The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Uchl1  -  ubiquitin carboxy-terminal hydrolase L1

Mus musculus

Synonyms: AW822034, C88048, Neuron cytoplasmic protein 9.5, PGP 9.5, PGP9.5, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Uchl1


Psychiatry related information on Uchl1

  • UCHL1 dysfunction has been associated with neurodegeneration in Parkinson's, Alzheimer's, and Huntington's disease patients [3].
  • (2006) now indicate that enhancing the activity of UCH-L1, a ubiquitin hydrolase, alleviates the synaptic dysfunction and memory loss associated with a mouse model of AD [5].
  • Our previous proteomic study identified UCH L-1 as one specific target of protein oxidation in Alzheimer's disease (AD) brain, establishing a link between the effect of oxidative stress on protein and the proteasomal dysfunction in AD [6].

High impact information on Uchl1

  • This work also raises the question of what role UCH-L1 might play in other diseases involving protein aggregation, such as Parkinson's Disease [5].
  • 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 system and testis [7].
  • Most importantly, loss of pain perception was largely prevented in RAGE(-/-) mice, although they were not protected from diabetes-induced loss of PGP9.5-positive plantar nerve fibers [8].
  • CNS-NSC (labeled with CM-DiI) were transplanted into the pylorus of mice and fluorescent double-labeling immunostaining for betaIII-tubulin or PGP 9.5 and nNOS was performed at 2, 4, and 8 weeks after transplantation [9].
  • We then looked in the mouse brain and found relatively low UCHL1 expression in granule neurons of the hippocampus and olfactory bulb, two well characterized types of replaceable neurons in mammals [3].

Biological context of Uchl1


Anatomical context of Uchl1


Associations of Uchl1 with chemical compounds

  • Some other markers of nasal chemosensory neurones, such as GAP-43/B-50, Protein Gene Product 9.5 (PGP 9.5) and carnosine are also transiently expressed in this ectopic site [15].
  • Thus, these results demonstrate that the Ag determinants recognized by the UCHL1 and the anti-220/205/190-kDa mAb, which are topographically unrelated, are associated with sialic acids from O-linked-type oligosaccharides, emphasizing the contribution of carbohydrates to the Ag heterogeneity of CD45 molecular complex [16].
  • The most prominent structure defined by this antibody is a 110-kDa molecule that is different from the 135-kDa, 160-kDa, and 185-kDa glycoproteins identified by anti-CDw29 antibody and the 180-kDa glycoprotein identified by UCHL-1 antibody [17].
  • Because taste buds are heterogeneous aggregates of cells, we used alpha-gustducin, neuronal cell adhesion molecule (NCAM), and neuronal ubiquitin carboxyl terminal hydrolase (PGP9.5), markers for defined subsets of mature taste cells, to demonstrate that liposome-mediated transfection targets multiple taste cell types [18].
  • The results in this paper reveal that a novel protein, p28, exists in the toad oocytes, is a UCH L1 homolog, was engaged in the process of progesterone-induced oocyte maturation possibly through an involvement in protein turnover and degradation [19].

Regulatory relationships of Uchl1


Other interactions of Uchl1

  • Rather, germ cell apoptosis was mainly detected in primary spermatocytes having weak or negative UCH-L1 expression but strong PCNA expression [11].
  • The testes of gracile axonal dystrophy (gad) mice, which lack UCH-L1, were resistant to cryptorchid stress-related injury and had reduced ubiquitin levels [10].
  • Given that UCH-L1 deficiency results in axonal degeneration and spheroid formation, our findings suggest that beta- and gamma-synuclein participate in the pathogenesis of axonal swelling in gad mice [21].
  • On the other hand, NT3-, and TrkB-immunoreactive cells included type-III cells, together with type-II, -I, and basal cells, because they were positive for PGP 9.5 and gustducin [22].
  • The development and innervation of vallate papillae and taste buds in mice were studied using antibodies against the neuronal marker, protein gene product 9.5 (PGP 9.5), and against nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) [23].

Analytical, diagnostic and therapeutic context of Uchl1

  • The present study examined developmental changes in the terminal morphology and neural density in homozygous mice with a targeted disruption of the nt-4/5 gene and wild-type mice by immunohistochemistry for protein gene product 9.5 (PGP 9.5), a general neuronal marker, and by quantitative analysis using an image analyzer [14].
  • In wild-type mice, western blot analysis demonstrated a high level of UCH-L1 expression in the caput epididymis, consistent with ubiquitin expression, whereas UCH-L3 expression was high in the cauda epididymis [24].
  • We also investigated the function of UCH-L1 and UCH-L3 in epididymal apoptosis induced by efferent duct ligation [24].
  • Imaging by confocal microscopy revealed few PGP 9.5-positive neurons at the start of culture; after 2 d clusters of neurons and nerve fibers had appeared along the lobar bronchus and after 5 d along the secondary and tertiary branches [25].
  • One week after nerve injury all neural functions were abolished in the operated hindpaw of all mice, no CGRP-immunoreactive (-ir) fibers were seen in the samples studied, while PGP 9.5 immunofluorescence remained at dim levels within nerve trunks, but disappeared from terminal innervation [26].


  1. Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine. Young, H.M., Bergner, A.J., Müller, T. J. Comp. Neurol. (2003) [Pubmed]
  2. Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Osaka, H., Wang, Y.L., Takada, K., Takizawa, S., Setsuie, R., Li, H., Sato, Y., Nishikawa, K., Sun, Y.J., Sakurai, M., Harada, T., Hara, Y., Kimura, I., Chiba, S., Namikawa, K., Kiyama, H., Noda, M., Aoki, S., Wada, K. Hum. Mol. Genet. (2003) [Pubmed]
  3. Replaceable neurons and neurodegenerative disease share depressed UCHL1 levels. Lombardino, A.J., Li, X.C., Hertel, M., Nottebohm, F. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. The development of colon innervation in trisomy 16 mice and Hirschsprung's disease. Li, J.C., Mi, K.H., Zhou, J.L., Busch, L., Kuhnel, W. World J. Gastroenterol. (2001) [Pubmed]
  5. Improving synaptic function in a mouse model of AD. Lansbury, P.T. Cell (2006) [Pubmed]
  6. Proteomic analysis of brain proteins in the gracile axonal dystrophy (gad) mouse, a syndrome that emanates from dysfunctional ubiquitin carboxyl-terminal hydrolase L-1, reveals oxidation of key proteins. Castegna, A., Thongboonkerd, V., Klein, J., Lynn, B.C., Wang, Y.L., Osaka, H., Wada, K., Butterfield, D.A. J. Neurochem. (2004) [Pubmed]
  7. Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice. Saigoh, K., Wang, Y.L., Suh, J.G., Yamanishi, T., Sakai, Y., Kiyosawa, H., Harada, T., Ichihara, N., Wakana, S., Kikuchi, T., Wada, K. Nat. Genet. (1999) [Pubmed]
  8. Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily. Bierhaus, A., Haslbeck, K.M., Humpert, P.M., Liliensiek, B., Dehmer, T., Morcos, M., Sayed, A.A., Andrassy, M., Schiekofer, S., Schneider, J.G., Schulz, J.B., Heuss, D., Neundörfer, B., Dierl, S., Huber, J., Tritschler, H., Schmidt, A.M., Schwaninger, M., Haering, H.U., Schleicher, E., Kasper, M., Stern, D.M., Arnold, B., Nawroth, P.P. J. Clin. Invest. (2004) [Pubmed]
  9. Neural stem cells express RET, produce nitric oxide, and survive transplantation in the gastrointestinal tract. Micci, M.A., Learish, R.D., Li, H., Abraham, B.P., Pasricha, P.J. Gastroenterology (2001) [Pubmed]
  10. Two closely related ubiquitin C-terminal hydrolase isozymes function as reciprocal modulators of germ cell apoptosis in cryptorchid testis. Kwon, J., Wang, Y.L., Setsuie, R., Sekiguchi, S., Sato, Y., Sakurai, M., Noda, M., Aoki, S., Yoshikawa, Y., Wada, K. Am. J. Pathol. (2004) [Pubmed]
  11. Overexpression of ubiquitin carboxyl-terminal hydrolase L1 arrests spermatogenesis in transgenic mice. Wang, Y.L., Liu, W., Sun, Y.J., Kwon, J., Setsuie, R., Osaka, H., Noda, M., Aoki, S., Yoshikawa, Y., Wada, K. Mol. Reprod. Dev. (2006) [Pubmed]
  12. Stimulation of the murine Uchl1 gene promoter by the B-Myb transcription factor. Long, E.M., Long, M.A., Tsirigotis, M., Gray, D.A. Lung Cancer (2003) [Pubmed]
  13. Developmental regulation of ubiquitin C-terminal hydrolase isozyme expression during spermatogenesis in mice. Kwon, J., Wang, Y.L., Setsuie, R., Sekiguchi, S., Sakurai, M., Sato, Y., Lee, W.W., Ishii, Y., Kyuwa, S., Noda, M., Wada, K., Yoshikawa, Y. Biol. Reprod. (2004) [Pubmed]
  14. Neurotrophin-4/5-depletion induces a delay in maturation of the periodontal Ruffini endings in mice. Maruyama, Y., Harada, F., Jabbar, S., Saito, I., Aita, M., Kawano, Y., Suzuki, A., Nozawa-Inoue, K., Maeda, T. Arch. Histol. Cytol. (2005) [Pubmed]
  15. Prenatal differentiation of mouse vomeronasal neurones. Tarozzo, G., Cappello, P., De Andrea, M., Walters, E., Margolis, F.L., Oestreicher, B., Fasolo, A. Eur. J. Neurosci. (1998) [Pubmed]
  16. Biochemical nature and topographic localization of epitopes defining four distinct CD45 antigen specificities. Conventional CD45, CD45R, 180 kDa (UCHL1) and 220/205/190 kDa. Pulido, R., Sánchez-Madrid, F. J. Immunol. (1989) [Pubmed]
  17. 1F7, a novel cell surface molecule, involved in helper function of CD4 cells. Morimoto, C., Torimoto, Y., Levinson, G., Rudd, C.E., Schrieber, M., Dang, N.H., Letvin, N.L., Schlossman, S.F. J. Immunol. (1989) [Pubmed]
  18. Liposome-mediated transfection of mature taste cells. Landin, A.M., Kim, J.W., Chaudhari, N. J. Neurobiol. (2005) [Pubmed]
  19. A novel ubiquitin carboxyl terminal hydrolase is involved in toad oocyte maturation. Sun, Z.G., Kong, W.H., Zhang, Y.J., Yan, S., Lu, J.N., Gu, Z., Lin, F., Tso, J.K. Cell Res. (2002) [Pubmed]
  20. Ubiquitin C-terminal hydrolase L1 regulates the morphology of neural progenitor cells and modulates their differentiation. Sakurai, M., Ayukawa, K., Setsuie, R., Nishikawa, K., Hara, Y., Ohashi, H., Nishimoto, M., Abe, T., Kudo, Y., Sekiguchi, M., Sato, Y., Aoki, S., Noda, M., Wada, K. J. Cell. Sci. (2006) [Pubmed]
  21. Accumulation of beta- and gamma-synucleins in the ubiquitin carboxyl-terminal hydrolase L1-deficient gad mouse. Wang, Y.L., Takeda, A., Osaka, H., Hara, Y., Furuta, A., Setsuie, R., Sun, Y.J., Kwon, J., Sato, Y., Sakurai, M., Noda, M., Yoshikawa, Y., Wada, K. Brain Res. (2004) [Pubmed]
  22. Immunohistochemical detection of neurotrophin-3 and -4, and their receptors in mouse taste bud cells. Takeda, M., Suzuki, Y., Obara, N., Tsunekawa, H. Arch. Histol. Cytol. (2005) [Pubmed]
  23. The distribution of PGP9. 5, BDNF and NGF in the vallate papilla of adult and developing mice. Chou, H.C., Chien, C.L., Lu, K.S. Anat. Embryol. (2001) [Pubmed]
  24. The region-specific functions of two ubiquitin C-terminal hydrolase isozymes along the epididymis. Kwon, J., Sekiguchi, S., Wang, Y.L., Setsuie, R., Yoshikawa, Y., Wada, K. Exp. Anim. (2006) [Pubmed]
  25. Development of neural tissue and airway smooth muscle in fetal mouse lung explants: a role for glial-derived neurotrophic factor in lung innervation. Tollet, J., Everett, A.W., Sparrow, M.P. Am. J. Respir. Cell Mol. Biol. (2002) [Pubmed]
  26. Comparison of immunohistochemical and functional reinnervation of skin and muscle after peripheral nerve injury. Verdu, E., Navarro, X. Exp. Neurol. (1997) [Pubmed]
WikiGenes - Universities