title: Structure-function relations, physiological roles, and evolution of mammalian ER-resident selenoproteins.
abstract: Selenium is an essential trace element in mammals. The major biological form of this micronutrient is the amino acid selenocysteine, which is present in the active sites of selenoenzymes. Seven of 25 mammalian selenoproteins have been identified as residents of the endoplasmic reticulum, including the 15-kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins K, M, N, S, and T. Most of these proteins are poorly characterized. However, recent studies implicate some of them in quality control of protein folding in the ER, retrotranslocation of misfolded proteins from the ER to the cytosol, metabolism of the thyroid hormone, and regulation of calcium homeostasis. In addition, some of these proteins are involved in regulation of glucose metabolism and inflammation. This review discusses evolution and structure-function relations of the ER-resident selenoproteins and summarizes recent findings on these proteins, which reveal the emerging important role of selenium and selenoproteins in ER function.
authors.affiliation: Redox Biology Center and Department of Biochemistry, University of Nebraska, Lincoln, NE, USA.
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Shchedrina
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Vyacheslav M
authors.initials: VM
authors.lastname: Labunskyy
authors.forename: Dolph L
authors.initials: DL
authors.lastname: Hatfield
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D017510:Protein Folding; D020033:Protein Isoforms / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012643:Selenium / Q000378:metabolism; D051140:Selenoproteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D020033:Protein Isoforms; D051140:Selenoproteins; D007453:Iodide Peroxidase; D012643:Selenium