The open reading frame YAL048c affects the secretion of proteinase A in S-cerevisiae

Over-expression of the yeast PEP4 gene encoding the vacuolar aspartic prote ase proteinase A (PrA) leads to saturation of the vacuolar targeting system of the cell and missorting of PrA to the growth medium. In a screen for ge nes affecting the secretion of over-expressed PrA we found that multiple co pies of the open reading frame (ORF) YAL048c enhanced PrA secretion. Since no function has hitherto been ascribed to YAL048c, we undertook further stu dies of this ORF. Deletion of YAL048c resulted in slightly reduced secretio n of over-produced PrA. Furthermore, strains deleted for YAL048c showed a g rowth inhibition phenotype resulting in wrinkled colony morphology when gro wn on rich medium containing high concentrations of calcium. YAL048c is pre dicted to encode a polypeptide of 662 amino acid residues containing two co nsensus ATP/GTP-binding site motifs and a putative carboxy-terminal transme mbrane region. In addition, the amino acid sequence contains two putative c alcium-binding domains. The YAL048c protein may be evolutionarily conserved , as homologues exist in humans and Caenorhabditis elegans. We suggest that the YAL048c protein is involved in vesicle transport in the secretory path way. Copyright (C) 1999 John Wiley & Sons, Ltd.