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Literature summary extracted from

  • Ye, Y.; Klenerman, D.; Finley, D.
    N-terminal ubiquitination of amyloidogenic proteins triggers removal of their oligomers by the proteasome holoenzyme (2020), J. Mol. Biol., 432, 585-596 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.2.25 recombinant expression of biotin-tagged enzyme in HEK-293T cells Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.3.2.25 additional information to obtain homogenous and pure ubiquitin (Ub)-modified alphasynuclein (alphaS) and tauK18, engineered constructs that expressed fusion proteins with a single Ub moiety immediately before the first residue of alphaS or tauK18 (Ub-alphaS and Ub-tauK18) are genetically engineered. These engineered N-terminal Ub-fusion proteins are protected from deubiquitination by a Gly76Ser substitution of the C-terminal residue of Ub. No filamentous aggregates from Ub-alphaS are detected under TEM, thus, the morphology of filamentous aggregates is affected by N-terminal Ub modification. Meanwhile, oligomers from both tauK18 and Ub-tauK18 are reproducibly detected early in the aggregation process. An apparent reduction of the fraction of soluble oligomers with time is detected in both unmodified and Ub-modified tauK18 beyond 50 and 70 h, respectively. Comparisons of modified and unmodified proteins' aggregation behaviour, overview. Proteasomes are able to target Ub-modified aggregates Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.2.25 S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N-terminal-amino acid Homo sapiens
-
[E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[acceptor protein]
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.3.2.25 Homo sapiens Q96B02
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.2.25 recombinant biotin-tagged enzyme from HEK-293T cells by NeutrAvidin affinity chromatography, release from the coloumn by TEV protease cleavage Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.2.25 HEK-293T cell
-
Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.2.25 additional information in vitro, UBE2W can modify the N-terminus of both alpha-synuclein and a tau tetra-repeat domain with a single ubiquitin. The reaction does not continue beyond monoubiquitination as UBE2W specifically recognizes disordered sequences at the N-terminus of the substrate Homo sapiens ?
-
-
2.3.2.25 S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N-terminal-amino acid
-
Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[acceptor protein]
-
?
2.3.2.25 S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [alpha-synuclein]-N-terminal-amino acid full-length alpha-synuclein Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[alpha-synuclein]
-
?
2.3.2.25 S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [tau tetra-repeat domain]-N-terminal-Lys18
-
Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[tau tetra-repeat domain]
-
?

Synonyms

EC Number Synonyms Comment Organism
2.3.2.25 UBE2W
-
Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.2.25 25
-
assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.2.25 7.5
-
assay at Homo sapiens

General Information

EC Number General Information Comment Organism
2.3.2.25 metabolism the proteasome can target soluble oligomers assembled from ubiquitin-modified proteins independently of its peptidase activity, consistent with our recently reported fibril-fragmenting activity. Proteasomes are able to target oligomers assembled from N-terminally ubiquitinated proteins. The results suggest a possible disassembly mechanism by which N-terminal ubiquitination and the proteasome may together impede aggregate formation Homo sapiens
2.3.2.25 physiological function UBE2W can modify the N-terminus of proteins with ubiquitin. An engineered N-terminal ubiquitin modification changes the aggregation process of both proteins, resulting in the formation of structurally distinct aggregates. The mammalian proteasome holoenzyme can target oligomers assembled from ubiquitinated tau aggregation domain (tauK18) and alpha-synuclein (alphaS), both tauK18 and alphaS may become ubiquitinated on the N-terminus by UBE2W enabling the proteasomes to target and remove oligomers assembled from these modified proteins. The reaction does not continue beyond monoubiquitination as UBE2W specifically recognizes disordered sequences at the N-terminus of the substrate Homo sapiens