Information on EC 3.4.19.12 - ubiquitinyl hydrolase 1

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
3.4.19.12
-
RECOMMENDED NAME
GeneOntology No.
ubiquitinyl hydrolase 1
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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)
show the reaction diagram
a 76-residue protein attached to proteins as an intracellular targeting signal
-
-
-
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)
show the reaction diagram
Cys90 and His161 are involved in catalytic rate enhancement
-
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)
show the reaction diagram
UCH-L1 is a neuro-specific multifunctional enzyme, deubiquinating, ubiquitinyl ligase, and also stabilizing ubiquitin monomers, C90 is the active site residue
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
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 UCH37
-
-
-
-
ubiquitin carboxy-terminal hydrolase
-
-
-
-
ubiquitin carboxyl-terminal hydrolase
-
-
-
-
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
-
-
-
-
yeast ubiquitin hydrolase
-
-
-
-
YUH1
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
189642-63-5
-
86480-67-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
4 isoenzymes L1, L2, L3, and H2; calf thymus
-
-
Manually annotated by BRENDA team
calf thymus
-
-
Manually annotated by BRENDA team
calf thymus; isozyme L3, adult brain
-
-
Manually annotated by BRENDA team
three isozymes UCHL1, UCHL2, and UCHL3
-
-
Manually annotated by BRENDA team
UCH-L1, SwissProt: P23356, PIR: S17561, B40085
-
-
Manually annotated by BRENDA team
gene cyk-3, defects are lethal
-
-
Manually annotated by BRENDA team
strain N2, Bristol
-
-
Manually annotated by BRENDA team
Caenorhabditis elegans N2
strain N2, Bristol
-
-
Manually annotated by BRENDA team
i.e. Danio rerio
SwissProt
Manually annotated by BRENDA team
SwissProt: P35122, PIR: S33955
-
-
Manually annotated by BRENDA team
3 isozymes of UCH-L1
-
-
Manually annotated by BRENDA team
; isozymes L1, L2, and L3
-
-
Manually annotated by BRENDA team
; two isozymes UCH-L1 and UCH-L3
-
-
Manually annotated by BRENDA team
expressed in Escherichia coli
Swissprot
Manually annotated by BRENDA team
gene rs5030732
SwissProt
Manually annotated by BRENDA team
gene uch-L1
SwissProt
Manually annotated by BRENDA team
gene uchl1
-
-
Manually annotated by BRENDA team
gene UCHL1; gene uchl1
SwissProt
Manually annotated by BRENDA team
gene usp21, dual substrate specificity for ubiquitin- and NEDD8-conjugates
SwissProt
Manually annotated by BRENDA team
isozyme L1
SwissProt
Manually annotated by BRENDA team
isozymes ISOT-S and ISOT-L
-
-
Manually annotated by BRENDA team
Taiwanese population, gene rs5030732
-
-
Manually annotated by BRENDA team
UBPY
SwissProt
Manually annotated by BRENDA team
UCH-L1, SwissProt: P09936, PIR: A25865, UCH-L3, SwissProt: P15374, PIR: A40085
-
-
Manually annotated by BRENDA team
strain Rafinesque, NWAC103, gene UCHL5
UniProt
Manually annotated by BRENDA team
Ictalurus punctatus Rafinesque
strain Rafinesque, NWAC103, gene UCHL5
UniProt
Manually annotated by BRENDA team
cynomolgus monkeys
-
-
Manually annotated by BRENDA team
; gene uchl1
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
; C57BL/6J mice
-
-
Manually annotated by BRENDA team
BDF1, gad (CBA/RFM) and Uchl3 knockout (C57BL/6J) female and male mice
-
-
Manually annotated by BRENDA team
C57/BL6 mice or APP/PS1 mice
-
-
Manually annotated by BRENDA team
C57BL/6J mice
-
-
Manually annotated by BRENDA team
CBA and RFM mice
-
-
Manually annotated by BRENDA team
DBA/2 mice
-
-
Manually annotated by BRENDA team
G93A-SOD1 transgenic mice
SwissProt
Manually annotated by BRENDA team
gene uch l1
-
-
Manually annotated by BRENDA team
gene uch-L1
-
-
Manually annotated by BRENDA team
gene uchl3
-
-
Manually annotated by BRENDA team
genes uchl1 and uchl3, C57BL/6J and gad, i.e. gracile axonal dystrophy, mice
-
-
Manually annotated by BRENDA team
ICR mice
-
-
Manually annotated by BRENDA team
isozymes L1 and L3
-
-
Manually annotated by BRENDA team
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
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-
Manually annotated by BRENDA team
neuron-specific isozyme UCH-L1, mice with gracile axonal dystrophy
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-
Manually annotated by BRENDA team
swiss mice
-
-
Manually annotated by BRENDA team
wild-type and gad, i.e. gracile axonal dystrophy, mice, isozymes UCH-L1, UCH-L3, UCH-L4, and UCH-L5
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-
Manually annotated by BRENDA team
wild-type and PIMT knock-out mice
SwissProt
Manually annotated by BRENDA team
wild-type C57BL/6 and mutant gad, i.e. gracile axonal dystrophy, mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
C57BL/6J mice
-
-
Manually annotated by BRENDA team
Mus musculus DBA/2
DBA/2 mice
-
-
Manually annotated by BRENDA team
Mus musculus ICR
ICR mice
-
-
Manually annotated by BRENDA team
no activity in Escherichia coli
-
-
-
Manually annotated by BRENDA team
3D7 strain
-
-
Manually annotated by BRENDA team
adult Sprague-Dawley rats
SwissProt
Manually annotated by BRENDA team
isozyme L1
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
UCH-L1, SwissProt: Q00981
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-
Manually annotated by BRENDA team
Doa4p ubiquitin isopeptidase
-
-
Manually annotated by BRENDA team
synthetic construct
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
altered UCH-L1 activity leads to deleterious effects on synapse structure and function. Inhibition of UCH-L1 activity affects synaptic protein clusters
malfunction
-
deficiency of UCH-L1 leads to vulnerability to lipid peroxidation both in vivo and in vitro
malfunction
-
elevation in UCH-L1 in cystic fibrosis cells represents a cellular adaptation to counterbalance excessive proteasomal degradation
malfunction
-
human UCHL1 gene and neurological diseases, wild-type and mutants I93M and S18Y, mutation I93M is proposed as a familial Parkinson’s disease mutation, PARK5, detailed overview
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 oxidative carbonyl modification of UCH-L1 causes dysfunction of UCH-L1 and finally induces neuron death
malfunction
-
increased UCH-L1 protein, together with the corresponding changes of Jab1, is detected in morphologically abnormal oocytes of prepubertal ovaries
malfunction
-
the deubiquitinating enzyme USP44 is a critical regulator of the spindle checkpoint, dysregulation of the spindle checkpoint can contribute to birth defects and tumorigenesis
malfunction
-
the enzyme expression is increased in lymph node metastasis associated with poor prognosis in colorectal cancer
malfunction
-
the hydrolase activity of UCH-L1 is implicated in Alzheimer's disease and cancer invasion
malfunction
-
ubiquitin thiolesterase polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese
malfunction
-
ubiquitination by UCH-L1 is involved in ischemia-reperfusion stress
malfunction
-
UCH enzymes and human malignancies are closely correlated with roles of UCH enzymes in oncogenesis, UCH-L1 enhances tumor cell invasion and migration capability via the Akt-mediated pathway, overview. Dysfunction of UCH-L1 hydrolase activity can lead to an accumulation of alpha-synuclein and neurofibrillary tangles, which links to Parkinson's disease and Alzheimer's disease, respectively. Increased levels of both UCH-L1 and UCH-L3 mRNA are associated with early tumor recurrence of invasive breast cancer and poor prognosis. UCH37 activity is up-regulated in cervical carcinoma biopsies as well as cell lines. UCH-L1 levels are high in various types of malignancies: acute lymphoblastic leukemia, non-small cell lung cancer, neuroblastoma, pancreatic, prostate, medullary thyroid, esophageal, colorectal and renal carcinomas, although lowered in cervical carcinomas
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
-
Uch-L1 is associated with Parkinson's disease, as alpha2-adrenergic receptor interacting protein. alpha2-Adrenergic receptor agonist-mediated activation of p44/42MAP kinase is drastically decreased in the presence of Uch-L1. Stimulation of recombinantly UCH-L1 expressing HEK-293 cells prior lysis with norepinephrine, yohimbine, phentolamine or moxonidine does also not significantly affect the interaction, as well as co-transfection of arrestin-3 or spinophilin-(Phe151-Lys446)
malfunction
-
UCH-L1 is highly expressed in Burkitt's lymphoma and is up-regulated upon infection of B lymphocytes with Epstein-Barr virus, EBV. Selective up-regulation of the ubiquitin C-terminal hydrolase UCH-L1 in a variety of metastatic tumours contributes to the malignant phenotype
malfunction
-
UCH-L1 is implicated in Parkinson’s disease and is present in neurofibrillary tangles or Lewy bodies
malfunction
Q00981
UCH-L1 is up-regulated in injured arteries, via posttranscriptional regulation, and local gene delivery of UCH-L1 inhibited vascular lesion formation with suppression of inflammatory responses in vasculature. ERK activation also contributes to the growth inhibitory effect of UCH-L1 in TNFalpha-inflamed vascular smooth muscle cells
malfunction
-
UCH-L1 levels are increased in cerebrospinal fluid in case of traumatic brain damage correlated with a negative survival prognosis, overview
malfunction
-
UCHL1 is overexpressed in over 50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy
malfunction
-
UCHL1 overexpression is associated with tumor progression and an altered von Hippel Lindau gene expression in renal cell carcinoma
malfunction
Mus musculus ICR
-
increased UCH-L1 protein, together with the corresponding changes of Jab1, is detected in morphologically abnormal oocytes of prepubertal ovaries
-
malfunction
Mus musculus C57BL/6J
-
deficiency of UCH-L1 leads to vulnerability to lipid peroxidation both in vivo and in vitro
-
metabolism
-
the proteasomal pathway is partially inhibited by UCH-L1M
metabolism
-
ubiquitin carboxyl-terminal hydrolase L1 is a member of the ubiquitin proteasome pathway
metabolism
-
UCH-L1 in cell signaling, detailed overview
metabolism
-
UCHL1 gene regulation, overview
physiological function
-
role of UCH-L1 in synaptic function in the brain, overview
physiological function
-
UCH L1 up-regulates beta-catenin/TCF signaling. UCH L1 forms endogenous complexes with beta-catenin, stabilizes it and up-regulates beta-catenin/TCF-dependent transcription. The deubiquitinating activity of UCH L1 is required for TCF4 transcriptional activity, overview
physiological function
Q00981
UCH-L1 appears to be a multi-functional protein and exerts cell type and/or tissue specific actions
physiological function
-
UCH-L1 is a deubiquitinating enzyme, it binds to and stabilize mono-ubiquitin in neurons, UCH-L1 is a deubiquitinating enzyme, it binds to and stabilizes mono-ubiquitin in neurons
physiological function
-
UCH-L1 is a deubiquitinating enzyme. UCH-L1 is a deubiquitinating enzyme. UCH-L1 increases the synthesis of cystic fibrosis transmembrane conductance, and endogenous UCH-L1 expression is positively correlated with CFTR biogenesis
physiological function
-
UCH-L1 is a functional protein that may play a significant role in cell migration
physiological function
-
UCH-L1 is a player in the signalling pathways that promote the proliferation and invasive capacity of malignant B cells
physiological function
-
Uch-L1 is involved in controling alpha2-adrenergic receptor receptor function and trafficking, it binds preferentially to the alpha2A-adrenergic receptor subtype and only with less affinity to alpha2B-adrenergic receptor and alpha2C-adrenergic receptor, specific interaction in vivo, mechanism, overview
physiological function
-
UCH-L1 is one of the major de-ubiquitinating enzymes in the brain which controls ubiquitin homeostasis. UCH-L1 function is required for synaptic plasticity and is itself regulated by synaptic activity. UCH-L1 activity is required for NMDA-induced up-regulation of free monomeric ubiquitin. UCH-L1 can also bind to ubiquitin and act as a ubiquitin stabilizer to prevent its degradation by lysosomes. UCH-L1 regulates spine morphology and density
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 a crucial role in regulating certain signalings. UCH-L1 forms endogenous complexes with beta-catenin, stabilizes it and up-regulates beta-catenin/TCF/Lef-dependent transcription. Reciprocally, as indicated, beta-catenin/TCF/Lef signaling up-regulates the expression of endogenous UCH-L1 mRNA and protein. UCH-L1 is responsible for hydrolyzing carboxyl terminal esters and amides of Ub. 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. Upregulation of TGF-beta signaling by UCH37
physiological function
-
UCH-L1 plays an important role in maintaining the intracellular levels of the ubiquitin
physiological function
B5KNK6
Uch-L1 plays an important role in the maintenance of intracellular monoubiquitin levels by generating ubiquitin through the hydrolysis of polyubiquitinated proteins, and regulates the ubiquitin pathway. It is important in gametogenesis and gonadal transformation
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
-
UCH-L3 promotes insulin signaling and adipogenesis
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 is involved in the degradation of unwanted, misfolded, or damaged proteins within the cell
physiological function
-
UCHL1 promotes disassembly of polyubiquitin chains during meiotic maturation. Conversely, UCHL1 regulates formation of polyubiquitin chains in bovine oocytes
physiological function
-
UCHL1/PGP 9.5 is important in the ubiquitin system, and functions of UCHL1/PGP 9.5 in neurones, detailed overview
physiological function
-
UCHL1/PGP 9.5 is important in the ubiquitin system, detailed overview
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
B6E460
UCHL5 is involved in the ubiquitin-proteasome pathway
physiological function
-
USP44 is a member of the ubiquitin proteasome pathway controlling intracellular protein degradation, functioning to maintain ubiquitin balance by associating with ubiquitin and by releasing ubiquitin from tandemly conjugated ubiquitin monomers and small adducts or unfolded proteins. Deubiquitinating enzyme USP44 is a critical regulator of the spindle checkpoint
physiological function
Mus musculus ICR
-
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
Mus musculus C57BL/6J
-
UCH-L1 mediates maintenance of the temporal integrity and persistence of cyclic AMP response element binding protein, CREB, phosphorylation in the brain
-
physiological function
Ictalurus punctatus Rafinesque
-
UCHL5 is involved in the ubiquitin-proteasome pathway
-
metabolism
-
USP44 is a member of the ubiquitin proteasome pathway controlling intracellular protein degradation, functioning to maintain ubiquitin balance by associating with ubiquitin and by releasing ubiquitin from tandemly conjugated ubiquitin monomers and small adducts or unfolded proteins
additional information
-
activity of UCHL1 stimulates ligase activity of this enzyme in bovine oocytes, resulting in increased protein stabilization or modification through K63-linked polyubiquitination
additional information
-
autoantigenicity of UCH-L1: UCH-L1 is an antigen for autoantibodies in CNS-Lupus, systemic lupus erythematosus manifested in central nervous system, an autoimmune disease, overview
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
additional information
-
UCHL1 is a Parkinson disease-associated, putative cysteine protease
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(His)8-Ub-CTAPIII + H2O
(His)8-Ub + CTAPII
show the reaction diagram
-
Ub i.e ubiquitin, CTAPII i.e. connective tissue-activating peptide
-
?
Ac-ALRGG-7-amido-4-trifluoromethylcoumarin
?
show the reaction diagram
-
-
-
-
?
Ac-ALRGG-7-amido-4-trifluoromethylcoumarin
?
show the reaction diagram
P45974, Q5VVQ6
-
-
-
?
Ac-LRGG-7-amido-4-trifluoromethylcoumarin
?
show the reaction diagram
-
-
-
-
?
Ac-LRGG-7-amido-4-trifluoromethylcoumarin
?
show the reaction diagram
P45974, Q5VVQ6
-
-
-
?
Ac-RLRGG-7-amido-4-trifluoromethylcoumarin
?
show the reaction diagram
-
-
-
-
?
Ac-RLRGG-7-amido-4-trifluoromethylcoumarin
?
show the reaction diagram
P45974, Q5VVQ6
-
-
-
?
activity-based haemagglutinin-tagged ubiquitin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-Tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
beta-tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
branched di-ubiquitin + H2O
ubiquitin
show the reaction diagram
-
recombinant substrate from expression in Escherichia coli
-
-
?
branched di-ubiquitin + H2O
ubiquitin
show the reaction diagram
-
recombinant substrate expressed in Escherichia coli
-
-
?
branched polyubiquitin + H2O
ubiquitin
show the reaction diagram
P40818
isopeptide-linked ubiquitin chains
-
?
branched polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
substrate is ligated to proteins via epsilon-NH-isopeptide bonds
-
?
conjugate of histone H2A and ubiquitin + H2O
ubiquitin + histone H2A
show the reaction diagram
-
best substrate
-
?
conjugate of histone H2A and ubiquitin + H2O
ubiquitin + histone H2A
show the reaction diagram
-
i.e. A24, structural chromatin protein, activity of the enzyme is confined to conjugates between ubiquitin and other proteins, formed through epsilon-(alpha-glycyl)lysine bonds
-
?
conjugate of histone H2A and ubiquitin + H2O
ubiquitin + histone H2A
show the reaction diagram
-
i.e. A24, structural chromatin protein, activity of the enzyme is confined to conjugates between ubiquitin and other proteins, formed through epsilon-(alpha-glycyl)lysine bonds
-
?
conjugate of histone H2A and ubiquitin + H2O
ubiquitin + histone H2A
show the reaction diagram
-
i.e. A24, structural chromatin protein, activity of the enzyme is confined to conjugates between ubiquitin and other proteins, formed through epsilon-(alpha-glycyl)lysine bonds
-
?
conjugate of histone H2A and ubiquitin + H2O
ubiquitin + histone H2A
show the reaction diagram
-
i.e. A24, structural chromatin protein, activity of the enzyme is confined to conjugates between ubiquitin and other proteins, formed through epsilon-(alpha-glycyl)lysine bonds
-
?
di-ubiquitin + H2O
ubiquitin
show the reaction diagram
-
recombinant linear substrate, expressed in Escherichia coli
-
-
-
di-ubiquitin + H2O
ubiquitin
show the reaction diagram
-
active with wild-type and mutant di-ubiquitin, the latter contains a distal mutant ubiquitin L8A/I44A
-
-
?
EBV ribonucleotide reductase
?
show the reaction diagram
P03186
is deubiquitinated by BPLF1 1-246
-
-
?
HCF-1 + H2O
?
show the reaction diagram
Q92560
HCF-1 is the principal Bap1-interacting protein. It is K48- and K63-ubiquitinated. Endogenous HCF-1C is ubiquitinated at lysine-1807 and/or lysine-1808
-
-
?
head-to-tail polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
recombinant substrate from expression in Escherichia coli
-
-
?
hemagglutinin-tagged ubiquitin-vinyl methyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
inhibitor of kappa B-alpha + H2O
?
show the reaction diagram
-
UCHL1 deubiquitinates, thereby resulting in nuclear factor-kappa B inactivation
-
-
?
K48-linked tetraubiquitin + H2O
K48-linked diubiquitin + diubiquitin
show the reaction diagram
-
-
-
-
?
K63-linked polyubiquitin + H2O
K63-linked polyubiquitin + ubiquitin
show the reaction diagram
-
-
-
-
?
KPC1
?
show the reaction diagram
Q6J1Y9
-
-
-
?
linear ubiquitin-beta-galactosidase + H2O
ubiquitin + protein
show the reaction diagram
-
recombinant fusion protein co-expressed with the enzyme in Escherichia coli
-
?
monoubiquitin + H2O
?
show the reaction diagram
-
-
-
-
?
N2-L-Asp-ubiquitin + H2O
ubiquitin + L-Asp
show the reaction diagram
-
-
-
?
N2-Lys-ubiquitin + H2O
ubiquitin + Lys
show the reaction diagram
-
ubiquitin amide of the alpha amino group of lysine
-
?
N6-(N2-acetyl)Lys-ubiquitin + H2O
ubiquitin + N2-acetyl-Lys
show the reaction diagram
-
ubiquitin amide of the alpha amino group of lysine
-
?
N6-Lys-ubiquitin + H2O
ubiquitin + Lys
show the reaction diagram
-
ubiquitin amide of the epsilon amino group of lysine
-
?
N6-Lys-ubiquitin + H2O
ubiquitin + Lys
show the reaction diagram
-
ubiquitin amide of the epsilon amino group of lysine
-
-
?
Nalpha-(diubiquitin)-[L-Lys] + H2O
?
show the reaction diagram
-
K48 linked diubiquitin
-
-
?
Nalpha-ubiquitin-[MQIFVRPR] + H2O
ubiquitin + MQIFVRPR
show the reaction diagram
-
-
-
-
?
Nedd-8 + H2O
?
show the reaction diagram
-
-
-
-
?
Nedd-8 + H2O
?
show the reaction diagram
-
-
-
-
?
NEDD8-protein + H2O
NEDD8 + protein
show the reaction diagram
Q9UK80
enzyme shows dual specificity for ubiquitin-conjugates and NEDD8-conjugates
-
?
Nepsilon-(diubiquitin)-[Nalpha-actyl-L-Lys] + H2O
?
show the reaction diagram
-
K48 linked diubiquitin
-
-
?
poly-His tagged di-ubiquitin + H2O
ubiquitin + ?
show the reaction diagram
-
-
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
-
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
-
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
B5KNK6
-
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
hydrolysis is restricted to the distal end of the substrate, i.e. ubiquitin farthest from the site of protein attachment in poly-ubiquitin conjugates, active with Lys48-, Lys6-, and Lys11-linked poly-ubiquitins
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
P40818
linear chains
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
dissambly of polyubiquitin
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
no activity with poly-ubiquitins that contain a distal mutant ubiquitin L8A/I44A
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
disassembly of polyubiquitin, terminal step of the proteasome pathway, scheme, inhibition by prostaglandins of the J series leads to accumulation of polyubiquitins of MW around 250 kDa
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
Cezanne deubiquitinates Lys48- or Lys63-polyubiquitinated cellular proteins
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
substrate of UCHL3, no activity with UCHL1/PGP 9.5
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
UCHL1/PGP 9.5, overview
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
Ictalurus punctatus, Ictalurus punctatus Rafinesque
B6E460
UCHL5 deubiquitylates the polyubiquitin chain into ubiquitin
-
-
?
Smad2 + H2O
?
show the reaction diagram
-
weaker association
-
-
?
Smad3 + H2O
?
show the reaction diagram
-
weaker association
-
-
?
Smad7 + H2O
?
show the reaction diagram
-
association with Smad7, which can act as an adaptor able to recruit UCH37 to the type I TGF-beta receptor and reverses Smurf-mediated ubiquitination
-
-
?
spermidine-ubiquitin + H2O
ubiquitine + spermidine
show the reaction diagram
-
-
-
-
?
type I TGF-beta receptor + H2O
?
show the reaction diagram
Q9Y5K5
UCH37 deubiquitinates and stabilizes type I TGF-beta receptor. Overexpression of UCH37 upregulates TGF-beta-dependent transcription
-
-
?
type I TGF-beta receptor + H2O
?
show the reaction diagram
-
UCH37 dramatically up-regulates TGF-beta-dependent gene expression by deubiquitinating and stabilizing the type I TGF-beta receptor
-
-
?
ubiquitin + H2O
?
show the reaction diagram
-
-
-
-
?
ubiquitin + H2O
?
show the reaction diagram
-
-
-
-
?
ubiquitin + H2O
?
show the reaction diagram
-
-
-
-
?
ubiquitin + H2O
?
show the reaction diagram
-
cleavage of the G76-D77 peptide bond of (L8A, I44A, V70A)-D77 ubiquitin
-
-
?
ubiquitin + H2O
monoubiquitin
show the reaction diagram
-
UCH-L1 removes and recycles ubiquitin molecules from degraded proteins
-
-
?
ubiquitin C-terminal amide + H2O
ubiquitin + NH3
show the reaction diagram
-
-
-
-
?
ubiquitin C-terminal-4-methyl-7-amido-coumarin + H2O
ubiquitin + 4-methyl-7-amino-coumarin
show the reaction diagram
-
UCHL3 is 200fold more active than UCHL1/PGP 9.5
-
-
?
ubiquitin ethyl ester + H2O
ubiquitin + ethanol
show the reaction diagram
-
-
-
-
?
ubiquitin ethyl ester + H2O
ubiquitin + ethanol
show the reaction diagram
-
-
-
-
?
ubiquitin ethyl ester + H2O
ubiquitin + ethanol
show the reaction diagram
-
-
-
-
?
ubiquitin ethylester + H2O
ubiquitin + an alcohol
show the reaction diagram
-
synthetic substrate
-
-
?
ubiquitin fused to 60% of its N-terminus + H2O
ubiquitin + 60% of ubiquitin N-terminus
show the reaction diagram
-
recombinant substrate, expressed in Escherichia coli
-
?
ubiquitin glycine methyl ester + H2O
ubiquitin + methanol
show the reaction diagram
-
-
-
-
?
ubiquitin metallothionein + H2O
?
show the reaction diagram
-
low activity, recombinant substrate, expressed in Escherichia coli, i.e. UbMT
-
-
?
ubiquitin thiol ester of dithiothreitol + H2O
ubiquitin + dithiothreitol
show the reaction diagram
-
-
-
-
?
ubiquitin-4-methylcoumarin 7-amide + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
ubiquitin-4-methylcoumarine 7-amide + H2O
ubiquitin + 7-amino-4-methylcoumarine
show the reaction diagram
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
P09936
-
-
-
ir
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
-
UCH-L1 and UCH-L3
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
P15374
ubiquitin makes modest contact with UCH-L1. The interaction is mainly electrostatic, contributed by conserved acidic residues E7, E11, D30, E35, and E37
-
-
?
ubiquitin-7-amino-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
P09936
recombinant wild-type isozyme L1 and mutants I93M and S18Y
-
-
?
ubiquitin-7-amino-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
Q9R0P9
recombinant wild-type isozyme L1
-
-
?
ubiquitin-7-amino-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
P09936
fluorogenic synthetic substrate
-
-
?
ubiquitin-7-amino-4-methylcoumarin + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-alcohol + H2O
ubiquitin + alcohol
show the reaction diagram
P09936
-
-
-
ir
ubiquitin-alpha-NH-dihydrofolate reductase + H2O
ubiquitin + dihydrofolate reductase
show the reaction diagram
-
-
-
-
?
ubiquitin-alpha-NH-MHISPPEPESEEEEHYC + H2O
ubiquitin + MHISPPEPESEEEEHYC
show the reaction diagram
-
-
-
?
ubiquitin-alphaNH-MHISPPEPESEEEEHYC + H2O
ubiquitin + MHISPPEPESEEEEHYC
show the reaction diagram
-
-
-
?
ubiquitin-alphaNH-MHISPPEPESEEEEHYC + H2O
ubiquitin + MHISPPEPESEEEEHYC
show the reaction diagram
-
-
-
?
ubiquitin-AMC
?
show the reaction diagram
P03186
BPLF1 1-246 expresses deubiquitinating activity, cleaves ubiquitin chains linked by K48 and K63
-
-
?
ubiquitin-AMC + H2O
?
show the reaction diagram
-
-
-
-
?
ubiquitin-AW + H2O
?
show the reaction diagram
synthetic construct
-
poor substrate for UCH-L1
-
-
?
ubiquitin-carboxyl extension protein + H2O
ubiquitin + ubiquitin-carboxyl extension protein
show the reaction diagram
-
UCH-1
-
?
ubiquitin-carboxyl extension protein + H2O
ubiquitin + ubiquitin-carboxyl extension protein
show the reaction diagram
-
carboxyl extension protein of 80 amino acids
-
?
ubiquitin-carboxyl extension protein + H2O
ubiquitin + ubiquitin-carboxyl extension protein
show the reaction diagram
-
carboxyl extension protein of 80 amino acids
-
?
ubiquitin-carboxyl extension protein + H2O
ubiquitin + ubiquitin-carboxyl extension protein
show the reaction diagram
-
carboxyl extension protein of 38 amino acids
-
-
?
ubiquitin-carboxyl extension protein + H2O
ubiquitin + ubiquitin-carboxyl extension protein
show the reaction diagram
-
carboxyl extension protein of 52 amino acids
-
-
ubiquitin-CEP52 + H2O
ubiquitin + CEP52
show the reaction diagram
-
substrate of UCHL1/PGP 9.5, no activity with UCHL3
-
-
?
ubiquitin-CEP80 + H2O
ubiquitin + CEP80
show the reaction diagram
-
substrate of UCHL3 and UCHL1/PGP 9.5
-
-
?
ubiquitin-Cys + H2O
ubiquitin + Cys
show the reaction diagram
-
-
-
?
ubiquitin-Cys-Cys + H2O
ubiquitin + Cys-Cys
show the reaction diagram
-
-
-
?
ubiquitin-Fur4p-conjugate + H2O
ubiquitin + Fur4p
show the reaction diagram
-
ubiquitin is bound to the Fur4p protein via its Lys63
-
?
ubiquitin-human carboxyl extension protein fusion protein + H2O
ubiquitin + human carboxyl extension protein
show the reaction diagram
-
i.e. HUbCEP-52, recombinant substrate, expressed in Escherichia coli
-
?
ubiquitin-magainin + H2O
magainin + ubiquitin
show the reaction diagram
-
is efficiently cleaved at the carboxyl terminus of ubquitin, yielding recombinant magainin with high antimicrobial activity
-
-
?
ubiquitin-peptide + H2O
?
show the reaction diagram
-
UCH enzymes may function to regenerate active ubiquitin from adducts with small nuceleophiles
-
-
-
ubiquitin-piscidin 1 + H2O
ubiquitin + piscidin 1
show the reaction diagram
P35127
-
-
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
-
-
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
Q9UK80
enzyme shows dual specificity for ubiquitin-conjugates and NEDD8-conjugates
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
-
involved in endocytotic pathway of plasma membrane proteins
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
-
enzyme is crucial for polarization of the actin cytoskeleton, to segregate germline determinants, to assemble an intact cleavage furrow, for cytokinesis and to maintain osmotic balance and execute actin-dependent processes in the early embryo
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
-
Doap4 enzyme form plays a general role in deubiquination of membrane-bound proteins
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
Q9UK80
important role in regulation of cell growth
-
?
ubiquitin-rhodamine110-glycine + H2O
rhodamine110
show the reaction diagram
-
-
-
-
?
ubiquitin-W + H2O
?
show the reaction diagram
synthetic construct
-
competent substrate for both UCH-L1 and UCH-L3
-
-
?
ubiquitin-W-G75A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-H68A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-I44A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-K11A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-K48A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-K63A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-K6A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-L71A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-L73A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-R42A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-R72A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-R74A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-W-V70A + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
ubiquitin-WA + H2O
?
show the reaction diagram
synthetic construct
-
poor substrate for UCH-L1
-
-
?
ubiquitinyl-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
Q9R0P9
-
-
-
?
ubiquitinyl-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
P09936
mechanistic studies
-
-
?
ubiquitinyl-peptide + H2O
ubiquitin + peptide
show the reaction diagram
-
catalyses the hydrolysis of an ester or amide bond involving the C-terminal Gly76 of ubiquitin
-
-
?
ubiquitinyl-peptide + H2O
ubiquitin + peptide
show the reaction diagram
-
UCH-L3 cleaves peptide extensions of up to 20 residues with high efficiency and low sequence preference
-
-
?
ubiquitinyldihydrofolate reductase + H2O
ubiquitin + dihydrofolate reductase
show the reaction diagram
-
UCH-1
-
?
Z-Arg-Leu-Arg-Gly-Gly-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
monoubiquitin + H2O
?
show the reaction diagram
-
the octapeptide amide DELRFNAI-NH2 from UCH-L3 binds to monoubiquitin
-
-
?
additional information
?
-
-
UCH-1 releases ubiquitins that are conjugated to proteins or adjacend ubiquitin molecules by epsilonNH-isopeptide linkages as well as alphaNH-peptide bonds
-
-
-
additional information
?
-
Q9UK80
no activity with Sentrin-1-conjugates
-
-
-
additional information
?
-
-
no activity with poly-His-tagged di-ubiquitin
-
-
-
additional information
?
-
-
core histones and H1 are not cleaved
-
-
-
additional information
?
-
-
enzyme contains ubiquitin-C-terminal hydrolase activity towards biosynthetic precursors of ubiquitin as well as isopeptidase activity towards ubiquitin histone conjugates as human ubiquitin carboxyl extension protein and ubiquitin C-terminal amide
-
-
-
additional information
?
-
P40818
enzyme inhibits cell proliferation
-
-
-
additional information
?
-
Q9R0P9
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
?
-
P09936
increased activity of neuronal isozyme L1 reduces the risk for Parkinson's disease
-
-
-
additional information
?
-
-
enzyme regulation
-
-
-
additional information
?
-
P40818
enzyme regulation
-
-
-
additional information
?
-
-
AMSH is a deubiquinating enzyme with functions at the endosome, it opposes the ubiquitin-dependent sorting of receptors to lysosomes, the enzyme influences the degradation of the EGF receptor by association to endosomes, model of the enzyme's physiological function
-
-
-
additional information
?
-
Q00981
de novo synthesis of isozyme UCH-L1 in rostral ventrolateral medulla is crucial to survival during mevinphos intoxication, the enzyme is involved in synthesis of ubiquitin which is required for protein targeting in degradation in the ubiquitin-proteasome pathway in neurons, UCH-L1 plays a neuroprotective role
-
-
-
additional information
?
-
P09936
gene uch-L1 is involved in development of Parkinson's disease
-
-
-
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 involved in generation of free monomeric ubiquitin, enzyme deficiency leads is involved in accumulation of ubiquitin and alpha-synuclein leading to aggregation in proteins conforming Lewy bodies and Lewy neurites leading to Parkinson's disease and dementia with Lewy bodies, the enzyme is down-regulated in Alzheimer's disease and in Parkinson's disease, comparison of enzyme expression to general protein synthesis and proteasome activity in brain
-
-
-
additional information
?
-
P15347
the enzyme is involved in spermatogenesis
-
-
-
additional information
?
-
Q60HC8
the enzyme is necessary for placental and fetal development
-
-
-
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
?
-
-
the full length UCH-L1 is a de-ubiquinating enzyme in brain, and a major target of oxidative damage in Alzheimer's diesease and Parkinson's disease brains, modified by cysteine and methionine oxidation and carbonyl formation
-
-
-
additional information
?
-
-
ubiquitin carboxy-terminal hydrolase L1 activates the P2X receptor leading to potentiation of ATP-induced currents in neurons
-
-
-
additional information
?
-
-
UCH-L1 functions in sperm quality control during epididymal maturation
-
-
-
additional information
?
-
-
UCH-L1 is involved in Parkinson's disease
-
-
-
additional information
?
-
P09936
UCH-L1 is involved in Parkinson's disease
-
-
-
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
?
-
Q9JKB1
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
?
-
-
AMSH interacts with the signal transducing adaptor molecule, STAM, via the SH3-domains
-
-
-
additional information
?
-
-
the enzyme shows de-ubiquinating activity
-
-
-
additional information
?
-
Q9R0P9
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
?
-
-
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
?
-
-
overexpression of UCH L1 potentiates ATP-induced currents due to the activation of P2X receptors that are widely distributed in the brain and involved in various biological activities including neurosecretion. UCH-L1 may play an important role in synaptic activity
-
-
-
additional information
?
-
-
oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinsons and Alzheimers diseases
-
-
-
additional information
?
-
-
the enzyme may play a significant role in implantation and placental development, and differentiation of embryonic ectoderm
-
-
-
additional information
?
-
Q9JKB1
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
?
-
Q6YI49
uch-L1 may have an important role in the development of neuronal cells in early embryos as well as in the degeneration and disease of neuronal cells in late adult brain. The gene for ubiquitin C-terminal hydrolase L1 is associated with inherited forms of Parkinson's disease
-
-
-
additional information
?
-
Q9R0P9
UCH-L1 may play an important role in neurodegeneration of amyloid lateral sclerosis
-
-
-
additional information
?
-
-
UCHL1 is an essential gene in cell survival under normal growth conditions and against oxidative stress, UCHL1 is an essential gene to maintain cell homeostasis under normal growth and oxidative stress conditions
-
-
-
additional information
?
-
-
UCHL1 is associated with Parkinsons disease
-
-
-
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
?
-
Q9CVD2
AT-3 carrying six consecutive glutamines undergoes fragmentation upon incubation at room temperature. Cys14 and His119 are involved in the autolytic activity
-
-
-
additional information
?
-
-
Bro1-Doa4 interaction involves the C-terminal proline-rich domain of Bro1 and a conserved ELC box motif in Doa4
-
-
-
additional information
?
-
-
deubiquitinating as well as deNeddylating activity. Active residues are Cys145, His220 and Asp235
-
-
-
additional information
?
-
-
deubiquitination by Doa4 of cargo proteins and/or some components of the multivesicular body sorting machinery is essential to correct sorting of cargoes into the multivesicular body pathway
-
-
-
additional information
?
-
-
H6YUH1 is unable to hydrolyze the linkage of ubiquitin with human growth hormone
-
-
-
additional information
?
-
-
neither Uch37 alone nor the Uch37-Adrm1 or Uch37-Adrm1-S1 complexes can hydrolyse di-ubiquitin efficiently, rather incorporation into the 19S complex is required to enable processing of polyubiquitin chains
-
-
-
additional information
?
-
-
UCH-L1 may directly destroy or neutralize oligomeric beta-amyloid peptide and may promote degradation of beta- and gamma secretase, or amyloid precursor protein
-
-
-
additional information
?
-
-
UCHL3 interacts with peripheral acrosomal plasma membrane proteins
-
-
-
additional information
?
-
-
wild-type UCH-L1 interacts with multiple proteins over 30 kDa. It shows no interaction with beta-actin
-
-
-
additional information
?
-
Q92560
Bap1 helps to control cell proliferation by regulating HCF-1 protein levels and by associating with genes involved in the G1-S transition
-
-
-
additional information
?
-
Q80TQ2
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
?
-
-
epigenetic inactivation of UCHL1 is common in primary hepatocellular carcinomas and other digestive tumors. UCHL1 appears to be a functional tumor suppressor involved in the tumorigenesis of hepatocellular carcinomas and other digestive cancers. Ectopic expression of UCHL1 induces apoptosis through intrinsic caspase-dependent pathway. UCHL1 directly interacts with p53 and inhibits p53 protein degradation
-
-
-
additional information
?
-
-
is overexpressed in alpha-tocopherol deficient mice
-
-
-
additional information
?
-
-
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic function of UCH-L1 in vivo, mono-ubiquitin and ubiquitin dimers may regulate the enzymatic function of UCH-L3 in vivo
-
-
-
additional information
?
-
-
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L3, in vivo
-
-
-
additional information
?
-
-
role for UCH-L1 and ubiquitin modification in podocyte differentiation and injury
-
-
-
additional information
?
-
P03186
shRNA decreases mRNA levels and reduces viral genome production. EBV deubiquitinating enzyme BPLF1 interacts with, deubiquitinates, and influences the activity of the Epstein-Barr virus ribonucleotide reductase
-
-
-
additional information
?
-
-
silencing of UCH-L1 in MCF7/Adr cells does not suppress cell growth. Overexpression of UCH-L1 in MCF7 cells induces apoptosis. Apoptosis triggered by UCH-L1 is, at least in part, probably through phosphoinositide 3-kinase/Akt signal pathway
-
-
-
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 key molecule to regulate tumor-cell invasion by upstream activation of Akt. Expression of UCH-L1 in tumor cells enhances their invasive potential in vitro and in vivo. UCH-L1 changes cell morphology by regulating cell adhesion through Akt-mediated pathway
-
-
-
additional information
?
-
-
UCH-L1 is a player in the signaling pathways that promote the proliferation and invasive capacity of malignant B-cells
-
-
-
additional information
?
-
B5KNK6
Uch-L1, via the ubiquitin-proteasome system, may play an important role not only in gametogenesis, but also in the gonadal transformation process in the rice field eel
-
-
-
additional information
?
-
-
Uch37 activities can be modulated both positively and negatively via dynamic interactions with partner proteins, whereby the proteasome and the hINO80 chromatin-remodeling complex may cooperate to regulate transcription or DNA repair
-
-
-
additional information
?
-
-
Cezanne-specific siRNA suppresses Cezanne mRNA and protein by at least 70% in culture cells. It leads to elevated NF-kappaB luciferase reporter gene activity and enhanced expression of IL-8 transcripts in TNFalpha-treated cells. Endogenous Cezanne can attenuate NF-kappaB activation and the induction of pro-inflammatory transcripts in response to TNF receptor signaling. Deubiquitinating activity of Cezanne is essential for NF-kappB suppression. Cezanne can be recruited to activated TNF receptors where it suppresses the build-up of polyubiquitinated RIP1 signal adapter proteins
-
-
-
additional information
?
-
P45974, Q5VVQ6
Iso-T shows high preference for the natural Leu-Arg-Gly motif in the P4–P2 positions. Only reactivity with norleucine at P4 and lysine at P3 mar the exquisite specificity
-
-
-
additional information
?
-
P45974, Q5VVQ6
OTU-1 shows similarly to UCH-L3 high specificity in the P2 and P3 positions and less specificity in the P4 position. The P4 position prefers norleucine over leucine, but other bulky amino acids are also accepted, such as tyrosine, tryptophan, phenylalanine or lysine
-
-
-
additional information
?
-
-
PLpro reveals very high specificity in the P4 position, where practically only leucine can be tolerated, and even higher specificity in the P2 position, with only glycine being accepted. However, the P3 position can accommodate a number of different amino acids, with some preference for the hydrophobes leucine and tyrosine, and also for the basic side chains of lysine and arginine, amino acids that possess a substantial hydrophobic character
-
-
-
additional information
?
-
-
UCH-L3 does not function to hydrolyze free ubiquitin dimers
-
-
-
additional information
?
-
-
UCH-L3 does not show hydrolase activity toward the K48-linked, K63-linked or linear ubiquitin dimer
-
-
-
additional information
?
-
P45974, Q5VVQ6
UCH-L3 shows a preference for leucine at P4, but also a broad tolerance of several other hydrophobic residues at this position. It also shows a surprising selectivity for alanine and valine at P2, in addition to the canonical glycine and high preference at the P3 position and relatively low specificity in the P4 position
-
-
-
additional information
?
-
-
interaction of the ubiquitin carboxyl terminal esterase L1 with alpha2-adrenergic receptors inhibits agonist-mediated p44/42 MAP kinase activation. Uch-L1 binds specifically to the third intracellular loop of alpha2A adrenergic receptor, but also to the respective loops of adrenergic receptors alpha2B, alpha2C, and beta2, overview
-
-
-
additional information
?
-
-
polyubiquitin processing, overview. UCHL1/PGP 9.5 also shows ligase activity when in a dimeric form, overview
-
-
-
additional information
?
-
-
the proteasomal pathway is partially inhibited by UCH-L1M
-
-
-
additional information
?
-
-
UCH L1 forms endogenous complexes with beta-catenin and stabilizes it. The expression and deubiquitinating activity of UCHL1 are required for its own basic promoter activity, therefore UCH L1 up-regulates its expression by activation of the oncogenic beta-catenin/TCF signaling in transformed cells
-
-
-
additional information
?
-
-
UCH-L1 can hydrolyze isopeptide bonds between the C-terminal glycine of Ub and the alpha- or gamma-amino group of lysine on the target proteins. UCH-L3 recognizes and hydrolyzes isopeptide bonds at the C-terminal glycine of either ubiquitin or Nedd8, a ubiquitin-like protein. It shows no ligase activity. UCH-L3 can interact with Lys48-linked ubiquitin dimers to protect it from degradation and meanwhile to inhibit its hydrolase activity, D33 and C95 are essential for the interaction with di-ubiquitin. Neither UCH37 alone nor the UCH37-Adrm1 or UCH37-Adrm1-hRpn2 complexes can hydrolyse Lys48-linked di-ubiquitin efficiently, rather, their incorporation into the 19S complex is required to enable UCH37 to process large ubiquitin protein conjugates such as di-ubiquitin
-
-
-
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme that catalyses the hydrolysis of polyubiquitin precursors and small ubiquitin adducts
-
-
-
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme, it binds to and stabilize mono-ubiquitin in neurons, UCH-L1 is a deubiquitinating enzyme, it binds to and stabilizes mono-ubiquitin in neurons
-
-
-
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme. UCH-L1 increases the synthesis of cystic fibrosis transmembrane conductance regulator, CFTR, but has little effect on the rate of post-translational degradation
-
-
-
additional information
?
-
-
UCHL1 can act as a ubiquitin hydrolase, and generate free ubiquitin species from precursor ubiquitin polypeptides. Synaptic activation of UCH-L1 is correlated with an increase in the levels of free monomeric ubiquitin
-
-
-
additional information
?
-
-
Phe214 is essential for distal-site substrate binding, and the loss of catalytic activity of the mutant may reflect its reduced affinity toward the substrate. The crystal structure of apo UCHL1 shows that the active-site residues are not aligned in a canonical form, with the nucleophilic cysteine being 7.7 A from the general base histidine, an arrangement consistent with an inactive form of the enzyme
-
-
-
additional information
?
-
-
purified PGP 9.5 from bovine brain exhibits a specific activity in cleaving ubiquitin-ethylester which is 40% of that shown by bovine thymus UCHL3. UCHL1/PGP 9.5 and UCHL3 hydrolysis rates of various synthetic ubiquitin conjugates compare to rates of hydrolysis of the generic substrate ubiquitin-ethylester. Both enzymes cleave ubiquitin from N-epsilon linked lysine or N-alpha-linked lysine equally well. Neither can cleave the Ub-K48 Ub bond, but both can cleave lysine from the C-terminal of this conjugate. UCHL3 can readily cleave a wide variety of peptides from the C-terminus of ubiquitin if the peptides are less than 20 residues, UCHL1/PGP 9.5 is at least a hundred times less active in this
-
-
-
additional information
?
-
-
the apparent catalytic triad of amino acids in UCHL1 is Cys90, His161 and Asp176 in the active site. The region forming a disordered crossover loop limiting access of substrates to the active site is located at positions 140-160, overview
-
-
-
additional information
?
-
B5KNK6
Uch-L1 binds to and interacts with monoubiqutin
-
-
-
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 SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
disassembly of polyubiquitin, terminal step of the proteasome pathway, scheme, inhibition by prostaglandins of the J series leads to accumulation of polyubiquitins of MW around 250 kDa
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
substrate of UCHL3, no activity with UCHL1/PGP 9.5
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
-
UCHL1/PGP 9.5, overview
-
-
?
polyubiquitin + H2O
ubiquitin
show the reaction diagram
Ictalurus punctatus, Ictalurus punctatus Rafinesque
B6E460
UCHL5 deubiquitylates the polyubiquitin chain into ubiquitin
-
-
?
type I TGF-beta receptor + H2O
?
show the reaction diagram
Q9Y5K5
UCH37 deubiquitinates and stabilizes type I TGF-beta receptor. Overexpression of UCH37 upregulates TGF-beta-dependent transcription
-
-
?
ubiquitin-CEP52 + H2O
ubiquitin + CEP52
show the reaction diagram
-
substrate of UCHL1/PGP 9.5, no activity with UCHL3
-
-
?
ubiquitin-CEP80 + H2O
ubiquitin + CEP80
show the reaction diagram
-
substrate of UCHL3 and UCHL1/PGP 9.5
-
-
?
ubiquitin-peptide + H2O
?
show the reaction diagram
-
UCH enzymes may function to regenerate active ubiquitin from adducts with small nuceleophiles
-
-
-
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
-
-
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
-
involved in endocytotic pathway of plasma membrane proteins
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
-
enzyme is crucial for polarization of the actin cytoskeleton, to segregate germline determinants, to assemble an intact cleavage furrow, for cytokinesis and to maintain osmotic balance and execute actin-dependent processes in the early embryo
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
-
Doap4 enzyme form plays a general role in deubiquination of membrane-bound proteins
-
?
ubiquitin-protein + H2O
ubiquitin + protein
show the reaction diagram
Q9UK80
important role in regulation of cell growth
-
?
additional information
?
-
P40818
enzyme inhibits cell proliferation
-
-
-
additional information
?
-
Q9R0P9
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
?
-
P09936
increased activity of neuronal isozyme L1 reduces the risk for Parkinson's disease
-
-
-
additional information
?
-
-
enzyme regulation
-
-
-
additional information
?
-
P40818
enzyme regulation
-
-
-
additional information
?
-
-
AMSH is a deubiquinating enzyme with functions at the endosome, it opposes the ubiquitin-dependent sorting of receptors to lysosomes, the enzyme influences the degradation of the EGF receptor by association to endosomes, model of the enzyme's physiological function
-
-
-
additional information
?
-
Q00981
de novo synthesis of isozyme UCH-L1 in rostral ventrolateral medulla is crucial to survival during mevinphos intoxication, the enzyme is involved in synthesis of ubiquitin which is required for protein targeting in degradation in the ubiquitin-proteasome pathway in neurons, UCH-L1 plays a neuroprotective role
-
-
-
additional information
?
-
P09936
gene uch-L1 is involved in development of Parkinson's disease
-
-
-
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 involved in generation of free monomeric ubiquitin, enzyme deficiency leads is involved in accumulation of ubiquitin and alpha-synuclein leading to aggregation in proteins conforming Lewy bodies and Lewy neurites leading to Parkinson's disease and dementia with Lewy bodies, the enzyme is down-regulated in Alzheimer's disease and in Parkinson's disease, comparison of enzyme expression to general protein synthesis and proteasome activity in brain
-
-
-
additional information
?
-
P15347
the enzyme is involved in spermatogenesis
-
-
-
additional information
?
-
Q60HC8
the enzyme is necessary for placental and fetal development
-
-
-
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
?
-
-
the full length UCH-L1 is a de-ubiquinating enzyme in brain, and a major target of oxidative damage in Alzheimer's diesease and Parkinson's disease brains, modified by cysteine and methionine oxidation and carbonyl formation
-
-
-
additional information
?
-
-
ubiquitin carboxy-terminal hydrolase L1 activates the P2X receptor leading to potentiation of ATP-induced currents in neurons
-
-
-
additional information
?
-
-
UCH-L1 functions in sperm quality control during epididymal maturation
-
-
-
additional information
?
-
-
UCH-L1 is involved in Parkinson's disease
-
-
-
additional information
?
-
P09936
UCH-L1 is involved in Parkinson's disease
-
-
-
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
?
-
Q9JKB1
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
?
-
Q9R0P9
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
?
-
-
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
?
-
-
overexpression of UCH L1 potentiates ATP-induced currents due to the activation of P2X receptors that are widely distributed in the brain and involved in various biological activities including neurosecretion. UCH-L1 may play an important role in synaptic activity
-
-
-
additional information
?
-
-
oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinsons and Alzheimers diseases
-
-
-
additional information
?
-
-
the enzyme may play a significant role in implantation and placental development, and differentiation of embryonic ectoderm
-
-
-
additional information
?
-
Q9JKB1
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
?
-
Q6YI49
uch-L1 may have an important role in the development of neuronal cells in early embryos as well as in the degeneration and disease of neuronal cells in late adult brain. The gene for ubiquitin C-terminal hydrolase L1 is associated with inherited forms of Parkinson's disease
-
-
-
additional information
?
-
Q9R0P9
UCH-L1 may play an important role in neurodegeneration of amyloid lateral sclerosis
-
-
-
additional information
?
-
-
UCHL1 is an essential gene in cell survival under normal growth conditions and against oxidative stress, UCHL1 is an essential gene to maintain cell homeostasis under normal growth and oxidative stress conditions
-
-
-
additional information
?
-
-
UCHL1 is associated with Parkinsons disease
-
-
-
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
?
-
Q92560
Bap1 helps to control cell proliferation by regulating HCF-1 protein levels and by associating with genes involved in the G1-S transition
-
-
-
additional information
?
-
Q80TQ2
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
?
-
-
epigenetic inactivation of UCHL1 is common in primary hepatocellular carcinomas and other digestive tumors. UCHL1 appears to be a functional tumor suppressor involved in the tumorigenesis of hepatocellular carcinomas and other digestive cancers. Ectopic expression of UCHL1 induces apoptosis through intrinsic caspase-dependent pathway. UCHL1 directly interacts with p53 and inhibits p53 protein degradation
-
-
-
additional information
?
-
-
is overexpressed in alpha-tocopherol deficient mice
-
-
-
additional information
?
-
-
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic function of UCH-L1 in vivo, mono-ubiquitin and ubiquitin dimers may regulate the enzymatic function of UCH-L3 in vivo
-
-
-
additional information
?
-
-
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L3, in vivo
-
-
-
additional information
?
-
-
role for UCH-L1 and ubiquitin modification in podocyte differentiation and injury
-
-
-
additional information
?
-
P03186
shRNA decreases mRNA levels and reduces viral genome production. EBV deubiquitinating enzyme BPLF1 interacts with, deubiquitinates, and influences the activity of the Epstein-Barr virus ribonucleotide reductase
-
-
-
additional information
?
-
-
silencing of UCH-L1 in MCF7/Adr cells does not suppress cell growth. Overexpression of UCH-L1 in MCF7 cells induces apoptosis. Apoptosis triggered by UCH-L1 is, at least in part, probably through phosphoinositide 3-kinase/Akt signal pathway
-
-
-
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 key molecule to regulate tumor-cell invasion by upstream activation of Akt. Expression of UCH-L1 in tumor cells enhances their invasive potential in vitro and in vivo. UCH-L1 changes cell morphology by regulating cell adhesion through Akt-mediated pathway
-
-
-
additional information
?
-
-
UCH-L1 is a player in the signaling pathways that promote the proliferation and invasive capacity of malignant B-cells
-
-
-
additional information
?
-
B5KNK6
Uch-L1, via the ubiquitin-proteasome system, may play an important role not only in gametogenesis, but also in the gonadal transformation process in the rice field eel
-
-
-
additional information
?
-
-
Uch37 activities can be modulated both positively and negatively via dynamic interactions with partner proteins, whereby the proteasome and the hINO80 chromatin-remodeling complex may cooperate to regulate transcription or DNA repair
-
-
-
additional information
?
-
-
interaction of the ubiquitin carboxyl terminal esterase L1 with alpha2-adrenergic receptors inhibits agonist-mediated p44/42 MAP kinase activation. Uch-L1 binds specifically to the third intracellular loop of alpha2A adrenergic receptor, but also to the respective loops of adrenergic receptors alpha2B, alpha2C, and beta2, overview
-
-
-
additional information
?
-
-
polyubiquitin processing, overview. UCHL1/PGP 9.5 also shows ligase activity when in a dimeric form, overview
-
-
-
additional information
?
-
-
the proteasomal pathway is partially inhibited by UCH-L1M
-
-
-
additional information
?
-
-
UCH L1 forms endogenous complexes with beta-catenin and stabilizes it. The expression and deubiquitinating activity of UCHL1 are required for its own basic promoter activity, therefore UCH L1 up-regulates its expression by activation of the oncogenic beta-catenin/TCF signaling in transformed cells
-
-
-
additional information
?
-
-
UCH-L1 can hydrolyze isopeptide bonds between the C-terminal glycine of Ub and the alpha- or gamma-amino group of lysine on the target proteins. UCH-L3 recognizes and hydrolyzes isopeptide bonds at the C-terminal glycine of either ubiquitin or Nedd8, a ubiquitin-like protein. It shows no ligase activity. UCH-L3 can interact with Lys48-linked ubiquitin dimers to protect it from degradation and meanwhile to inhibit its hydrolase activity, D33 and C95 are essential for the interaction with di-ubiquitin. Neither UCH37 alone nor the UCH37-Adrm1 or UCH37-Adrm1-hRpn2 complexes can hydrolyse Lys48-linked di-ubiquitin efficiently, rather, their incorporation into the 19S complex is required to enable UCH37 to process large ubiquitin protein conjugates such as di-ubiquitin
-
-
-
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme that catalyses the hydrolysis of polyubiquitin precursors and small ubiquitin adducts
-
-
-
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme, it binds to and stabilize mono-ubiquitin in neurons, UCH-L1 is a deubiquitinating enzyme, it binds to and stabilizes mono-ubiquitin in neurons
-
-
-
additional information
?
-
-
UCH-L1 is a deubiquitinating enzyme. UCH-L1 increases the synthesis of cystic fibrosis transmembrane conductance regulator, CFTR, but has little effect on the rate of post-translational degradation
-
-
-
additional information
?
-
-
UCHL1 can act as a ubiquitin hydrolase, and generate free ubiquitin species from precursor ubiquitin polypeptides. Synaptic activation of UCH-L1 is correlated with an increase in the levels of free monomeric ubiquitin
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cu2+
-
0.2 mol per mol of protein, native isozyme ISOT-S
Divalent cations
-
most divalent cations, except Mg2+ and Ca2+ are inhibitory
Ni2+
-
0.5 mol per mol of protein, native isozyme ISOT-S
Zn2+
-
0.9 mol per mol of protein, native isozyme ISOT-S; absolutely required, apoenzyme is inactive; both isozymes contain each two Zn2+-binding sites: one essential for proteolytic activity with high affinity as part of a cryptic nitrilo-triacetate-resistant pocket, a second which is enclosed with an excess of Zn2+; isozyme ISOT-S: Ni2+ can substitute by 90% for Zn2+, Cu2+ by 10%; removal and reconstitution methods, overview; the Zn2+ bound to binding site 1 can be removed slowly by dialysis against 1,10-phenanthroline at pH 5.5, or rapidly by treatment at pH 3.0 in presence of 6 M urea followed by gel filtration at neutral pH
Zn2+
-
AMSH contains the JAMM motif, i.e. JAB1/MPN/Mov34 metalloenzyme motif, in the active site
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3E)-1-(3,4-dichlorobenzyl)-4-methoxy-5-phenyl-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0061 mM
(3E)-1-(3,4-dichlorobenzyl)-5-iodo-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.00094 mM; IC50: 0.016 mM
(3E)-1-(3,4-dichlorobenzyl)-5-methoxy-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0029 mM
(3E)-1-{2-bromo-2-[3-(trifluoromethyl)phenyl]ethyl}-5-chloro-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0095 mM
(3E)-3-[(acetyloxy)imino]-1-(3,4-dichlorobenzyl)-2-oxoindoline-5-carbonitrile
-
IC50: 0.012 mM
(3E)-3-[(acetyloxy)imino]-1-(3,4-dichlorobenzyl)-2-oxoindoline-5-carboxamide
-
IC50: 0.0041 mM
(3E)-3-[(acetyloxy)imino]-1-(3,4-dichlorobenzyl)-2-oxoindoline-5-carboxylic acid
-
IC50: 0.05 mM
(3E)-5-(trifluoromethoxy)-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0034 mM
(3E)-5-(trifluoromethoxy)-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.078 mM
(3E)-5-bromo-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.00081 mM
(3E)-5-chloro-1-(2,3-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0027 mM
(3E)-5-chloro-1-(2,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0012 mM
(3E)-5-chloro-1-(2,5-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.00088 mM
(3E)-5-chloro-1-(2-chloro-5-fluorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0065 mM
(3E)-5-chloro-1-(2-naphthylmethyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.014 mM
(3E)-5-chloro-1-(2-phenylethyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.019 mM
(3E)-5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0018 mM; IC50: 0.017 mM
(3E)-5-chloro-1-(3,5-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0013 mM
(3E)-5-chloro-1-(3-chloro-4-methoxybenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.021 mM
(3E)-5-chloro-1-(3-methoxybenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.013 mM
(3E)-5-chloro-1-(4-chlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.012 mM
(3E)-5-chloro-1-(4-methoxybenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.052 mM
(3E)-5-chloro-1-[2-(3,4-dichlorophenoxy)ethyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0062 mM
(3E)-5-chloro-1-[2-(3,4-dichlorophenyl)ethyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0013 mM
(3E)-5-chloro-1-[2-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.018 mM
(3E)-5-chloro-1-[2-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.321 mM
(3E)-5-chloro-1-[3-(3,4-dichlorophenyl)propyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.016 mM
(3E)-5-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.006 mM; IC50: 0.036 mM
(3E)-5-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.114 mM
(3E)-5-chloro-1-[4-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.012 mM
(3E)-5-chloro-1-[4-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.013 mM
(3E)-5-chloro-1-{1-[2-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0088 mM
(3E)-5-chloro-1-{1-[2-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-oxime
-
IC50: 0.045 mM
(3E)-5-chloro-1-{1-[3-(trichloromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0034 mM
(3E)-5-chloro-1-{1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-oxime
-
IC50: 0.022 mM
(3E)-5-chloro-1-{2-ethoxy-2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.095 mM
(3E)-5-chloro-1-{2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.019 mM
(3E)-5-chloro-1-{2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0041 mM
(3E)-5-chloro-1-{2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-oxime
-
IC50: 0.08 mM
(3E)-5-chloro-7-methyl-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.012 mM
(3E)-5-fluoro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0061 mM
(3E)-5-fluoro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.043 mM
(3E)-6-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0058 mM
1-(1,3-benzodioxol-5-ylmethyl)-4-(4-([(4-chlorophenyl)thio]methyl)benzoyl) piperazine
-
slight inhibition of UCH-L1
1-benzyl-3-hydroxy-4-(5-methyl-2-furoyl)-5-(3-pyridinyl)-1,5-dihydro-2H-pyrrol-2-one
-
is a competitive inhibitor of UCH-L3, significantly inhibits hydrolysis activity of UCH-L3 by 83.2%
15-deoxy-DELTA12,14-prostaglandin J2
-
modification of UCH-L1 by cyclopentenone prostaglandins causes unfolding and aggregation. A single thiol group on Cys152 reacts with the alpha,beta-unsaturated carbonyl center in the cyclopentenone ring of prostaglandins, resulting in a covalent adduct, spectral analysis, overview
2-([4-(2-furylmethyl)-5-(2-thienylmethyl)-4H-1,2,4-triazol-3-yl]thio)-N-(2-methoxydibenzo[b,d]furan-3-yl)acetamide
-
-
2-propenal
-
carbonyl modification with 0.1 mM
2-[(5-ethyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)thio]-N-(4-methyl-2-pyridinyl)acetamide
-
-
3-amino-2-(4-methylbenzoyl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylaic acid
-
an uncompetitive inhibitor of UCHL1 that binds only to the Michaelis complex and not to free enzyme
3-amino-2-(cyclohexylcarbonyl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-keto-7Hthieno[2,3-b]pyridin-6-one derivative
-
-
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
-
-
3-hydroxy-5-(4-methoxyphenyl)-1-(1,3,4-thiadiazol-2-yl)-4-(2-thienylcarbonyl)-1,5-dihydro-2H-pyrrol-2-one
-
significantly inhibits hydrolysis activity of UCH-L3 by 76.5%
3-[4-methyl-5-(([3-(2-thienyl)-1,2,4-oxadiazol-5-yl]methyl)thio)-4H-1,2,4-triazol-3-yl]-1H-indole
-
inhibits hydrolysis activity by 16.2%
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
4-([benzyl(methyl)amino]sulfonyl)-N-[5-(benzylthio)-1,3,4-thiadiazol-2-yl]benzamide
-
-
4-hydroxy-2-hexenal
-
carbonyl modification in a dose-dependent manner
4-hydroxy-2-nonenal
-
carbonyl modification with 0.01-0.1 mM leads to decreased ubiquitin binding, and both increased insolubility and interactions with proteins over 30 kDa compared with the wild-type
5-(4-fluorophenyl)-3-hydroxy-4-(5-methyl-2-furoyl)-1-(3-pyridinylmethyl)-1,5-dihydro-2H-pyrrol-2-one
-
significantly inhibits hydrolysis activity of UCH-L3 by 76.8%
5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0018 mM
5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-oxime
-
IC50: 0.012 mM
8-[(1H-benzimidazol-2-ylmethyl)sulfanyl]-2,2-dimethyl-5-(morpholin-4-yl)-1,4-dihydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine
-
-
aldehyde product of fatty acid peroxidation
P09936
i.e. HNE; modifies isozyme L1 at physiological concentrations of 0.01-0.1 mM and reduces enzyme activity, excess N-acetyl-L-cysteine protects
-
amyloid beta
-
30% inhibition
-
Antibody
-
anti-UCH antibodies increase the rate of polyspermy during in vitro fertilization by reducing UCH enzymatic activity
-
Ca2+
-
59% inhibition at 5 mM
dimethyl sulfoxide
-
catalytic activity decreases slightly with increasing dimethyl sulfoxide concentrations. At 2% (v/v) dimethyl sulfoxide, the proteolytic activity of UCH-L3 is reduced by ca. 5% in comparison to dimethyl sulfoxide-free conditions
dipicolinic acid
-
-
DTT
-
erythrocyte isozyme ISOT-S and ISOT-L, inhibition by chelating of Zn2+
EDTA
-
-
EGTA
-
-
epoxysuccinyl-leucylamido-(4-guanidino) butane
-
reduces UCH-L1 mRNA, protein level and activity. Caspase-mediated apoptosis in epoxysuccinyl-leucylamido-(4-guanidino) butane-treated fibroblasts is reversed by transfection with a UCH-L1 plasmid
iodoacetamide
-
Cys-residue for catalysis
iodoacetamide
-
-
iodoacetamide
-
-
iodoacetamide
-
-
iodoacetamide
-
is a non-competitive inhibitor of UCH-L3
iodoacetamide
-
prevents deubiquitination
isatin O-acyl oximes
-
reversible and competitive inhibition, inhibitory potency and features of the drivatives, specific inhibition of UCH-L1, poor inhibition of UCH-L3, IC50 values, overview
J series prostaglandins
-
inhibition of the enzyme is involved in disruption of the proteasome pathway and leads to apoptosis
-
KCl
-
92% inhibition at 0.2 M
LDN 57 444
-
UCH-L1 inhibition leads to a time and concentration-dependent formation of membrane protrusions, accompanied by redistribution of alpha-actinin-4 to the membrane. Expression level of alpha-actinin-4 remains stable, whereas the beta-catenin content increases. Inhibition of UCH-L1 does not induce apoptosis
LDN-57444
-
reversible, competitive, active site-directed isatin oxime, 70% inhibition with 0.005 mM
LDN-57444
-
a reversible, competitive, active site-directed isatin oxime with consistent preference for UCHL1 over UCHL3 by 28fold
LDN-57444
-
i.e. 3-(O-acetyloxime), 5-chloro-1-[(2,5-dichlorophenyl)methyl]-1H-indole-2,3-dione
Mg2+
-
61% inhibition at 5 mM
Mn2+
-
-
N,N'-(oxydi-4,1-phenylene)dibenzenesulfonamide
-
slight inhibition of UCH-L1
N,N'-4,4'-biphenyldiylbis(4-ethylbenzenesulfonamide)
-
strong inhibition of UCH-L1
N-(2-[(6,7-dimethoxy-1-isoquinolinyl)methyl]-4,5-dimethoxyphenyl)-4-(2-oxo-1-pyrrolidinyl)benzenesulfonamide
-
slight inhibition of UCH-L1
N-(3,6-dichloro-2-pyridinyl)-N'-([(4,6-diphenyl-2-pyrimidinyl)amino]carbonyl)sulfamide
-
-
N-(4-([(4-ethoxyphenyl)amino]sulfonyl)phenyl)-2-naphthalenesulfonamide
-
slight inhibition of UCH-L1
N-(4-([(4-methylphenyl)amino]sulfonyl)phenyl)-2-phenyl-2-(phenylthio)acetamide
-
slight inhibition of UCH-L1
N-ethylmaleimide
-
UCH-8
N-ethylmaleimide
P40818
UBPY
N-[2-(4-benzyl-1-piperazinyl)-2-oxoethyl]-N-(3-methylphenyl)benzenesulfonamide
-
slight inhibition of UCH-L1
nitrilo-triacetate
-
-
oligomeric Abeta
-
treatment of hippocampal slices produces a deficit in long term potentiation. Effect can be reversed by coadministering a recombinant UCH-L1 protein
-
peptides
-
containing either of the cleavage site sequence found in ubiquitin polymers, but not unrelated peptides
RNAi
-
knockdown of UCH37, abolishes TGF-beta-dependent transcriptional responses
-
RNAi
-
knockdown of UCHL1, leads to short lifespan of animals and earlier accumulation of aging specific lipofucsin with increasing age when compared with the wild-type
-
RNAi
-
knockdown of UCH-L1, inhibits the proliferation of BL cells in suspension and semisolid agar and activates strong LFA-1 dependent homotypic adhesion
-
RNAi
-
suppressing UCH-L1 expression by RNAi significantly suppresses the invasion in vitro and in vivo, and the activation of Akt and downstream mitogen activates protein kinases c-Jun N-terminal kinases and p38, but not ERK
-
siRNA
-
knockdown of UCHL1 by small interfering RNA results in increased nuclear factor-kappa B activity in A7r5 cells
-
siRNA
-
inhibits the expression of UCH-L1 in normal control fibroblasts, followed by a remarkable increase of apoptosis both in the presence and in the absence of epoxysuccinyl-leucylamido-(4-guanidino) butane. UCH-L1 siRNA 14311 almost completely inhibits synthesis of UCH-L1 protein in about 70% of cells and reduces the UCH-L1 mRNA level more then 7fold
-
siRNA
-
knockdown of UCH-L3 leads to a decrease of epithelial sodium channel currents
-
siRNA
Q92560
stabilization of HCF-1 through depletion of Bap1. Knockdown of Bap1 results in a modest increase in the steady-state levels of HCF-1, which presumably helps to promote the transition from G1 into S-phase
-
tosyl-L-phenylalanine chloromethyl ketone
Q9CVD2
inhibits fragmentation of AT-3 carrying six consecutive glutamines
ubiquitin
-
product inhibition
ubiquitin
-
submicromolar concentrations activate while higher concentrations inhibit the enzyme, regulatory function, 2-step inhibition mechanism via 2 ubiquitin binding sites extending the active site
ubiquitin
-
-
ubiquitin
-
; isozyme L1
ubiquitin
-
-
ubiquitin
-
free ubiquitin acts as a specific, competitive, noncovalent inhibitor
ubiquitin
P45974, Q5VVQ6
increasing ubiquitin concentrationin reveals a decrease in the cleavage efficiency, presumably as a result of competition between the second (substrate) ubiquitin molecule and the fluorigenic substrate binding to the enzyme active centre; increasing ubiquitin concentrationin reveals a decrease in the cleavage efficiency, presumably as a result of competition between the second (substrate) ubiquitin molecule and the fluorigenic substrate binding to the enzyme active centre. In the case of OTU-1 full-length ubiquitin does not result in any substantial decrease or increase of the processing of the fluorigenic substrate; increasing ubiquitin concentrationin reveals a decrease in the cleavage efficiency, presumably as a result of competition between the second (substrate) ubiquitin molecule and the fluorigenic substrate binding to the enzyme active centre. In the case of UCH-L3 inhibition of the fluorigenic substrate by elevated concentrations of full-length ubiquitin
Ubiquitin aldehyde
-
carboxy-terminal aldehyde of ubiquitin
-
Ubiquitin aldehyde
-
inhibition in absence of ubiquitin, competitive to ubiquitin
-
Ubiquitin aldehyde
-
UCH-8
-
Ubiquitin aldehyde
-
inhibition mechanism
-
Ubiquitin aldehyde
-
specific nonpermeating UCH inhibitor, signficantly increases rates of sperm-zona pellucida penetration and polyspermy during in vitro fertilization by reducing UCH enzymatic activity in motile boar spermatozoa. Ipase-T and ubiquitin aldehyde cancel each other out when added concomitantly to the fertilization medium
-
Ubiquitin aldehyde
-
specific inhibitor for UCH, partly inhibits maturation of ubiquitin precursor derivative in living oocytes
-
Ubiquitin aldehyde
-
-
-
ubiquitin vinyl methyl ester
-
a ubiquitin-based suicide substrate, binding structure analysis with wild-type and mutant S18Y enzymes, overview
-
ubiquitin vinylmethyl ester
P15374
inhibitor forms a covalent adduct with the active site cysteine of the enzyme
-
ubiquitin vinylsulfone
-
irreversible inhibitor that covalently modifies the active-site cysteines of DUBs
-
ubiquitin-aldehyde
-
-
ubiquitin-aldehyde
-
-
Mn2+
-
98% inhibition at 5 mM
additional information
-
not inhibited by phenylmethylsulfonyl fluoride, 1,10-phenanthroline
-
additional information
-
no inhibition by PMSF, EDTA, and o-phenanthroline
-
additional information
-
IC50 above 0.1 mM: (3E)-5-chloro-1-(pyridin-3-ylmethyl)-1H-indole-2,3-dione 3-(O-acetyloxime), (3E)-5-chloro-1-(pyridin-4-ylmethyl)-1H-indole-2,3-dione 3-(O-acetyloxime), 4-({(3E)-3-[(acetyloxy)imino]-5-chloro-2-oxo-2,3-dihydro-1H-indol-1-yl}methyl)benzoic acid
-
additional information
-
the enzyme is inhibited by zinc-chelating agents
-
additional information
-
not inhibited by N1-cyclopropyl-N2-(4-methoxyphenyl)-N2-[(4-methylphenyl)sulfonyl]glycinamide, N-(3-[1-acetyl-5-(2-thienyl)-4,5-dihydro-1H-pyrazol-3-yl]phenyl)ethanesulfonamide, N1-cyclopropyl-N2-[(4-methoxyphenyl)sulfonyl]-N2-(4-methylphenyl)glycinamide, N1-cyclopentyl-N2-(3-methoxyphenyl)-N2-(phenylsulfonyl)glycinamide and 4-(([5-(2-furyl)-4-phenyl-4H-1,2,4-triazol-3-yl]thio)methyl)-1,3-thiazol-2-amine
-
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
Q9CVD2
EDTA, HgCl2 and p-chloro-mecuribenzoate do not inhibit fragmentation of AT-3 carrying six consecutive glutamines
-
additional information
-
no carbonyl modification with 0.1 mM or 0.5 mM methylglyoxal and 0.1 mM or 0.5 mM malondialdehyde
-
additional information
-
monoubiquitination inhibits ubiquitin binding in vitro and prevents UCH-L1 from regulating free ubiquitin levels in cells involving auto-deubiquitination. Intramolecular deubiquitination, which is dependent on the hydrolytic activity of UCH-L1, regulates the lifetime of monoubiquitination, thereby affecting the cellular level of monoubiquitinated UCH-L1
-
additional information
-
phenylmethylsulfonyl fluoride does not affect significantly the UCH-enzyme activity
-
additional information
P45974, Q5VVQ6
very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity, most dramatic for OTU-1, which is due to enzyme precipitation in the assay
-
additional information
-
very high sodium citrate concentrations reveal a decrease in activity. Full-length ubiquitin does not result in any substantial decrease or increase of the processing of the fluorigenic substrate
-
additional information
-
in high metastatic potential clones, two isoforms of UCH-L1 are downregulated
-
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
-
additional information
-
in vitro, K48-linked ubiquitin dimers pronouncedly inhibit the hydrolase activity of UCH-L3; mono-ubiquitin, a previously identified interacting protein, inhibits the hydrolase activity of UCH-L1
-
additional information
-
kinetics and inhibitor docking study using crystal structure data of PDB code 2ETL, overview. No or poor inhibition by 3-methyl-8-(4-methyl-1-piperazinyl)-7-(3-phenylpropyl)-3,7-dihydro-1Hpurine-2,6-dione, 1-(4-methoxyphenyl)-4-([3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]methyl)piperazine, N1-cyclopropyl-N2-(4-ethoxyphenyl)-N2-[(4-methylphenyl)sulfonyl]glycinamide, N-[6-((2-[(4-chlorophenyl)thio]acetyl)amino)-1,3-benzothiazol-2-yl]butanamide and N-1,3-benzothiazol-2-yl-2-([5-(4-morpholinylmethyl)-4-phenyl-4H-1,2,4-triazol-3-yl]thio)acetamide
-
additional information
-
UCH-L1 is easily affected by redox status
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
active-site thiol is very sensitive to oxidation and requires reductants
4-hydroxy-2-alkenal
-
modification of UCH-L1 promotes direct interactions between UCH-L1 and tubulin
4-hydroxy-2-nonenal
-
modification of UCH-L1 promotes direct interactions between UCH-L1 and tubulin
Adrm1
-
recruits Uch37 to the proteasome. Binds the carboxy-terminal tail of Uch37. Following binding, Adrm1 relieves Uch37 autoinhibition, accelerating the hydrolysis of ubiquitin-7-amido-4-methylcoumarin
-
DTT
-
active-site thiol is very sensitive to oxidation and requires reductants
DTT
-
inactivated in absence of DTT
DTT
-
required, hydrolase activity of UCH-L1 in vitro is decreased when reducing dithiothreitol is omitted from the reaction buffer
ethyl 1-[N-(4-methylphenyl)-N-(methylsulfonyl)alanyl]-4-piperidinecarboxylate
-
-
poly-L-Arg
-
activation
poly-L-Lys
-
activation
Sodium citrate
P45974, Q5VVQ6
activation of the enzymes with increasing salt concentration, reaching a maximum above 0.8 M. Most effective activation in the case of UCH-L3, where 1.1 M sodium citrate enhances catalysis on the synthetic substrate Ac-LRGG-7-amido-4-trifluoromethylcoumarin about 24fold, compared with low-salt conditions. The tetrapeptide substrate Ac-LRGG-7-amido-4-trifluoromethylcoumarin and the pentapeptide substrate containing alanine at position P5, namely Ac-ALRGG-7-amido-4-trifluoromethylcoumarin, both demonstrate a salt effect, but the pentapeptide substrate containing arginine in position P5, Ac-RLRGG-7-amido-4-trifluoromethylcoumarin, does not demonstrate one; activation of the enzymes with increasing salt concentration, reaching a maximum above 0.8 M. The tetrapeptide substrate Ac-LRGG-7-amido-4-trifluoromethylcoumarin and the pentapeptide substrate containing alanine at position P5, namely Ac-ALRGG-7-amido-4-trifluoromethylcoumarin, both demonstrate a salt effect, but the pentapeptide substrate containing arginine in position P5, Ac-RLRGG-7-amido-4-trifluoromethylcoumarin, does not demonstrate one; activation of the enzymes with increasing salt concentration, reaching a maximum above 0.8 M. Weakest activation in the case of IsoT, where there is almost no increase in catalysis compared with low salt conditions. The tetrapeptide substrate Ac-LRGG-7-amido-4-trifluoromethylcoumarin and the pentapeptide substrate containing alanine at position P5, namely Ac-ALRGG-7-amido-4-trifluoromethylcoumarin, both demonstrate a salt effect, but the pentapeptide substrate containing arginine in position P5, Ac-RLRGG-7-amido-4-trifluoromethylcoumarin, does not demonstrate one
TNFalpha
-
inducer
-
tumor necrosis factor-alpha
-
treatment of cultured vascular smooth muscle cells for 24 and 48 hours does not significantly alter UCHL1 mRNA levels, whereas long term treatment (96 hours) significantly increases UCHL1 mRNA levels. Treatment of aortic endothelial cells and aortic smooth muscle cells with tumor necrosis factor-alpha for 24 hours does not significantly alter UCHL1 mRNA levels
-
ubiquitin
-
submicromolar concentrations activate while higher concentrations inhibit the enzyme, regulatory function, binding via 2 ubiquitin binding sites extending the active site
ubiquitin
P45974, Q5VVQ6
20fold enhancement of the cleavage of Ac-LRGG-7-amido-4-trifluoromethylcoumarin by IsoT in the presence of equimolar ubiquitin; iIn the case of OTU-1 full-length ubiquitin does not result in any substantial decrease or increase of the processing of the fluorigenic substrate
H2O2
-
-
additional information
-
enzymatic activation mediated by substrate binding; enzyme activation modeling
-
additional information
-
treatment of aortic endothelial cells and aortic smooth muscle cells with human recombinant epidermal growth factor, fibroblast growth factor-2, vascular endothelial growth factor, lipopolysaccharide, angiotensin II or hydrogen peroxide for 24 hours does not significantly alter UCHL1 mRNA levels
-
additional information
-
6-hydroxydopamine induces oxidative stress in human neuroblastoma SH-SY5Y cells. UCH-L1 is an oxidative-stress-reporting biomarker
-
additional information
-
activation of the enzyme with increasing salt concentration, reaching a maximum above 0.8 M
-
additional information
-
UCH-L1 expression correlates with podocyte ubiquitin content and internalization of the podocyte-specific proteins nephrin and alpha-actinin-4
-
additional information
-
UCH-L1 is significantly elevated in cerebrospinal fluid following controlled cortical impact and middle cerebral artery occlusion, as a model of ischemic stroke, in rats, overview
-
additional information
-
UCH-L1 activity is regulated by synaptic activity. Stimulation of synaptic activity by NMDA/glycine significantly up-regulates UCH-L1 activity in cultured neurons. NMDA-induced up-regulation of UCH-L1 activity is efficiently blocked by pre-treatment of neurons with the NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid
-
additional information
-
UCH-L1 is easily affected by redox status
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
branched dimeric ubiquitin
-
pH 7.2, 37°C
-
0.0006
ubiquitin ethyl ester
-
-
-
0.0006
ubiquitin ethyl ester
-
isozyme L1
-
0.0006
ubiquitin ethyl ester
-
pH 8.0, 37°C, isozyme L3
-
0.0012
ubiquitin ethyl ester
-
pH 8.0, 37°C, isozyme L1
-
0.008
ubiquitin ethyl ester
-
pH 8.0, 37°C, isozyme H2
-
0.03
ubiquitin ethyl ester
-
pH 8.0, 37°C, isozyme L2
-
0.0000833
ubiquitin-7-amido-4-methylcoumarin
-
-
-
0.00004
ubiquitin-7-amino-4-methylcoumarin
synthetic construct
-
with UCH-L1
-
0.00011
ubiquitin-7-amino-4-methylcoumarin
P09936
recombinant mutant I93M isozyme L1, pH 7.8, room temperature
-
0.00012
ubiquitin-7-amino-4-methylcoumarin
P09936
recombinant wild-type isozyme L1, pH 7.8, room temperature
-
0.00014
ubiquitin-7-amino-4-methylcoumarin
P09936
recombinant mutant S18Y isozyme L1, pH 7.8, room temperature
-
0.00016
ubiquitin-7-amino-4-methylcoumarin
-
recombinant wild-type isozyme L1, pH 7.5, 25°C
-
0.00008
ubiquitin-AW
synthetic construct
-
with UCH-L1
-
0.000034
ubiquitin-rhodamine110-glycine
-
-
-
0.00013
ubiquitin-W
synthetic construct
-
with UCH-L1
-
0.0001
ubiquitin-W-G75A
synthetic construct
-
with UCH-L1
-
0.0004
ubiquitin-W-G75A
synthetic construct
-
with UCH-L3
-
0.0011
ubiquitin-W-G76A
synthetic construct
-
with UCH-L3
-
0.002
ubiquitin-W-G76A
synthetic construct
-
with UCH-L1
-
0.0005
ubiquitin-W-H68A
synthetic construct
-
with UCH-L1; with UCH-L3
-
0.00031
ubiquitin-W-I44A
synthetic construct
-
with UCH-L1
-
0.0004
ubiquitin-W-I44A
synthetic construct
-
with UCH-L3
-
0.0011
ubiquitin-W-K11A
synthetic construct
-
with UCH-L1
-
0.0023
ubiquitin-W-K11A
synthetic construct
-
with UCH-L3
-
0.0003
ubiquitin-W-K48A
synthetic construct
-
with UCH-L1
-
0.0007
ubiquitin-W-K48A
synthetic construct
-
with UCH-L3
-
0.0004
ubiquitin-W-K63A
synthetic construct
-
with UCH-L1
-
0.0008
ubiquitin-W-K63A
synthetic construct
-
with UCH-L3
-
0.0009
ubiquitin-W-K6A
synthetic construct
-
with UCH-L1
-
0.0014
ubiquitin-W-K6A
synthetic construct
-
with UCH-L3
-
0.008
ubiquitin-W-L71A
synthetic construct
-
with UCH-L1
-
0.0198
ubiquitin-W-L71A
synthetic construct
-
with UCH-L3
-
0.0058
ubiquitin-W-L73A
synthetic construct
-
with UCH-L1
-
0.0104
ubiquitin-W-L73A
synthetic construct
-
with UCH-L3
-
0.0282
ubiquitin-W-L8A
synthetic construct
-
with UCH-L3
-
0.03
ubiquitin-W-L8A
synthetic construct
-
with UCH-L1
-
0.0001
ubiquitin-W-R42A
synthetic construct
-
with UCH-L1; with UCH-L3
-
0.0006
ubiquitin-W-R72A
synthetic construct
-
with UCH-L1
-
0.0019
ubiquitin-W-R72A
synthetic construct
-
with UCH-L3
-
0.0002
ubiquitin-W-R74A
synthetic construct
-
with UCH-L1
-
0.0045
ubiquitin-W-R74A
synthetic construct
-
with UCH-L3
-
0.0006
ubiquitin-W-V70A
synthetic construct
-
with UCH-L1
-
0.0011
ubiquitin-W-V70A
synthetic construct
-
with UCH-L3
-
0.00045
ubiquitin-WA
synthetic construct
-
with UCH-L1
-
0.000035
ubiquitinyl-7-amido-4-methylcoumarin
-
pH 7.5, 25°C
0.00016
ubiquitinyl-7-amido-4-methylcoumarin
-
25°C
0.0033
wild-type di-ubiquitin
-
pH 8.0, 37°C
-
0.015
head-to-tail dimeric ubiquitin
-
pH 7.2, 37°C
-
additional information
additional information
-
-
-
additional information
additional information
-
substrate-binding affinity of isozyme L3
-
additional information
additional information
-
kinetics
-
additional information
additional information
-
Km with several mutant ubiquitin substrates
-
additional information
additional information
-
kinectis
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.02
ubiquitin-7-amino-4-methylcoumarin
-
recombinant wild-type isozyme L1, pH 7.5, 25°C
-
0.02
ubiquitin-7-amino-4-methylcoumarin
synthetic construct
-
with UCH-L1
-
0.0794
ubiquitin-7-amino-4-methylcoumarin
P09936
recombinant mutant I93M isozyme L1, pH 7.8, room temperature
-
0.174
ubiquitin-7-amino-4-methylcoumarin
P09936
recombinant wild-type isozyme L1, pH 7.8, room temperature
-
0.196
ubiquitin-7-amino-4-methylcoumarin
P09936
recombinant mutant S18Y isozyme L1, pH 7.8, room temperature
-
0.0001
ubiquitin-AW
synthetic construct
-
with UCH-L1
-
4.72
ubiquitin-rhodamine110-glycine
-
-
-
0.03
ubiquitin-W
synthetic construct
-
with UCH-L1
-
0.01
ubiquitin-W-G75A
synthetic construct
-
with UCH-L1
-
2.9
ubiquitin-W-G75A
synthetic construct
-
with UCH-L3
-
0.0011
ubiquitin-W-G76A
synthetic construct
-
with UCH-L1
-
1.7
ubiquitin-W-G76A
synthetic construct
-
with UCH-L3
-
0.06
ubiquitin-W-H68A
synthetic construct
-
with UCH-L1
-
4.6
ubiquitin-W-H68A
synthetic construct
-
with UCH-L3
-
0.09
ubiquitin-W-I44A
synthetic construct
-
with UCH-L1
-
1.6
ubiquitin-W-I44A
synthetic construct
-
with UCH-L3
-
0.03
ubiquitin-W-K11A
synthetic construct
-
with UCH-L1
-
3.4
ubiquitin-W-K11A
synthetic construct
-
with UCH-L3
-
0.04
ubiquitin-W-K48A
synthetic construct
-
with UCH-L1
-
2.4
ubiquitin-W-K48A
synthetic construct
-
with UCH-L3
-
0.03
ubiquitin-W-K63A
synthetic construct
-
with UCH-L1
-
2.4
ubiquitin-W-K63A
synthetic construct
-
with UCH-L3
-
0.03
ubiquitin-W-K6A
synthetic construct
-
with UCH-L1
-
4
ubiquitin-W-K6A
synthetic construct
-
with UCH-L3
-
0.03
ubiquitin-W-L71A
synthetic construct
-
with UCH-L1
-
9.2
ubiquitin-W-L71A
synthetic construct
-
with UCH-L3
-
0.01
ubiquitin-W-L73A
synthetic construct
-
with UCH-L1
-
5.7
ubiquitin-W-L73A
synthetic construct
-
with UCH-L3
-
6.6
ubiquitin-W-L8A
synthetic construct
-
with UCH-L3
-
0.02
ubiquitin-W-R42A
synthetic construct
-
with UCH-L1
-
0.2
ubiquitin-W-R42A
synthetic construct
-
with UCH-L3
-
0.03
ubiquitin-W-R72A
synthetic construct
-
with UCH-L1
-
4.4
ubiquitin-W-R72A
synthetic construct
-
with UCH-L3
-
0.01
ubiquitin-W-R74A
synthetic construct
-
with UCH-L1
-
0.3
ubiquitin-W-R74A
synthetic construct
-
with UCH-L3
-
0.05
ubiquitin-W-V70A
synthetic construct
-
with UCH-L1
-
6.7
ubiquitin-W-V70A
synthetic construct
-
with UCH-L3
-
0.0005
ubiquitin-WA
synthetic construct
-
with UCH-L1
-
0.001
ubiquitinyl-7-amido-4-methylcoumarin
-
pH 7.5, 25°C
0.02
ubiquitinyl-7-amido-4-methylcoumarin
-
25°C
0.0728
wild-type di-ubiquitin
-
pH 8.0, 37°C
-
additional information
additional information
-
rate with several ubiquitin mutant substrates
-
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
-
-
0.0028
3-amino-2-keto-7Hthieno[2,3-b]pyridin-6-one derivative
-
-
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
-
-
0.017
Mn2+
-
pH 8.0, 37°C, isozyme L1
0.026
Mn2+
-
pH 8.0, 37°C, isozyme L3
0.047
Mn2+
-
pH 8.0, 37°C, isozyme L2
0.00014
ubiquitin
-
-
0.00019
ubiquitin
-
-
0.0006
ubiquitin
-
pH 8.0, 37°C, isozyme L3
0.0012
ubiquitin
-
pH 8.0, 37°C, isozyme L1
0.0033
ubiquitin
-
25°C; pH 7.5, 25°C, recombinant wild-type isozyme L1
0.005
ubiquitin
-
pH 8.0, 37°C
0.008
ubiquitin
-
pH 8.0, 37°C, isozyme H2
0.03
ubiquitin
-
pH 8.0, 37°C, isozyme L2
0.000001
Ubiquitin aldehyde
-
below, pH 7.5, 25°C, inhibition kinectis
-
0.0000001
ubiquitin-aldehyde
-
at 0.0006 mM ubiquitin, pH 7.8, 25°C
0.0000023
ubiquitin-aldehyde
-
in absence of ubiquitin, pH 7.8, 25°C
0.043
ubiquitin-aldehyde
-
pH 8.0, 37°C, isozyme L2
0.073
ubiquitin-aldehyde
-
pH 8.0, 37°C, isozyme H2
0.08
ubiquitin-aldehyde
-
pH 8.0, 37°C, isozyme L1
0.091
ubiquitin-aldehyde
-
pH 8.0, 37°C, isozyme L3
0.069
Mn2+
-
pH 8.0, 37°C, isozyme H2
additional information
additional information
-
inhibition kinetics
-
additional information
additional information
-
inhibition kinetics of isatin O-acyl oximes, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0061
(3E)-1-(3,4-dichlorobenzyl)-4-methoxy-5-phenyl-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0061 mM
0.00094
(3E)-1-(3,4-dichlorobenzyl)-5-iodo-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.00094 mM
0.016
(3E)-1-(3,4-dichlorobenzyl)-5-iodo-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.016 mM
0.0029
(3E)-1-(3,4-dichlorobenzyl)-5-methoxy-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0029 mM
0.0095
(3E)-1-{2-bromo-2-[3-(trifluoromethyl)phenyl]ethyl}-5-chloro-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0095 mM
0.012
(3E)-3-[(acetyloxy)imino]-1-(3,4-dichlorobenzyl)-2-oxoindoline-5-carbonitrile
-
IC50: 0.012 mM
0.0041
(3E)-3-[(acetyloxy)imino]-1-(3,4-dichlorobenzyl)-2-oxoindoline-5-carboxamide
-
IC50: 0.0041 mM
0.05
(3E)-3-[(acetyloxy)imino]-1-(3,4-dichlorobenzyl)-2-oxoindoline-5-carboxylic acid
-
IC50: 0.05 mM
0.0034
(3E)-5-(trifluoromethoxy)-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0034 mM
0.078
(3E)-5-(trifluoromethoxy)-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.078 mM
0.00081
(3E)-5-bromo-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.00081 mM
0.0027
(3E)-5-chloro-1-(2,3-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0027 mM
0.0012
(3E)-5-chloro-1-(2,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0012 mM
0.00088
(3E)-5-chloro-1-(2,5-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.00088 mM
0.0065
(3E)-5-chloro-1-(2-chloro-5-fluorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0065 mM
0.014
(3E)-5-chloro-1-(2-naphthylmethyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.014 mM
0.019
(3E)-5-chloro-1-(2-phenylethyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.019 mM
0.0018
(3E)-5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0018 mM
0.017
(3E)-5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.017 mM
0.0013
(3E)-5-chloro-1-(3,5-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0013 mM
0.021
(3E)-5-chloro-1-(3-chloro-4-methoxybenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.021 mM
0.013
(3E)-5-chloro-1-(3-methoxybenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.013 mM
0.012
(3E)-5-chloro-1-(4-chlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.012 mM
0.052
(3E)-5-chloro-1-(4-methoxybenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.052 mM
0.0062
(3E)-5-chloro-1-[2-(3,4-dichlorophenoxy)ethyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0062 mM
0.0013
(3E)-5-chloro-1-[2-(3,4-dichlorophenyl)ethyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0013 mM
0.018
(3E)-5-chloro-1-[2-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.018 mM
0.321
(3E)-5-chloro-1-[2-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.321 mM
0.016
(3E)-5-chloro-1-[3-(3,4-dichlorophenyl)propyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.016 mM
0.006
(3E)-5-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.006 mM
0.036
(3E)-5-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.036 mM
0.114
(3E)-5-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.114 mM
0.012
(3E)-5-chloro-1-[4-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.012 mM
0.013
(3E)-5-chloro-1-[4-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.013 mM
0.0088
(3E)-5-chloro-1-{1-[2-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0088 mM
0.045
(3E)-5-chloro-1-{1-[2-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-oxime
-
IC50: 0.045 mM
0.0034
(3E)-5-chloro-1-{1-[3-(trichloromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0034 mM
0.022
(3E)-5-chloro-1-{1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-oxime
-
IC50: 0.022 mM
0.095
(3E)-5-chloro-1-{2-ethoxy-2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.095 mM
0.019
(3E)-5-chloro-1-{2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.019 mM
0.0041
(3E)-5-chloro-1-{2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0041 mM
0.08
(3E)-5-chloro-1-{2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-oxime
-
IC50: 0.08 mM
0.012
(3E)-5-chloro-7-methyl-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.012 mM
0.0061
(3E)-5-fluoro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0061 mM
0.043
(3E)-5-fluoro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.043 mM
0.0058
(3E)-6-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0058 mM
0.103
1-benzyl-3-hydroxy-4-(5-methyl-2-furoyl)-5-(3-pyridinyl)-1,5-dihydro-2H-pyrrol-2-one
-
-
0.154
3-hydroxy-5-(4-methoxyphenyl)-1-(1,3,4-thiadiazol-2-yl)-4-(2-thienylcarbonyl)-1,5-dihydro-2H-pyrrol-2-one
-
-
0.123
5-(4-fluorophenyl)-3-hydroxy-4-(5-methyl-2-furoyl)-1-(3-pyridinylmethyl)-1,5-dihydro-2H-pyrrol-2-one
-
-
0.0018
5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0018 mM
0.015
N,N'-4,4'-biphenyldiylbis(4-ethylbenzenesulfonamide)
-
-
0.00074
ubiquitin
-
-
0.012
5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-oxime
-
IC50: 0.012 mM
0.1
additional information
-
IC50 above 0.1 mM: (3E)-5-chloro-1-(pyridin-3-ylmethyl)-1H-indole-2,3-dione 3-(O-acetyloxime), (3E)-5-chloro-1-(pyridin-4-ylmethyl)-1H-indole-2,3-dione 3-(O-acetyloxime), 4-({(3E)-3-[(acetyloxy)imino]-5-chloro-2-oxo-2,3-dihydro-1H-indol-1-yl}methyl)benzoi
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0185
-
partially purified enzyme
0.033
-
partially purified isozyme L1, substrate ubiquitin ethyl ester
0.16
-
partially purified isozyme H2, substrate ubiquitin ethyl ester
0.21
-
partially purified isozyme L2, substrate ubiquitin ethyl ester
2.5
-
partially purified isozyme L3, substrate ubiquitin ethyl ester
14.75
-
purified enzyme, substrate A24
25
-
purified isozyme L3, adult brain, substrate ubiquitin ethyl ester; purified wild-type isozyme L1, substrate ubiquitin ethyl ester
30
-
purified recombinant isozyme L1, substrate ubiquitin ethyl ester; UCH-L1, ubiquitin ethyl ester as substrate
110
-
purified recombinant isozyme L3, substrate ubiquitin ethyl ester; UCH-L3, ubiquitin ethyl ester as substrate
additional information
-
-
additional information
-
-
additional information
Q00981
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2 - 8.3
-
broad optimum
7.2
-
assay at
7.2
-
assay at
7.4
-
assay at
7.5 - 8
-
UCH-8
7.5
-
assay at
7.5
-
assay at
7.8
-
assay at
7.8
-
assay at
7.8
-
assay at
8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 11
-
inactive above and below
6 - 9
-
analysis of pH dependence of the reaction, overview
7 - 9
-
little or no activity below pH 7.0 and above pH 9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
P09936
room temperature, assay at
22
-
assay at room temperature
25
-
assay at
25
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
analysis of temperature dependence of the reaction, overview
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.84
B6E460
UCHL5, sequence calculation
5
-
about
5.12
-
UCH-L1, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Q00981
vascular smooth muscle cells. UCH-L1 is up-regulated in injured arteries
Manually annotated by BRENDA team
-
mRNA and protein expression, expressed in endothelial cells in atherosclerotic lesions from human carotid arteries
Manually annotated by BRENDA team
-
mRNA and protein expression
Manually annotated by BRENDA team
-
UCH-L1 present in the outer layer cells of the trophectoderm. UCH-L3 present in the inner cells
Manually annotated by BRENDA team
-
accounts for about 2% of soluble protein in brain
Manually annotated by BRENDA team
-
isozymes ISOT-S and ISOT-L
Manually annotated by BRENDA team
-
isozymes L1, specific for neuronal cells, testis and ovary, and L3
Manually annotated by BRENDA team
-
isozyme L1, adult
Manually annotated by BRENDA team
P09936
isozyme L1, adult
Manually annotated by BRENDA team
Q9UK80
usp21 gene expression
Manually annotated by BRENDA team
-
embryonic, UCH-L1 expression in the ventricular zone changes during neurogenesis and gliogenesis, high expression level in cortical plate and ventricular zone, overview
Manually annotated by BRENDA team
-
frontal cortex
Manually annotated by BRENDA team
-
frontal cortex of healthy, Alzheimer's disease, and Parkinson's disease brains, 3 isozymes of UCH-L1, UCH-L1 is down-regulated in Alzheimer's diesease and Parkinson's disease brains
Manually annotated by BRENDA team
B5KNK6
slight expression
Manually annotated by BRENDA team
-
specific for
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
gracile axonal dystrophy is a syndrome that emanates from dysfunctional ubiquitin carboxyl-terminal hydrolase L-1
Manually annotated by BRENDA team
-
oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinsons and Alzheimers diseases
Manually annotated by BRENDA team
-
predominantly neuronal, uniformly expressed throughout brain
Manually annotated by BRENDA team
-
ubiquitin C-terminal hydrolase is localized especially on the olfactory organ including the olfactory bulb and olfactory epithelium in olfactory rosetta, suggesting the involvement of the protein in chemoreceptive function
Manually annotated by BRENDA team
-
highly expressed. UCH-L1 expression and protein level are downregulated in the brain of patients with Alzheimer´s disease
Manually annotated by BRENDA team
-
reduced levels of UCH-L1 mRNA (30%) and protein in a mouse model of Sandhoff disease as compared with their wild-type siblings
Manually annotated by BRENDA team
B5KNK6
expression of both mRNA and protein
Manually annotated by BRENDA team
-
cortex, UCH-L1M omprises about 30% of total UCH-L1 in diseased and normal human brain
Manually annotated by BRENDA team
-
high content of UCHL1
Manually annotated by BRENDA team
-
high content of UCHL1, distribution in brain tissues, overview
Manually annotated by BRENDA team
-
in mouse brain regions, e.g. cortex, hippocampus, striatum, and midbrain, both UCH-L1M and UCH-L1S occur in varying relative amounts
Manually annotated by BRENDA team
-
neuron-specific expression of UCH-L1
Manually annotated by BRENDA team
-
PGP 9.5 represents a ubiquitin carboxy-terminal hydrolase highly, localized in nervous tissue
Manually annotated by BRENDA team
-
specific expression of UCH-L1
Manually annotated by BRENDA team
-
UCH-L1 forms 1-5% of total brain protein
Manually annotated by BRENDA team
-
UCH-L1 is one of the most abundant proteins in the mammalian brain
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
neuron-specific expression of UCH-L1
-
Manually annotated by BRENDA team
-
mRNA expression levels in normal breast tissue are not significantly different between premenopausal and postmenopausal women for both UCH-L1 and UCH-L3
Manually annotated by BRENDA team
-
UCH-L3 mRNA level is significantly upregulated and UHCL1 mRNA level also show a non-significant increase in breast cancer tissue compared to adjacent normal breast tissue. Both UCH-L1 and UCH-L3 mRNA levels are significantly higher in high histological grade tumors than in low histological grade tumors. UCH-L1 mRNA level in tumors is approximately 10 times higher than that of UCH-L3
Manually annotated by BRENDA team
-
UCH-L1 is highly expressed
Manually annotated by BRENDA team
P40818
human cervical carcinoma cell line
Manually annotated by BRENDA team
-
high expression of UCH-L1, high expression level of UCH-L1 in caput epididymis
Manually annotated by BRENDA team
-
UCHL3 and UCH37 are upregulated in the majority of tumor tissues compared to the adjacent normal tissues. UCH-L1 activity is lower in a significant proportion of the tumors but to a less extent in advanced tumors
Manually annotated by BRENDA team
-
high expression of UCH-L3, high expression level of UCH-L3 in caudate epididymis
Manually annotated by BRENDA team
-
down-regulation of UCHL-1 mRNA and protein in dementia with Lewy bodies, either in pure forms not associated with Alzheimer disease, and in common forms, with accompanying Alzheimer disease changes, but not in Parkinson disease. UCHL-3 expression reduced in Parkinson disease and dementia with Lewy bodies
Manually annotated by BRENDA team
-
prefrontal. UCH L1 is 1.1-1.2fold decreased in alcoholics
Manually annotated by BRENDA team
-
UCH-L1 is significantly elevated in cerebrospinal fluid following controlled cortical impact and middle cerebral artery occlusion, as a model of ischemic stroke, in rats, overview
Manually annotated by BRENDA team
-
UCH-L1 levels are specifically increased in cerebrospinal fluid in case of traumatic brain damage, quantitative determination in different samples, overview
Manually annotated by BRENDA team
-
UCHL1 content determination in benign and malign samples, overview
Manually annotated by BRENDA team
-
in accordance with the relatively low UCH-L1 activity in tumor biopsies, UCH-L1 is detected only in one out of eight cervical carcinoma lines
Manually annotated by BRENDA team
-
colorectal mucosa
Manually annotated by BRENDA team
-
lymph node metastasis, increased expression
Manually annotated by BRENDA team
Q60HC8
of chorionic plate and villi
Manually annotated by BRENDA team
Q60HC8
of decidua basalis
Manually annotated by BRENDA team
-
chinese hamster cell line DON
Manually annotated by BRENDA team
Q6YI49
spatiotemporal expression of gene uch-L1 mRNA during embryo development
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
Mus musculus DBA/2
-
-
-
Manually annotated by BRENDA team
-
regiospecific expression of uchl1 and uchl3 in cauda, corpus, and caput, overview
Manually annotated by BRENDA team
-
UCH-L3 is the predominant deubiquitinating enzyme in endosomal compartments of collecting duct epithelial cells
Manually annotated by BRENDA team
-
parietal epithelial cells of Bowman's capsules and some tubular epithelia in the kidney
Manually annotated by BRENDA team
-
native isozyme ISOT-S
Manually annotated by BRENDA team
-
level of UCH-L3 decreases with age, while the level of UCH-L1 increases with age in wild-type mice
Manually annotated by BRENDA team
P40818
accumulated upon growth stimulation of starved human fibroblasts
Manually annotated by BRENDA team
B5KNK6
in male gonad epithelium
Manually annotated by BRENDA team
-
non-small cell lung cancer cell line
Manually annotated by BRENDA team
Q9UK80
usp21 gene expression, high content
Manually annotated by BRENDA team
-
UCHL1 expression is low, which is well correlated with its promoter methylation status
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
UCHL1 expression is low, which is well correlated with its promoter methylation status
Manually annotated by BRENDA team
-
a bronchial epithelial cell line, the cells show increased UCH-L1 expression, overview
Manually annotated by BRENDA team
Ictalurus punctatus Rafinesque
-
-
-
Manually annotated by BRENDA team
-
only UCH-L3 is clearly identified in primary keratinocytes. UCH-L1 and UCH-L3 activity is upregulated following HPV E6/E7 immortalization of keratinocytes
Manually annotated by BRENDA team
Q9UK80
usp21 gene expression
Manually annotated by BRENDA team
-
parietal epithelial cells of Bowman's capsules and some tubular epithelia in the kidney
Manually annotated by BRENDA team
Ictalurus punctatus Rafinesque
-
-
-
Manually annotated by BRENDA team
-
different cell lines
Manually annotated by BRENDA team
-
a B lymphoblastoid cell line
Manually annotated by BRENDA team
-
present in patients with sporadic Parkinson´s disease
Manually annotated by BRENDA team
Q9UK80
usp21 gene expression
Manually annotated by BRENDA team
-
healthy persons, and liver cirrhosis and HCC patients, quantitative USP44 determination, overview
Manually annotated by BRENDA team
Ictalurus punctatus Rafinesque
-
-
-
Manually annotated by BRENDA team
Q80TQ2
expression level of CYLD is extremely low
Manually annotated by BRENDA team
Q00981
rostral ventrolateral, expression analysis of isozyme UCH-L1 during mevinphos intoxication, overview
Manually annotated by BRENDA team
-
UCHL-1 mRNA and protein expressions reduced in Parkinson disease
Manually annotated by BRENDA team
-
pectoralis
Manually annotated by BRENDA team
-
lung cancer cell line, non-small cell lung cancer cell line
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
high content of UCHL1. UCHL1/PGP 9.5 is a highly conserved protein present in virtually all neurones and neuroendocrine cells as a major component of soluble cytoplasmic protein
Manually annotated by BRENDA team
-
UCHL1 is neuroendocrine cell-specific. Neuroendocrine gene expression in the large and small airway epithelium, UCHL1 is overexpressed in over 50% of lung cancers, overview
Manually annotated by BRENDA team
-
present in patients with Alzheimer´s disease
Manually annotated by BRENDA team
-
high expression of UCH-L1
Manually annotated by BRENDA team
-
neuron-specific isozyme UCH-L1
Manually annotated by BRENDA team
-
the enzyme insures ubiquitin stability within neurons
Manually annotated by BRENDA team
-
interneuron and motor neuron
Manually annotated by BRENDA team
-
high content of UCHL1, distribution in neuron types and cellular compartments, overview
Manually annotated by BRENDA team
-
high content of UCHL1. UCHL1/PGP 9.5 is a highly conserved protein present in virtually all neurones and neuroendocrine cells as a major component of soluble cytoplasmic protein
Manually annotated by BRENDA team
-
neuron-specific UCH-L1
Manually annotated by BRENDA team
-
primary dopaminergic neurons
Manually annotated by BRENDA team
-
primary hippocampal neuronal culture
Manually annotated by BRENDA team
-
UCH-L1 is abundantly expressed in neuronal cell
Manually annotated by BRENDA team
-
UCH-L1 is localized on the inside of the plasma membrane of dorsal root ganglion neurons
Manually annotated by BRENDA team
-
UCH-L1 is present in almost all neurons
Manually annotated by BRENDA team
-
UCHL1 is abundantly and selectively expressed in neurons
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
UCH-L1 is localized on the inside of the plasma membrane of dorsal root ganglion neurons
-
Manually annotated by BRENDA team
-
down regulation of UCHL1 is detected immediately after oxygen-glucose deprivation treatment and its expression is subsequently restored and increased 6 h after oxygen-glucose deprivation treatment as well as during reoxygenation. A lower level of UCHL1 is detected only in apoptotic cells with severe loss of mitochondrial membrane potential. Down-regulation of endogenous UCHL1 by antisense cDNA in mouse N2a neuroblastoma cells increased the cell’s sensitivity to oxygen-glucose deprivation. This down-regulation of endogenous UCHL1 leads to the accumulation of p27, suggesting that UCHL1 is an essential gene to maintain cell homeostasis under normal growth and oxidative stress conditions
Manually annotated by BRENDA team
-
distribution in cellular compartments, overview
Manually annotated by BRENDA team
-
the olfactory receptor neurones (replaceable) appear to be strongly immunoreactive as do the principal neurones (mitral and mitral/tufted cells), while in the olfactory bulb the replaceable periglomerular and granule cells appear to be non-reactive, distribution in cellular compartments, overview
Manually annotated by BRENDA team
-
overall level of UCH-L1 increases during maturation
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
UCHL1 present in the cortex, UCHL3 is primarly associated with the meiotic spindle of metaphase II ova
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
subcortical localization of native UCHL1 in bovine oocytes during maturation. Expression of UCHL1 monomer does not change during meiotic maturation of bovine oocytes. Developmental competence is unaffected in parthenogenetic embryos that originated from UCH-L1 inhibitor treated oocytes
Manually annotated by BRENDA team
-
UCH-L1 is associated with the plasma membrane of oocytes
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
Mus musculus ICR
-
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
-
Manually annotated by BRENDA team
Mus musculus ICR
-
-
-
Manually annotated by BRENDA team
-
isozyme L1, specific for neuronal cells, testis and ovary
Manually annotated by BRENDA team
-
high expression of UCH-L1
Manually annotated by BRENDA team
-
ubiquitin C-terminal hydrolase localizes especially in pre-vitellogenic oocytes, suggesting that the enzyme activity could be important in oocyte growth
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
B5KNK6
expression of both mRNA and protein mainly in the developing ovary and slightly in the mature ovary
Manually annotated by BRENDA team
-
analysis of the ovarian UCH-L1 expression, overview
Manually annotated by BRENDA team
B5KNK6
slight expression, in degraded ovaries
Manually annotated by BRENDA team
-
strong cytoplasmic staining of ova in primordial and developing follicles with moderate staining of the theca externa and the corpus luteum
Manually annotated by BRENDA team
Mus musculus ICR
-
analysis of the ovarian UCH-L1 expression, overview
-
Manually annotated by BRENDA team
B5KNK6
during the intersex stage, both mRNA and protein is expressed in the male gonad epithelium and degraded ovary, dominant expression
Manually annotated by BRENDA team
Q9UK80
usp21 gene expression, high content
Manually annotated by BRENDA team
-
including sensory and motor nerves
Manually annotated by BRENDA team
Q9UK80
usp21 gene expression
Manually annotated by BRENDA team
Q60HC8
decidua basalis, the amount of UCH-L1 increases during pregnancy progression
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
Q60HC8
UCH-L1 is necessary for placental and fetal development in primate placenta
Manually annotated by BRENDA team
-
UCHL1 expression is low, which is well correlated with its promoter methylation status
Manually annotated by BRENDA team
-
expresses UCH-L1 and expression correlates with the differentiation status. In the cortex of normal biopsies, UCH-L1 is predominantly expressed in distal tubules, macula densa, and nerve fibres. A subset of human glomerulopathies associated with podocyte foot process effacement (membranous nephropathy, SLE class V, FSGS) de novo express UCH-L1 in podocyte cell bodies, nuclei, and processes
Manually annotated by BRENDA team
-
cell culture, expression of UCH-L1 and the regulation of this expression in podocytes, overview
Manually annotated by BRENDA team
Q80TQ2
CYLD is drastically upregulated during RANKL-induced differentiation of preosteoclasts
Manually annotated by BRENDA team
-
colorectal mucosa
Manually annotated by BRENDA team
P09936
expression analysis of UCHL! in the renal cell carcinoma system, profiling, overview
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
photoreceptor cells, bipolar cells, and amacrine cells are devoid of staining while the dendrites and axons of both the horizontal cells and the ganglion cells stain strongly
Manually annotated by BRENDA team
-
UCHL1/PGP 9.5, photoreceptor cells, bipolar cells, and amacrine cells are devoid of staining while the dendrites and axons of both the horizontal cells and the ganglion cells stain strongly
Manually annotated by BRENDA team
Q00981
de novo synthesis of UCH-L1, leading to an enhanced dissassembly of ubiquitin-protein conjugates in the rostral ventrolateral medulla, is essential to maintenance of the pro-life phase of mevinphos intoxication via prevention of cardiovascular depression, leading to neuroprotection
Manually annotated by BRENDA team
-
a bronchial epithelial cell line, the cells show increased UCH-L1 expression, overview
Manually annotated by BRENDA team
P15347
UCH-L1 protein
Manually annotated by BRENDA team
P15347
UCH-L1 may act during mitotic proliferation of spermatogonial stem cells
Manually annotated by BRENDA team
-
a neuroblastoma cell line
Manually annotated by BRENDA team
Q9UK80
usp21 gene expression
Manually annotated by BRENDA team
-
level of UCH-L1 mRNA is significantly reduced in fibroblasts of patients affected with lysosomal storage disorders
Manually annotated by BRENDA team
-
UCHL1 expression is low, which is well correlated with its promoter methylation status
Manually annotated by BRENDA team
-
UCHL3 is localized to the acrosomal surface. UCHL1 is absent from the sperm surface
Manually annotated by BRENDA team
P15347
UCH-L3 protein
Manually annotated by BRENDA team
P15347
UCH-L3 may function in the meiotic differentiation of spermatocytes into spermatids
Manually annotated by BRENDA team
-
UCHL3 mainly localized to the round spermatids (acrosomal cap) and elongating spermatids (caudal manchette and acrosome)
Manually annotated by BRENDA team
P15347
UCH-L3 protein
Manually annotated by BRENDA team
P15347
UCH-L3 may function in the meiotic differentiation of spermatocytes into spermatids
Manually annotated by BRENDA team
P15347
UCH-L1 protein
Manually annotated by BRENDA team
P15347
UCH-L1 may act during mitotic proliferation of spermatogonial stem cells
Manually annotated by BRENDA team
-
expression level of UCH-L1, high or low, is associated with spermatogonial stem cell self-renewal and differentiation, overview
Manually annotated by BRENDA team
-
spermatogonia in humans can be subdivided into three types, overview
Manually annotated by BRENDA team
-
spermatogonia in monkeys can be subdivided into three types, overview
Manually annotated by BRENDA team
Mus musculus ICR
-
-
-
Manually annotated by BRENDA team
-
UCHL1 is expressed in defective spermatozoa but not in normal spermatozoa
Manually annotated by BRENDA team
Q9R0P9
specific carbonyl level of UCH-L1 is significantly increased in spinal cord of G93A-SOD1 transgenic mice compared to that of nontransgenic mice
Manually annotated by BRENDA team
Ictalurus punctatus Rafinesque
-
-
-
Manually annotated by BRENDA team
-
UCHL-1 protein reduced in cases with Lewy body pathology
Manually annotated by BRENDA team
-
strong expression of UCHL1, no expression of UCHL3
Manually annotated by BRENDA team
-
isozyme L1, specific for neuronal cells, testis and ovary
Manually annotated by BRENDA team
-
cryptorchid and healthy
Manually annotated by BRENDA team
-
high expression of UCH-L1
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
UCHL1 and UCHL3
Manually annotated by BRENDA team
B5KNK6
expression of both mRNA and protein in developing germ cells, dominant expression
Manually annotated by BRENDA team
-
UCH-L1 is exclusively expressed in spermatogonia among male germ cells. In the adult testis, UCH-L1, high or low, is expressed only in a single layer of spermatogonia at the basement membrane
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
P40818
human osteosarcoma cell line
Manually annotated by BRENDA team
-
UCH37 activity is up-regulated in cervical carcinoma biopsies as well as cell lines, while UCH-L1 activity is lower in cervical carcinomas
Manually annotated by BRENDA team
-
mRNA and protein expression, expressed in vascular smooth muscle cells in atherosclerotic lesions from human carotid arteries
Manually annotated by BRENDA team
P40818
human fibroblast cell line
Manually annotated by BRENDA team
additional information
-
no isozyme L1 expression in embryonic fibroblasts, isozyme L3 is universally expressed in all tissues
Manually annotated by BRENDA team
additional information
-
PA700 regulatory complex of 26S proteasome
Manually annotated by BRENDA team
additional information
P15347
expression pattern of UCH isozymes in Sertoli cells, spermatids, spermatocytes, and spermatogonia, overview
Manually annotated by BRENDA team
additional information
-
no expression of UCH-L1 in healthy lung tissue
Manually annotated by BRENDA team
additional information
-
proteomic analysis
Manually annotated by BRENDA team
additional information
-
quantitative testicular expression analysis of UCHL1
Manually annotated by BRENDA team
additional information
-
the enzyme is absent in tissues other than brain
Manually annotated by BRENDA team
additional information
Q6YI49
tissue-specific regulation of uhc-L1 gene expression, analysis, overview
Manually annotated by BRENDA team
additional information
-
3T3 cell
Manually annotated by BRENDA team
additional information
-
absence of UCHL1 in the gracile axonal dystrophy mouse, which results in neurodegeneration
Manually annotated by BRENDA team
additional information
-
HMVEC cells from newborn foreskins
Manually annotated by BRENDA team
additional information
-
is highly abundant in the PA700 complex
Manually annotated by BRENDA team
additional information
-
the human papilloma virus-negative C33A cell line is the only cell line lacking detectable UCH-L3 activity
Manually annotated by BRENDA team
additional information
-
UCH-L1 is upregulated and more abundantly expressed in germ line stem cells than in embryonic stem cells
Manually annotated by BRENDA team
additional information
-
UCHL1 is consistently up-regulated in airway epithelium of smokers compared with nonsmokers. UCHL1 expression is evident only in neuroendocrine cells of the airway epithelium in nonsmokers, whereas it is expressed in neuroendocrine cells and in ciliated epithelial cells in smokers
Manually annotated by BRENDA team
additional information
-
UCHL1 is downregulated in the frontal cortex of frontotemporal dementia and parkinsonism linked to chromosome 17
Manually annotated by BRENDA team
additional information
-
vasculature
Manually annotated by BRENDA team
additional information
-
four UCH-L1 isoforms in SN12C clones
Manually annotated by BRENDA team
additional information
Q6J1Y9
FR3T3 cell
Manually annotated by BRENDA team
additional information
-
normal kidneys express no UCH-L1 and little ubiquitin. Decrease of expression with differentiation. Minimal change glomerulonephritis demonstrates minimal UCH-L1 and ubiquitin expression with intact alpha-actinin-4 but internalized nephrin. Glomerular kidney diseases typically not associated with foot process effacement (SLE class IV, ANCA+ necrotizing GN, amyloidosis, IgA nephritis) express intermediate to no UCH-L1 and ubiquitin
Manually annotated by BRENDA team
additional information
-
present in HuH-4 cells. Cancer cell lines HCT-116, EC-109, Hep-3B, HuH-1, HuH-6, Mahlavu, SNU-387 and SNU-449 have silenced UCHL1, which is well correlated with its promoter methylation status
Manually annotated by BRENDA team
additional information
-
UCH-L1 is highly expressed in H157 cells, having high invasive potential. In Akt-negative mutants, overexpression of UCH-L1 does not affect the invasion and migration capability of H157 cells
Manually annotated by BRENDA team
additional information
B5KNK6
Uch-L1 is upregulated during gonadal transformation, especially from the beginning of the intersex stage onwards
Manually annotated by BRENDA team
additional information
-
immunohistochemic analysis, overview
Manually annotated by BRENDA team
additional information
-
in pigs, gonocytes and spermatogonia expressing UCH-L1 include the population expressing PLZF, a known determinant of undifferentiated spermatogonial stem cells, asymmetric segregation of UCH-L1 and PLZF in spermatogonia in vivo and in vitro, overview
Manually annotated by BRENDA team
additional information
-
increased expression and activity of UCH L1 in EBV-immortalized cell lines
Manually annotated by BRENDA team
additional information
B5KNK6
no expression in heart, liver, kidney, or spleen. Uch-L1 is upregulated during gonadal transformation from female to male, overview
Manually annotated by BRENDA team
additional information
-
the deubiquitinating enzyme, ubiquitin C-terminal hydrolase-L1, is highly expressed in cystic fibrosis airway epithelial cells in vitro and in vivo
Manually annotated by BRENDA team
additional information
-
tissue distribution and immunohistochemic analysis, overview
Manually annotated by BRENDA team
additional information
-
UCH-L1 expression in podocytes is significantly higher in acute proliferative glomerulonephritis, lupus nephritis, membranous glomerulonephritis, and IgA nephropathy than that in focal segmental glomerulosclerosis, minimal change disease, minor abnormality and normal kidney tissues, overview
Manually annotated by BRENDA team
additional information
-
UCH-L1 is enriched in the central nervous system
Manually annotated by BRENDA team
additional information
-
UCH-L1 is exclusively expressed in brain and testis
Manually annotated by BRENDA team
additional information
-
UCH-L1 is present in neurofibrillary tangles or Lewy bodies
Manually annotated by BRENDA team
additional information
-
UCH-L1 levels are high in various types of malignancies: acute lymphoblastic leukemia, non-small cell lung cancer, neuroblastoma, pancreatic, prostate, medullary thyroid, esophageal, colorectal and renal carcinomas
Manually annotated by BRENDA team
additional information
-
UCHL1/PGP 9.5 is present prominently in brain, in addition to its neuronal localization, UCHL1/PGP 9.5 is also present in cells of the diffuse neuroendocrine system, traces of the protein are also seen in large intestine, kidney, ovary, and testis. Tissue distribution and immunohistochemic analysis, overview. Enzyme activity in the diffuse neuroendocrine system, e.g. in gastroenteropancreatic system, prostate, pulmonary neuroendocrine system, and cerebral cortex, detailed overview
Manually annotated by BRENDA team
additional information
B6E460
UCHL5 is constitutively expressed in several tissues, expression analysis, overview
Manually annotated by BRENDA team
additional information
Mus musculus C57BL/6J
-
UCH-L1 is exclusively expressed in brain and testis
-
Manually annotated by BRENDA team
additional information
Mus musculus DBA/2
-
UCH-L1 is upregulated and more abundantly expressed in germ line stem cells than in embryonic stem cells
-
Manually annotated by BRENDA team
additional information
Ictalurus punctatus Rafinesque
-
UCHL5 is constitutively expressed in several tissues, expression analysis, overview
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
undifferentiated podocytes exhibit strong UCH-L1 expression at the cell membrane along leading edges
-
Manually annotated by BRENDA team
-
UCH-L1 is slightly expressed both in interneuron and motor neuron. After 3 hours ischemia, UCH-L1 is upregulated in cytoplasm of both neurons. After 6 hours, UCH-L1 in cytoplasm is preserved in motor neuron, whereas it returns to almost the same level as the sham group in interneuron
Manually annotated by BRENDA team
-
UCH-L3 concentrated in the cytoplasm of oocytes and developing embryos
Manually annotated by BRENDA team
-
UCHL-1 in the cytoplasm of neurons in the cerebral cortex and medulla oblongata in control and diseased brains
Manually annotated by BRENDA team
-
UCHL3 diffusely distributed in the zygotic cytoplasm after fertilization
Manually annotated by BRENDA team
P03186
BPLF1 1-246 is expressed alone or with ribonucleotide reductase 1 or ribonucleotide reductase 2
Manually annotated by BRENDA team
Q92560
only Bap1, no presence of HCF-1
Manually annotated by BRENDA team
-
undifferentiated podocytes exhibit strong UCH-L1 expression in cytoplasm
Manually annotated by BRENDA team
Q6J1Y9
USP19 stabilizes the ubiquitin ligase KPC1 and, like KPC1, it is localized in the cytosol
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
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
-
Manually annotated by BRENDA team
-
membrane associated form UCH-L1M, C-terminal farnesylation promotes the association of UCH-L1 with the membrane
Manually annotated by BRENDA team
-
associated to
Manually annotated by BRENDA team
-
the C-terminal proline-rich domain of Bro1 participates in recruitment of the Doa4 ubiquitin hydrolase to the endosome
Manually annotated by BRENDA team
-
the important function of Doa4 in Gap1 endocytosis operates at the late endosome stage
Manually annotated by BRENDA team
-
membrane associated form UCH-L1M, C-terminal farnesylation promotes the association of UCH-L1 with cellular membranes, including the endoplasmic reticulum
Manually annotated by BRENDA team
-
minor enzyme portion of UCHL1/PGP 9.5, tightly bound
Manually annotated by BRENDA team
-
minor enzyme portion of UCHL1/PGP 9.5, tightly bound, UCHL3
Manually annotated by BRENDA team
P03186
BPLF1 1-246 is expressed alone or with ribonucleotide reductase 1 or ribonucleotide reductase 2
Manually annotated by BRENDA team
Q92560
HCF-1 and Bap1 are similarly distributed throughout the nucleoplasm. HCF-1 interacts with Bap1 through its beta-propeller domain
Manually annotated by BRENDA team
-
Uch37 is associated with the human Ino80 chromatin-remodeling complex. In the Ino80 chromatin-remodeling complex, Uch37 is held in an inactive state
Manually annotated by BRENDA team
-
UCH-L1 most abundant at the plasma membrane of oocytes in developing follicles and in developing embryos
Manually annotated by BRENDA team
-
the membrane-associated UCH-L1M form is associated with the plasma membrane of oocytes, C-terminal farnesylation promotes the association of UCH-L1 with the membrane
Manually annotated by BRENDA team
-
the membrane-associated UCH-L1M form, C-terminal farnesylation promotes the association of UCH-L1 with the membrane
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
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
-
Manually annotated by BRENDA team
-
Uch-L1 protein fused to the transduction domain of HIV-transactivator protein exclusively present in the soluble fraction of hippocampal homogenates
-
Manually annotated by BRENDA team
-
soluble UCH-L1 form, UCH-L1S
-
Manually annotated by BRENDA team
-
UCH-L1 is membrane-associated and co-localizes with the ribosomal subunit RPS6 and the ER retention signal KDEL. UCH-L1 is partially co-localized to the site of CFTR protein synthesis
Manually annotated by BRENDA team
additional information
-
perinucleus
-
Manually annotated by BRENDA team
additional information
-
proteasome
-
Manually annotated by BRENDA team
additional information
Q9XSJ0
proteasome
-
Manually annotated by BRENDA team
additional information
-
UCH-L1 is not detectable in nuclei of interneuron and motor neuron. UCH-L1 is upregulated strongly at 3 hours and somewhat decreased at 6 hours of ischemia, is well preserved until 1 day, whereas it is not detectable in nuclei of motor neuron after ischemia
-
Manually annotated by BRENDA team
additional information
-
UCH-L1 exists in a membrane-associated form, UCH-L1M, in addition to the commonly studied soluble form
-
Manually annotated by BRENDA team
additional information
-
UCHL1 expression is detected in both soma and dendrites of hippocampal neurons. UCH-L1 is distributed in a micropunctate fashion, localized to dendritic spines of neurons, and partially co-localized with PSD-95, overview
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Crimean-Congo hemorrhagic fever virus (strain Nigeria/IbAr10200/1970)
Human coronavirus EMC
Human herpesvirus 1 (strain 17)
Human herpesvirus 1 (strain 17)
Human SARS coronavirus
Human SARS coronavirus
Human SARS coronavirus
Human SARS coronavirus
Human SARS coronavirus
Human SARS coronavirus
Human SARS coronavirus
Human SARS coronavirus
Murine coronavirus (strain A59)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
24000
-
UCHL1 or UCHL3, Western blot analysis, immunocytochemistry
678561
24000
-
Western blot analysis
681040
24800
-
-
698057
25000
-
UCH-L1, gel filtration, SDS-PAGE
36451
25000
-
immunoblot analysis
679101
25000
-
Western blot analysis
682875
26000
B5KNK6
Western blot analysis
697865
27000
-
-
669672
29000
-
gel filtration, SDS-PAGE
36455
30000
-
gel filtration
36453, 646091
35000
-
gel filtration, SDS-PAGE
36449
35000
-
UCH-1, gel filtration
36452
38000
-
gel filtration
646096
45000
-
UCH-3, gel filtration
36452
50000
-
UCH-2, gel filtration
36452
54000
-
UCH-6, UCH-9, UCH-10, gel filtration
36452
54000
-
predicted
681994
100000
-
UCH-4, gel filtration
36452
100000
-
immunoprecipitation, SDS-PAGE and tandem mass spectrometry
681994
110000
-
analytical ultracentrifugation
646094
200000
-
UCH-8, gel filtration
36452
240000
-
UCH-8, gel filtration
646101
810000
-
UCH-7, gel filtration
36452
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 27000, SDS-PAGE
?
Q60HC8
x * 28000, SDS-PAGE
?
P40818
x * 130000, SDS-PAGE
?
-
x '* 28900, SDS-PAGE
?
-
x * 25100, UCH-L1, SDS-PAGE
?
-
x * 25902, UCH-L1, mass spectrometry
?
B6E460
x * 37600, about, UCHL5, sequence calculation
?
Ictalurus punctatus Rafinesque
-
x * 37600, about, UCHL5, sequence calculation
-
dimer
-
2 * 130000, reducing SDS-PAGE
dimer
-
crystallography, in crystal structure
dimer
-
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
dimer
B5KNK6
SDS-PAGE, Uch-L1 undergoes dimerization and oligomerization in gonads, whereby the relative level of dimerization/oligomerization decreases during gonadal transformation. Rates of dimerization and oligomerization are high in ovary and lower in ovotestis, whereas monomers are mainly formed in testis, 2 * 26000, SDS-PAGE, rates of dimerization and oligomerization are high in ovary and lower in ovotestis, whereas monomers are mainly formed in testis. The dimerization/oligomerization level of Uch-L1 decreases during gonadal transformation from female to male. UCH-L1 structure modelling
dimer
-
UCH-L1 can form dimers, whose form seems to act as another enzymatic activity in UCH-L1, ubiquitin ligase activity
monomer
-
1 * 35000, SDS-PAGE
monomer
-
1 * 25000, UCH-L1, SDS-PAGE
monomer
-
1 * 110000, SDS-PAGE, monomeric under reducing conditions
monomer
-
in solution, sedimentation equilibrium analysis, in solution, sedimentation equilibrium experiments
monomer
-
1 * 29000, SDS-PAGE or calculated from the deduced amino acid sequence
monomer
B5KNK6
1 * 26000, SDS-PAGE, rates of dimerization and oligomerization are high in ovary and lower in ovotestis, whereas monomers are mainly formed in testis. The dimerization/oligomerization level of Uch-L1 decreases during gonadal transformation from female to male. UCH-L1 structure modelling
monomer
-
no dimerization of UCH-L3
additional information
P09936
secondary structure analysis of wild-type and mutant isozyme L1 by circular dichroism spectroscopy
additional information
-
AMSH contains the JAMM motif, i.e. JAB1/MPN/Mov34 metalloenzyme motif, in the active site
additional information
-
structure-function relationship
additional information
-
the wild-type enzyme is a rotating ellipsoidal dimer, small-angle neutron scattering
additional information
-
NMR structure determination of purified GST-tagged UCH-L1, resonance assignments in conjunction with the crystal structure of UCH-L1, PDB entry 2ETL, overview
additional information
-
presumptive oligomeric forms of UCHL1 increase in the presence of UCHL1 inhibitors
additional information
-
the catalytic domain, the UCH-domain, i.e. UCH37N, of UCH37 comprises residues 1-228 residues. UCH37N is composed of a central six-stranded anti-parallel beta-sheet, with seven alpha-helices on either side of the sheet causing it to form a bilobal structure, loop and active site structures, overview
additional information
-
the crystal structure of apo UCHL1 shows that the active-site residues are not aligned in a canonical form, with the nucleophilic cysteine being 7.7 A from the general base histidine, an arrangement consistent with an inactive form of the enzyme
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
ubiquitination
-
monoubiquitination is a posttranslational modification of UCH-L1 that controls the function of UCH-L1. It may occur reversibly to a lysine residue near the active site, probably K157, of UCH-L1. This modification restricts enzyme activity by preventing binding to the ubiquitinated targets, and permanent mono-ubiquitination, as mimicked by a ubiquitin-UCH-L1 fusion, inhibits UCH-L1 in its capacity to increase free ubiquitin levels. However, the lifetime of this modification on UCH-L1 is regulated by auto-deubiquitination
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
additional information
Mus musculus C57BL/6J
-
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
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
at 2.4 A resolution, x-ray crystallography. Overall fold resembles that of other ubiquitin hydrolases, including UCHL3. Geometry of the catalytic residues in the active site of UCH-L1 is distorted in such a way that the hydrolytic activity appears to be impossible without substrate induced conformational rearrangements; purified recombinant wild-type and mutant GST-tagged enzymes, 35 mg/ml protein in 50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 10 mM DTT, crystallization at room temperature, X-ray diffraction structure determination and analysis at 2.6 A resolution, molecular modeling, structure-function relationship
-
hanging drop vapour diffusion method, 1.45 A resolution crystal structure of human UCH-L3 in complex with the inhibitor ubiquitin vinylmethyl ester
P15374
purified recombinant UCH37 catalytic domain, i.e. UCH37N, selenomethionine-substituted UCH37N, and of mutant C88A, sitting-drop vapor diffusion method, 14 mg/ml protein in 25 mM Tris-HCl, pH 7.5, 1 mM DTT, 20°C, versus a reservoir solution containing 22% PEG 4000, 0.2 M MgCl2, 0.1 M Tris-HCl, pH 8.5, and 3.5% xylitol, microseeding, X-ray diffraction structure determination and analysis at 2.2 A resolution
-
purified recombinant wild-type UCH-L1 and the Parkinson disease-associated variant of the enzyme, mutant S18Y, bound to a ubiquitin-based suicide substrate, ubiquitin vinyl methyl ester, hanging drop vapour diffusion method, 25 mg/ml enzyme-UbVMe complex in 50 mM Tris-HCl, pH 7.4, 150 mM NaCl, and 10 mM DTT, are mixed with 2.4 M ammonium sulfate and 0.1 M bicine, pH 9.0, 2 months, X-ray diffraction structure determination and analysis at 2.4-2.85 A resolution, molecular replacement
-
UCH-L3, crystal structure at 1.8 A resolution
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
60 min, 70% loss of activity towards A24, no loss of activity towards ubiquitin C-terminal amide and human ubiquitin carboxyl extension protein
36453
52
-
reversible denaturation of wild-type isozymes L1 and L3, and of L1 mutants C90S, H161D, H161K, H161Y, thermodynamics; thermodynamic of denaturation, enthalpy, entropy, Gibbs energy
36456
additional information
-
H6YUH1 shows 3.2 and 1.4 h of half lives at 4°C and 52°C, respectively. Immobilized YUH1 in 50% glycerol solution at -20°C results in 52% of decrease in specific activity for 7 days, corresponding to a 2.7fold increase compared with that of free YUH1 incubated in the same solution at 4°C
682683
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
repeated freezing and thawing inactivates
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
active-site thiol is very sensitive to oxidation and requires reductants
-
35003
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C
-
-60°C
-
-20°C, 20 mM sodium phosphate buffer, pH 7.4, 100% glycerol
P35127
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
175fold; partial
-
4 isozymes; partial
-
native isozymes UCHL1-L3 from thymus by anion exchange chromatography and gel filtration, isozyme UCHL1 to homogeneity after this step. PGP 9.5 purified from bovine brain, isozyme UCHL3 is further specifically purified by ubiquitin affinity chromatography
-
UCH-L1, UCH-L2, UCH-L3
-
recombinant UCH purified to homogeneity by gel filtration, fusion protein purified by Ni-NTA chromatography
-
UCH-8, to homogeneity
-
affinity purified; affinity purified
-
by anion exchange chromatography and gel filtration
-
by gel filtration; recombinant wild-type and mutant GST-tagged enzymes from Escherichia coli by glutathione affinity chromatography and gel filtration
-
isozyme ISOT-S from erythrocytes; partial, recombinant wild-type and mutant isozymes ISOT-S and ISOT-L from Escherichia coli
-
on Ni-NTA column
-
on Ni-NTA resin
-
purification of GST-tagged UCH-L1 by gel filtration
-
recombinant
P15374
recombinant GST-tagged enzyme from Escherichia coli
-
recombinant GST-tagged UCH-L1 from Escherichia coli strain Rosetta BL21(DE3) by glutathione affinity chromatography
-
recombinant GST-tagged wild-type UCHL1 and mutant S18Y from Escherichia coli strain BL21(Rosetta) by glutathione affinity chromatography, cleavage of the tag, and gel filtration
-
recombinant His-tagged wild-type and mutants of isozyme L1 expressed in Escherichia coli DH5alphaPRO
P09936
recombinant N-terminally GST-tagged UCH37 catalytic domain from Escherichia coli BL21(RIPL) by glutathione affinity chromatography, proteolytic removal of the GST-tag, and gel filtration
-
recombinant truncated GST-fusion protein of UBPY
P40818
recombinant wild-type and mutants of isozymes L1 and L3 from Escherichia coli BL21(DE3), to near homogeneity; UCH-L1, UCH-L3
-
UCH-L3 purified on Ni-NTA column
P45974, Q5VVQ6
wild-type and mutant Bap1-flag proteins immunopurified with alpha-flag beads
Q92560
BPLF1 1-246 and BPLF1 C61S purified by immunoprecipitation
P03186
fusion proteins purified by ProBond purification system
-
recombinant His-tagged wild-type and mutants of isozyme L1 expressed in Escherichia coli
-
by Ni-NTA affinity chromatography, to more than 90% homogeneity
-
by two purification steps, gel filtration
P35127
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression of EGFP-tagged UCHL1 in oocytes
-
gene cyk-3, chromosome mapping, co-expression of cyk-3 with Doa4p of Saccharomyces cerevisiae and ubiquitin-beta-galactosidase fusion protein in Escherichia coli
-
; gene uch-L1, DNA and amino acid sequence determination and analysis, determination and cloning of the promoter sequence, promoter activity and expression analysis, overexpression of the gene and promoter in zebrafish embryos by microinjection
Q6YI49
active C-terminal His-tagged UCH expressed in Pichia pastoris
-
COS-7 cells co-transfected with plasmids encoding His-tagged UCH-L1 and FLAG-tagged ubiquitin
-
determination of the UCHL1 promoter DNA methylation status and the mechanisms for the heterogeneous UCHL1 expression pattern in renal epithelium and in renal cell carcinoma, overview. Semi-quantitative and real-time RT-PCR analysis
-
expressed in BAEC cells; human UCHL1 and bovine eNOS subcloned into D-TOPO and transferred into the mammalian expression vector pcDNA3.1 or pCAGGS, transfection of plasmid DNA in rat carotid artery
-
expressed in COS-7 cells
-
expressed in Escherichia coli
-
expressiom of GFP-tagged wild-type UCH L1 and mutants in PC12 Tet-off cells and in CHO-AA8-Luc1 cells
-
expression in Escherichia coli as GST-tagged enzyme
-
expression of a catalytically active UCH-L1 in a UCH-L1 negative EBV transformed lymphoblastoid cell line
-
expression of GST-tagged UCH-L1 in Escherichia coli strain Rosetta BL21(DE3)
-
expression of GST-tagged wild-type and mutant enzymes in HEK-293 cells
-
expression of GST-tagged wild-type UCHL1 and mutant S18Y in Escherichia coli strain BL21(Rosetta)
-
expression of HA-tagged wild-type and mutant enzymes in HEK-293 cells
-
expression of His-tagged wild-type and mutant enzymes
-
expression of UCH-L1 in H1299 cells
-
expression vectors encoding HA epitope-tagged Cezanne (pHM6-Cezanne), GFP-tagged Cezanne (pEGFP-Cezanne) and enzymatically inactive forms mutated at the catalytic cysteine (pHM6-Cezanne C209S and pEGFP-Cezanne C209S). Expressed in HEK293 cells
-
FLAG-HA tagged UCH-3 expressed in HeLa cells
-
FLAG-tagged UCH-L1 overexpression in the SH-SY5Y human neuroblastoma cell line, which endogenously expresses UCH-L1 and alpha-synuclein, can be cytotoxic at high expression levels in these cells. Coexpression of wild-type UCH-L1, but not of the protective S18Y variant, in COS-7 cells increases levels of transfected alpha-synuclein by inhibiting its degradation, the amount of UCH-L1M in transfected cells correlates with the intracellular level of alpha-synuclein
-
Flag-tagged wild-type or mutant Bap1 expressed in HEK-293 cells. HA-tagged Bap1 transiently expressed in HeLa cells
Q92560
gene rs5030732, genotyping
P09936
gene rs5030732, genotyping and UCHL1 polymorphisms, expression analysis, overview
-
gene uch-L1, DNA and amino acid sequence determination and analysis
P09936
gene usp21, DNA sequence determination and analysis, located on chromosome 1q21, expression in COS cells, overexpression in U2O2 cells
Q9UK80
HEK-293 cells transiently transfected with FLAG (DYKDDDDK)-tagged UCH37 expression construct
-
into the pcDNA3.1-TOPO vector and expressed in HCT-116 or EC-109 cells
-
isozyme L1: expression of wild-type and mutants in Escherichia coli DH5alphaPRO as His-tagged proteins
P09936
isozymes ISOT-S and ISOT-L, cloning from brain mRNA, expression of both isozyme wild-types and mutant isozyme ISOT-S C335S in Escherichia coli strain MC1061
-
overexpression of wild-type and mutant GST-tagged enzymes in Escherichia coli; subcloned from pcDNA-UCH-L1 vector into pGEX-6P-1 vector. The resulting N-terminally fused GST-tagged protein expressed in Escherichia coli Rosetta strain
-
overexpression of wild-type and mutant isozymes L1 and L3 in Escherichia coli BL21(DE3); UCH-L1, UCH-L3
-
pcDNA3.1-UCH-L1 plasmid overexpressed in MCF7 and MCF7/Adr cells
-
plasmids containing wild-type UCH-L1 and mutants with or without FLAG tag transiently transfected into Neuro2a, SH-SY5Y or COS-7 cells. NIH-3T3 cells stably expressing human UCH-L1 with a FLAG-HA double tag at the N-terminus. PGEX UCH-L1 vectors transformed into Escherichia coli BL21
-
recombinant UCH37 catalytic domain as N-terminally GST-tagged protein is expressed in Escherichia coli BL21(RIPL)
-
stable expression of HA-tagged wild-type UCH-L1 in murine NIH-3T3 cells, expression of FLAG-tagged or GFP-tagged wild-type UCH-L1 and mutants D30A and C90S in murine neural progenitor NP cells, the expression level is lower in NP cells derived from gad, i.e. gracile axonal dystrophy, mice compared to NP cells from wild-type mice, overview
-
UBPY, DNA sequence determination and analysis, expression of gene fragment, residues 9-188, fused to GST in a bacterial expression system; UBPY, expression of wild-type enzyme and mutant D786A in NIH 3T3 cells
P40818
UCH-L3 subcloned into a pET28 expression vector bearing an N-terminal histidine tag. Full-length UCH-L3 expressed in Escherichia coli BL21(DE3) cells
P45974, Q5VVQ6
Uch37N (amino acids 1-237) expressed from pET21a with a C-terminal 6× histidine tag in Escherichia coli BL21(DE3). HEK293 cells stably expressing Uch37 containing an amino-terminal 2 × HA epitope. Uch37 expressed as a carboxy- or amino-terminal fusion to the Gal4 activation domain or the Gal4 DNA-binding domain. GST-Uch37, GST-Uch37N (1-237), GST-Uch37C (238-329), wild-type 6× His-Flag-Uch37 and mutant C88A subcloned into pBacPAK8 with their respective epitope tags and expressed using the BacPAK baculovirus expression system, expressed in Sf21 insect cells. DNA encoding human Uch37FL, Uch37N (1-237), Adrm1, and the 19S complex subunits S1, S2, S3, S4, S5a, S5b, S6, S6’, S7, S8, S9, S10a, S10b, S11, S12, S13, S14, S15 and p55 subcloned into pGAD or pGBD yeast two-hybrid vectors and transformed into the YRG-2 yeast strain
-
UCHL1 gene, the gene and its proximal promoter with a classic TATA box 25 bp upstream of a G base determined to be the transcription start site from mRNA 5'-mapping analyses, gene ragulation, detailed overview
-
BPLF1 N-terminal fragment containing the first 246 amino acids cloned into the pFLAG-CMV-2 vector. Expression of the fragment or mutant in HEK-293T cells
P03186
gene UCHL5, DNA and amino acid sequence determination and analysis
B6E460
gene uchl1, phylogenetic analysis
B5KNK6
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
Q9CVD2
expressed in KR-4 cells; UCH-L1 expression analysis by microarray, quantitative real time-PCR
-
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
-
into vector pcDNA3.1(+) in frame with a C-terminal HA epitope tag and expressed in Escherichia coli
-
Flag-USP19 transfected into FR3T3 cells. 293VSV cells transfected with pLXSN plasmid encoding N-terminally Flag3-tagged USP19
Q6J1Y9
co-expression of Doa4p with cyk-3 of Caenorhabditis elegans and ubiquitin-beta-galactosidase fusion protein in Escherichia coli
-
two plasmids with two types of YUH1 with the 6 histidine tag at the N-terminus (H6YUH1) or C-terminus (YUH1H6) expressed in Escherichia coli DH5alpha
-
YUH gene ligated with the pET-23d vector, expressed in Escherichia coli Rosetta(DE3)pLysS
P35127
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
aberrant expression of UCHL1/PGP 9.5 in Schwann cells after nerve transection and even in fibroblasts after skin wounds
-
promoter hypermethylation represents a mechanism for the silencing of the UCHL1 gene expression in in renal carcinoma cells as a concept of an epigenetic control for the expression of UCHL1 during disease progression. Restoration of UCHL1 expression in renal carcinoma cells by treatment with DAC, overview
-
2'-deoxy-5-azacytidine, DAC, induces UCHL1 expression in renal carcinoma cell lines linked to the demethylation degree of the UCHL1 promoter DNA. Restoration of UCHL1 expression in renal carcinoma cells by treatment with DAC, overview
-
the enzyme expression is increased in lymph node metastasis associated with poor prognosis in colorectal cancer
-
UCHL1 is consistently up-regulated in smokers compared with nonsmokers
-
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
-
camptothecin induces enzyme expression, also in RNAi silenced 293T and KR4 cells
-
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
-
increased UCH-L1 protein, together with the corresponding changes of Jab1, is detected in morphologically abnormal oocytes of prepubertal ovaries
Mus musculus ICR
-
-
UCH-L1 expression is significantly decreased in middle cerebral artery occlusion, MCAO, rats
-
TNFalpha up-regulates UCH-L1via a translational regulation to inhibit ERK activity, thereby providing a negative feedback to control its growth promoting signaling in vascular smooth muscle cells
Q00981
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C132A
-
site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C132S
-
no effect on protein insolubility or interactions
C152A
-
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
-
binds to monoubiquitin in both 4-hydroxy-2-nonenal-treated cells and untreated cells
C201A
-
site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C209S
-
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
-
site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C220S
-
sie-directed mutagenesis, structure analysis in comparison to the wild-type enzyme
C220S
-
no effect on protein insolubility or interactions
C220S
-
the mutant has in vitro ubiquitin hydrolase activity comparable to the wild-type protein
C335S
-
site-directed mutagenesis of active site Cys335, unaltered substrate binding
C37A
Q9UK80
site-directed mutagenesis
C47A
-
site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C786A
P40818
site-directed mutagenesis, no activity
C88A
-
is inactive
C88A
-
mutant structure determination and comparison to the wild-type enzyme
C90A
-
site-directed mutagenesis, the mutant behaves similar to the wild-type enzyme
C90S
-
site-directed mutagenesis, isozyme L1, inactive
C90S
P09936
exchange of the active site cysteine
C90S
-
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
-
site-directed mutagenesis, the mutant enzyme shows no hydrolase and ubiquitin binding activity
C90S
-
increases cellular monoubiquitin levels, 30% is monoubiquitinated, whereas only 5-10% of wild-type is monoubiquitinated
C90S
-
lacks hydrolase activity but maintains binding affinity for ubiquitin, does not exhibit notably increased insolubility upon 4-hydroxy-2-nonenal-treatment compared with UCH-L1 wild-type, has no effect on the interaction of UCH-L1 and tubulin
C90S
-
a catalytically inactive mutant of UCHL1
C90S
-
a UCH L1 mutant, that shows no binding to beta-catenin
C90S/K157R
-
reduces monoubiquitination
C91A
Q92560
catalytically inactive mutant, can still associate with the HCF-1 beta-propeller but cannot remove ubiquitin chains
C95A
-
enhances the interaction of ubiquitin dimers with UCH-L3
C95S
-
active site mutant of UCH-L1, active site mutant of UCH-L3, enhances the interaction of ubiquitin dimers with UCH-L3
D176N
-
site-directed mutagenesis, isozyme L1, 97.5% reduced activity compared to wild-type
D30A
-
site-directed mutagenesis, the mutant enzyme shows highly reduced hydrolase and ubiquitin binding activity
D30K
-
deficient in ubiquitin binding, is unable to increase cellular monoubiquitin levels
D30K
-
lacks hydrolase activity and binding affinity for ubiquitin, has no effect on the interaction of UCH-L1 and tubulin
D33A
-
ubiquitin affinity deficient mutant, diminishes the interaction of ubiquitin dimers with UCH-L3
D348A
-
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
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
-
site-directed mutagenesis, isozyme L1, very low activity
H161D
-
30% is monoubiquitinated, whereas only 5-10% of wild-type is monoubiquitinated
H161D
-
a UCH L1 mutant, that shows no binding to beta-catenin
H161K
-
catalytically inactive, site-directed mutagenesis, isozyme L1, nearly inactive
H161N
-
catalytically inactive, site-directed mutagenesis, isozyme L1, nearly inactive
H161Q
-
catalytically inactive, site-directed mutagenesis, isozyme L1, nearly inactive
H161Y
-
catalytically inactive, site-directed mutagenesis, isozyme L1, nearly inactive
H185A
-
displays increased interactions with tubulin
H97N
-
85% activity compared to wild-type, site-directed mutagenesis, isozyme L1, slightly reduced activity
H97Q
-
85% activity compared to wild-type, site-directed mutagenesis, isozyme L1, slightly reduced activity
I93M
P09936
site-directed mutagenesis, isozyme L1, mutant shows increased risk for Parkinson's disease, 45.6% enzyme activity compared to wild-type
I93M
-
the mutation is linked to familial Parkinson's disease, the mutant dimer conformation is different from the wild-type enzyme deforming the globular form, 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
-
approximately doubles the monoubiquitination level of UCH-L1
I93M
-
missense mutation in the UCH-L1 gene in a German family with a familial case of Parkinson´s disease, decreases hydrolytic activity
I93M
-
mutation in UCH-L1 associated with familial Parkinson’s disease, shows increased insolubility and elevated interactions with multiple proteins, promotes tubulin polymerization
I93M
-
naturally occuring mutation involved in Parkinson's disease
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
Q37R
-
site-directed mutagenesis, isozyme L1, unaltered activity
R63A
-
displays increased interactions with tubulin, causes a decrease in tubulin polymerization
S18Y
P09936
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
-
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
-
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
-
does not affect cellular levels of monoubiquitinated UCH-L1
S18Y
-
monomeric in solution
S18Y
-
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
-
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
-
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
P09936
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 involved in Parkinson'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/I93M
-
increased insolubility
C61S
P03186
loss of deubiquitinating enzyme activity, does not decrease viral ribonucleotide reductase activity
C14A
Q9CVD2
mutant of ataxin-3 carrying six consecutive glutamines, does not undergo proteolytic fragmentation on incubation at room temperature
C14A/H119L
Q9CVD2
mutant of ataxin-3 carrying six consecutive glutamines, does not undergo proteolytic fragmentation on incubation at room temperature
C90S
-
site-directed mutagenesis, isozyme L1, inactive, exchange of the active site cysteine
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
C95S
-
retains the affinity to interact with ubiquitin dimers
D30K
-
site-directed mutagenesis, isozyme L1, inactive
D33A
-
loses the affinity to interact with ubiquitin dimers. D33A mutant expressing cells do not show any signs of free ubiquitin dimers accumulation
C545A
Q6J1Y9
catalytically inactive USP19 mutant, destabilizes ubiquitin ligase KPC1
C571S
-
is unable to maintain normal ubiquitin levels. In doa4delta cells expressing C571S, CPS is missorted to the limiting membrane of the vacuole
W782R
-
is solely cytoplasmic, defect in endosomal localization, Bro1-Doa4 interaction is disrupted
additional information
-
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
I93M
-
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
additional information
-
enzyme downregulation in HeLa cells by siRNA, enzyme inhibition influences the degradation of the EGF receptor
additional information
-
silencing of UCH-L1 by expression of siRNA in H1299 cells
additional information
-
fusion protein UbVV/L8A-UCH-L1 contains an L8A mutation in the ubiquitin moiety. Efficiently binds ubiquitin, increases cellular monoubiquitin levels
additional information
-
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
-
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
Q92560
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
-
gene rs5030732, genotyping and UCHL1 polymorphisms, expression analysis, overview
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
-
UCH L1 silencing with siRNAs leads to accumulation of beta-catenin
H119L
Q9CVD2
mutant of ataxin-3 carrying six consecutive glutamines, does not undergo proteolytic fragmentation on incubation at room temperature
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 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
P15347
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
-
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
Q80TQ2
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
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
Mus musculus C57BL/6J
-
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, 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, 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
-
doa4delta
-
defect in endosomal localization
additional information
-
-
additional information
-
enzyme deficient strain accumulates membrane-bound ubiquitin-conjugated Fur4p
additional information
-
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
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
reconstitution of the apoenzyme with Zn2+ at pH 5.5 under nondenaturing conditions completely restores activity
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
molecular biology
-
Pichia pastoris is a robust system to express the secreted form of Drosophila melanogaster UCH
analysis
-
the proportion of inclusion-bearing cells showing high levels of ubiquitin C-terminal hydrolase may provide a marker of the activity of a degenerative process
degradation
-
a natural dodecapeptide amide from UCH-L3 with the sequence DPDELRFNAIAL is capable of binding to monoubiquitin and may enable the design of peptides with different affinities towards K48- and K63-linked polyubiquitin
diagnostics
-
ubiquitin C-terminal hydrolase is a biomarker in humans for severe traumatic brain injury
diagnostics
-
UCH-L1 is a biomarker for lymph node metastasis in colorectal cancer
diagnostics
-
UCHL1 is a potential cerebrospinal fluid biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage and presumably other CNS damage and disease states, overview
drug development
-
three-step docking (DOCK, rough GOLD, and fine GOLD) and in vitro enzyme assay methods to identify UCH-L3 inhibitors. UCH-L3 inhibitors may be useful for future apoptosis-inducing anti-cancer drug development
medicine
-
interactions of mutant or carbonyl-modified UCH-L1 with other proteins constitute one of the causes of not only familial Parkinson’s disease, but also sporadic Parkinson’s disease. Carbonyl-modified and mutant UCH-L1 share common properties, e.g. adopt a similar aberrant structure, promote tubulin polymerization, show decreased ubiquitin binding, and both increased insolubility and interactions with proteins over 30 kDa compared with the wild-type
medicine
-
overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy
medicine
-
overexpression of UCHL1 significantly attenuates tumor necrosis factor-alpha–induced nuclear factor-kappa B activity in vascular cells and increases inhibitor of kappa B-alpha, possibly through the attenuation of kappa B-alpha ubiquitination, leading to decreased neointima in the balloon-injured artery
medicine
-
Parkinson disease-associated UCH-L1 is regulated by reversible monoubiquitination involving auto-deubiquitination
medicine
-
possible involvement of UCH-L1 and UCH-L3 in the pathogenesis and progression of breast cancer. High UCH-L1 mRNA level is significantly associated with negative estrogen receptor status and negative progesterone receptor status. Patients with both UCH-L1 and UCH-L3 mRNA high tumors show a significantly poorer prognosis than those in the UCH-L1 or UCH-L3 mRNA low group
medicine
-
targeting the UCH37-Smad7 complex may provide a new approach for treating human diseases in which there is overt up-regulation in TGF-beta signalling activity. Competing effects of ubiquitin ligases and DUBs in complex with Smad7 can serve to fine-tune responses to TGF-betas under various physiological and pathological conditions
medicine
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UCH-L1 deficiency and impairment of the ubiquitin-dependent protein degradation pathway contributes to increased cell death observed in many lysosomal storage disorders
medicine
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UCH-L1 has a putative but still undefined role in the ubiquitin-dependent protein degradation pathway. Postmortem analysis of human brains shows this pathway to be compromised in Alzheimer’s disease. A polymorphism in the UCH-L1 gene increases the risk of Alzheimer’s disease in females and also effects the risk of Parkinson’s disease in Asian populations
medicine
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UCH-L1 is a potent molecular biomarker for monitoring early stage of neurodegeneration occurring under oxidative stress in elderly people of advanced age
medicine
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UCH-L1 is an important component of the ubiquitin-proteasome system and is linked to Parkinson´s, Huntington´s, Alzheimer´s disease and other neurodegenerative disorders. UCH-L1 is an attractive target for the development of new therapeutic approaches to Alzheimer´s disease
medicine
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UCHL-1 expression is a contributory factor in the abnormal protein aggregation in dementia with Lewy bodies. Putative therapeutic target in the treatment of dementia with Lewy bodies
medicine
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UCHL1 is aberrantly regulated in frontotemporal dementia and parkinsonism linked to chromosome 17
medicine
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UCH-L1 expression seems to be associated with the metastatic potential of human renal cell carcinoma cell SN12C clones
pharmacology
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enzyme is a target for the development of antineoplastic agents
analysis
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UCH-L1 is a neuronal marker
degradation
Q9R0P9
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
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ubiquitin hydrolase Uch-L1 could be an attractive target for the development of new therapeutic approaches to Alzheimer's disease
medicine
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activation of UCH-L1 may be a useful therapeutic approach for treating Alzheimer’s 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 Alzheimer’s 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
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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 Parkinson’s disease and some forms of cancer
medicine
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UCH-L1 deficiency and impairment of the ubiquitin-dependent protein degradation pathway contributes to increased cell death observed in many lysosomal storage disorders
medicine
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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
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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 Alzheimer’s 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
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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
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Uchl3-deficient mice represent a model for adultonset retinal degeneration associated with mitochondrial impairment
medicine
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mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L1 in vivo
medicine
Mus musculus C57BL/6J
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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
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medicine
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transient ischemia induces selective delayed motor neuronal death and affects the profile of expression of ubiquitin, parkin, and UCH-L1. Vulnerability of motor neuron of the spinal cord may be partially attributed to the different response in ubiquitin-mediated stress response after transient ischemia
drug development
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UCH54, homologous to human UCH37, may represent a target for pharmacological intervention
synthesis
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used as molecular scissors for releasing a peptide or protein product
medicine
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expression of UCH-L1 is increased during long-term facilitation, which is related to synaptic plasticity and learning
additional information
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UCHL1 is related to cellular senescence process
additional information
Caenorhabditis elegans N2
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UCHL1 is related to cellular senescence process
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additional information
Q6YI49
the enzyme and the zebrafish can be utilized as an animal model for analysis of development of Parkinson's disease
medicine
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membrane-associated farnesylated UCH-L1 is a therapeutic target for Parkinson's disease
additional information
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UCH-L1 and UCH-L3 may have a role in growth transformation
additional information
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Uch37 is responsible for isopeptidase activity
additional information
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UCHL1 is a candidate aging-related protein
medicine
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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
additional information
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dynamic regulation of apically located epithelial sodium channel by recycling, which is facilitated by UCH-L3
diagnostics
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UCH-L1 is a biomarker for ischemic and traumatic brain injury in rats
additional information
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direct role of Doa4 in multivesicular body sorting pathway that is linked to its catalytic activity. Doa4 mediates a deubiquitination step required for sorting of CPS into the multivesicular body pathway
additional information
P35127
YUH effciently cleaves the ubiquitin-piscidin fusion protein, and since it can easily be prepared in the lab, it provides a cost-effective way of preparing the antimicrobial target peptide piscidin as compared to other systems
medicine
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sperm acrosomal UCHs are involved in sperm-zona pellucida interactions and antipolyspermy defense. Modulation of spermal UCH activity may facilitate the management of polyspermy during in vitro fertilization and provide insights into male fertility. Recombinant UCHs reduce polyspermy and proportionally increase the rate of monospermic fertilization during in vitro fertilization. Oocyte-secreted UCHs are not necessary for antipolyspermy defense during in vitro fertilization
additional information
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essential role of UCH-L1 in oocyte maturation and in the completion of the first meiosis and its transition to anaphase