Selenoprotein K binds multiprotein complexes and is involved in the regulation of endoplasmic reticulum homeostasis

J Biol Chem. 2011 Dec 16;286(50):42937-48. doi: 10.1074/jbc.M111.310920. Epub 2011 Oct 20.


Selenoprotein K (SelK) is an 11-kDa endoplasmic reticulum (ER) protein of unknown function. Herein, we defined a new eukaryotic protein family that includes SelK, selenoprotein S (SelS), and distantly related proteins. Comparative genomics analyses indicate that this family is the most widespread eukaryotic selenoprotein family. A biochemical search for proteins that interact with SelK revealed ER-associated degradation (ERAD) components (p97 ATPase, Derlins, and SelS). In this complex, SelK showed higher affinity for Derlin-1, whereas SelS had higher affinity for Derlin-2, suggesting that these selenoproteins could determine the nature of the substrate translocated through the Derlin channel. SelK co-precipitated with soluble glycosylated ERAD substrates and was involved in their degradation. Its gene contained a functional ER stress response element, and its expression was up-regulated by conditions that induce the accumulation of misfolded proteins in the ER. Components of the oligosaccharyltransferase complex (ribophorins, OST48, and STT3A) and an ER chaperone, calnexin, were found to bind SelK. A glycosylated form of SelK was also detected, reflecting its association with the oligosaccharyltransferase complex. These data suggest that SelK is involved in the Derlin-dependent ERAD of glycosylated misfolded proteins and that the function defined by the prototypic SelK is the widespread function of selenium in eukaryotes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Blotting, Western
  • Cell Line
  • Chromatography, Liquid
  • Computational Biology
  • Electrophoresis, Polyacrylamide Gel
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum-Associated Degradation / drug effects
  • Endoplasmic Reticulum-Associated Degradation / physiology
  • HeLa Cells
  • Homeostasis / drug effects
  • Humans
  • Immunoprecipitation
  • Mass Spectrometry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microscopy, Fluorescence
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Protein Binding / drug effects
  • Protein Binding / genetics
  • Protein Folding
  • Selenoproteins / genetics
  • Selenoproteins / metabolism*
  • Thioredoxin-Disulfide Reductase / genetics
  • Thioredoxin-Disulfide Reductase / metabolism
  • Tunicamycin / pharmacology


  • DERL1 protein, human
  • DERL2 protein, human
  • Membrane Proteins
  • Multiprotein Complexes
  • Selenoproteins
  • Tunicamycin
  • Thioredoxin-Disulfide Reductase