title: Genetics of the first seven proprotein convertase enzymes in health and disease.
abstract: 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.
authors.affiliation: Immunoregulation, Institute of Biomedical Technology, University of Tampere, and BioMediTech, Tampere, Finland;
authors.forename: Hannu
authors.initials: H
authors.lastname: Turpeinen
authors.affiliation: Immunoregulation, Institute of Biomedical Technology, University of Tampere, and BioMediTech, Tampere, Finland;
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Ortutay
authors.affiliation: Immunoregulation, Institute of Biomedical Technology, University of Tampere, and BioMediTech, Tampere, Finland; ; Fimlab laboratories, Pirkanmaa Hospital District, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Pesu
keywords: Association.; FURIN; Genetics; Proprotein convertase