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malfunction
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altered UCH-L1 activity leads to deleterious effects on synapse structure and function. Inhibition of UCH-L1 activity affects synaptic protein clusters
malfunction
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deficiency of UCH-L1 leads to vulnerability to lipid peroxidation both in vivo and in vitro
malfunction
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elevation in UCH-L1 in cystic fibrosis cells represents a cellular adaptation to counterbalance excessive proteasomal degradation
malfunction
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human UCHL1 gene and neurological diseases, wild-type and mutants I93M and S18Y, mutation I93M is proposed as a familial Parkinsons disease mutation, PARK5, detailed overview
malfunction
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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
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increased oxidative carbonyl modification of UCH-L1 causes dysfunction of UCH-L1 and finally induces neuron death
malfunction
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increased UCH-L1 protein, together with the corresponding changes of Jab1, is detected in morphologically abnormal oocytes of prepubertal ovaries
malfunction
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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
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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
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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
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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
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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
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UCH-L1 is implicated in Parkinsons disease and is present in neurofibrillary tangles or Lewy bodies
malfunction
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
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UCH-L1 levels are increased in cerebrospinal fluid in case of traumatic brain damage correlated with a negative survival prognosis, overview
malfunction
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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
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UCHL1 overexpression is associated with tumor progression and an altered von Hippel Lindau gene expression in renal cell carcinoma
malfunction
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10-week-old K256E-ACTN4pod+/UCHL1-/- mice exhibit reduced albuminuria, glomerulosclerosis, foot process effacement, glomerular basement membrane thickening, glomerular and tubular cell apoptosis, and ameliorated renal pathology. Observations coincide with decreased polyubiquitinated protein levels and increased K256E-alpha-actinin-4 levels in K256E-ACTN4pod+/UCHL1-/-mice kidneys, suggesting impaired proteolysis of K256E-alpha-actinin-4
malfunction
gain- and loss of-function studies reveals that UCH-L1 enhances proliferation of multiple cell types
malfunction
RNA interference of UCH-L1 reduces the growth of human xenograft tumors in mice
malfunction
gene knockdown of UCHL1 by siRNA results in a significant decrease in cell proliferation but marked acceleration of cell differentiation and myotube formation. UCHL1 gene knockdown upregulates myogenic factors myoD and Myogenin (MyoG)
malfunction
UCH-L1 dysfunction is implicated in neurodegenerative disease
malfunction
UCH-L1 dysfunction is implicated in neurodegenerative disease
malfunction
UCH-L1-deficient mice develop proteinuria, without gross changes in glomerular morphology. Tubular cells, endothelial cells, and podocytes show signs of stress with an accumulation of oxidative modified and polyubiquitinated proteins. Mechanistically, abnormal protein accumulation results from an altered proteasome abundance leading to decreased proteasomal activity. UCH-L1-deficient mice exhibit an exacerbated course of disease with increased tubulointerstitial and glomerular damage, acute renal failure, and death, the latter most likely a result of general neurologic impairment
malfunction
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deficiency of UCH-L1 leads to vulnerability to lipid peroxidation both in vivo and in vitro
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malfunction
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increased UCH-L1 protein, together with the corresponding changes of Jab1, is detected in morphologically abnormal oocytes of prepubertal ovaries
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metabolism
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the proteasomal pathway is partially inhibited by UCH-L1M
metabolism
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ubiquitin carboxyl-terminal hydrolase L1 is a member of the ubiquitin proteasome pathway
metabolism
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UCH-L1 in cell signaling, detailed overview
metabolism
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UCH-L1 in cell signaling, detailed overview
metabolism
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UCHL1 gene regulation, overview
metabolism
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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
metabolism
overexpression of ubiquitin carboxyl terminal hydrolase-L1 enhances multidrug resistance and invasion/metastasis in breast cancer by sctivating the MAPK/Erk signaling pathway
metabolism
the enzyme de-ubiquitinates both ubiquitinyl-Smad2 and ubiquitinyl-Smad3 and up-regulates their stability. It mitigates TGFbeta-1 signaling by stabilizing Smad2/Smad3. Inhibition or down-regulation of ubiquitin carboxyl-terminal hydrolase-L5 reduces Smad2/Smad3 levels and TGFbeta-1-induces the expression of fibronectin and alpha-SMA in human lung fibroblast
metabolism
the enzyme is required for regulated protein degradation through the ubiquitin proteasome system in kidney
metabolism
UCH-L1 associates with lipid rafts as with other Parkinson's disease-associated gene products. In addition, UCH-L1 regulates lipid raft-dependent endocytosis and it is not dependent on the expression and degradation of caveolin-1 or flotillin-1. UCH-L1 regulates cell-to-cell transmission of alpha-synuclein. The study provides evidence that many Parkinson's disease-associated gene products share common signaling pathways to explain the pathogenesis of Parkinson's disease
physiological function
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role of UCH-L1 in synaptic function in the brain, overview
physiological function
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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
UCH-L1 appears to be a multi-functional protein and exerts cell type and/or tissue specific actions
physiological function
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UCH-L1 is a deubiquitinating enzyme, it binds to and stabilize mono-ubiquitin in neurons
physiological function
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UCH-L1 is a deubiquitinating enzyme, it binds to and stabilizes mono-ubiquitin in neurons
physiological function
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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
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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
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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
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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
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UCH-L1 mediates maintenance of the temporal integrity and persistence of cyclic AMP response element binding protein, CREB, phosphorylation in the brain
physiological function
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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
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
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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
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UCH-L3 promotes insulin signaling and adipogenesis
physiological function
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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
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UCHL1 is involved in the degradation of unwanted, misfolded, or damaged proteins within the cell
physiological function
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UCHL1 promotes disassembly of polyubiquitin chains during meiotic maturation. Conversely, UCHL1 regulates formation of polyubiquitin chains in bovine oocytes
physiological function
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UCHL1/PGP 9.5 is important in the ubiquitin system, and functions of UCHL1/PGP 9.5 in neurones, detailed overview
physiological function
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UCHL1/PGP 9.5 is important in the ubiquitin system, detailed overview
physiological function
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UCHL1/PGP 9.5 is important in the ubiquitin system, detailed overview
physiological function
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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
UCHL5 is involved in the ubiquitin-proteasome pathway
physiological function
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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
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both biomarkers UCH-L1 and glial fibrillary acidic protein(GFAP) discriminate between traumatic brain injury (TBI) patients with intracranial lesions on CT scan from those without such lesions. GFAP measures are significantly more sensitive and specific than UCH-L1. The addition of UCH-L1 values marginally improved upon GFAP alone in predicting dichotomized Glasgow Outcome Scale Extended (GOS-E) at 3 months after injury
physiological function
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compared with controls, CO-poisoned patients have significantly elevated serum levels of UCH-L1 at each time point after poisoning. There are significantly higher levels of UCH-L1 in CO-poisoned patients with a lower Glasgow coma scale (GCS) score as well as in those with a poor 6-month outcome dichotomized Glasgow outcome scale (GOS)
physiological function
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
physiological function
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high glucose increases the TGF-betaR1 protein expression via the PI3K-UCHL5 pathway in mesangial cells
physiological function
isoform UCHL1 physically interacts with high affinity choline transporter CHT, which is a key protein regulating Ach re-synthesis. Reduction of UCHL1 by siRNA gene knockdown significantly increases polyubiquitinated CHT and decreased native CHT protein level, but does not affect CHT mRNA expression. Gene knockdown of UCHL1 significantly reduces cytosolic CHT but has no significant effect on membrane CHT level
physiological function
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
physiological function
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over-expression of dUCH in the eye imaginal discs induces a rough eye phenotype in the adult, at least partly resulting from the induction of caspase-dependent apoptosis followed by compensatory proliferation. The over-expression of dUCH specifically impairs R7 photoreceptor cell differentiation with a reduction in activated extracellular-signal regulated kinase signals. The dUCH-induced rough eye phenotype is rescued by co-expression of the sevenless gene or the Draf gene, a downstream component of the mitogen-activated protein kinase (MAPK) cascade
physiological function
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RNAi-mediated knockdown of the ubiquitin hydrolase, USP22, results in 2fold increase in monoubiquitinated histone H2B, and 2fold decrease in transcriptional elongation at IRF1. USP22 depletion diminishes 3'-end cleavage/polyadenylation by 2- to 3fold. The polyadenylation factor CPSF73 is not effectively recruited, and serine 2 phosphorylation of the C-terminal domain of RNA polymerase II is also disrupted. Results suggest that ubiquitinated histone H2B helps recruit polyadenylation factors to STAT1-activated genes
physiological function
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
physiological function
UCH-L1 physically interacts with CDK1, CDK4, and CDK5, enhancing their kinase activity
physiological function
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UCHL5 is required for high glucose-induced reduction of TGFbetaR1 protein ubiquitination, p21WAF1 protein expression, cell hypertrophy and fibronectin protein expression
physiological function
major deubiquitinating enzyme of the nervous system and associated with the development of neurodegenerative diseases
physiological function
the enzyme is not essential for neuronal development but it is absolutely required for the maintenance of axonal integrity
physiological function
the enzyme is required for regulated protein degradation in the kidney by controlling proteasome abundance
physiological function
the enzyme plays a key role in angiogenesis by regulating hydrogen peroxide generated by NADPH oxidase 4
physiological function
UCH-L1 is required for the maintenance of axonal integrity
physiological function
UCH-L1 may play pathogenic roles in many neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease
physiological function
UCHL1 may play a role in myogenesis by promoting myoblast proliferation and inhibiting differentiation
physiological function
the enzyme is essential for viral replication
physiological function
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UCH-L1 mediates maintenance of the temporal integrity and persistence of cyclic AMP response element binding protein, CREB, phosphorylation in the brain
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physiological function
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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
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physiological function
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UCHL5 is involved in the ubiquitin-proteasome pathway
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additional information
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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
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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
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ectopic expression of UCH-L3 promotes the phosphorylation of insulin/IGF-I receptor and adipocyte differentiation in fibroblasts, overview
additional information
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membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity, mechanism, overview
additional information
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membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity, mechanism, overview
additional information
UCHL1 is a Parkinson disease-associated, putative cysteine protease