Gene Symbol: Uchl1
Description: ubiquitin C-terminal hydrolase L1
Alias: ubiquitin carboxyl-terminal hydrolase isozyme L1, PGP 9.5, PGP9.5, UCH-L1, neuron cytoplasmic protein 9.5, ubiquitin carboxy-terminal hydrolase L1, ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase), ubiquitin thioesterase L1
Species: rat
Products:     Uchl1

Top Publications

  1. Liu H, Li W, Ahmad M, Miller T, Rose M, Poloyac S, et al. Modification of ubiquitin-C-terminal hydrolase-L1 by cyclopentenone prostaglandins exacerbates hypoxic injury. Neurobiol Dis. 2011;41:318-28 pubmed publisher
    ..These studies indicate that UCH-L1 function is important in hypoxic neuronal death and that excessive production of CyPGs after stroke may exacerbate ischemic injury by modification and inhibition of UCH-L1. ..
  2. Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, et al. The ubiquitin pathway in Parkinson's disease. Nature. 1998;395:451-2 pubmed
  3. Koharudin L, Liu H, Di Maio R, Kodali R, Graham S, Gronenborn A. Cyclopentenone prostaglandin-induced unfolding and aggregation of the Parkinson disease-associated UCH-L1. Proc Natl Acad Sci U S A. 2010;107:6835-40 pubmed publisher
    ..Our findings suggest a possible mechanistic link between UCH-L1 modification by cyclopentenone prostaglandins and the etiology of neurodegeneration. ..
  4. Choi J, Levey A, Weintraub S, Rees H, Gearing M, Chin L, et al. Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseases. J Biol Chem. 2004;279:13256-64 pubmed
    ..Together, these results provide evidence supporting a direct link between oxidative damage to the neuronal ubiquitination/de-ubiquitination machinery and the pathogenesis of sporadic AD and PD. ..
  5. Osaka H, Wang Y, Takada K, Takizawa S, Setsuie R, Li H, et al. Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Hum Mol Genet. 2003;12:1945-58 pubmed
    Mammalian neuronal cells abundantly express a deubiquitylating enzyme, ubiquitin carboxy-terminal hydrolase 1 (UCH L1). Mutations in UCH L1 are linked to Parkinson's disease as well as gracile axonal dystrophy (gad) in mice...
  6. Liu Y, Fallon L, Lashuel H, Liu Z, Lansbury P. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002;111:209-18 pubmed
    ..Thus, the ligase activity as well as the hydrolase activity of UCH-L1 may play a role in proteasomal protein degradation, a critical process for neuronal health. ..
  7. Saigoh K, Wang Y, Suh J, Yamanishi T, Sakai Y, Kiyosawa H, et al. Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice. Nat Genet. 1999;23:47-51 pubmed
    ..Here we find that the gad mutation is caused by an in-frame deletion including exons 7 and 8 of Uchl1, encoding the ubiquitin carboxy-terminal hydrolase (UCH) isozyme (Uch-l1) selectively expressed in the nervous ..
  8. Kajimoto Y, Hashimoto T, Shirai Y, Nishino N, Kuno T, Tanaka C. cDNA cloning and tissue distribution of a rat ubiquitin carboxyl-terminal hydrolase PGP9.5. J Biochem. 1992;112:28-32 pubmed
    ..The availability of the rat PGP9.5 clone provides a new approach to examine the function of PGP9.5 and the role that it plays in the pathology of neurodegenerative diseases. ..
  9. Sosna J, Voigt S, Mathieu S, Kabelitz D, Trad A, Janssen O, et al. The proteases HtrA2/Omi and UCH-L1 regulate TNF-induced necroptosis. Cell Commun Signal. 2013;11:76 pubmed publisher
    ..Since UCH-L1 clearly contributes to the non-apoptotic death of podocytes, interference with the necroptotic properties of HtrA2/Omi and UCH-L1 may prove beneficial for the treatment of patients, e.g. in kidney failure. ..

More Information


  1. Takami Y, Nakagami H, Morishita R, Katsuya T, Cui T, Ichikawa T, et al. Ubiquitin carboxyl-terminal hydrolase L1, a novel deubiquitinating enzyme in the vasculature, attenuates NF-kappaB activation. Arterioscler Thromb Vasc Biol. 2007;27:2184-90 pubmed
    We identified a ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene, which encodes a deubiquitinating enzyme and is expressed in the vasculature, by functional screening of a human endothelial cell (EC) cDNA library...
  2. Miura H, Oda K, Endo C, Yamazaki K, Shibasaki H, Kikuchi T. Progressive degeneration of motor nerve terminals in GAD mutant mouse with hereditary sensory axonopathy. Neuropathol Appl Neurobiol. 1993;19:41-51 pubmed
  3. Larsen C, Krantz B, Wilkinson K. Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. Biochemistry. 1998;37:3358-68 pubmed
  4. Bishop P, Rubin P, Thomson A, Rocca D, Henley J. The ubiquitin C-terminal hydrolase L1 (UCH-L1) C terminus plays a key role in protein stability, but its farnesylation is not required for membrane association in primary neurons. J Biol Chem. 2014;289:36140-9 pubmed publisher
    ..These data indicate that UCH-L1 is differently processed in neurons compared with clonal cell lines and that farnesylation does not account for the membrane association in neurons. ..
  5. Krasteva G, Canning B, Hartmann P, Veres T, Papadakis T, Mühlfeld C, et al. Cholinergic chemosensory cells in the trachea regulate breathing. Proc Natl Acad Sci U S A. 2011;108:9478-83 pubmed publisher
    ..This identifies brush cells as cholinergic sensors of the chemical composition of the lower airway luminal microenvironment that are directly linked to the regulation of respiration...
  6. Castro Dias E, Vieira A, Werneck C, Langone F, Novello J, Martins de Souza D. Proteome analysis of lumbar spinal cord from rats submitted to peripheral lesion during neonatal period. J Neural Transm (Vienna). 2010;117:689-93 pubmed publisher
  7. Weber B, Schaper C, Wang Y, Scholz J, Bein B. Interaction of the ubiquitin carboxyl terminal esterase L1 with alpha(2)-adrenergic receptors inhibits agonist-mediated p44/42 MAP kinase activation. Cell Signal. 2009;21:1513-21 pubmed publisher
    ..These findings may present a mechanism contributing to subtype-specific alpha(2)AR trafficking and a potential pathway for the neuroprotective effects of alpha(2)AR agonists. ..
  8. Kameda Y, Nishimaki T, Takeichi M, Chisaka O. Homeobox gene hoxa3 is essential for the formation of the carotid body in the mouse embryos. Dev Biol. 2002;247:197-209 pubmed
    ..The superior cervical ganglion rather showed hypertrophic features in Hoxa3 homozygous mutants lacking the carotid body. ..
  9. Guo Y, Lu Y, Zheng Y, Chen X, Dong J, Yuan R, et al. Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) Promotes Hippocampus-Dependent Memory via Its Deubiquitinating Effect on TrkB. J Neurosci. 2017;37:5978-5995 pubmed publisher
    ..Overall, our study provides novel insights into the mechanisms of UCH-L1-mediated neurobiological functions and suggests that ubiquitination is an important regulatory signal for TrkB functions. ..
  10. Poon W, Carlos A, Aguilar B, Berchtold N, Kawano C, Zograbyan V, et al. ?-Amyloid (A?) oligomers impair brain-derived neurotrophic factor retrograde trafficking by down-regulating ubiquitin C-terminal hydrolase, UCH-L1. J Biol Chem. 2013;288:16937-48 pubmed publisher
    ..Further, our results support the idea that in AD, A? may down-regulate UCH-L1 in the AD brain, which in turn impairs BDNF/TrkB-mediated retrograde signaling, compromising synaptic plasticity and neuronal survival. ..
  11. Liu J, Jiang Y, Huang C, Fang H. [Study of zinc on the modulation of Uch-L1 expression in hippocampus of growing rats]. Wei Sheng Yan Jiu. 2009;38:32-5 pubmed
    ..Uch-L1 protein and mRNA expression levels in hippocampus significantly reduced in comparison with ZA and PF groups. Zinc deficiency could induce downregulation of Uch-L1 expression. ..
  12. Orojan I, Szigeti C, Varszegi S, Dobo E, Gulya K. Dithranol abolishes UCH-L1 immunoreactivity in the nerve fibers of the rat orofacial skin. Brain Res. 2006;1121:216-20 pubmed
    ..This phenomenon may be due to the ability of dithranol to cause oxidative damage to the UCH-L1 protein, and to the antioxidant activity of the corticosteroids countering this effect. ..
  13. Kurihara L, Kikuchi T, Wada K, Tilghman S. Loss of Uch-L1 and Uch-L3 leads to neurodegeneration, posterior paralysis and dysphagia. Hum Mol Genet. 2001;10:1963-70 pubmed
    ..This study is the first to successfully document dysphagia in the mouse and is a potentially valuable resource for understanding human neurodegenerative disorders that cause swallowing defects. ..
  14. Suh J, Yamazaki A, Tomita T. Breeding of the gad-mdx mouse: influence of genetically induced denervation on dystrophic muscle fibers. Lab Anim Sci. 1994;44:42-6 pubmed
  15. Chandran A, Oda K, Shibasaki H, Kikuchi T, Pisharodi M. Stimulus induced repetitive muscle potentials in the gracile axonal dystrophy (GAD) mouse. Electromyogr Clin Neurophysiol. 1995;35:225-30 pubmed
  16. Huang X, Glushakova O, Mondello S, Van K, Hayes R, Lyeth B. Acute Temporal Profiles of Serum Levels of UCH-L1 and GFAP and Relationships to Neuronal and Astroglial Pathology following Traumatic Brain Injury in Rats. J Neurotrauma. 2015;32:1179-89 pubmed publisher
    ..Studies of relative changes in biomarker levels in CSF and serum suggest that different mechanisms may underlie the transport and/or clearance of UCH-L1 and GFAP in these two compartments. ..
  17. Cole R, Hart G. Cytosolic O-glycosylation is abundant in nerve terminals. J Neurochem. 2001;79:1080-9 pubmed
    ..We propose that O-GlcNAc modifications in the nerve terminal help regulate the functions of these and other synaptosome proteins, and that O-GlcNAc may play a role in neurodegenerative disease. ..
  18. Mukoyama M, Yamazaki K, Kikuchi T, Tomita T. Neuropathology of gracile axonal dystrophy (GAD) mouse. An animal model of central distal axonopathy in primary sensory neurons. Acta Neuropathol. 1989;79:294-9 pubmed
    ..These may reflect some stagnation of axonal transport. The distribution of the lesions suggest that the GAD mouse has a central distal axonopathy involving primary sensory neurons of the lumbar dorsal root ganglia. ..
  19. Dibas A, Yang M, He S, Bobich J, Yorio T. Changes in ocular aquaporin-4 (AQP4) expression following retinal injury. Mol Vis. 2008;14:1770-83 pubmed
    ..The decreased ubiquitination in the optic nerve may lead to increased levels of proapoptotic proteins known to be degraded by the proteasome, and thus to axonal degeneration in glaucoma. ..
  20. Moss A, Blackburn Munro G, Garry E, Blakemore J, Dickinson T, Rosie R, et al. A role of the ubiquitin-proteasome system in neuropathic pain. J Neurosci. 2002;22:1363-72 pubmed
  21. Wakisaka S, Miyawaki Y, Youn S, Kato J, Kurisu K. Protein gene-product 9.5 in developing mouse circumvallate papilla: comparison with neuron-specific enolase and calcitonin gene-related peptide. Anat Embryol (Berl). 1996;194:365-72 pubmed
    ..5-IR nerve fibers. The present results indicate that invasion by nerve fibers of the epithelium of lingual papillae occurs in a complex manner, and that these nerve fibers may participate in the formation of the taste buds. ..
  22. Larsen C, Price J, Wilkinson K. Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues. Biochemistry. 1996;35:6735-44 pubmed
    ..6 microM). The binding is primarily electrostatic in nature and indicates the existence of a specific and extensive binding site for ubiquitin on the surface of the enzyme. ..
  23. Martinez L, Aras Lopez R, Lancha S, Vallejo Cremades M, Pederiva F, Xiaomei L, et al. Abnormal development of the enteric nervous system in rat embryos and fetuses with congenital diaphragmatic hernia. Pediatr Surg Int. 2011;27:165-73 pubmed publisher
    ..These anomalies could account in part for the long-term gastrointestinal morbidity observed in CDH survivors. ..
  24. Oda K, Yamazaki K, Miura H, Shibasaki H, Kikuchi T. Dying back type axonal degeneration of sensory nerve terminals in muscle spindles of the gracile axonal dystrophy (GAD) mutant mouse. Neuropathol Appl Neurobiol. 1992;18:265-81 pubmed
  25. Galter D, Westerlund M, Belin A, Olson L. DJ-1 and UCH-L1 gene activity patterns in the brains of controls, Parkinson and schizophrenia patients and in rodents. Physiol Behav. 2007;92:46-53 pubmed
    ..The abundant expression of DJ-1 in certain peripheral tissues and of UCH-L1 in peripheral neurons may also be of relevance for the spectrum of symptoms in different forms of PD. ..
  26. Guha U, Gomes W, Samanta J, Gupta M, Rice F, Kessler J. Target-derived BMP signaling limits sensory neuron number and the extent of peripheral innervation in vivo. Development. 2004;131:1175-86 pubmed
  27. Yamazaki K, Wakasugi N, Tomita T, Kikuchi T, Mukoyama M, Ando K. Gracile axonal dystrophy (GAD), a new neurological mutant in the mouse. Proc Soc Exp Biol Med. 1988;187:209-15 pubmed
    ..The mutation is inherited as an autosomal recessive trait. It was, therefore, named gracile axonal dystrophy (GAD) with the gene symbol gad. The mice could be a new pathological model for the study of neuroaxonal dystrophy. ..
  28. Simpson M, MacLaurin J, Xu D, Ferguson K, Vanderluit J, Davoli M, et al. Caspase 3 deficiency rescues peripheral nervous system defect in retinoblastoma nullizygous mice. J Neurosci. 2001;21:7089-98 pubmed
    ..These findings suggest that PNS neurons are dependent on caspase 3 for the execution of apoptosis and that caspase 3 may serve as a key therapeutic target for neuroprotection after injury of this cell type. ..
  29. Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne D, et al. P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci. 2001;21:5670-7 pubmed
    ..These data strongly suggest a major sensory role for urothelially released ATP acting via P2X(3) receptors on a subpopulation of pelvic afferent fibers. ..
  30. Yu T, Calvo L, Anta B, L pez Benito S, L pez Bellido R, Vicente Garc a C, et al. In vivo regulation of NGF-mediated functions by Nedd4-2 ubiquitination of TrkA. J Neurosci. 2014;34:6098-106 pubmed publisher
    ..Our results indicate that the ubiquitination of the TrkA neurotrophin receptor plays a critical role in NGF-mediated functions, such as neuronal survival and sensitivity to pain...
  31. Brackeva B, De Punt V, Kramer G, Costa O, Verhaeghen K, Stangé G, et al. Potential of UCHL1 as biomarker for destruction of pancreatic beta cells. J Proteomics. 2015;117:156-67 pubmed publisher
    ..Ubiquitin COOH-terminal hydrolase 1 (UCHL1) was identified as abundant protein in rat and human beta cells, showing promising beta cell-selectivity, and was ..
  32. Ciechanover A, Brundin P. The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron. 2003;40:427-46 pubmed
    ..This raises hopes for a better understanding of the pathogenetic mechanisms involved in these diseases and for the development of novel, mechanism-based therapeutic modalities. ..
  33. Løes S, Kettunen P, Kvinnsland H, Luukko K. Mouse rudimentary diastema tooth primordia are devoid of peripheral nerve fibers. Anat Embryol (Berl). 2002;205:187-91 pubmed
  34. Kwon J, Kikuchi T, Setsuie R, Ishii Y, Kyuwa S, Yoshikawa Y. Characterization of the testis in congenitally ubiquitin carboxy-terminal hydrolase-1 (Uch-L1) defective (gad) mice. Exp Anim. 2003;52:1-9 pubmed
    ..Expression of other UCH isozyme mRNAs was not apparently affected by Uch-L1 deficiency in 25-week-old gad mice. This study is the first report on the testis of gad mutant mouse. ..
  35. Liu J, Jiang Y, Huang C, Fang H, Fang H, Pang W. Depletion of intracellular zinc down-regulates expression of Uch-L1 mRNA and protein, and CREB mRNA in cultured hippocampal neurons. Nutr Neurosci. 2008;11:96-102 pubmed publisher
  36. Hoffman L. Patient education: how we designed our own program. Group Pract. 1976;25:21-4 pubmed
  37. Harada T, Harada C, Wang Y, Osaka H, Amanai K, Tanaka K, et al. Role of ubiquitin carboxy terminal hydrolase-L1 in neural cell apoptosis induced by ischemic retinal injury in vivo. Am J Pathol. 2004;164:59-64 pubmed
    ..These results demonstrate that UCH-L1 is involved in ubiquitin expression after stress stimuli, but excessive ubiquitin induction following ischemic injury may rather lead to neural cell apoptosis in vivo. ..
  38. Seta Y, Seta C, Barlow L. Notch-associated gene expression in embryonic and adult taste papillae and taste buds suggests a role in taste cell lineage decisions. J Comp Neurol. 2003;464:49-61 pubmed
    ..Similarly, Notch gene expression in adult taste buds suggests continued roles in cell lineage determination and cell turnover. ..