3.4.19.12: ubiquitinyl hydrolase 1
This is an abbreviated version!
For detailed information about ubiquitinyl hydrolase 1, go to the full flat file.
Word Map on EC 3.4.19.12
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3.4.19.12
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nerve
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proteasome
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neurodegenerative
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fiber
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innervation
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deubiquitinase
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polyglutamine
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ataxia
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parkinsonism
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spinocerebellar
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ubiquitin-proteasome
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polyubiquitinated
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glial
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sars-cov-2
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coronavirus
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covid-19
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calcitonin
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neurofilament
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fibrillary
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neuropeptide
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neuron-specific
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traumatic
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gene-related
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cyld
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parkin
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polyq
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synaptophysin
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ubiquitin-like
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polyproteins
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usp7
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ubiquitin-dependent
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alpha-synuclein
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deubiquitylating
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npy
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myenteric
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3clpro
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monoubiquitination
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nedd8
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cd45ro
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isg15
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intraepidermal
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k48-linked
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spermatogonial
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mono-ubiquitinated
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ubiquitin-binding
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3c-like
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mers-cov
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medicine
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isopeptide
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degradation
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synthesis
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diagnostics
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anti-sars-cov-2
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molecular biology
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analysis
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concussion
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pharmacology
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drug development
- 3.4.19.12
- nerve
- proteasome
- neurodegenerative
- fiber
-
innervation
-
deubiquitinase
-
polyglutamine
- ataxia
- parkinsonism
- spinocerebellar
-
ubiquitin-proteasome
-
polyubiquitinated
- glial
- sars-cov-2
- coronavirus
- covid-19
- calcitonin
- neurofilament
-
fibrillary
-
neuropeptide
-
neuron-specific
-
traumatic
-
gene-related
- cyld
- parkin
-
polyq
-
synaptophysin
-
ubiquitin-like
- polyproteins
- usp7
-
ubiquitin-dependent
- alpha-synuclein
-
deubiquitylating
- npy
-
myenteric
- 3clpro
-
monoubiquitination
- nedd8
-
cd45ro
- isg15
-
intraepidermal
-
k48-linked
- spermatogonial
-
mono-ubiquitinated
-
ubiquitin-binding
-
3c-like
- mers-cov
- medicine
-
isopeptide
- degradation
- synthesis
- diagnostics
-
anti-sars-cov-2
- molecular biology
- analysis
- concussion
- pharmacology
- drug development
Reaction
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal) =
Synonyms
A20, AD-019, AMSH, associated molecule with the SH3-domain of STAM, AT-3, ataxin-3, BAP1, BPLF1, BRCA1-associated protein-1, C-terminal hydrolases UCHL3, C-terminal ubiquitin hydrolase, Cezanne, CGI-70, CYLD, de-ubiquitinating enzyme, deubiquinating isopeptidase T, deubiquitinating enzyme, Doa4, Doa4 ubiquitin hydrolase, Doa4p ubiquitin isopeptidase, DUB, dUCH, EC 3.1.2.15, esterase, ubiquitin thiol-, hydrolase, ubiquitin carboxyl-terminal, hydrolase, ubiquitin carboxyl-terminal (Aplysia californica gene Ap-uch), Iso-T, isopeptidase, isopeptidase T, More, Neuron cytoplasmic protein 9.5, neuronal-specific protein gene product 9.5, OsUCH1, OsUCH2, OsUCH3, OsUCH4, OsUCH5, OTU-1, OTUB1, OTUB2, Otubain-1, Otubain-2, ovarian tumour 1, PA-700 associated isopeptidase, papain-like protease, PGP 9.5, PGP 9.5/UCHL1, PGP9.5, PGP9.5.1, PLP2, PLpro, Ub isopeptidase, ubiquitin C terminal hydrolase 1, ubiquitin C-terminal hydrolase, ubiquitin C-terminal hydrolase (Aplysia californica gene Ap-uch), ubiquitin C-terminal hydrolase 1, ubiquitin C-terminal hydrolase 37, ubiquitin C-terminal hydrolase 8, ubiquitin C-terminal hydrolase isoform L3, ubiquitin C-terminal hydrolase L-1, ubiquitin C-terminal hydrolase L1, ubiquitin C-terminal hydrolase L3, Ubiquitin C-terminal hydrolase UCH37, ubiquitin C-terminal hydrolase-1, ubiquitin C-terminal hydrolase-L1, ubiquitin C-terminal hydrolase-L3, ubiquitin C-terminal hydrolase-L5, ubiquitin C-terminal hydrorase-L1, ubiquitin carboxy terminal hydrolase-L1, ubiquitin carboxy terminal hydrolase-L3, ubiquitin carboxy-terminal hydrolase, ubiquitin carboxy-terminal hydrolase 1, ubiquitin carboxy-terminal hydrolase L1, ubiquitin carboxy-terminal hydrolase-L1, ubiquitin carboxy-terminal hydrolase-L3, ubiquitin carboxyhydrolase L3, ubiquitin carboxyl terminal esterase L1, ubiquitin carboxyl terminal hydrolase 1, ubiquitin carboxyl terminal hydrolase L1, ubiquitin carboxyl terminal hydrolase-L1, ubiquitin carboxyl-terminal hydrolase, ubiquitin carboxyl-terminal hydrolase 1, ubiquitin carboxyl-terminal hydrolase 44, ubiquitin carboxyl-terminal hydrolase isozyme L1, ubiquitin carboxyl-terminal hydrolase L-1, ubiquitin carboxyl-terminal hydrolase L1, ubiquitin carboxyl-terminal hydrolase l3, ubiquitin carboxyl-terminal hydrolase L5, ubiquitin carboxyl-terminal hydrolase-L1, ubiquitin carboxyl-terminal hydrolase-L5, ubiquitin carboxyterminal hydrolase L1, ubiquitin carboxyterminal hydrolase L3, ubiquitin carboxyterminal hydrolase-L1, ubiquitin hydrolase, ubiquitin hydrolase Uch-L1, ubiquitin hydrolase UCH-L3, ubiquitin isopeptidase, Ubiquitin thiolesterase, Ubiquitin thiolesterase L1, Ubiquitin thiolesterase L3, Ubiquitin thiolesterase L4, Ubiquitin thiolesterase L5, ubiquitin-C-terminal hydrolase L1, ubiquitin-carboxyl-terminal hydrolase PGP-9.5, ubiquitin-specific protease 44, UBPY, UCH, UCH L-1, UCH L1, UCH-1, UCH-8, UCH-L1, UCH-L2, UCH-L3, UCH-L4, UCH-L5, UCH37, UCH54, UCHL-1, UCHL-3, UCHL1, UCHL1/PGP 9.5, UCHL2, Uchl3, UCHL5, UCHL5N240, USP19, USP22, USP44, yeast ubiquitin hydrolase, YUH, YUH1
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3.4.19.12 ubiquitinyl hydrolase 1Advanced search results
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results (Engineering
Engineering on EC 3.4.19.12 - ubiquitinyl hydrolase 1
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C132A
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site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C152A
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site-directed mutagenesis, removal of the C152 thiol group by mutation renders the protein refractory to attack by 15-deoxy-DELTA12,14-prostaglandin J2
C152S
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binds to monoubiquitin in both 4-hydroxy-2-nonenal-treated cells and untreated cells
C201A
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site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C209S
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catalytically inactive, does not suppress NF-kappaB nuclear translocation and transcriptional activity by targeting the TNFR signaling pathway at the level of the IkappaB kinase complex or upstream from it. Does not suppress polyubiquitinated RIP1 and does not enhance the levels of monubiquinated or unmodified RIP1 as compared to the wild-type
C220A
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site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C220S
C335S
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site-directed mutagenesis of active site Cys335, unaltered substrate binding
C47A
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site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C88A
C90A
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site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C90S
C91A
catalytically inactive mutant, can still associate with the HCF-1 beta-propeller but cannot remove ubiquitin chains
C95S
D176A
mutant shows an increased interaction with CDK4 compared to wild-type
D176N
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site-directed mutagenesis, isozyme L1, 97.5% reduced activity compared to wild-type
D30A
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site-directed mutagenesis, the mutant enzyme shows highly reduced hydrolase and ubiquitin binding activity
D30K
D33A
ubiquitin affinity deficient mutant, diminishes the interaction of ubiquitin dimers with UCH-L3
D348A
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site-directed mutagenesis, inactive mutant, leads to accumulation of ubiquitin on endosomes and the concomitant stabilization of an ubiquinated form of the signal transducing adeptor molecule, STAM
DELTA148-190
deletion mutant containing amino acids 148-190 interacts with CDK4
DELTA148-223
deletion mutant containing amino acids 148-223 interacts with CDK4
DELTA160-190
deletion mutant containing amino acids 160-190 interacts with CDK4
DELTA160-223
deletion mutant containing amino acids 160-223 interacts with CDK4
DELTA188-223
deletion mutant containing amino acids 188-223 does not interact with CDK4
E174A
mutant shows an increased interaction with CDK4 compared to wild-type
E7A
point mutation in UCH-L1 is identified as the cause of early onset neurodegeneration in three siblings who appear normal at birth, but became blind at 5 years old and suffer progressive neurological dysfunction and cerebellar ataxia, and are unable to stand by the age of 30
F214A
the F214A mutant binds with approximately 60fold less affinity to ubiquitin compared to the wild-type UCH-L1, it shows highly reduced activity compared tot he wild-type enzyme
H161D
H161K
H161N
H161Q
H161Y
H165A
mutant shows an increased interaction with CDK4 compared to wild-type
H97N
H97Q
I93M
Q82A
kcat and Km can not be determined individually because, even at concentrations of ubiquitin 7-amido-4-methylcoumarin as high as 12 microM, the Michaelis-Menten plot is still rising linearly with substrate concentration, not reaching the plateau that is diagnostic of saturation
Q84A
Km (ubiquitin 7-amido-4-methylcoumarin) increased compared to wild-type, kcat (ubiquitin 7-amido-4-methylcoumarin) decreased
Q89A
Km (ubiquitin 7-amido-4-methylcoumarin) increased compared to wild-type, kcat (ubiquitin 7-amido-4-methylcoumarin) decreased
R63A
S18Y
C61S
loss of deubiquitinating enzyme activity, does not decrease viral ribonucleotide reductase activity
C14A
mutant of ataxin-3 carrying six consecutive glutamines, does not undergo proteolytic fragmentation on incubation at room temperature
C14A/H119L
mutant of ataxin-3 carrying six consecutive glutamines, does not undergo proteolytic fragmentation on incubation at room temperature
C90S
D33A
loses the affinity to interact with ubiquitin dimers. D33A mutant expressing cells do not show any signs of free ubiquitin dimers accumulation
H119L
mutant of ataxin-3 carrying six consecutive glutamines, does not undergo proteolytic fragmentation on incubation at room temperature
S18Y
mutant of the Uch-L1 protein fused to the transduction domain of HIV-transactivator protein, has similar hydrolase activity than the unmutated fusion protein
C545A
catalytically inactive USP19 mutant, destabilizes ubiquitin ligase KPC1
C571S
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is unable to maintain normal ubiquitin levels. In doa4delta cells expressing C571S, CPS is missorted to the limiting membrane of the vacuole
W782R
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is solely cytoplasmic, defect in endosomal localization, Bro1-Doa4 interaction is disrupted
additional information
C220S
sie-directed mutagenesis, structure analysis in comparison to the wild-type enzyme
C220S
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the mutant has in vitro ubiquitin hydrolase activity comparable to the wild-type protein
C88A
mutant structure determination and comparison to the wild-type enzyme
C90S
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site-directed mutagenesis, the mutant enzyme lacks C-terminal hydrolase activity but retains ubiquitin binding activity, the mutant shows similar physiological effects in recombinant transfected cells as the wild-type enzyme, overview
C90S
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site-directed mutagenesis, the mutant enzyme shows no hydrolase and ubiquitin binding activity
C90S
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increases cellular monoubiquitin levels, 30% is monoubiquitinated, whereas only 5-10% of wild-type is monoubiquitinated
C90S
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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
C90S
mutant shows same interaction pattern as wild-type. Mutant shows no hydrolase activity
C95S
active site mutant of UCH-L3, enhances the interaction of ubiquitin dimers with UCH-L3
C95S
active-site mutant. In highly metastatic prostate PC-3 cells, presence of UCH-L3 inhibits the cell migration and invasion but mutant C95S has no effects
D30K
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deficient in ubiquitin binding, is unable to increase cellular monoubiquitin levels
D30K
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lacks hydrolase activity and binding affinity for ubiquitin, has no effect on the interaction of UCH-L1 and tubulin
H161D
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30% is monoubiquitinated, whereas only 5-10% of wild-type is monoubiquitinated
I93M
site-directed mutagenesis, isozyme L1, mutant shows increased risk for Parkinson's disease, 45.6% enzyme activity compared to wild-type
I93M
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the mutation is linked to familial Parkinson's disease, the mutant dimer conformation is different from the wild-type enzyme deforming the globular form
I93M
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wild-type enzyme, mutant I93M (linked to familial Parkinson's disease) and S18Y (linked to reduced risk of Parkinson's disease) are all self-assembled dimers. The configuration of these dimers are quite different. The wild-type is a rotating ellipsoidal
I93M
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missense mutation in the UCH-L1 gene in a German family with a familial case of Parkinson´s disease, decreases hydrolytic activity
I93M
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mutation in UCH-L1 associated with familial Parkinsons disease, shows increased insolubility and elevated interactions with multiple proteins, promotes tubulin polymerization
I93M
naturally occuring mutation of Uch-L1 involved in the Parkinson's disease
I93M
the mutant is a Parkinson disease-associated variant of UCH-L1, structure determination and comparison
I93M
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the UCH-L1 mutant is associated with Parkinson's disease. The mutant enzyme protein is well-folded, structurally similar to the wild-type protein, and aggregates upon conjugation by cyclopentenone prostaglandins
I93M
mutant shows a stronger interaction with CDK1, CDK4 and CDK5 compared to wild-type. Hydrolase and ligase activity are reduced in mutant compared to wild-type
I93M
transgenic mice expressing the human I93M gene are born normally and are fertile. They do display aberrant dopaminergic neuron morphology in the substantia nigra at 12 weeks, consistent with degeneration and a loss of dopaminergic neurons at 20 weeks. The I93M mutation decreases UCHL1 solubility, corresponding with an apparent loss of alpha-helical structure seen via circular dichroism, and a reduction in hydrolytic activity by approximately 50%
R63A
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displays increased interactions with tubulin, causes a decrease in tubulin polymerization
R63A
mutant shows an increased interaction with CDK4 compared to wild-type
S18Y
site-directed mutagenesis, isozyme L1, mutant shows decreased risk for Parkinson's disease, 112.6% enzyme activity compared to wild-type
S18Y
sie-directed mutagenesis, structure analysis in comparison to the wild-type enzyme
S18Y
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the mutation is linked to reduced risk of Parkinson's disease, the mutant dimer conformation is different from the wild-type enzyme promoting the globularitiy
S18Y
variant of the ubiquitin carboxy-terminal hydrolase L1 gene is associated with Parkinson's disease
S18Y
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wild-type enzyme, mutant I93M (linked to familial Parkinson's disease) and S18Y (linked to reduced risk of Parkinson's disease) are all self-assembled dimers. The configuration of these dimers are quite different. The wild-type is a rotating ellipsoidal
S18Y
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reduces risk of Parkinson´s disease. The protective role reflects a restricted mechanism only applied in sporadic Parkinson´s disease patients. The mutant is less likely to form dimers. Mutation also present in patients with earlier/later onset of Huntington´s disease
S18Y
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UCH-L1 mutant with protective effect, is significantly inversely associated with sporadic Parkinson's disease in Sweden and with a low age of onset (less-than-or-equal 50 years)
S18Y
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a naturally occuring polymorph, replacing the weak CKAA farnesylation motif with the optimal CVIM motif (S18Y/CVIM UCH-L1) leads to significantly increased accumulation of alpha-synuclein relative to S18Y
S18Y
a naturally occuring UCHL1 polymorphism, genotyping and allele frequencies in healthy persons and Alzheimer's disease patients of Swedish population, overview. The UCHL1 S18Y polymorphism does not show a protective effect against Alzheimer's disease
S18Y
naturally occuring mutation of Uch-L1 involved in the Huntington's disease
S18Y
the mutant is a Parkinson disease-associated variant of UCH-L1, structure determination and comparison
S18Y
mutation in UCH-L1 exerts a neuroprotective effect against Parkinson's disease. The S18Y mutant is initially reported as a polymorphism, present in approximately 46-61% of those studied in Asian populations, and 16-24% in European Caucasian populations who show a reduced risk of Parkinson's disease
C90S
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inhibits the protective action of endogenous UCH-L1. C90S-fusion protein does not rescue the deficit in long term potentiation induced by Abeta, acts as a dominant negative mutant, causes a deficit in long term potentiation in the absence of oligomeric Abeta
C90S
mutant of the Uch-L1 protein fused to the transduction domain of HIV-transactivator protein, has little activity
additional information
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gene cyk-3 null mutants are lethal, mutants fail to polarize the actin cytoskeleton, to segregate germline determinants, to assemble an intact cleavage furrow, and are intrinsically defective in osmotic regulation and cytokinesis, the latter defect can be partially rescued by providing osmotic support
additional information
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enzyme downregulation in HeLa cells by siRNA, enzyme inhibition influences the degradation of the EGF receptor
additional information
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silencing of UCH-L1 by expression of siRNA in H1299 cells
additional information
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fusion protein UbVV/L8A-UCH-L1 contains an L8A mutation in the ubiquitin moiety. Efficiently binds ubiquitin, increases cellular monoubiquitin levels
additional information
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model simulations indicate that mutation in UCH-L1 causes more rapid accumulation and aggregation of alpha-synuclein than occurs in the sporadic forms of Parkinson´s disease
additional information
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a catalytic mutant has no effect on proliferation of a UCH-L1 negative EBV transformed lymphoblastoid cell line and on inhibiting cell adhesion
additional information
a catalytic mutant has no effect on proliferation of a UCH-L1 negative EBV transformed lymphoblastoid cell line and on inhibiting cell adhesion
additional information
wild type Bap1 and the NHNY/AAAA mutant display robust activity. Mutation of the NHNY sequence abolishes the association with HCF-1 but does not alter the intrinsic enzymatic activity of the ubiquitin C-terminal hydrolase domain
additional information
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gene rs5030732, genotyping and UCHL1 polymorphisms, expression analysis, overview
additional information
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knockdown of UCH-L1 by RNAi inhibits the proliferation of Burkitt's lymphoma cells in suspension and semisolid agar and activates strong LFA-1-dependent homotypic adhesion. Recombinant expression of a catalytically active UCH-L1 promotes the proliferation of a UCH-L1-negative EBV transformed lymphoblastoid cell line, LCL, and inhibited cell adhesion, whereas a catalytic mutant has no effect
additional information
knockdown of UCH-L1 by RNAi inhibits the proliferation of Burkitt's lymphoma cells in suspension and semisolid agar and activates strong LFA-1-dependent homotypic adhesion. Recombinant expression of a catalytically active UCH-L1 promotes the proliferation of a UCH-L1-negative EBV transformed lymphoblastoid cell line, LCL, and inhibited cell adhesion, whereas a catalytic mutant has no effect
additional information
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UCH L1 silencing with siRNAs leads to accumulation of beta-catenin
additional information
C-terminal deletion of the final four Rrsidues of isoform UCH-L1 (CKAA) leads to increased membrane association and decreased solubility. Deletion disrupts the protein secondary structure, leads to abrogation of substrate binding, increased cell death, and an abnormal intracellular distribution
additional information
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gad mouse null mutants of isozyme L1 show reduced monoubiquitin level in neurons, overexpression of the isozyme L1 leads to an increased monoubiquitin level
additional information
gad mouse null mutants of isozyme L1 show reduced monoubiquitin level in neurons, overexpression of the isozyme L1 leads to an increased monoubiquitin level
additional information
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gad, i.e. gracile axonal dystrophy, mice testis lack isozyme UCH-L1
additional information
gad, i.e. gracile axonal dystrophy, mice testis lack isozyme UCH-L1
additional information
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gad, i.e. gracile axonal dystrophy, mice testis lack isozyme UCH-L1 and are resistant to cryptorchid stress-related injury, the show reduced ubiquitin levels, uchl3 knockout mice show profound testicular atrophy and apoptotic germ cell loss after cryptorchid injury, but unaltered ubiquitin levels compared to wild-type mice, testicular phenotype of mutant mice, overview
additional information
gad, i.e. gracile axonal dystrophy, mice testis lack isozyme UCH-L1 and are resistant to cryptorchid stress-related injury, the show reduced ubiquitin levels, uchl3 knockout mice show profound testicular atrophy and apoptotic germ cell loss after cryptorchid injury, but unaltered ubiquitin levels compared to wild-type mice, testicular phenotype of mutant mice, overview
additional information
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UCH-L1-deficient gad mice show progressively decreasing spermatogonial stem cell proliferation
additional information
UCH-L1-deficient gad mice show progressively decreasing spermatogonial stem cell proliferation
additional information
UCH-L1-deficient gad mice show progressively decreasing spermatogonial stem cell proliferation
additional information
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in gracile axonal dystrophy mice with a spontaneous deletion in the Uch-l1 gene, memory in passive avoidance learning, exploratory behaviour and hippocampal CA1 long-term potentiation are reduced, whereas cyclic AMP response element binding protein phosphorylation is altered
additional information
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mutant of the Uch-L1 protein fused to the transduction domain of HIV-transactivator protein with a 57 amino acid deletion (130-186) including the H161 site, is inactive
additional information
mutant of the Uch-L1 protein fused to the transduction domain of HIV-transactivator protein with a 57 amino acid deletion (130-186) including the H161 site, is inactive
additional information
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UCH-L1-deficient ova of gad female mice have a significantly increased rate of polyspermy in in vitro fertilization assays, although the rate of fertilization does not differ significantly from wild-type mice. Litter size of gad female mice is significantly reduced compared with wild-type mice
additional information
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Uchl3 deletion mutant displays retinal degeneration, muscular degeneration, and mild growth retardation. No significant morphological abnormalities during retinal development, prominent retinal degeneration becomes manifested after 3 weeks of age associated with photoreceptor cell apoptosis. Decreased area of mitochondrial cristae and vacuolar changes in the degenerated inner segment. Loss of UCH-L3 leads to mitochondrial oxidative stress-related photoreceptor cell apoptosis in a caspase-independent manner
additional information
mice with a genetic deficiency of CYLD have aberrant osteoclast differentiation and develop severe osteoporosis. Cultured osteoclast precursors derived from CYLD-deficient mice are hyperresponsive to RANKL-induced differentiation and produce more and larger osteoclasts than do controls upon stimulation
additional information
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construction of UCH-L1 knockout mice by targeted deletion of the UCH-L1 gene, in the absence of UCH-L1, synaptic transmission at the neuromuscular junctions is markedly impaired and it leads to ultrastructural defects of presynaptic nerve terminals at the neuromuscular junctions. UCH-L1 null mutation leads to progressive paralysis and premature death in mice, external phenotype and survival rate, overview
additional information
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deficiency of UCH-L1 of gad mice, i.e. UCH-L1-deficient mutant gracile axonal dystrophy mice, leads to vulnerability to lipid peroxidation both in vivo and in vitro. When neurons from dorsal root ganglions are cultured in the vitamin E-free medium, cell death is increased in the neurons of gad mice. Oxidative stress, especially lipid peroxidation, augments the neuronal cell death of gad mice
additional information
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embryonic fibroblasts from Uchl3-/- mice show an accumulation of polyubiquitinated proteins, the polyubiquitinated protein accumulation in Uchl3-/- embryonic fibroblasts is attenuated by the exogenous expression of wild-type, but not hydrolase activity deficient UCH-L3, overview
additional information
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enzyme downregulation by RNAi. UCH L1 suppression inhibits cell proliferation and migration and induces G0/G1 arrest and apoptosis
additional information
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gad, i.e. gracile axonal dystrophy, mice are analogous to a null mutants of UCH-L1, they display the dying-back-type of axonal degeneration in sensory neurons. The level of mono-ubiquitin is decreased in neurons, especially in axons of the sciatic nerve, in gad mice
additional information
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in UCH-L3 knockout mice, the levels of both Nedd8 and the apoptotic protein p53 and Bax are elevated upon cryptorchid injury, the accumulation of Nedd8-conjugated proteins in UCH-L3 knockout mice contributed to profound germ cell loss via apoptosis
additional information
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isolated loss of UCHL1/PGP 9.5 function, seen in the gracile axonal dystrophy, GAD, mouse due to a deletion in its gene results in a failure of axonal transport and a dying-back axonopathy beginning distally in long axons, the characteristic lesion in the GAD mouse is axonal dystrophy, gad mouse neuronal function phenotype, detailed overview
additional information
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melanopsin-Ir is significantly reduced in the retina of gracile axonal dystrophy, i.e. gad, mice with a spontaneous deletion in the Uch-l1 gene, resulting in impairment of circadian light perception in gad mice, overview. In constant darkness, gad mice show circadian rhythms in locomotor activity, indicating the integrity of the endogenous circadian rhythm generator. In addition, gad mice show increased locomotor activity in the light period when kept in a standard photoperiod and entrainment to phase shifts is significantly slower than in wild-type mice
additional information
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UCHL1-deficient gracile axonal dystrophy, i.e. gad, mice are spontaneous mutants with an in-frame deletion in exons 7 and 8 of Uch-l1. Deletion of the gene encoding UCH-L1 leads to a reduction in memory in passive avoidance learning, exploratory behaviour and synaptic plasticity in mice, overview
additional information
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Uchl3-deficient mice show reduced content of white adipose tissue and reduced adipogenesis due to attenuated insulin responses, ectopic expression of wild-type UCH-L3 restores the phosphorylation of insulin/IGF-I receptor and adipocyte differentiation in UCH-L3-/- mouse embyronic fibroblasts, overview. Hydrolase-deficient UCH-L3 does not enhance insulin signalling and expression of gluta4, fabp4, and adiponectin, resulting in impaired formation of large lipid droplets
additional information
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in gracile axonal dystrophy mice with a spontaneous deletion in the Uch-l1 gene, memory in passive avoidance learning, exploratory behaviour and hippocampal CA1 long-term potentiation are reduced, whereas cyclic AMP response element binding protein phosphorylation is altered
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additional information
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UCHL1-deficient gracile axonal dystrophy, i.e. gad, mice are spontaneous mutants with an in-frame deletion in exons 7 and 8 of Uch-l1. Deletion of the gene encoding UCH-L1 leads to a reduction in memory in passive avoidance learning, exploratory behaviour and synaptic plasticity in mice, overview
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additional information
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deficiency of UCH-L1 of gad mice, i.e. UCH-L1-deficient mutant gracile axonal dystrophy mice, leads to vulnerability to lipid peroxidation both in vivo and in vitro. When neurons from dorsal root ganglions are cultured in the vitamin E-free medium, cell death is increased in the neurons of gad mice. Oxidative stress, especially lipid peroxidation, augments the neuronal cell death of gad mice
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additional information
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enzyme deficient strain accumulates membrane-bound ubiquitin-conjugated Fur4p
additional information
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multivesicular body sorting of Gap1 is defective in a doa4delta mutant, which is not suppressed by restoring the ubiquitin pool. In the doa4delta ypt6delta strain, the pool of monomeric ubiquitin is as reduced as in the single doa4delta mutant
