title: The islet-specific glucose-6-phosphatase-related protein, implicated in diabetes, is a glycoprotein embedded in the endoplasmic reticulum membrane.
abstract: The islet-specific glucose-6-phosphatase-related protein (IGRP) has no known catalytic activity, but is of interest because it is the source of the peptide autoantigen targeted by a prevalent population of pathogenic CD8(+) T cells in non-obese diabetic mice. To better understand the potential roles of this protein in diabetes mellitus, we examine the subcellular localization and membrane topography of human IGRP. We show that IGRP is a glycoprotein, held in the endoplasmic reticulum by nine transmembrane domains, which is degraded in cells predominantly through the proteasome pathway that generates the major histocompatibility complex class I-presented peptides.
authors.affiliation: Section on Cellular Differentiation, Heritable Disorders Branch, National Institute of Child Health and Human Development, Building 10, Room 9S241, National Institutes of Health, Bethesda, MD 20892-1830, USA.
authors.forename: Jeng-Jer
authors.initials: JJ
authors.lastname: Shieh
authors.forename: Chi-Jiunn
authors.initials: CJ
authors.lastname: Pan
authors.forename: Brian C
authors.initials: BC
authors.lastname: Mansfield
authors.forename: Janice Yang
authors.initials: JY
authors.lastname: Chou
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D037282:Calreticulin / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005952:Glucose-6-Phosphatase; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D037282:Calreticulin; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D011993:Recombinant Fusion Proteins; C067713:lactacystin; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human; C117983:G6pc2 protein, mouse; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine