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Literature summary extracted from

  • Hagiwara, M.; Ling, J.; Koenig, P.A.; Ploegh, H.L.
    Posttranscriptional regulation of glycoprotein quality control in the endoplasmic reticulum is controlled by the E2 Ub-conjugating enzyme UBC6e (2016), Mol. Cell, 63, 753-767 .
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.3.2.23 additional information Derlin2 interacts with UBC6e in the complex involved in the regulation of ERAD enhancers. Derlin2 levels do not change in UBC6e-/- cells transduced with any of the UBC6e mutants, suggesting that it is not a substrate regulated by UBC6e, but is a member of a UBC6e complex Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
2.3.2.23 additional information generation of UbeC6 deletion mice, phenotype, detailed overview. Generation of Derlin2-/- mice showing that not only ERAD enhancers but also UBC6e itself are upregulated Mus musculus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.2.23 endoplasmic reticulum UBC6e localizes to the ER via its tail-anchor, functional UBC6e requires its precise location in the endoplasmic reticulum to form a supramolecular complex with Derlin2 Mus musculus 5783
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Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.2.23 S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine Mus musculus
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 [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
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 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.2.23 Mus musculus Q9JJZ4
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Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.2.23 embryonic fibroblast MEFs Mus musculus
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Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.2.23 S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
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 Mus musculus [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
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 ?

Subunits

EC Number Subunits Comment Organism
2.3.2.23 More UBC6e exists in at least two different configurations: as an apparent monomer and as part of a complex Mus musculus

Synonyms

EC Number Synonyms Comment Organism
2.3.2.23 E2 Ub-conjugating enzyme
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 Mus musculus
2.3.2.23 UBC6e
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 Mus musculus
2.3.2.23 Ube2J1
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 Mus musculus

General Information

EC Number General Information Comment Organism
2.3.2.23 malfunction ablation of UBC6e causes upregulation of active ERAD enhancers and so increases clearance not only of terminally misfolded substrates, but also of wild-type glycoproteins that fold comparatively slowly in vitro and in vivo. The absence of UBC6e increases the levels of ERAD enhancers with a corresponding increase in the rate of clearance of misfolded and/or incompletely folded substrates. UBC6e-/- MEFs show accelerated mannose trimming and premature substrate release from CNX, initiated by ER mannosidase-dependent eviction of substrate from the CNX cycle. Finally, by deletion of UBC6e, accelerated degradation is observed in tissue culture and in vivo, not only for canonical ERAD substrates, but also for folding intermediates of proteins that fold slowly, such as tyrosinase. The UBC6e loss-of-function mutation thus produces a gain-of-function with respect to ERAD activity, overview. Increased degradation of tyrosinase in UBC6e-/- cells and reduced skin tyrosinase levels in UBC6e-/- mice Mus musculus
2.3.2.23 metabolism the enzyme UbeC6 is involved in the endoplasmic reticulum (ER) associated degradation (ERAD) Mus musculus
2.3.2.23 physiological function UBC6e is an E2 ubiquitin conjugating enzyme that localizes to the ER via its tail-anchor. Functional UBC6e requires its precise location in the endoplasmic reticulum (ER) to form a supramolecular complex with Derlin2. This complex targets ERAD enhancers for degradation, a function that depends on UBC6e's enzymatic activity. UBC6e-/- cells upregulate ERAD enhancers selectively, but UBC6e downregulates EDEM1, EDEM3, OS-9 and SEL1L (ERAD enhancers) in the absence of ER stress. Homeostasis of SEL1L, EDEM1 and OS-9 requires enzymatic activity of UBC6e. UBC6e's function depends strictly on its E2 enzymatic activity but not its phosphorylation status. The exact ER membrane localization of UBC6e and the supramolecular complexes in which UBC6e participates determine its activity, and directly control the levels of components essential for ERAD activity. Only the Derlin2-complexed UBC6e controls the levels of ERAD enhancers Mus musculus