A protein translocation defect linked to ubiquitin conjugation at the endoplasmic reticulum.
Ubiquitin-conjugating enzymes function in selective proteolysis pathways and catalyse the covalent attachment of ubiquitin to proteolytic substrates. Here we report the identification of an integral membrane ubiquitin-conjugating enzyme. This enzyme, UBC6, localizes to the endoplasmic reticulum (ER), with the catalytic domain facing the cytosol. ubc6 loss-of-function mutants suppress the protein translocation defect caused by a mutation in SEC61, which encodes a key component of a multisubunit protein translocation apparatus of the ER. The expression of the sec61 mutant phenotype requires both the activity of UBC6 and its localization at the ER membrane. This suggests that UBC6 may mediate selective degradation of ER membrane proteins and that the protein translocation defect of sec61 may be caused by proteolysis of components of a structurally distorted mutant translocation apparatus.
Friedrich-Miescher-Laboratorium der Max-Planck-Gesellschaft, Tübingen, Germany.
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D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D003001:Cloning, Molecular; D004271:DNA, Fungal; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005656:Fungal Proteins / Q000235:genetics; D005800:Genes, Fungal; D007425:Intracellular Membranes / Q000378:metabolism; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D000069816:SEC Translocation Channels; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*
D004271:DNA, Fungal; D005656:Fungal Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; C499383:SEC61 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C082461:UBC6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases