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Literature summary for 2.3.2.25 extracted from

  • Wang, B.; Zeng, L.; Merillat, S.A.; Fischer, S.; Ochaba, J.; Thompson, L.M.; Barmada, S.J.; Scaglione, K.M.; Paulson, H.L.
    The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntingtons disease protein, huntingtin (2018), Neurobiol. Dis., 109, 127-136 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.3.2.25

Cloned(Commentary)

Cloned (Comment) Organism
gene UBE2W, recombinant expression in HEK-293 cells. When wild-type Ube2W is coexpressed with Httex1Q103, inclusion number and size significantly increases, whereas coexpression of either Ube2W mutant markedly decreases Httex1Q103 inclusion number and average size Mus musculus

Protein Variants

Protein Variants Comment Organism
C91A site-directed mutagenesis of an active site residue, the mutation eliminates the ability of Ube2W to transfer ubiquitin (Ub) to substrates while still allowing Ube2W to bind substrates, it disrupts Ube2W-mediated ubiquitination Mus musculus
additional information absence of Ube2W increases soluble, monomeric mutant huntingtin (HTT) in a knock-in mouse model of Huntington's disease. The absence of Ube2W in HdhQ200 KI mice significantly increases levels of soluble monomeric mHTT while reducing insoluble oligomeric species Mus musculus
W144E site-directed mutagenesis, the mutation eliminates substrate binding and disrupts Ube2W-mediated ubiquitination Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
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 Mus musculus 5829
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N-terminal-amino acid Mus musculus
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 [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[acceptor protein]
-
 ?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N-terminal-amino acid Mus musculus C57BL/6
-
 [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[acceptor protein]
-
 ?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [huntingtin]-N-terminal-amino acid Mus musculus
-
 [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[huntingtin]
-
 ?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [huntingtin]-N-terminal-amino acid Mus musculus C57BL/6
-
 [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[huntingtin]
-
 ?

Organism

Organism UniProt Comment Textmining
Mus musculus Q8VDW4
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-
Mus musculus C57BL/6 Q8VDW4
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-

Source Tissue

Source Tissue Comment Organism Textmining
neuron primary cell culture from cortical neurons Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N-terminal-amino acid
-
 Mus musculus [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[acceptor protein]
-
 ?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N-terminal-amino acid
-
 Mus musculus C57BL/6 [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[acceptor protein]
-
 ?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [huntingtin]-N-terminal-amino acid
-
 Mus musculus [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[huntingtin]
-
 ?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [huntingtin]-N-terminal-amino acid the relatively disordered nature of the N-terminal domain of HTT predicts it to be a potential candidate target for Ube2W Mus musculus [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[huntingtin]
-
 ?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [huntingtin]-N-terminal-amino acid
-
 Mus musculus C57BL/6 [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[huntingtin]
-
 ?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [huntingtin]-N-terminal-amino acid the relatively disordered nature of the N-terminal domain of HTT predicts it to be a potential candidate target for Ube2W Mus musculus C57BL/6 [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[huntingtin]
-
 ?

Synonyms

Synonyms Comment Organism
UBE2W
-
 Mus musculus
ubiquitin conjugating enzyme
-
 Mus musculus

General Information

General Information Comment Organism
malfunction the absence of Ube2W in HdhQ200 KI mice significantly increases levels of soluble monomeric mHTT while reducing insoluble oligomeric species. Ube2W null mice show an incompletely penetrant multi-organ defect and post-natal lethality. Mutational analysis reveals that neither wild-type Ube2W nor enzyme mutants alter cell viability. Ube2W deficiency results in decreased mHTT inclusion formation and reduced neurotoxicity, overview. Ube2W deficiency does not alter transcript levels of Htt or striatal markers in HdhQ200 mice Mus musculus
metabolism ubiquitin (Ub) conjugation requires the sequential action of enzymes to target ubiquitin to substrates: Ub activating enzyme (E1), Ub conjugating enzyme (E2) and Ub ligase (E3). Given the diversity in Ub-chain lengths, linkages and substrate attachment sites, dramatically different kinds of ubiquitination can occur. Ube2W can function with various ubiquitin ligases including the C-terminus of Hsc-70-interacting protein (CHIP) and the BRCA1/BARD1 complex to mono-ubiquitinate select substrates at their N-termini Mus musculus
additional information amino acid W144 near the C-terminus of Ube2W is critically important for substrate binding Mus musculus
physiological function the ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin (HTT). Potential function of the non-canonical ubiquitin-conjugating enzyme, Ube2W, in the polyQ neurodegenerative disease, Huntington's Disease (HD). Ube2W increases HTT inclusion formation in cultured cells. The effect of Ube2W on HTT most likely occurs post-translationally. But as an E2 that ubiquitinates N-termini, Ube2W can act cotranslationally by interacting with the nascent N-terminal polypeptide as it exits the ribosome and thus alter the rate of HTT protein synthesis itself Mus musculus