Abstract
PC1/3 is a neuroendocrine-specific member of the mammalian subtilisin-like proprotein convertase family. This seven-member family is involved in the endoproteolytic cleavage of a large number of precursor proteins including prohormones, proneuropeptides, zymogens, and proreceptors. PC1/3 is synthesized as a zymogen, proPC1/3, and its propeptide is rapidly and autocatalytically cleaved in the endoplasmic reticulum. The mature protein is sorted and stored in dense-core secretory vesicles, together with its substrates. Compound-inactivating mutations in the PCSK1 gene, which encodes PC1/3, cause monogenic obesity. Furthermore, the contribution of two common nonsynonymous variants in PCSK1 to polygenic obesity risk has recently been established. Additional rare variants have been identified in non-consanguineous extremely obese Europeans but functional characterization has not yet been described. Sequencing efforts of larger cohorts of obese patients might reveal more variants conferring risk of obesity.
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Acknowledgments
This work was supported by GOA2008/16, “FWO Vlaanderen,” Le Conseil Régional Nord Pas de Calais/FEDER, and the Agence Nationale de la Recherche.
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Choquet, H., Stijnen, P., Creemers, J.W. (2011). Genetic and Functional Characterization of PCSK1. In: Mbikay, M., Seidah, N. (eds) Proprotein Convertases. Methods in Molecular Biology, vol 768. Humana Press. https://doi.org/10.1007/978-1-61779-204-5_13
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DOI: https://doi.org/10.1007/978-1-61779-204-5_13
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