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Information on EC 3.4.19.12 - ubiquitinyl hydrolase 1 and Organism(s) Mus musculus
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3.4.19.12 ubiquitinyl hydrolase 1Specify your search results
Word Map
- 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
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
uch-l1, uchl1, ataxin-3, deubiquitinating enzyme, pgp 9.5, usp22, pgp9.5, plpro, otub1, isopeptidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AD-019
-
-
-
-
CGI-70
-
-
-
-
esterase, ubiquitin thiol-
-
-
-
-
hydrolase, ubiquitin carboxyl-terminal
-
-
-
-
hydrolase, ubiquitin carboxyl-terminal (Aplysia californica gene Ap-uch)
-
-
-
-
isopeptidase
-
-
-
-
isopeptidase T
-
-
-
-
Neuron cytoplasmic protein 9.5
-
-
-
-
PGP 9.5
PGP9.5
ubiquitin C-terminal hydrolase
ubiquitin C-terminal hydrolase (Aplysia californica gene Ap-uch)
-
-
-
-
ubiquitin C-terminal hydrolase L1
Ubiquitin C-terminal hydrolase UCH37
-
-
-
-
ubiquitin carboxy terminal hydrolase-L1
ubiquitin carboxy-terminal hydrolase
-
-
-
-
ubiquitin carboxy-terminal hydrolase L1
ubiquitin carboxyl-terminal hydrolase
-
-
-
-
ubiquitin carboxyl-terminal hydrolase L1
Ubiquitin thiolesterase
Ubiquitin thiolesterase L1
-
-
-
-
Ubiquitin thiolesterase L3
-
-
-
-
Ubiquitin thiolesterase L4
-
-
-
-
Ubiquitin thiolesterase L5
-
-
-
-
ubiquitin-carboxyl-terminal hydrolase PGP-9.5
-
-
-
-
UCH-1
-
-
-
-
UCH-L1
UCH-L2
-
-
-
-
UCH-L3
UCH-L4
-
-
-
-
UCH-L5
-
-
-
-
UCHL1
Uchl3
yeast ubiquitin hydrolase
-
-
-
-
YUH1
-
-
-
-
additional information
PGP 9.5
-
-
-
-
PGP9.5
-
-
-
-
ubiquitin C-terminal hydrolase
-
-
-
-
Ubiquitin thiolesterase
-
-
-
-
UCH-L1
-
-
-
-
UCH-L1
-
-
UCH-L1
-
UCH-L3
-
-
-
-
additional information
-
the enzymes belong to the deubiquitinating enzymes of the protease superfamily, and are cysteine peptidases of subfamily ubiquitin C-terminal hydrolases, UCHs, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
189642-63-5
-
86480-67-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ubiquitinyl-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
recombinant wild-type isozyme L1
-
-
?
additional information
?
-
-
isozyme L1 associates and colocalizes with monoubiquitin and elongates ubiquitin half-life, null mutants show a reduced monoubiquitin level in neurons, while overexpression causes an increase in monoubiquitin level, mechanism
-
-
?
additional information
?
-
isozyme L1 associates and colocalizes with monoubiquitin and elongates ubiquitin half-life, null mutants show a reduced monoubiquitin level in neurons, while overexpression causes an increase in monoubiquitin level, mechanism
-
-
?
additional information
?
-
-
the closely related isozymes UCH-L1 and UCH-L3 function as reciprocal modulators of germ cell apoptosis in cryptorchid testis
-
-
?
additional information
?
-
the closely related isozymes UCH-L1 and UCH-L3 function as reciprocal modulators of germ cell apoptosis in cryptorchid testis
-
-
?
additional information
?
-
-
the enzyme is essential for the early apoptotic wave of germinal cells and for sperm quality control during spermatogenesis
-
-
?
additional information
?
-
the enzyme is essential for the early apoptotic wave of germinal cells and for sperm quality control during spermatogenesis
-
-
?
additional information
?
-
the enzyme is involved in spermatogenesis
-
-
?
additional information
?
-
the enzyme is involved in spermatogenesis
-
-
?
additional information
?
-
-
the enzyme plays a role in neural cell apoptosis induced by ischemic retinal injury, e.g. in mice with gracile axonal dystrophy, overview
-
-
?
additional information
?
-
-
UCH-L1 functions in sperm quality control during epididymal maturation
-
-
?
additional information
?
-
UCH-L1 functions in sperm quality control during epididymal maturation
-
-
?
additional information
?
-
-
UCH-L1 regulates the morphology of neural progenitor cells and modulates their differentiation, it mediates and enhances neurogenesis in the embryonic brain
-
-
?
additional information
?
-
UCH-L1 regulates the morphology of neural progenitor cells and modulates their differentiation, it mediates and enhances neurogenesis in the embryonic brain
-
-
?
additional information
?
-
-
Uchl3 is involved in working memory, and plays a role in learning, memory, and synaptic plasticity, uchl3-deficient mice are impaired in acquisition of hippocampus-dependent tasks requiring learning and remembering, but show wild-type long-term memory for context and cued fear conditioning, uchl3-/- mice exhibit wild-type synaptic transmission and plasticity in hippocampal area CA1, overview
-
-
?
additional information
?
-
Uchl3 is involved in working memory, and plays a role in learning, memory, and synaptic plasticity, uchl3-deficient mice are impaired in acquisition of hippocampus-dependent tasks requiring learning and remembering, but show wild-type long-term memory for context and cued fear conditioning, uchl3-/- mice exhibit wild-type synaptic transmission and plasticity in hippocampal area CA1, overview
-
-
?
additional information
?
-
the enzyme shows de-ubiquinating activity
-
-
?
additional information
?
-
-
affects ubiquitin degradation and alters its metabolism. UCH-L1-mediated increases in ubiquitin levels are a function of UCH L1 affinity for ubiquitin rather than hydrolase activity. The enzyme insures ubiquitin stability within neurons
-
-
?
additional information
?
-
affects ubiquitin degradation and alters its metabolism. UCH-L1-mediated increases in ubiquitin levels are a function of UCH L1 affinity for ubiquitin rather than hydrolase activity. The enzyme insures ubiquitin stability within neurons
-
-
?
additional information
?
-
gracile axonal dystrophy is a syndrome that emanates from dysfunctional ubiquitin carboxyl-terminal hydrolase L-1
-
-
?
additional information
?
-
-
gracile axonal dystrophy is a syndrome that emanates from dysfunctional ubiquitin carboxyl-terminal hydrolase L-1
-
-
?
additional information
?
-
mice overexpressing EF1alpha promoter-driven UCH-L1 in the testis are sterile due to a block during spermatogenesis at an early stage of meiosis. Overexpression of UCH-L1 affects spermatogenesis during meiosis and, in particular, induces apoptosis in primary spermatocytes. UCH-L-1 plays a specific role in the process of mitotic proliferation and differentiation of spermatogonial stem cells during spermatogenesis
-
-
?
additional information
?
-
-
mice overexpressing EF1alpha promoter-driven UCH-L1 in the testis are sterile due to a block during spermatogenesis at an early stage of meiosis. Overexpression of UCH-L1 affects spermatogenesis during meiosis and, in particular, induces apoptosis in primary spermatocytes. UCH-L-1 plays a specific role in the process of mitotic proliferation and differentiation of spermatogonial stem cells during spermatogenesis
-
-
?
additional information
?
-
the enzyme may play a significant role in implantation and placental development, and differentiation of embryonic ectoderm
-
-
?
additional information
?
-
-
the enzyme may play a significant role in implantation and placental development, and differentiation of embryonic ectoderm
-
-
?
additional information
?
-
-
ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory
-
-
?
additional information
?
-
ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory
-
-
?
additional information
?
-
-
ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory
-
-
?
additional information
?
-
ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory
-
-
?
additional information
?
-
UCH-L1 may play an important role in neurodegeneration of amyloid lateral sclerosis
-
-
?
additional information
?
-
-
UCH-L1 may play an important role in neurodegeneration of amyloid lateral sclerosis
-
-
?
additional information
?
-
-
UCHL1 is required for normal spermatogenesis and sperm quality control. UCHL1-dependent apoptosis is important in spermatogonial cell and sperm maturation
-
-
?
additional information
?
-
UCHL1 is required for normal spermatogenesis and sperm quality control. UCHL1-dependent apoptosis is important in spermatogonial cell and sperm maturation
-
-
?
additional information
?
-
AT-3 carrying six consecutive glutamines undergoes fragmentation upon incubation at room temperature. Cys14 and His119 are involved in the autolytic activity
-
-
?
additional information
?
-
CYLD negatively regulates RANK signaling by inhibiting TRAF6 ubiquitination and activation of downstream signaling events. CYLD interacts physically with the signaling adaptor p62 and thereby is recruited to TRAF6. CYLD is a crucial negative regulator of osteoclastogenesis and may be involved in the p62/TRAF6 signaling axis
-
-
?
additional information
?
-
is overexpressed in alpha-tocopherol deficient mice
-
-
?
additional information
?
-
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L3, in vivo
-
-
?
additional information
?
-
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L3, in vivo
-
-
?
additional information
?
-
UCH-L1 expression levels show a time-dependent upregulation in mice ischemia-reperfusion injury condition. Germ cell apoptosis triggers downregulation of UCH-L1 at both mRNA and protein levels, thus, ubiquitination level is impaired. Eevidences of UCH-L1/ubiquitination signaling to the testis ischemia-reperfusion injury in vivo
-
-
?
additional information
?
-
-
UCH-L1 expression levels show a time-dependent upregulation in mice ischemia-reperfusion injury condition. Germ cell apoptosis triggers downregulation of UCH-L1 at both mRNA and protein levels, thus, ubiquitination level is impaired. Eevidences of UCH-L1/ubiquitination signaling to the testis ischemia-reperfusion injury in vivo
-
-
?
additional information
?
-
UCH-L3 does not function to hydrolyze free ubiquitin dimers
-
-
?
additional information
?
-
UCH-L3 does not function to hydrolyze free ubiquitin dimers
-
-
?
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme, it binds to and stabilize mono-ubiquitin in neurons
-
-
?
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme, it binds to and stabilizes mono-ubiquitin in neurons
-
-
?
additional information
?
-
-
UCH-L3 is capable of cleaving Ub from the Ub chains in vitro, and UCH-L3 directly hydrolyses polyubiquitinated proteins. Wild-type, but not its hydrolase activity or ubiquitin binding activity deficient, UCH-L3 shows the ability to cleave ubiquitin from polyubiquitinated lysozyme in vitro, which is no substrate of UCH-L1
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
isozyme L1 associates and colocalizes with monoubiquitin and elongates ubiquitin half-life, null mutants show a reduced monoubiquitin level in neurons, while overexpression causes an increase in monoubiquitin level, mechanism
-
-
?
additional information
?
-
isozyme L1 associates and colocalizes with monoubiquitin and elongates ubiquitin half-life, null mutants show a reduced monoubiquitin level in neurons, while overexpression causes an increase in monoubiquitin level, mechanism
-
-
?
additional information
?
-
-
the closely related isozymes UCH-L1 and UCH-L3 function as reciprocal modulators of germ cell apoptosis in cryptorchid testis
-
-
?
additional information
?
-
the closely related isozymes UCH-L1 and UCH-L3 function as reciprocal modulators of germ cell apoptosis in cryptorchid testis
-
-
?
additional information
?
-
-
the enzyme is essential for the early apoptotic wave of germinal cells and for sperm quality control during spermatogenesis
-
-
?
additional information
?
-
the enzyme is essential for the early apoptotic wave of germinal cells and for sperm quality control during spermatogenesis
-
-
?
additional information
?
-
the enzyme is involved in spermatogenesis
-
-
?
additional information
?
-
the enzyme is involved in spermatogenesis
-
-
?
additional information
?
-
-
the enzyme plays a role in neural cell apoptosis induced by ischemic retinal injury, e.g. in mice with gracile axonal dystrophy, overview
-
-
?
additional information
?
-
-
UCH-L1 functions in sperm quality control during epididymal maturation
-
-
?
additional information
?
-
UCH-L1 functions in sperm quality control during epididymal maturation
-
-
?
additional information
?
-
-
UCH-L1 regulates the morphology of neural progenitor cells and modulates their differentiation, it mediates and enhances neurogenesis in the embryonic brain
-
-
?
additional information
?
-
UCH-L1 regulates the morphology of neural progenitor cells and modulates their differentiation, it mediates and enhances neurogenesis in the embryonic brain
-
-
?
additional information
?
-
-
Uchl3 is involved in working memory, and plays a role in learning, memory, and synaptic plasticity, uchl3-deficient mice are impaired in acquisition of hippocampus-dependent tasks requiring learning and remembering, but show wild-type long-term memory for context and cued fear conditioning, uchl3-/- mice exhibit wild-type synaptic transmission and plasticity in hippocampal area CA1, overview
-
-
?
additional information
?
-
Uchl3 is involved in working memory, and plays a role in learning, memory, and synaptic plasticity, uchl3-deficient mice are impaired in acquisition of hippocampus-dependent tasks requiring learning and remembering, but show wild-type long-term memory for context and cued fear conditioning, uchl3-/- mice exhibit wild-type synaptic transmission and plasticity in hippocampal area CA1, overview
-
-
?
additional information
?
-
-
affects ubiquitin degradation and alters its metabolism. UCH-L1-mediated increases in ubiquitin levels are a function of UCH L1 affinity for ubiquitin rather than hydrolase activity. The enzyme insures ubiquitin stability within neurons
-
-
?
additional information
?
-
affects ubiquitin degradation and alters its metabolism. UCH-L1-mediated increases in ubiquitin levels are a function of UCH L1 affinity for ubiquitin rather than hydrolase activity. The enzyme insures ubiquitin stability within neurons
-
-
?
additional information
?
-
gracile axonal dystrophy is a syndrome that emanates from dysfunctional ubiquitin carboxyl-terminal hydrolase L-1
-
-
?
additional information
?
-
-
gracile axonal dystrophy is a syndrome that emanates from dysfunctional ubiquitin carboxyl-terminal hydrolase L-1
-
-
?
additional information
?
-
mice overexpressing EF1alpha promoter-driven UCH-L1 in the testis are sterile due to a block during spermatogenesis at an early stage of meiosis. Overexpression of UCH-L1 affects spermatogenesis during meiosis and, in particular, induces apoptosis in primary spermatocytes. UCH-L-1 plays a specific role in the process of mitotic proliferation and differentiation of spermatogonial stem cells during spermatogenesis
-
-
?
additional information
?
-
-
mice overexpressing EF1alpha promoter-driven UCH-L1 in the testis are sterile due to a block during spermatogenesis at an early stage of meiosis. Overexpression of UCH-L1 affects spermatogenesis during meiosis and, in particular, induces apoptosis in primary spermatocytes. UCH-L-1 plays a specific role in the process of mitotic proliferation and differentiation of spermatogonial stem cells during spermatogenesis
-
-
?
additional information
?
-
the enzyme may play a significant role in implantation and placental development, and differentiation of embryonic ectoderm
-
-
?
additional information
?
-
-
the enzyme may play a significant role in implantation and placental development, and differentiation of embryonic ectoderm
-
-
?
additional information
?
-
-
ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory
-
-
?
additional information
?
-
ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory
-
-
?
additional information
?
-
-
ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory
-
-
?
additional information
?
-
ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory
-
-
?
additional information
?
-
UCH-L1 may play an important role in neurodegeneration of amyloid lateral sclerosis
-
-
?
additional information
?
-
-
UCH-L1 may play an important role in neurodegeneration of amyloid lateral sclerosis
-
-
?
additional information
?
-
-
UCHL1 is required for normal spermatogenesis and sperm quality control. UCHL1-dependent apoptosis is important in spermatogonial cell and sperm maturation
-
-
?
additional information
?
-
UCHL1 is required for normal spermatogenesis and sperm quality control. UCHL1-dependent apoptosis is important in spermatogonial cell and sperm maturation
-
-
?
additional information
?
-
CYLD negatively regulates RANK signaling by inhibiting TRAF6 ubiquitination and activation of downstream signaling events. CYLD interacts physically with the signaling adaptor p62 and thereby is recruited to TRAF6. CYLD is a crucial negative regulator of osteoclastogenesis and may be involved in the p62/TRAF6 signaling axis
-
-
?
additional information
?
-
is overexpressed in alpha-tocopherol deficient mice
-
-
?
additional information
?
-
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L3, in vivo
-
-
?
additional information
?
-
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L3, in vivo
-
-
?
additional information
?
-
UCH-L1 expression levels show a time-dependent upregulation in mice ischemia-reperfusion injury condition. Germ cell apoptosis triggers downregulation of UCH-L1 at both mRNA and protein levels, thus, ubiquitination level is impaired. Eevidences of UCH-L1/ubiquitination signaling to the testis ischemia-reperfusion injury in vivo
-
-
?
additional information
?
-
-
UCH-L1 expression levels show a time-dependent upregulation in mice ischemia-reperfusion injury condition. Germ cell apoptosis triggers downregulation of UCH-L1 at both mRNA and protein levels, thus, ubiquitination level is impaired. Eevidences of UCH-L1/ubiquitination signaling to the testis ischemia-reperfusion injury in vivo
-
-
?
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme, it binds to and stabilize mono-ubiquitin in neurons
-
-
?
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme, it binds to and stabilizes mono-ubiquitin in neurons
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-amino-2-(cyclohexylcarbonyl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(2-methoxyphenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(4-chlorophenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(4-methylphenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(4-tert-butylphenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(naphthalen-1-yloxy)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(naphthalen-2-yloxy)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-6-oxo-2-[[4-(trifluoromethyl)phenyl]carbonyl]-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
4,5,6,7-tetrachloroindan-1,3-dione
-
UCH-L3 inhibition reduces epithelial sodium channel currents, decreases apical membrane epithelial sodium channel expression and increases epithelial sodium channel ubiquitination at the apical surface
LDN-57444
reversible, competitive, active site-directed isatin oxime, 70% inhibition with 0.005 mM
oligomeric Abeta
-
treatment of hippocampal slices produces a deficit in long term potentiation. Effect can be reversed by coadministering a recombinant UCH-L1 protein
-
siRNA
-
knockdown of UCH-L3 leads to a decrease of epithelial sodium channel currents
-
tosyl-L-phenylalanine chloromethyl ketone
inhibits fragmentation of AT-3 carrying six consecutive glutamines
additional information
-
class of 3-amino-2-keto-7H-thieno[2,3-b]pyridin-6-one derivatives are moderately potent UCH-L1 inhibitors. Carboxylate at the 5-position and the 6-pyridinone ring are necessary for inhibitory activity. Inhibitory activity is dependent on the nature of the ketone substituent at the 2-position, with 4-Me-Ph and 2-naphthyl being best. Compounds are uncompetitive inhibitors of UCH-L1, binding only to the Michaelis-complex and not to free enzyme. Active compounds are selective for UCH-L1, exhibiting no inhibition of other cysteine hydrolases or cytotoxicity in serum starved N2A cells. Not inhibited by compound 9, 17, 19, 22, 24, 27, 28, 29, 30, 32 and 33
-
additional information
-
treatment of hippocampal slices with a small-molecule inhibitor of UCH-L1 enzymatic activity produces a deficit in long term potentiation
-
additional information
EDTA, HgCl2 and p-chloro-mecuribenzoate do not inhibit fragmentation of AT-3 carrying six consecutive glutamines
-
additional information
magnitude of induction of uchl1 is lower in asymptomatic, 8-month old, alpha-tocopherol transfer protein deficient mice and in 8-month old mice fed an alpha-tocopherol-depleted diet
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DTT
-
required, hydrolase activity of UCH-L1 in vitro is decreased when reducing dithiothreitol is omitted from the reaction buffer
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00016
ubiquitin-7-amido-4-methylcoumarin
recombinant wild-type isozyme L1, pH 7.5, 25°C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.02
ubiquitin-7-amido-4-methylcoumarin
recombinant wild-type isozyme L1, pH 7.5, 25°C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
3-amino-2-(cyclohexylcarbonyl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
0.0053
3-amino-2-[(2-methoxyphenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
0.0012
3-amino-2-[(4-chlorophenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
0.00091
3-amino-2-[(4-methylphenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
0.0014
3-amino-2-[(4-tert-butylphenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
0.0015
3-amino-2-[(naphthalen-1-yloxy)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
0.00074
3-amino-2-[(naphthalen-2-yloxy)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
0.0036
3-amino-6-oxo-2-[[4-(trifluoromethyl)phenyl]carbonyl]-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
genes uchl1 and uchl3, C57BL/6J and gad, i.e. gracile axonal dystrophy, mice
-
-
male gracile axonal dystrophy, gad, mice lacking UCH-L1, and male uchl3 knockout mice, two isozymes UCH-L1 and UCH-L3 encoded by genes uchl1 and uchl3
-
-
wild-type and gad, i.e. gracile axonal dystrophy, mice, isozymes UCH-L1, UCH-L3, UCH-L4, and UCH-L5
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
UCH-L1 present in the outer layer cells of the trophectoderm. UCH-L3 present in the inner cells
-
UCH-L3 is the predominant deubiquitinating enzyme in endosomal compartments of collecting duct epithelial cells
-
level of UCH-L3 decreases with age, while the level of UCH-L1 increases with age in wild-type mice
the enzyme is found in tubular and parietal cells of the kidney and is expressed de novo in injured podocytes. Constitutive UCH-L1 expression in tubulointerstitial and glomerular cells
at 6.5 day of gestation of PGP9.5 is detected at various levels in decidual and primary trophoblast giant cells in the placenta. At 10.5 and 14 day of gestation PGP9.5 is expressed at moderate to strong levels in neurons. At 10.5 and 14 day of gestation PGP9.5 is expressed rarely
CYLD is drastically upregulated during RANKL-induced differentiation of preosteoclasts
specific carbonyl level of UCH-L1 is significantly increased in spinal cord of G93A-SOD1 transgenic mice compared to that of nontransgenic mice
strong expression of UCHL1, no expression of UCHL3
additional information
embryonic, UCH-L1 expression in the ventricular zone changes during neurogenesis and gliogenesis, high expression level in cortical plate and ventricular zone, overview
embryo, expression pattern in the ventricular zone changes between embryonic day 14 and 16, which corresponds to the transition from neurogenesis to gliogenesis. At embryonic day 14, UCH-L1 is highly expressed in the ventricular zone, where neurogenesis actively occurs, whereas its expression is prominent in the cortical plate at embroynic day 16. UCH-L1 is very weakly detected in the ventricular zone at embryonic day 16, which corresponds to the start of gliogenesis. UCH-L1 spatially mediates and enhances neurogenesis in the embryonic brain by regulating progenitor cell morphology
gracile axonal dystrophy is a syndrome that emanates from dysfunctional ubiquitin carboxyl-terminal hydrolase L-1
-
reduced levels of UCH-L1 mRNA (30%) and protein in a mouse model of Sandhoff disease as compared with their wild-type siblings
-
in mouse brain regions, e.g. cortex, hippocampus, striatum, and midbrain, both UCH-L1M and UCH-L1S occur in varying relative amounts
ubiquitin C-terminal hydrolase L1 is an extremely abundant protein in the brain. It is estimated to make up 1-5% of total neuronal protein
at 6.5 day of gestation of PGP9.5 is detected at various levels in embryonic ectoderm cells. At 10.5 and 14 day of gestation PGP9.5 is expressed at moderate to strong levels in neurons
brain, expression pattern in the ventricular zone changes between embryonic day 14 and 16, which corresponds to the transition from neurogenesis to gliogenesis. At embryonic day 14, UCH-L1 is highly expressed in the ventricular zone, where neurogenesis actively occurs, whereas its expression is prominent in the cortical plate at embroynic day 16. UCH-L1 is very weakly detected in the ventricular zone at embryonic day 16, which corresponds to the start of gliogenesis. UCH-L1 spatially mediates and enhances neurogenesis in the embryonic brain by regulating progenitor cell morphology
-
UCH-L1 and UCH-L3 present during all of the embryonic stages. UCH-L1 is essentially constant in all cases, but the level of UCH-L3 is lower in the blastocyst stage. Developing embryos of gad and Uchl3 knockout mice are negative for UCH-L1 and UCH-L3
regiospecific expression of uchl1 and uchl3 in cauda, corpus, and caput, overview
at least two populations exist in the embryonic brain, cell culture
in cultured proliferating NPCs, UCH-L1 is coexpressed with nestin. In differentiating cells, UCH-L1 is highly co-expressed with the early neuronal marker TuJ1
-
high content of UCHL1, distribution in neuron types and cellular compartments, overview
-
UCH-L1 is localized on the inside of the plasma membrane of dorsal root ganglion neurons
beyond its expression in neurons UCH-L1 has only very limited expression in other healthy tissues but it is highly expressed in several forms of cancer
-
UCH-L1 and UCH-L3 present in mature oocytes. Oocytes of gad and Uchl3 knockout mice ovaries are negative for UCH-L1 and UCH-L3, respectively
-
expression of UCH-L1 in oocytes in prepubertal mouse ovaries, immunohistochemic analysis. Significant decrease in the follicular pool during the period of day 21 to day 28 after birth
-
UCHL1 and UCHL3 are present in the oocyte throughout the oestrous cycle in wild-type mice, but appropriately immunoreactivity for UCHL1 is absent from the gad mouse and UCHL3 immunoreactivity is absent from the UCHL3 knock-out mouse, overview
-
UCH-L1 and UCH-L3 are expressed in ovaries during proestrus, estrus, metestrus, and diestrus. Both proteins are present at all estrous cycle stages in wild-type mice. UCH-L1 is absent from gad ovaries and UCH-L3 from Uchl3 knockout ovaries
the enzyme is found in tubular and parietal cells of the kidney and is expressed de novo in injured podocytes
-
localization of UCH-L3 in the wild-type retina is altered with age. UCH-L3 is enriched in the photoreceptor inner segment that contains abundant mitochondria. UCH-L1 is expressed in both genotypes in the inner retina, which consists of the inner nuclear layer, inner plexiform layer, and ganglion cell layer
UCH-L1 may act during mitotic proliferation of spermatogonial stem cells
UCH-L3 may function in the meiotic differentiation of spermatocytes into spermatids
UCH-L3 may function in the meiotic differentiation of spermatocytes into spermatids
UCH-L1 may act during mitotic proliferation of spermatogonial stem cells
UCHL1 is expressed in defective spermatozoa but not in normal spermatozoa
absence of UCH-L1 causes resistance to cryptorchid-induced testicular germ cell apoptosis. UCH-L1 and UXH-L3 have reciprocal functions, with respect to mediating injury after experimental cryptorchidism
absence of UCH-L3 promotes germ cell apoptosis after cryptorchid injury. UCH-L1 and UXH-L3 have reciprocal functions, with respect to mediating injury after experimental cryptorchidism
mice overexpressing EF1alpha promoter-driven UCH-L1 in the testis are sterile due to a block during spermatogenesis at an early stage of meiosis. Overexpression of UCH-L1 affects spermatogenesis during meiosis and, in particular, induces apoptosis in primary spermatocytes. UCH-L-1 plays a specific role in the process of mitotic proliferation and differentiation of spermatogonial stem cells during spermatogenesis
additional information
isozyme L3 is universally expressed in all tissues
additional information
-
expression pattern of UCH isozymes in Sertoli cells, spermatids, spermatocytes, and spermatogonia, overview
additional information
expression pattern of UCH isozymes in Sertoli cells, spermatids, spermatocytes, and spermatogonia, overview
additional information
expression pattern of UCH isozymes in Sertoli cells, spermatids, spermatocytes, and spermatogonia, overview
additional information
quantitative testicular expression analysis of UCHL1
additional information
-
absence of UCHL1 in the gracile axonal dystrophy mouse, which results in neurodegeneration
additional information
-
UCH-L1 is upregulated and more abundantly expressed in germ line stem cells than in embryonic stem cells
additional information
-
increased expression and activity of UCH L1 in EBV-immortalized cell lines
additional information
-
tissue distribution and immunohistochemic analysis, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
membrane associated form UCH-L1M, C-terminal farnesylation promotes the association of UCH-L1 with the membrane
additional information
-
UCH-L1 exists in a membrane-associated form, UCH-L1M, in addition to the commonly studied soluble form
-
-
UCH-L3 concentrated in the cytoplasm of oocytes and developing embryos
-
UCH-L1 itself is a soluble protein and has no transmembrane domain, but UCH-L1 directly and specifically binds to phosphatidic acid thereby interacting with the menbrane
-
membrane associated form UCH-L1M, C-terminal farnesylation promotes the association of UCH-L1 with cellular membranes, including the endoplasmic reticulum
-
UCH-L1 most abundant at the plasma membrane of oocytes in developing follicles and in developing embryos
-
the membrane-associated UCH-L1M form, C-terminal farnesylation promotes the association of UCH-L1 with the membrane
-
UCH-L1 itself is a soluble protein and has no transmembrane domain, but UCH-L1 directly and specifically binds to phosphatidic acid thereby interacting with the menbrane. Monoubiquitin can possibly regulate the interaction between UCH-L1 and phosphatidic acid since bound UCH-L1 is increased in the presence of monoubiquitin
Uch-L1 protein fused to the transduction domain of HIV-transactivator protein exclusively present in the soluble fraction of hippocampal homogenates
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
-
deficiency of UCH-L1 leads to vulnerability to lipid peroxidation both in vivo and in vitro
malfunction
-
in the absence of UCH-L1, synaptic transmission at the neuromuscular junctions is markedly impaired. Loss of normal UCH-L1 activity may result in neurodegeneration in the peripheral nervous system
malfunction
-
increased UCH-L1 protein, together with the corresponding changes of Jab1, is detected in morphologically abnormal oocytes of prepubertal ovaries
malfunction
ubiquitination by UCH-L1 is involved in ischemia-reperfusion stress
malfunction
-
UCH L1 is expressed in a number of malignancies, it might be involved in oncogenic processes. UCH L1 suppression induces G0/G1 arrest and apoptosis
malfunction
-
10-week-old K256E-ACTN4pod+/UCHL1-/- mice exhibit reduced albuminuria, glomerulosclerosis, foot process effacement, glomerular basement membrane thickening, glomerular and tubular cell apoptosis, and ameliorated renal pathology. Observations coincide with decreased polyubiquitinated protein levels and increased K256E-alpha-actinin-4 levels in K256E-ACTN4pod+/UCHL1-/-mice kidneys, suggesting impaired proteolysis of K256E-alpha-actinin-4
malfunction
gene knockdown of UCHL1 by siRNA results in a significant decrease in cell proliferation but marked acceleration of cell differentiation and myotube formation. UCHL1 gene knockdown upregulates myogenic factors myoD and Myogenin (MyoG)
malfunction
UCH-L1 dysfunction is implicated in neurodegenerative disease
malfunction
UCH-L1-deficient mice develop proteinuria, without gross changes in glomerular morphology. Tubular cells, endothelial cells, and podocytes show signs of stress with an accumulation of oxidative modified and polyubiquitinated proteins. Mechanistically, abnormal protein accumulation results from an altered proteasome abundance leading to decreased proteasomal activity. UCH-L1-deficient mice exhibit an exacerbated course of disease with increased tubulointerstitial and glomerular damage, acute renal failure, and death, the latter most likely a result of general neurologic impairment
metabolism
the enzyme is required for regulated protein degradation through the ubiquitin proteasome system in kidney
physiological function
-
role of UCH-L1 in synaptic function in the brain, overview
physiological function
-
UCH-L1 is a deubiquitinating enzyme, it binds to and stabilize mono-ubiquitin in neurons
physiological function
-
UCH-L1 is a deubiquitinating enzyme, it binds to and stabilizes mono-ubiquitin in neurons
physiological function
-
UCH-L1 is responsible for hydrolyzing carboxyl terminal esters and amides of ubiquitin. Additionally, it possesses ubiquitin ligase activity and functions as a mono-ubiquitin stabilizer, which is independent of enzymatic activity, and is also involved in the co-translational processing of pro-ubiquitin and ribosomal proteins translated as ubiquitin fusions. UCH-L3 is a kind of ubiquitin-protein hydrolase involved in the processing of both ubiquitin precursors and ubiquitinated substrates, generating free monomeric ubiquitin. UCH37, different from other UCH members, is responsible for the Ub isopeptidase activity in the 19S proteasome regulatory complex, overview. UCH-L3 shows deneddylating activity, the only target proteins for neddylation are cullins, which are involved in cell-cycle control, therefore UCH-L3 might function as a cell-cycle regulator
physiological function
-
UCH-L1 mediates maintenance of the temporal integrity and persistence of cyclic AMP response element binding protein, CREB, phosphorylation in the brain
physiological function
UCH-L1 plays an important role in maintaining the intracellular levels of the ubiquitin
physiological function
-
UCH-L3 functions as a de-ubiquitinating enzyme in vivo. The polyubiquitinated protein accumulation in Uchl3-/- embryonic fibroblasts is attenuated by the exogenous expression of wild-type, but not hydrolase activity deficient UCH-L3
physiological function
-
UCHL1 is a component of the ubiquitin system, and the UCH-L1-dependent apoptosis is important for spermatogenesis. UCH-L1 plays an important role, possibly in association with Jab1 and p27Kip1, in selective elimination of abnormal oocytes during mouse prepubertal development
physiological function
-
UCHL1/PGP 9.5 is important in the ubiquitin system, detailed overview. UCHL1/PGP 9.5 might be involved in blocking polyspermy, particularly at the plasma membrane
physiological function
-
high glucose increases the TGF-betaR1 protein expression via the PI3K-UCHL5 pathway in mesangial cells
physiological function
isoform UCHL1 physically interacts with high affinity choline transporter CHT, which is a key protein regulating Ach re-synthesis. Reduction of UCHL1 by siRNA gene knockdown significantly increases polyubiquitinated CHT and decreased native CHT protein level, but does not affect CHT mRNA expression. Gene knockdown of UCHL1 significantly reduces cytosolic CHT but has no significant effect on membrane CHT level
physiological function
-
UCHL5 is required for high glucose-induced reduction of TGFbetaR1 protein ubiquitination, p21WAF1 protein expression, cell hypertrophy and fibronectin protein expression
physiological function
major deubiquitinating enzyme of the nervous system and associated with the development of neurodegenerative diseases
physiological function
the enzyme is required for regulated protein degradation in the kidney by controlling proteasome abundance
physiological function
UCH-L1 is required for the maintenance of axonal integrity
physiological function
UCHL1 may play a role in myogenesis by promoting myoblast proliferation and inhibiting differentiation
additional information
-
ectopic expression of UCH-L3 promotes the phosphorylation of insulin/IGF-I receptor and adipocyte differentiation in fibroblasts, overview
additional information
-
membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity, mechanism, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TNAP3_MOUSE
775
0
87654
Swiss-Prot
other Location (Reliability: 4)
UBP33_MOUSE
909
0
102728
Swiss-Prot
other Location (Reliability: 1)
UBP34_MOUSE
3582
0
408214
Swiss-Prot
other Location (Reliability: 2)
UBP22_MOUSE
525
0
59954
Swiss-Prot
other Location (Reliability: 2)
UBP24_MOUSE
2617
0
294001
Swiss-Prot
other Location (Reliability: 1)
UBP25_MOUSE
1055
0
121420
Swiss-Prot
other Location (Reliability: 2)
UBP26_MOUSE
835
0
95452
Swiss-Prot
other Location (Reliability: 2)
UBP27_MOUSE
438
1
49599
Swiss-Prot
other Location (Reliability: 1)
UBP28_MOUSE
1051
0
119318
Swiss-Prot
other Location (Reliability: 1)
UBP8_MOUSE
1080
0
122611
Swiss-Prot
other Location (Reliability: 1)
UCHL5_MOUSE
329
0
37617
Swiss-Prot
other Location (Reliability: 2)
JOS1_MOUSE
202
0
23152
Swiss-Prot
other Location (Reliability: 2)
JOS2_MOUSE
188
0
20776
Swiss-Prot
other Location (Reliability: 3)
U17PA_MOUSE
526
0
59073
Swiss-Prot
other Location (Reliability: 2)
U17PB_MOUSE
468
0
52114
Swiss-Prot
other Location (Reliability: 2)
U17PD_MOUSE
545
0
61450
Swiss-Prot
other Location (Reliability: 2)
U17PE_MOUSE
540
0
60219
Swiss-Prot
other Location (Reliability: 1)
UBP4_MOUSE
962
0
108343
Swiss-Prot
other Location (Reliability: 2)
UBP50_MOUSE
390
0
44543
Swiss-Prot
other Location (Reliability: 2)
UBP51_MOUSE
661
0
74783
Swiss-Prot
other Location (Reliability: 1)
UCHL1_MOUSE
223
0
24838
Swiss-Prot
other Location (Reliability: 3)
UCHL3_MOUSE
230
0
26152
Swiss-Prot
other Location (Reliability: 2)
UCHL4_MOUSE
233
0
26450
Swiss-Prot
other Location (Reliability: 2)
VCIP1_MOUSE
1220
0
134503
Swiss-Prot
other Location (Reliability: 3)
UBP29_MOUSE
869
0
97823
Swiss-Prot
Mitochondrion (Reliability: 3)
UBP2_MOUSE
613
0
68845
Swiss-Prot
other Location (Reliability: 4)
UBP30_MOUSE
517
1
58221
Swiss-Prot
Mitochondrion (Reliability: 1)
BAP1_MOUSE
728
0
80492
Swiss-Prot
other Location (Reliability: 5)
OTUB2_MOUSE
234
0
27300
Swiss-Prot
other Location (Reliability: 1)
OTUD1_MOUSE
454
0
48823
Swiss-Prot
other Location (Reliability: 3)
OTUD3_MOUSE
396
0
44576
Swiss-Prot
other Location (Reliability: 4)
OTUD4_MOUSE
1107
0
123055
Swiss-Prot
other Location (Reliability: 2)
OTUD5_MOUSE
566
0
60306
Swiss-Prot
other Location (Reliability: 2)
OTUL_MOUSE
352
0
40320
Swiss-Prot
other Location (Reliability: 4)
UBP19_MOUSE
1360
1
150549
Swiss-Prot
other Location (Reliability: 3)
UBP1_MOUSE
784
0
87456
Swiss-Prot
other Location (Reliability: 3)
UBP5_MOUSE
858
0
95833
Swiss-Prot
other Location (Reliability: 2)
UBP7_MOUSE
1103
0
128475
Swiss-Prot
other Location (Reliability: 2)
ATX3_MOUSE
355
0
40533
Swiss-Prot
other Location (Reliability: 1)
MINY3_MOUSE
444
0
49612
Swiss-Prot
other Location (Reliability: 3)
MINY4_MOUSE
744
0
82937
Swiss-Prot
other Location (Reliability: 2)
OTU1_MOUSE
343
0
37485
Swiss-Prot
other Location (Reliability: 3)
UBP36_MOUSE
1098
0
119913
Swiss-Prot
other Location (Reliability: 1)
UBP37_MOUSE
979
0
110063
Swiss-Prot
other Location (Reliability: 2)
UBP38_MOUSE
1042
0
116102
Swiss-Prot
other Location (Reliability: 2)
UBP3_MOUSE
520
0
58868
Swiss-Prot
other Location (Reliability: 1)
USP9X_MOUSE
2559
0
290711
Swiss-Prot
other Location (Reliability: 2)
EIF3F_MOUSE
361
0
37984
Swiss-Prot
other Location (Reliability: 4)
UBP15_MOUSE
981
0
112325
Swiss-Prot
other Location (Reliability: 1)
UBP16_MOUSE
825
0
93434
Swiss-Prot
other Location (Reliability: 3)
ZUP1_MOUSE
577
0
65593
Swiss-Prot
other Location (Reliability: 1)
DESI2_MOUSE
194
0
21434
Swiss-Prot
other Location (Reliability: 3)
UBP20_MOUSE
916
0
102140
Swiss-Prot
other Location (Reliability: 1)
UBP21_MOUSE
566
0
62673
Swiss-Prot
other Location (Reliability: 4)
UBP46_MOUSE
366
0
42442
Swiss-Prot
other Location (Reliability: 2)
UBP47_MOUSE
1376
0
157455
Swiss-Prot
other Location (Reliability: 1)
UBP48_MOUSE
1052
1
120631
Swiss-Prot
other Location (Reliability: 3)
UBP49_MOUSE
685
0
78272
Swiss-Prot
other Location (Reliability: 3)
ALG13_MOUSE
1166
0
128664
Swiss-Prot
other Location (Reliability: 3)
CYLD_MOUSE
952
0
106586
Swiss-Prot
other Location (Reliability: 2)
MINY1_MOUSE
468
0
51226
Swiss-Prot
other Location (Reliability: 1)
MINY2_MOUSE
601
0
65637
Swiss-Prot
other Location (Reliability: 1)
OTU6A_MOUSE
290
0
33738
Swiss-Prot
other Location (Reliability: 3)
OTU6B_MOUSE
294
0
33758
Swiss-Prot
other Location (Reliability: 1)
OTU7A_MOUSE
926
0
100797
Swiss-Prot
other Location (Reliability: 4)
OTU7B_MOUSE
840
0
91983
Swiss-Prot
other Location (Reliability: 1)
OTUB1_MOUSE
271
0
31270
Swiss-Prot
other Location (Reliability: 1)
UBP10_MOUSE
792
0
87022
Swiss-Prot
other Location (Reliability: 1)
UBP11_MOUSE
921
0
105384
Swiss-Prot
other Location (Reliability: 2)
ZRAN1_MOUSE
708
0
80934
Swiss-Prot
other Location (Reliability: 1)
U17LC_MOUSE
545
0
61483
Swiss-Prot
other Location (Reliability: 2)
UBP12_MOUSE
370
0
42914
Swiss-Prot
other Location (Reliability: 4)
UBP13_MOUSE
858
0
96723
Swiss-Prot
Mitochondrion (Reliability: 5)
UBP14_MOUSE
493
0
56002
Swiss-Prot
other Location (Reliability: 3)
UBP40_MOUSE
1235
0
139952
Swiss-Prot
other Location (Reliability: 1)
UBP42_MOUSE
1324
0
146223
Swiss-Prot
other Location (Reliability: 1)
UBP43_MOUSE
1132
0
123874
Swiss-Prot
other Location (Reliability: 5)
UBP44_MOUSE
711
0
80479
Swiss-Prot
other Location (Reliability: 2)
UBP45_MOUSE
813
0
90361
Swiss-Prot
other Location (Reliability: 1)
A0A0U1RP71_MOUSE
81
0
8953
TrEMBL
other Location (Reliability: 4)
A0A1W2P7K8_MOUSE
551
0
63048
TrEMBL
other Location (Reliability: 1)
A0A1L1SV73_MOUSE
1376
0
157155
TrEMBL
other Location (Reliability: 1)
Q5DTK8_MOUSE
747
0
83456
TrEMBL
other Location (Reliability: 1)
E9PYI8_MOUSE
458
0
52319
TrEMBL
other Location (Reliability: 2)
Q3TDY8_MOUSE
517
0
55860
TrEMBL
other Location (Reliability: 2)
Q8VCJ2_MOUSE
321
0
36429
TrEMBL
other Location (Reliability: 3)
D6RHQ6_MOUSE
334
0
38074
TrEMBL
other Location (Reliability: 3)
Q0VJ69_MOUSE
526
0
59139
TrEMBL
other Location (Reliability: 2)
F6T5L3_MOUSE
287
0
32959
TrEMBL
other Location (Reliability: 1)
Q3U4W8_MOUSE
835
0
93355
TrEMBL
other Location (Reliability: 2)
Q7TQD1_MOUSE
775
0
87698
TrEMBL
other Location (Reliability: 4)
B2RTM4_MOUSE
233
0
26450
TrEMBL
other Location (Reliability: 2)
A4FTZ0_MOUSE
303
0
33789
TrEMBL
Mitochondrion (Reliability: 2)
Q8C2N2_MOUSE
775
0
87568
TrEMBL
other Location (Reliability: 4)
A0A140LJD5_MOUSE
97
1
11001
TrEMBL
other Location (Reliability: 3)
A0A140T8J5_MOUSE
542
0
60478
TrEMBL
other Location (Reliability: 1)
Q3TT00_MOUSE
482
0
54579
TrEMBL
other Location (Reliability: 1)
Q921M8_MOUSE
915
0
103753
TrEMBL
other Location (Reliability: 2)
F6SXD2_MOUSE
142
0
16025
TrEMBL
other Location (Reliability: 3)
B2RU65_MOUSE
526
0
59063
TrEMBL
other Location (Reliability: 2)
D6RGU8_MOUSE
88
0
9853
TrEMBL
other Location (Reliability: 3)
D6REU0_MOUSE
230
0
25630
TrEMBL
other Location (Reliability: 3)
Q8VCY7_MOUSE
97
1
11021
TrEMBL
other Location (Reliability: 3)
A2AES4_MOUSE
571
0
60750
TrEMBL
other Location (Reliability: 2)
A0A0A6YVY7_MOUSE
734
0
82186
TrEMBL
other Location (Reliability: 2)
D6RG90_MOUSE
90
0
9797
TrEMBL
other Location (Reliability: 4)
Q05DM9_MOUSE
739
0
81993
TrEMBL
other Location (Reliability: 4)
C4IXT3_MOUSE
733
0
82729
TrEMBL
other Location (Reliability: 1)
A0A087WPL4_MOUSE
146
0
16615
TrEMBL
other Location (Reliability: 5)
A2AES5_MOUSE
567
0
60377
TrEMBL
other Location (Reliability: 2)
A0A0N4SVL4_MOUSE
600
0
66756
TrEMBL
other Location (Reliability: 2)
B7ZMR0_MOUSE
468
0
51226
TrEMBL
other Location (Reliability: 1)
Q6NXV6_MOUSE
961
0
108171
TrEMBL
other Location (Reliability: 2)
A0A0R4J260_MOUSE
1106
0
122927
TrEMBL
other Location (Reliability: 2)
Q6IS37_MOUSE
134
0
14717
TrEMBL
other Location (Reliability: 1)
I7ENE7_MOUSE
147
0
16244
TrEMBL
other Location (Reliability: 3)
Q8CAH4_MOUSE
198
0
21937
TrEMBL
Mitochondrion (Reliability: 3)
F6QWP5_MOUSE
143
0
15620
TrEMBL
other Location (Reliability: 2)
F8VPX1_MOUSE
1103
0
128474
TrEMBL
other Location (Reliability: 2)
G3UZF0_MOUSE
476
0
53674
TrEMBL
other Location (Reliability: 1)
Q80UN0_MOUSE
458
0
52234
TrEMBL
other Location (Reliability: 2)
E9PV45_MOUSE
2618
0
294129
TrEMBL
other Location (Reliability: 1)
F6Z9V3_MOUSE
64
0
7347
TrEMBL
other Location (Reliability: 2)
Q4FE56_MOUSE
2554
0
290215
TrEMBL
other Location (Reliability: 2)
E9PXY8_MOUSE
1143
0
132847
TrEMBL
Mitochondrion (Reliability: 5)
D3Z7K0_MOUSE
95
0
11245
TrEMBL
other Location (Reliability: 1)
Q80T83_MOUSE
1245
0
137270
TrEMBL
Mitochondrion (Reliability: 4)
A0A2I3BQ39_MOUSE
265
0
29702
TrEMBL
Secretory Pathway (Reliability: 5)
A0A0U1RNI9_MOUSE
123
0
13610
TrEMBL
other Location (Reliability: 3)
D6RGT9_MOUSE
135
0
14865
TrEMBL
other Location (Reliability: 3)
D3Z5R6_MOUSE
121
0
14251
TrEMBL
other Location (Reliability: 4)
Q3T9G9_MOUSE
775
0
87569
TrEMBL
other Location (Reliability: 4)
A0A1B0GQZ6_MOUSE
372
0
42000
TrEMBL
other Location (Reliability: 1)
J3QSN2_MOUSE
857
0
96595
TrEMBL
other Location (Reliability: 5)
A0A0R4J0M9_MOUSE
1220
0
134443
TrEMBL
other Location (Reliability: 3)
A0A0A6YWN9_MOUSE
991
1
110579
TrEMBL
Mitochondrion (Reliability: 4)
G3UZF4_MOUSE
257
0
30147
TrEMBL
other Location (Reliability: 1)
Q8C478_MOUSE
184
0
20930
TrEMBL
other Location (Reliability: 2)
Q810M8_MOUSE
319
0
36389
TrEMBL
Mitochondrion (Reliability: 4)
Q91XW2_MOUSE
2556
0
292177
TrEMBL
other Location (Reliability: 2)
Q9CVR9_MOUSE
305
0
34632
TrEMBL
other Location (Reliability: 1)
Q80VA4_MOUSE
393
0
45203
TrEMBL
Secretory Pathway (Reliability: 1)
A0A087WRL3_MOUSE
167
0
19565
TrEMBL
other Location (Reliability: 1)
H3BKW8_MOUSE
685
0
76223
TrEMBL
other Location (Reliability: 4)
Q0VJ56_MOUSE
729
0
78580
TrEMBL
other Location (Reliability: 1)
A0A140LIJ7_MOUSE
67
0
7491
TrEMBL
other Location (Reliability: 3)
D3Z0Y8_MOUSE
323
0
37066
TrEMBL
Mitochondrion (Reliability: 1)
Q5M8S1_MOUSE
296
0
33757
TrEMBL
other Location (Reliability: 1)
A0A5F8MPZ7_MOUSE
969
0
107050
TrEMBL
other Location (Reliability: 2)
A0A1L1STF0_MOUSE
600
0
65509
TrEMBL
other Location (Reliability: 1)
Q8BWQ9_MOUSE
211
0
23662
TrEMBL
other Location (Reliability: 2)
Q3UQ26_MOUSE
988
0
111834
TrEMBL
other Location (Reliability: 1)
Q58E42_MOUSE
419
0
48121
TrEMBL
other Location (Reliability: 2)
B7ZP07_MOUSE
540
0
60680
TrEMBL
other Location (Reliability: 1)
E9Q8W9_MOUSE
482
0
54565
TrEMBL
other Location (Reliability: 1)
Q3UMT4_MOUSE
729
0
80845
TrEMBL
other Location (Reliability: 3)
F8VPU6_MOUSE
2556
0
292267
TrEMBL
other Location (Reliability: 2)
A2ALR8_MOUSE
631
1
72684
TrEMBL
other Location (Reliability: 3)
A0A0A0MQF5_MOUSE
325
0
37187
TrEMBL
other Location (Reliability: 3)
A0A1L1SQ24_MOUSE
734
0
84106
TrEMBL
other Location (Reliability: 2)
A0A1B0GS33_MOUSE
540
0
60128
TrEMBL
other Location (Reliability: 1)
A0A0A6YW28_MOUSE
915
0
103723
TrEMBL
other Location (Reliability: 2)
D6RCI2_MOUSE
80
0
8803
TrEMBL
other Location (Reliability: 3)
Q3UB96_MOUSE
540
0
61309
TrEMBL
other Location (Reliability: 1)
Q3V059_MOUSE
306
0
34937
TrEMBL
other Location (Reliability: 2)
F6S1I0_MOUSE
160
0
17583
TrEMBL
other Location (Reliability: 2)
D3YTZ7_MOUSE
146
0
16120
TrEMBL
other Location (Reliability: 5)
Q3TEX8_MOUSE
962
0
108341
TrEMBL
other Location (Reliability: 2)
A0A0A6YWB5_MOUSE
86
0
9696
TrEMBL
other Location (Reliability: 4)
A2ALR9_MOUSE
1036
1
118771
TrEMBL
other Location (Reliability: 3)
D6RDE6_MOUSE
67
0
7516
TrEMBL
other Location (Reliability: 3)
F6WJB7_MOUSE
3602
0
409940
TrEMBL
other Location (Reliability: 4)
Q3U695_MOUSE
775
0
87709
TrEMBL
other Location (Reliability: 4)
Q546X9_MOUSE
355
0
40533
TrEMBL
other Location (Reliability: 1)
D3YWF6_MOUSE
241
0
28037
TrEMBL
other Location (Reliability: 1)
Q8C9A6_MOUSE
210
0
22948
TrEMBL
other Location (Reliability: 1)
E9PUE2_MOUSE
566
0
62620
TrEMBL
other Location (Reliability: 4)
A0A0R4J2D0_MOUSE
979
0
110031
TrEMBL
other Location (Reliability: 2)
Q91VW2_MOUSE
104
0
11287
TrEMBL
other Location (Reliability: 1)
G3UXT9_MOUSE
534
0
60616
TrEMBL
Mitochondrion (Reliability: 5)
D3YVU1_MOUSE
754
0
85382
TrEMBL
other Location (Reliability: 3)
Q3V3H6_MOUSE
248
0
28326
TrEMBL
other Location (Reliability: 2)
Q0VF82_MOUSE
517
0
58292
TrEMBL
other Location (Reliability: 2)
V5SJE7_MOUSE
479
0
53389
TrEMBL
other Location (Reliability: 4)
A0A0H2UKB8_MOUSE
897
0
101482
TrEMBL
other Location (Reliability: 1)
Q80TK2_MOUSE
837
0
94815
TrEMBL
other Location (Reliability: 2)
F8VPZ3_MOUSE
1604
0
181733
TrEMBL
other Location (Reliability: 2)
Q3TBB9_MOUSE
593
0
67056
TrEMBL
other Location (Reliability: 4)
Q3TCH2_MOUSE
225
0
25079
TrEMBL
Secretory Pathway (Reliability: 1)
A2AES3_MOUSE
517
0
55923
TrEMBL
other Location (Reliability: 2)
A0A087WP81_MOUSE
225
0
25571
TrEMBL
other Location (Reliability: 1)
Z4YLQ1_MOUSE
810
0
94291
TrEMBL
other Location (Reliability: 3)
E9Q717_MOUSE
291
0
33435
TrEMBL
other Location (Reliability: 1)
Q5DTP2_MOUSE
512
0
58593
TrEMBL
other Location (Reliability: 2)
UBP25_MOUSE
1055
0
121420
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
UCH-L1 can form dimers, whose form seems to act as another enzymatic activity in UCH-L1, ubiquitin ligase activity
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
-
C-terminal farnesylation promotes the association of UCH-L1 with membranes. Inhibition of UCH-L1 farnesylation by farnesyltransferase inhibitor FTI-277
additional information
-
cysteine residues of UCH-L1 are readily carbonylated by 4-hydroxy-2-nonenal or other unsaturated aldehydes, and the carbonylated UCH-L1 exhibits altered properties in hydrolase activity and protein-protein interactions
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
additional information
C90S
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
enzyme downregulation by RNAi. UCH L1 suppression inhibits cell proliferation and migration and induces G0/G1 arrest and apoptosis
additional information
-
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
-
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
-
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
-
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
-
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
-
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutants of isozyme L1 expressed in Escherichia coli
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
ataxin-3 carrying six consecutive glutamines cloned into plasmid pGEX6P-1 and expressed as a GST fusion protein in the Escherichia coli Codon Plus-RIL strain
expression of wild-type and hydrolase-deficient mutant UCH-L3 in mouse embryonic finbroblasts
-
isozyme L1: expression of wild-type and mutants in Escherichia coli as His-tagged proteins
overexpression of isozyme L1 in mouse embryonic fibroblasts via adenovirus transfection
recombinant fusion proteins expressed in Escherichia Coli BL21(DE3)pLysS cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
camptothecin induces enzyme expression, also in RNAi silenced 293T and KR4 cells
-
enzyme downregulation by RNAi in C33A cells. UCH L1 suppression inhibits cell proliferation and migration and induces G0/G1 arrest and apoptosis
-
germ cell apoptosis after testicular torsion treatment triggers downregulation of UCH-L1 in testis at both mRNA and protein levels
increased UCH-L1 protein, together with the corresponding changes of Jab1, is detected in morphologically abnormal oocytes of prepubertal ovaries
-
treatment with LiCl induces UCH L1 expression in 3T3 cells, no induction by TCF-4, but synergistic effects of TCF-4 and LiCl, TCF4 binds to the endogenous uchl1 promoter
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
degradation
protein L-isoaspartate O-methyltransferase initiates the repair of isoaspartyl residues in aged or stress-damaged proteins in vivo, e.g. UCHL1 is a substrate for the L-isoaspartate methyltransferase in vivo
medicine
additional information
-
dynamic regulation of apically located epithelial sodium channel by recycling, which is facilitated by UCH-L3
medicine
ubiquitin hydrolase Uch-L1 could be an attractive target for the development of new therapeutic approaches to Alzheimer's disease
medicine
-
activation of UCH-L1 may be a useful therapeutic approach for treating Alzheimers disease. Administration of a UCH-L1 fused to the transduction domain of the HIV-transactivator protein to supplement endogenous UCH-L1 has a protective effect on memory loss in a mouse model of Alzheimers disease. It restores long term potentiation and contextual memory to normal levels, whereas levels of the regulatory subunit of protein kinase A decrease, which, in turn, leads to increased levels of phosopho-cAMP response element binding protein
medicine
-
class of 3-amino-2-keto-7H-thieno[2,3-b]pyridin-6-one derivatives as UCH-L1 inhibitors provide useful tools for investigating the role of UCH-L1 in normal cellular physiology, as well as in pathological conditions, such as Parkinsons disease and some forms of cancer
medicine
-
UCH-L1 deficiency and impairment of the ubiquitin-dependent protein degradation pathway contributes to increased cell death observed in many lysosomal storage disorders
medicine
-
UCH-L1 is required for maintenance of memory in a passive avoidance test, exploratory behaviour in a novel environment, and a transcription-dependent component of theta-burst stimulation-induced long-term potentiation in area CA1 of the hippocampus
medicine
Uch-L1 is required for normal synaptic and cognitive function. Uch-L1 activity plays a role in normal contextual fear learning. Transduction of Uch-L1 protein fused to the transduction domain of HIV-transactivator protein restores normal enzymatic activity and synaptic function both in hippocampal slices treated with oligomeric Ab and in the APP/PS1 mouse model of Alzheimers disease. Intraperitoneal injections with the fusion protein improve the retention of contextual learning in APP/PS1 mice over time. Beneficial effect of the Uch-L1 fusion protein is associated with restoration of normal levels of the protein kinase A-regulatory subunit IIa, PKA activity, and cAMP response element binding protein phosphorylation
medicine
-
UCH-L1 is selectively expressed on the plasma membrane of mouse ova, where it may regulate membrane penetration by spermatozoa. The unique expression patterns of UCH-L1 and UCH-L3 suggest that these proteins have distinct functions during oogenesis and embryogenesis. UCH-L1 functions in the polyspermy block during mammalian fertilization
medicine
-
Uchl3-deficient mice represent a model for adultonset retinal degeneration associated with mitochondrial impairment
medicine
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L1 in vivo
medicine
uchl1 genes as novel targets of alpha-tocopherol deficiency may offer molecular correlates of well documented descriptions of neuromuscular dysfunctions in alpha-tocopherol-deficient rodents
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Osaka, H.; Wang, Y.L.; Takada, K.; Takizawa, S.; Setsuie, R.; Li, H.; Sato, Y.; Nishikawa, K.; Sun, Y.J.; Sakurai, M.; Harada, T.; Hara, Y.; Kimura, I.; Chiba, S.; Namikawa, K.; Kiyama, H.; Noda, M.; Aoki, S.; Wada, K.
Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron
Hum. Mol. Genet.
12
1945-1958
2003
Mus musculus, Mus musculus (Q9R0P9)
Harada, T.; Harada, C.; Wang, Y.L.; Osaka, H.; Amanai, K.; Tanaka, K.; Takizawa, S.; Setsuie, R.; Sakurai, M.; Sato, Y.; Noda, M.; Wada, K.
Role of ubiquitin carboxy terminal hydrolase-L1 in neural cell apoptosis induced by ischemic retinal injury in vivo
Am. J. Pathol.
164
59-64
2004
Mus musculus
Kwon, J.; Wang, Y.L.; Setsuie, R.; Sekiguchi, S.; Sato, Y.; Sakurai, M.; Noda, M.; Aoki, S.; Yoshikawa, Y.; Wada, K.
Two closely related ubiquitin C-terminal hydrolase isozymes function as reciprocal modulators of germ cell apoptosis in cryptorchid testis
Am. J. Pathol.
165
1367-1374
2004
Mus musculus, Mus musculus (Q9R0P9)
Kwon, J.; Wang, Y.L.; Setsuie, R.; Sekiguchi, S.; Sakurai, M.; Sato, Y.; Lee, W.W.; Ishii, Y.; Kyuwa, S.; Noda, M.; Wada, K.; Yoshikawa, Y.
Developmental regulation of ubiquitin C-terminal hydrolase isozyme expression during spermatogenesis in mice
Biol. Reprod.
71
515-521
2004
Mus musculus, Mus musculus (P15347), Mus musculus (Q9R0P9)
Kwon, J.; Mochida, K.; Wang, Y.L.; Sekiguchi, S.; Sankai, T.; Aoki, S.; Ogura, A.; Yoshikawa, Y.; Wada, K.
Ubiquitin C-terminal hydrolase L-1 is essential for the early apoptotic wave of germinal cells and for sperm quality control during spermatogenesis
Biol. Reprod.
73
29-35
2005
Mus musculus, Mus musculus (Q9R0P9)
Kwon, J.; Sekiguchi, S.; Wang, Y.L.; Setsuie, R.; Yoshikawa, Y.; Wada, K.
The region-specific functions of two ubiquitin C-terminal hydrolase isozymes along the epididymis
Exp. Anim.
55
35-43
2006
Mus musculus, Mus musculus (Q9R0P9)
Wood, M.A.; Kaplan, M.P.; Brensinger, C.M.; Guo, W.; Abel, T.
Ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory
Hippocampus
15
610-621
2005
Mus musculus, Mus musculus (Q9JKB1)
Sakurai, M.; Ayukawa, K.; Setsuie, R.; Nishikawa, K.; Hara, Y.; Ohashi, H.; Nishimoto, M.; Abe, T.; Kudo, Y.; Sekiguchi, M.; Sato, Y.; Aoki, S.; Noda, M.; Wada, K.
Ubiquitin C-terminal hydrolase L1 regulates the morphology of neural progenitor cells and modulates their differentiation
J. Cell Sci.
119
162-171
2006
Homo sapiens, Mus musculus, Mus musculus (Q9R0P9)
Dong, X.; Yagita, K.; Zhang, J.; Okamura, H.
Expression of ubiquitin-related enzymes in the suprachiasmatic nucleus with special reference to ubiquitin carboxy-terminal hydrolase UchL1
Biomed. Res.
26
43-49
2005
Mus musculus (Q9R0P9)
Gong, B.; Cao, Z.; Zheng, P.; Vitolo, O.V.; Liu, S.; Staniszewski, A.; Moolman, D.; Zhang, H.; Shelanski, M.; Arancio, O.
Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory
Cell
126
775-788
2006
Mus musculus, Mus musculus (Q9R0P9)
Sekiguchi, S.; Yoshikawa, Y.; Tanaka, S.; Kwon, J.; Ishii, Y.; Kyuwa, S.; Wada, K.; Nakamura, S.; Takahashi, K.
Immunohistochemical analysis of protein gene product 9.5, a ubiquitin carboxyl-terminal hydrolase, during placental and embryonic development in the mouse
Exp. Anim.
52
365-369
2003
Mus musculus (Q9R0P9), Mus musculus
Poon, H.F.; Hensley, K.; Thongboonkerd, V.; Merchant, M.L.; Lynn, B.C.; Pierce, W.M.; Klein, J.B.; Calabrese, V.; Butterfield, D.A.
Redox proteomics analysis of oxidatively modified proteins in G93A-SOD1 transgenic mice--a model of familial amyotrophic lateral sclerosis
Free Radic. Biol. Med.
39
453-462
2005
Mus musculus (Q9R0P9), Mus musculus
Castegna, A.; Thongboonkerd, V.; Klein, J.; Lynn, B.C.; Wang, Y.L.; Osaka, H.; Wada, K.; Butterfield, D.A.
Proteomic analysis of brain proteins in the gracile axonal dystrophy (gad) mouse, a syndrome that emanates from dysfunctional ubiquitin carboxyl-terminal hydrolase L-1, reveals oxidation of key proteins
J. Neurochem.
88
1540-1546
2004
Mus musculus (Q9R0P9), Mus musculus
Wang, Y.L.; Liu, W.; Sun, Y.J.; Kwon, J.; Setsuie, R.; Osaka, H.; Noda, M.; Aoki, S.; Yoshikawa, Y.; Wada, K.
Overexpression of ubiquitin carboxyl-terminal hydrolase L1 arrests spermatogenesis in transgenic mice
Mol. Reprod. Dev.
73
40-49
2006
Mus musculus (Q9R0P9), Mus musculus
Sano, Y.; Furuta, A.; Setsuie, R.; Kikuchi, H.; Wang, Y.L.; Sakurai, M.; Kwon, J.; Noda, M.; Wada, K.
Photoreceptor cell apoptosis in the retinal degeneration of Uchl3-deficient mice
Am. J. Pathol.
169
132-141
2006
Mus musculus
Sekiguchi, S.; Kwon, J.; Yoshida, E.; Hamasaki, H.; Ichinose, S.; Hideshima, M.; Kuraoka, M.; Takahashi, A.; Ishii, Y.; Kyuwa, S.; Wada, K.; Yoshikawa, Y.
Localization of ubiquitin C-terminal hydrolase L1 in mouse ova and its function in the plasma membrane to block polyspermy
Am. J. Pathol.
169
1722-1729
2006
Mus musculus
Mermerian, A.H.; Case, A.; Stein, R.L.; Cuny, G.D.
Structure-activity relationship, kinetic mechanism, and selectivity for a new class of ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitors
Bioorg. Med. Chem. Lett.
17
3729-3732
2007
Mus musculus
Lansbury, P.T.
Improving synaptic function in a mouse model of AD
Cell
126
655-657
2006
Aplysia sp., Homo sapiens, Mus musculus
Bifsha, P.; Landry, K.; Ashmarina, L.; Durand, S.; Seyrantepe, V.; Trudel, S.; Quiniou, C.; Chemtob, S.; Xu, Y.; Gravel, R.A.; Sladek, R.; Pshezhetsky, A.V.
Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway
Cell Death Differ.
14
511-523
2007
Mus musculus, Homo sapiens (P09936), Homo sapiens
Sakurai, M.; Sekiguchi, M.; Zushida, K.; Yamada, K.; Nagamine, S.; Kabuta, T.; Wada, K.
Reduction in memory in passive avoidance learning, exploratory behaviour and synaptic plasticity in mice with a spontaneous deletion in the ubiquitin C-terminal hydrolase L1 gene
Eur. J. Neurosci.
27
691-701
2008
Mus musculus, Mus musculus C57/BL6J
Mauri, P.L.; Riva, M.; Ambu, D.; De Palma, A.; Secundo, F.; Benazzi, L.; Valtorta, M.; Tortora, P.; Fusi, P.
Ataxin-3 is subject to autolytic cleavage
FEBS J.
273
4277-4286
2006
Mus musculus (Q9CVD2)
Vigneswara, V.; Lowenson, J.D.; Powell, C.D.; Thakur, M.; Bailey, K.; Clarke, S.; Ray, D.E.; Carter, W.G.
Proteomic identification of novel substrates of a protein isoaspartyl methyltransferase repair enzyme
J. Biol. Chem.
281
32619-32629
2006
Mus musculus (Q9R0P9)
Butterworth, M.B.; Edinger, R.S.; Ovaa, H.; Burg, D.; Johnson, J.P.; Frizzell, R.A.
The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel
J. Biol. Chem.
282
37885-37893
2007
Mus musculus
Fujino, R.S.; Ishikawa, Y.; Tanaka, K.; Kanatsu-Shinohara, M.; Tamura, K.; Kogo, H.; Shinohara, T.; Hara, T.
Capillary morphogenesis gene (CMG)-1 is among the genes differentially expressed in mouse male germ line stem cells and embryonic stem cells
Mol. Reprod. Dev.
73
955-966
2006
Mus musculus, Mus musculus DBA/2
Sun, J.; Ying, M.; Li, H.; Shang, X.; He, Y.; Chen, K.; Cheng, H.; Zhou, R.
Role of UCH-L1/ubiquitin in acute testicular ischemia-reperfusion injury
Biochem. Biophys. Res. Commun.
366
539-544
2008
Mus musculus (Q9R0P9), Mus musculus
Vasu, V.T.; Ott, S.; Hobson, B.; Rashidi, V.; Oommen, S.; Cross, C.E.; Gohil, K.
Sarcolipin and ubiquitin carboxy-terminal hydrolase 1 mRNAs are over-expressed in skeletal muscles of alpha-tocopherol deficient mice
Free Radic. Res.
43
106-116
2009
Mus musculus (Q9R0P9)
Jin, W.; Chang, M.; Paul, E.M.; Babu, G.; Lee, A.J.; Reiley, W.; Wright, A.; Zhang, M.; You, J.; Sun, S.C.
Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice
J. Clin. Invest.
118
1858-1866
2008
Mus musculus (Q80TQ2)
Lu, Y.; Adegoke, O.A.; Nepveu, A.; Nakayama, K.I.; Bedard, N.; Cheng, D.; Peng, J.; Wing, S.S.
USP19 deubiquitinating enzyme supports cell proliferation by stabilizing KPC1, a ubiquitin ligase for p27Kip1
Mol. Cell. Biol.
29
547-558
2009
Mus musculus (Q3UJD6), Rattus norvegicus (Q6J1Y9)
Setsuie, R.; Sakurai, M.; Sakaguchi, Y.; Wada, K.
Ubiquitin dimers control the hydrolase activity of UCH-L3
Neurochem. Int.
54
314-321
2009
Homo sapiens (P09936), Homo sapiens (P15374), Mus musculus (Q9JKB1), Mus musculus (Q9R0P9)
Fang, Y.; Fu, D.; Shen, X.Z.
The potential role of ubiquitin C-terminal hydrolases in oncogenesis
Biochim. Biophys. Acta
1806
1-6
2010
Homo sapiens, Mus musculus
Suzuki, M.; Setsuie, R.; Wada, K.
Ubiquitin carboxyl-terminal hydrolase l3 promotes insulin signaling and adipogenesis
Endocrinology
150
5230-5239
2009
Mus musculus
Pfeffer, M.; Plenzig, S.; Gispert, S.; Wada, K.; Korf, H.W.; Von Gall, C.
Disturbed sleep/wake rhythms and neuronal cell loss in lateral hypothalamus and retina of mice with a spontaneous deletion in the ubiquitin carboxyl-terminal hydrolase L1 gene
Neurobiol. Aging
33
393-403
2012
Mus musculus
Goto, A.; Wang, Y.L.; Kabuta, T.; Setsuie, R.; Osaka, H.; Sawa, A.; Ishiura, S.; Wada, K.
Proteomic and histochemical analysis of proteins involved in the dying-back-type of axonal degeneration in the gracile axonal dystrophy (gad) mouse
Neurochem. Int.
54
330-338
2009
Mus musculus
Setsuie, R.; Suzuki, M.; Tsuchiya, Y.; Wada, K.
Skeletal muscles of Uchl3 knockout mice show polyubiquitinated protein accumulation and stress responses
Neurochem. Int.
56
911-918
2010
Mus musculus
Nagamine, S.; Kabuta, T.; Furuta, A.; Yamamoto, K.; Takahashi, A.; Wada, K.
Deficiency of ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) leads to vulnerability to lipid peroxidation
Neurochem. Int.
57
102-110
2010
Mus musculus, Mus musculus C57/BL6J
Bheda, A.; Yue, W.; Gullapalli, A.; Whitehurst, C.; Liu, R.; Pagano, J.S.; Shackelford, J.
Positive reciprocal regulation of ubiquitin C-terminal hydrolase L1 and beta-catenin/TCF signaling
PLoS ONE
4
e5955
2009
Homo sapiens, Mus musculus
Bheda, A.; Shackelford, J.; Pagano, J.S.
Expression and functional studies of ubiquitin C-terminal hydrolase L1 regulated genes
PLoS ONE
4
e6764
2009
Mus musculus
Liu, Z.; Meray, R.K.; Grammatopoulos, T.N.; Fredenburg, R.A.; Cookson, M.R.; Liu, Y.; Logan, T.; Lansbury, P.T.
Membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity and is a therapeutic target for Parkinsons disease
Proc. Natl. Acad. Sci. USA
106
4635-4640
2009
Homo sapiens, Mus musculus
Chen, F.; Sugiura, Y.; Myers, K.G.; Liu, Y.; Lin, W.
Ubiquitin carboxyl-terminal hydrolase L1 is required for maintaining the structure and function of the neuromuscular junction
Proc. Natl. Acad. Sci. USA
107
1636-1641
2010
Mus musculus
Day, I.N.; Thompson, R.J.
UCHL1 (PGP 9.5): neuronal biomarker and ubiquitin system protein
Prog. Neurobiol.
90
327-362
2010
Bos taurus, Homo sapiens, Macaca fuscata, Mus musculus, Rattus norvegicus
Gu, Y.Q.; Chen, Q.J.; Gu, Z.; Shi, Y.; Yao, Y.W.; Wang, J.; Sun, Z.G.; Tso, J.K.
Ubiquitin carboxyl-terminal hydrolase L1 contributes to the oocyte selective elimination in prepubertal mouse ovaries
Sheng Li Xue Bao
61
175-184
2009
Mus musculus, Mus musculus ICR
Ko, Y.M.; Chang, C.Y.; Chiou, S.J.; Hsu, F.J.; Huang, J.S.; Yang, Y.L.; Guh, J.Y.; Chuang, L.Y.
Ubiquitin C-terminal hydrolase-L5 is required for high glucose-induced transforming growth factor-beta receptor I expression and hypertrophy in mesangial cells
Arch. Biochem. Biophys.
535
177-186
2013
Mus musculus
Read, N.C.; Gutsol, A.; Holterman, C.E.; Carter, A.; Coulombe, J.; Gray, D.A.; Kennedy, C.R.
Ubiquitin C-terminal hydrolase L1 deletion ameliorates glomerular injury in mice with ACTN4-associated focal segmental glomerulosclerosis
Biochim. Biophys. Acta
1842
1028-1040
2014
Mus musculus
Hartnett, S.; Zhang, F.; Abitz, A.; Li, Y.
Ubiquitin C-terminal hydrolase L1 interacts with choline transporter in cholinergic cells
Neurosci. Lett.
564
115-119
2014
Mus musculus (Q9R0P9)
Gao, H.; Hartnett, S.; Li, Y.
Ubiquitin C-terminal hydrolase L1 regulates myoblast proliferation and differentiation
Biochem. Biophys. Res. Commun.
492
96-102
2017
Mus musculus (Q9R0P9), Mus musculus
Bishop, P.; Rocca, D.; Henley, J.M.
Ubiquitin C-terminal hydrolase L1 (UCH-L1) structure, distribution and roles in brain function and dysfunction
Biochem. J.
473
2453-2462
2016
Homo sapiens (P09936), Mus musculus (Q9R0P9)
Radon, V.; Czesla, M.; Reichelt, J.; Fehlert, J.; Hammel, A.; Rosendahl, A.; Knop, J.H.; Wiech, T.; Wenzel, U.O.; Sachs, M.; Reinicke, A.T.; Stahl, R.A.K.; Meyer-Schwesinger, C.
Ubiquitin C-terminal hydrolase L1 is required for regulated protein degradation through the ubiquitin proteasome system in kidney
Kidney Int.
93
110-127
2018
Mus musculus (Q9R0P9)
EXTERNAL LINKS (specific for EC-Number 3.4.19.12)
Transporter Classification Database (TCDB): 3.A.31.1.1, 3.A.16.1.2
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