title: Genetic and functional characterization of PCSK1.
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.
authors.affiliation: CNRS-8090-Institute of Biology, Pasteur Institute, Lille, France. hchoquet@gallo.ucsf.edu
authors.forename: Hélène
authors.initials: H
authors.lastname: Choquet
authors.forename: Pieter
authors.initials: P
authors.lastname: Stijnen
authors.forename: John W M
authors.initials: JW
authors.lastname: Creemers
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D045664:Proprotein Convertase 1 / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D017422:Sequence Analysis, DNA / Q000379:methods*; D044465:White People
chemical_list: D011498:Protein Precursors; D045664:Proprotein Convertase 1