Erv2 and quiescin sulfhydryl oxidases: Erv-domain enzymes associated with the secretory pathway.

SIGNIFICANCE: Members of the Erv/ALR/QSOX protein family contain an Erv sequence module and catalyze protein disulfide bond formation. Erv enzymes impact protein function within and outside cells that affects both normal and malignant cell growth. This protein family is named for its founding members: Erv1 (essential for respiratory and vegetative growth 1) and ALR (augmenter of liver regeneration), homologous mitochondrial proteins from yeast and mammals, respectively, and QSOX (quiescin sulfhydryl oxidase), an oxidase secreted from quiescent cells. This review will focus on a subset of Erv proteins that are localized within the secretory pathway: Erv2-like proteins, proteins present in the endoplasmic reticulum of fungi, and QSOX proteins, proteins localized within the secretory pathway and extracellular space and present in most eukaryotes, but not fungi. RECENT ADVANCES: A wealth of structural and biochemical data has been obtained for Erv2 and QSOX proteins. These data have identified a generally conserved catalytic mechanism and structure for the Erv2 and QSOX proteins with unique features for each enzyme. CRITICAL ISSUES: Many fundamental questions remain about the activity for these proteins in living cells including the partners, pathways, and locations utilized by these enzymes in vivo. FUTURE DIRECTIONS: A more comprehensive understanding of the cellular roles for Erv2 and QSOX enzymes will require identification of their partners and substrates. Also, determining when Erv2 and QSOX function during growth and development, and how changes in levels of active Erv2 and QSOX impact cell function, is necessary to facilitate a better understanding of these intriguing enzymes.