3.4.19.12: ubiquitinyl hydrolase 1
This is an abbreviated version!
For detailed information about ubiquitinyl hydrolase 1, go to the full flat file.
Reaction
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal)
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Synonyms
A20, AD-019, AMSH, associated molecule with the SH3-domain of STAM, AT-3, ataxin-3, BAP1, BPLF1, BRCA1-associated protein-1, C-terminal hydrolases UCHL3, C-terminal ubiquitin hydrolase, Cezanne, CGI-70, CYLD, de-ubiquitinating enzyme, deubiquinating isopeptidase T, deubiquitinating enzyme, Doa4, Doa4 ubiquitin hydrolase, Doa4p ubiquitin isopeptidase, DUB, dUCH, EC 3.1.2.15, esterase, ubiquitin thiol-, hydrolase, ubiquitin carboxyl-terminal, hydrolase, ubiquitin carboxyl-terminal (Aplysia californica gene Ap-uch), Iso-T, isopeptidase, isopeptidase T, More, Neuron cytoplasmic protein 9.5, neuronal-specific protein gene product 9.5, OsUCH1, OsUCH2, OsUCH3, OsUCH4, OsUCH5, OTU-1, OTUB1, OTUB2, Otubain-1, Otubain-2, ovarian tumour 1, PA-700 associated isopeptidase, papain-like protease, PGP 9.5, PGP 9.5/UCHL1, PGP9.5, PGP9.5.1, PLP2, PLpro, Ub isopeptidase, ubiquitin C terminal hydrolase 1, ubiquitin C-terminal hydrolase, ubiquitin C-terminal hydrolase (Aplysia californica gene Ap-uch), ubiquitin C-terminal hydrolase 1, ubiquitin C-terminal hydrolase 37, ubiquitin C-terminal hydrolase 8, ubiquitin C-terminal hydrolase isoform L3, ubiquitin C-terminal hydrolase L-1, ubiquitin C-terminal hydrolase L1, ubiquitin C-terminal hydrolase L3, Ubiquitin C-terminal hydrolase UCH37, ubiquitin C-terminal hydrolase-1, ubiquitin C-terminal hydrolase-L1, ubiquitin C-terminal hydrolase-L3, ubiquitin C-terminal hydrolase-L5, ubiquitin C-terminal hydrorase-L1, ubiquitin carboxy terminal hydrolase-L1, ubiquitin carboxy terminal hydrolase-L3, ubiquitin carboxy-terminal hydrolase, ubiquitin carboxy-terminal hydrolase 1, ubiquitin carboxy-terminal hydrolase L1, ubiquitin carboxy-terminal hydrolase-L1, ubiquitin carboxy-terminal hydrolase-L3, ubiquitin carboxyhydrolase L3, ubiquitin carboxyl terminal esterase L1, ubiquitin carboxyl terminal hydrolase 1, ubiquitin carboxyl terminal hydrolase L1, ubiquitin carboxyl terminal hydrolase-L1, ubiquitin carboxyl-terminal hydrolase, ubiquitin carboxyl-terminal hydrolase 1, ubiquitin carboxyl-terminal hydrolase 44, ubiquitin carboxyl-terminal hydrolase isozyme L1, ubiquitin carboxyl-terminal hydrolase L-1, ubiquitin carboxyl-terminal hydrolase L1, ubiquitin carboxyl-terminal hydrolase l3, ubiquitin carboxyl-terminal hydrolase L5, ubiquitin carboxyl-terminal hydrolase-L1, ubiquitin carboxyl-terminal hydrolase-L5, ubiquitin carboxyterminal hydrolase L1, ubiquitin carboxyterminal hydrolase L3, ubiquitin carboxyterminal hydrolase-L1, ubiquitin hydrolase, ubiquitin hydrolase Uch-L1, ubiquitin hydrolase UCH-L3, ubiquitin isopeptidase, Ubiquitin thiolesterase, Ubiquitin thiolesterase L1, Ubiquitin thiolesterase L3, Ubiquitin thiolesterase L4, Ubiquitin thiolesterase L5, ubiquitin-C-terminal hydrolase L1, ubiquitin-carboxyl-terminal hydrolase PGP-9.5, ubiquitin-specific protease 44, UBPY, UCH, UCH L-1, UCH L1, UCH-1, UCH-8, UCH-L1, UCH-L2, UCH-L3, UCH-L4, UCH-L5, UCH37, UCH54, UCHL-1, UCHL-3, UCHL1, UCHL1/PGP 9.5, UCHL2, Uchl3, UCHL5, UCHL5N240, USP19, USP22, USP44, yeast ubiquitin hydrolase, YUH, YUH1
ECTree
Application
Application on EC 3.4.19.12 - ubiquitinyl hydrolase 1
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molecular biology
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Pichia pastoris is a robust system to express the secreted form of Drosophila melanogaster UCH
synthesis
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used as molecular scissors for releasing a peptide or protein product
analysis
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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
analysis
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UCH-L1 is a neuronal marker
degradation
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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
degradation
protein L-isoaspartate O-methyltransferase initiates the repair of isoaspartyl residues in aged or stress-damaged proteins in vivo, e.g. UCHL1 is a substrate for the L-isoaspartate methyltransferase in vivo
diagnostics
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ubiquitin C-terminal hydrolase is a biomarker in humans for severe traumatic brain injury
diagnostics
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UCH-L1 is a biomarker for ischemic and traumatic brain injury in rats
diagnostics
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UCH-L1 is a biomarker for lymph node metastasis in colorectal cancer
diagnostics
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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
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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
drug development
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UCH54, homologous to human UCH37, may represent a target for pharmacological intervention
drug development
the enzyme may contribute to the pathogenesis of idiopathic pulmonary fibrosis and may be a potential therapeutic target
medicine
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 Alzheimers disease. Administration of a UCH-L1 fused to the transduction domain of the HIV-transactivator protein to supplement endogenous UCH-L1 has a protective effect on memory loss in a mouse model of Alzheimers disease. It restores long term potentiation and contextual memory to normal levels, whereas levels of the regulatory subunit of protein kinase A decrease, which, in turn, leads to increased levels of phosopho-cAMP response element binding protein
medicine
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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 Parkinsons disease and some forms of cancer
medicine
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expression of UCH-L1 is increased during long-term facilitation, which is related to synaptic plasticity and learning
medicine
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interactions of mutant or carbonyl-modified UCH-L1 with other proteins constitute one of the causes of not only familial Parkinsons disease, but also sporadic Parkinsons disease. Carbonyl-modified and mutant UCH-L1 share common properties, e.g. adopt a similar aberrant structure, promote tubulin polymerization, show decreased ubiquitin binding, and both increased insolubility and interactions with proteins over 30 kDa compared with the wild-type
medicine
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overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy
medicine
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overexpression of UCHL1 significantly attenuates tumor necrosis factor-alphainduced 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
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Parkinson disease-associated UCH-L1 is regulated by reversible monoubiquitination involving auto-deubiquitination
medicine
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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
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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
medicine
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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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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
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
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 Alzheimers disease. A polymorphism in the UCH-L1 gene increases the risk of Alzheimers disease in females and also effects the risk of Parkinsons disease in Asian populations
medicine
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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UCH-L1 is required for maintenance of memory in a passive avoidance test, exploratory behaviour in a novel environment, and a transcription-dependent component of theta-burst stimulation-induced long-term potentiation in area CA1 of the hippocampus
medicine
Uch-L1 is required for normal synaptic and cognitive function. Uch-L1 activity plays a role in normal contextual fear learning. Transduction of Uch-L1 protein fused to the transduction domain of HIV-transactivator protein restores normal enzymatic activity and synaptic function both in hippocampal slices treated with oligomeric Ab and in the APP/PS1 mouse model of Alzheimers disease. Intraperitoneal injections with the fusion protein improve the retention of contextual learning in APP/PS1 mice over time. Beneficial effect of the Uch-L1 fusion protein is associated with restoration of normal levels of the protein kinase A-regulatory subunit IIa, PKA activity, and cAMP response element binding protein phosphorylation
medicine
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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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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
UCHL1 is aberrantly regulated in frontotemporal dementia and parkinsonism linked to chromosome 17
medicine
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Uchl3-deficient mice represent a model for adultonset retinal degeneration associated with mitochondrial impairment
medicine
mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L1 in vivo
medicine
UCH-L1 expression seems to be associated with the metastatic potential of human renal cell carcinoma cell SN12C clones
medicine
uchl1 genes as novel targets of alpha-tocopherol deficiency may offer molecular correlates of well documented descriptions of neuromuscular dysfunctions in alpha-tocopherol-deficient rodents
medicine
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membrane-associated farnesylated UCH-L1 is a therapeutic target for Parkinson's disease
medicine
expression of isoform UCHL1 is elevated in osteosarcoma compared with normal bone tissue. UCHL1 expression level is correlated with tumor maximum diameter, high rate of lung metastases and short survival time. Knockdown of UCHL1 in osteosarcoma cell MG-63 inhibits cell proliferation and significantly increases cell population in the G1 phase. Cyclins promoting G1/S phase transition are reduced after UCHL1 knockdown, including cell cycle regulator cyclin D1, cyclin E1 and CDK6. Inhibition of UCHL1 in MG-63 cells dramatically induces cell apoptosis. Downregulation of UCHL1 in MG-63 significantly inhibits cell invasion. There is a positive correlation between UCHL1 expression level and the Akt and ERK phosphorylation status
medicine
melanoma cells show a a widespread loss or reduced expression of ubiquitin C-terminal hydrolase UCHL1, which is directly correlated with promoter DNA hypermethylation. The subset of melanoma cells, which still express UCHL1, shows altered growth properties and tolerances against reactive oxygen species as compared to UCHL1-negative cells. UCHL1 may function as a new diagnostic biomarker or therapeutic target for the treatment of UCHL1-positive melanomas
medicine
ubiquitin C-terminal hydrolase UCH-L3 is upregulated in normal or non-metastatic prostate cancer cells and is downregulated in metastatic prostate cancer cell lines. Knockdown of UCH-L3 in normal prostate cell line RWPE1 promotes epithelial-to-mesenchymal transition, an important process for cancer cell invasion and metastasis. The induction of epithelial-to-mesenchymal transition by UCH-L3 knockdown results in an increase of cell migration and invasion. Overexpression of UCH-L3 in highly metastatic prostate cancer cell line PC3 reverses epithelial-to-mesenchymal transition but an active site mutant of UCH-L3 does not
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
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pharmacology
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enzyme is a target for the development of antineoplastic agents
pharmacology
covalent docking plus MD refinement of a representative set of known SARS-CoV inhibitors into OTUB2, OTUB1, and the PLpro from SARS-CoV-2 to probe their inhibitor binding and rationalize a deubiquitinase selectivity. It is pointed out that the structural differences in cellular deubiquitinases suggest that these enzymes may be different enough to be selectively targeted
additional information
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the enzyme and the zebrafish can be utilized as an animal model for analysis of development of Parkinson's disease
additional information
the enzyme and the zebrafish can be utilized as an animal model for analysis of development of Parkinson's disease
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
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dynamic regulation of apically located epithelial sodium channel by recycling, which is facilitated by UCH-L3
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
additional information
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UCH-L1 and UCH-L3 may have a role in growth transformation
additional information
Uch37 is responsible for isopeptidase activity
additional information
UCHL1 is a candidate aging-related protein
additional information
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UCHL1 is related to cellular senescence process
additional information
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
additional information
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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
additional information
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UCHL1 is related to cellular senescence process
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