Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:A protein translocation defect linked to ubiquitin conjugation at the endoplasmic reticulum. 839 28

Ubiquitin fold modifier 1 (UFM1) is a small, metazoan-specific, ubiquitin-like protein modifier that is essential for embryonic development. Although loss-of-function mutations in UFM1 conjugation are linked to endoplasmic reticulum (ER) stress, neither the biological function nor the relevant cellular targets of this protein modifier are known. Here, we show that a largely uncharacterized ribosomal protein, RPL26, is the principal target of UFM1 conjugation. RPL26 UFMylation and de-UFMylation is catalyzed by enzyme complexes tethered to the cytoplasmic surface of the ER and UFMylated RPL26 is highly enriched on ER membrane-bound ribosomes and polysomes. Biochemical analysis and structural modeling establish that UFMylated RPL26 and the UFMylation machinery are in close proximity to the SEC61 translocon, suggesting that this modification plays a direct role in cotranslational protein translocation into the ER. These data suggest that UFMylation is a ribosomal modification specialized to facilitate metazoan-specific protein biogenesis at the ER.
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PMID:Ribosomal protein RPL26 is the principal target of UFMylation. 3062 44