Literature summary for 3.4.19.12 extracted from

Kabuta, T.; Setsuie, R.; Mitsui, T.; Kinugawa, A.; Sakurai, M.; Aoki, S.; Uchida, K.; Wada, K.
Aberrant molecular properties shared by familial Parkinsons disease-associated mutant UCH-L1 and carbonyl-modified UCH-L1 (2008), Hum. Mol. Genet., 17, 1482-1496.

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Activating Compound

Activating Compound	Comment	Organism	Structure
4-hydroxy-2-alkenal	modification of UCH-L1 promotes direct interactions between UCH-L1 and tubulin	Homo sapiens
4-hydroxy-2-nonenal	modification of UCH-L1 promotes direct interactions between UCH-L1 and tubulin	Homo sapiens

Application

Application	Comment	Organism
medicine	interactions of mutant or carbonyl-modified UCH-L1 with other proteins constitute one of the causes of not only familial Parkinsons disease, but also sporadic Parkinsons disease. Carbonyl-modified and mutant UCH-L1 share common properties, e.g. adopt a similar aberrant structure, promote tubulin polymerization, show decreased ubiquitin binding, and both increased insolubility and interactions with proteins over 30 kDa compared with the wild-type	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
plasmids containing wild-type UCH-L1 and mutants with or without FLAG tag transiently transfected into Neuro2a, SH-SY5Y or COS-7 cells. NIH-3T3 cells stably expressing human UCH-L1 with a FLAG-HA double tag at the N-terminus. PGEX UCH-L1 vectors transformed into Escherichia coli BL21	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
C132S	no effect on protein insolubility or interactions	Homo sapiens
C152S	binds to monoubiquitin in both 4-hydroxy-2-nonenal-treated cells and untreated cells	Homo sapiens
C220S	no effect on protein insolubility or interactions	Homo sapiens
C90S	lacks hydrolase activity but maintains binding affinity for ubiquitin, does not exhibit notably increased insolubility upon 4-hydroxy-2-nonenal-treatment compared with UCH-L1 wild-type, has no effect on the interaction of UCH-L1 and tubulin	Homo sapiens
D30K	lacks hydrolase activity and binding affinity for ubiquitin, has no effect on the interaction of UCH-L1 and tubulin	Homo sapiens
H185A	displays increased interactions with tubulin	Homo sapiens
I93M	mutation in UCH-L1 associated with familial Parkinsons disease, shows increased insolubility and elevated interactions with multiple proteins, promotes tubulin polymerization	Homo sapiens
R63A	displays increased interactions with tubulin, causes a decrease in tubulin polymerization	Homo sapiens
S18Y/I93M	increased insolubility	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
2-propenal	carbonyl modification with 0.1 mM	Homo sapiens
4-hydroxy-2-hexenal	carbonyl modification in a dose-dependent manner	Homo sapiens
4-hydroxy-2-nonenal	carbonyl modification with 0.01-0.1 mM leads to decreased ubiquitin binding, and both increased insolubility and interactions with proteins over 30 kDa compared with the wild-type	Homo sapiens
additional information	no carbonyl modification with 0.1 mM or 0.5 mM methylglyoxal and 0.1 mM or 0.5 mM malondialdehyde	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
purification of GST-tagged UCH-L1 by gel filtration	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
alpha-tubulin + H2O	-	Homo sapiens	?	-	?
beta-tubulin + H2O	-	Homo sapiens	?	-	?
monoubiquitin + H2O	-	Homo sapiens	?	-	?
additional information	wild-type UCH-L1 interacts with multiple proteins over 30 kDa. It shows no interaction with beta-actin	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
ubiquitin C-terminal hydrolase L1	-	Homo sapiens
UCH-L1	-	Homo sapiens

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Release 2023.1 (January 2023)