title: Identification of the PDI-family member ERp90 as an interaction partner of ERFAD.
abstract: In the endoplasmic reticulum (ER), members of the protein disulfide isomerase (PDI) family perform critical functions during protein maturation. Herein, we identify the previously uncharacterized PDI-family member ERp90. In cultured human cells, we find ERp90 to be a soluble ER-luminal glycoprotein that comprises five potential thioredoxin (Trx)-like domains. Mature ERp90 contains 10 cysteine residues, of which at least some form intramolecular disulfides. While none of the Trx domains contain a canonical Cys-Xaa-Xaa-Cys active-site motif, other conserved cysteines could endow the protein with redox activity. Importantly, we show that ERp90 co-immunoprecipitates with ERFAD, a flavoprotein involved in ER-associated degradation (ERAD), through what is most likely a direct interaction. We propose that the function of ERp90 is related to substrate recruitment or delivery to the ERAD retrotranslocation machinery by ERFAD.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Riemer
authors.forename: Henning G
authors.initials: HG
authors.lastname: Hansen
authors.forename: Christian
authors.initials: C
authors.lastname: Appenzeller-Herzog
authors.forename: Linda
authors.initials: L
authors.lastname: Johansson
authors.forename: Lars
authors.initials: L
authors.lastname: Ellgaard
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005420:Flavoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017385:Sequence Homology
chemical_list: D000951:Antigens, Neoplasm; C560606:FOXRED2 protein, human; D005420:Flavoproteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D011994:Recombinant Proteins; C000593135:TXNDC16 protein, human; D049452:Green Fluorescent Proteins; D019704:Protein Disulfide-Isomerases