Genetics of the First Seven Proprotein Convertase Enzymes in Health and Disease
Hannu Turpeinen, Zsuzsanna Ortutay and Marko Pesu
Affiliation: Institute of Biomedical Technology, BioMediTech, University of Tampere FinnMedi 2, 5th floor, Biokatu 8 FI-33520 Tampere, Finland
Keywords: Proprotein convertase, Genetics, FURIN, Association.
Members of the substilisin/kexin like proprotein convertase (PCSK) protease family cleave and convert immature
pro-proteins into their biologically active forms. By cleaving for example prohormones, cytokines and cell membrane
proteins, PCSKs participate in maintaining the homeostasis in a healthy human body. Conversely, erratic enzymatic function
is thought to contribute to the pathogenesis of a wide variety of diseases, including obesity and hypercholestrolemia.
The first characterized seven PCSK enzymes (PCSK1-2, FURIN, PCSK4-7) process their substrates at a motif made up of
paired basic amino acid residues. This feature results in a variable degree of biochemical redundancy in vitro, and consequently,
shared substrate molecules between the different PCSK enzymes. This redundancy has confounded our understanding
of the specific biological functions of PCSKs. The physiological roles of these enzymes have been best illustrated
by the phenotypes of genetically engineered mice and patients that carry mutations in the PCSK genes. Recent developments
in genome-wide methodology have generated a large amount of novel information on the genetics of the first
seven proprotein convertases. In this review we summarize the reported genetic alterations and their associated phenotypes.
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