Characteristics of YAP3, a New Prohormone Processing Aspartic Protease from S. Cerevisiae

Abstract

Neuropeptides and peptide hormones are synthesized as large precursors that are cleaved at paired, or less frequently at single basic amino acid residues by endoproteases to release biologically active peptides [1,2]. In the yeast Saccharomyces cerevisiae, processing of the pheromone precursor, pro-α-mating factor, is carried out by kexin, a subtilisin-related proprotein convertase that is the product of the KEX2 gene [3,4]. In 1990, a S. cerevisiae aspartic protease gene (YAP3) which was induced when pro-α-mating factor was over-expressed in a KEX2-deficient mutant was described [5]. The YAP3 gene product was able to catalyze the processing of the α-mating factor precursor on the COOH-terminal side of paired basic residues to yield the active pheromone in KEX2-deficient mutants, suggesting that YAP3 may be an alternative pro-α-mating factor processing protease. YAP3 has sequence similarity to the classical two-domain active site region of other aspartic proteinases such as pepsin, renin, cathepsin D and penicillopepsin that exhibit specificity for hydrophobic residues [6]. Despite this sequence similarity, YAP3 exhibits novel specificity for basic residues.

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