ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum

Oxidizing conditions must be maintained in the endoplasmic reticulum (ER) t o allow the formation of disulfide bonds in secretory proteins. Here we rep ort the cloning and characterization of a mammalian gene (ERO1-L) that shar es extensive homology with the Saccharomyces cerevisiae ERO1 gene, required in yeast for oxidative protein folding. When expressed in mammalian cells, the product of the human ERO1-L gene co localizes with ER markers and disp lays Endo-H-sensitive glycans, In isolated microsomes, ERO1-L behaves as a type II integral membrane protein. ERO1-L is able to complement several phe notypic traits of the yeast thermosensitive mutant ero1-1, including temper ature and dithiothreitol sensitivity, and intrachain disulfide bond formati on in carboxypeptidase Y, ERO1-L is no longer functional when either one of the highly conserved Cys-394 or Cys-397 is mutated. These results strongly suggest that ERO1-L is involved in oxidative ER protein folding in mammali an cells.