title: ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum.
abstract: Oxidizing conditions must be maintained in the endoplasmic reticulum (ER) to allow the formation of disulfide bonds in secretory proteins. Here we report the cloning and characterization of a mammalian gene (ERO1-L) that shares 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 displays Endo-H-sensitive glycans. In isolated microsomes, ERO1-L behaves as a type II integral membrane protein. ERO1-L is able to complement several phenotypic traits of the yeast thermosensitive mutant ero1-1, including temperature and dithiothreitol sensitivity, and intrachain disulfide bond formation 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 mammalian cells.
authors.affiliation: Department of Biological and Technological Research, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy. caribbo.andrea@hsr.it
authors.forename: A
authors.initials: A
authors.lastname: Cabibbo
authors.forename: M
authors.initials: M
authors.lastname: Pagani
authors.forename: M
authors.initials: M
authors.lastname: Fabbri
authors.forename: M
authors.initials: M
authors.lastname: Rocchi
authors.forename: M R
authors.initials: MR
authors.lastname: Farmery
authors.forename: N J
authors.initials: NJ
authors.lastname: Bulleid
authors.forename: R
authors.initials: R
authors.lastname: Sitia
mesh_terms: D000595:Amino Acid Sequence; D004220:Disulfides / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005816:Genetic Complementation Test; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; D014176:Protein Biosynthesis; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D004220:Disulfides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C405327:ERO1A protein, human; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C485767:ERO1B protein, human