have minimal or no kininogenase activity (4)(5).