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Gene Review

UCHL3  -  ubiquitin carboxyl-terminal esterase L3...

Homo sapiens

Synonyms: UCH-L3, Ubiquitin carboxyl-terminal hydrolase isozyme L3, Ubiquitin thioesterase L3
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Disease relevance of UCHL3

  • Because the amino acid sequence of UCH-L1 is similar to that of other ubiquitin C-terminal hydrolases, including the ubiquitously expressed UCH-L3, which appear to be unconnected to neurodegenerative disease, the structure of UCH-L1 and the effects of disease associated mutations on the structure and function are of considerable importance [1].
  • UCH-L3 mRNA level was significantly upregulated in breast cancer tissue compared to adjacent normal breast tissue (P < 0.005), and UHC-L1 mRNA level also showed a non-significant increase in tumor tissue compared to adjacent normal breast tissue [2].
  • One fraction that exhibited reactivity with 9/15 colon cancer sera was subjected to mass spectrometry leading to the identification of ubiquitin C-terminal hydrolase isozyme 3 (UCH-L3) as a constituent [3].

High impact information on UCHL3


Biological context of UCHL3


Anatomical context of UCHL3


Associations of UCHL3 with chemical compounds

  • By utilizing high-throughput screening (HTS) to find inhibitors and traditional medicinal chemistry to optimize their affinity and specificity, we have identified a class of isatin O-acyl oximes that selectively inhibit UCH-L1 as compared to its systemic isoform, UCH-L3 [9].
  • UCH-6 belonged to members of the UCH family containing highly conserved Cys, His, and Asp domains and showed 86% amino acid identity to human UCH-L3 [6].

Enzymatic interactions of UCHL3

  • However, UCH-L3 had no detectable activity toward ubiquitinated I kappa B alpha, thus suggesting a degree of enzymatic specificity in the deubiquitination of I kappa B alpha [10].

Other interactions of UCHL3

  • The activity of the C-terminal hydrolases UCH-L3 and UCH37 was upregulated in the majority of tumor tissues compared to the adjacent normal tissues [11].
  • To develop an enzymatic assay for the search of UCH-L3 and USP2 inhibitors, C-terminally labeled ubiquitin substrates were enzymatically synthesized [12].
  • To determine whether specificity may be conferred by recognition of a primary cognate sequence, the substrate preferences of two DUBs, UCH-L3 and isopeptidase T (IsoT), were profiled using a positional scanning branched peptide library [13].

Analytical, diagnostic and therapeutic context of UCHL3


  1. Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1. Das, C., Hoang, Q.Q., Kreinbring, C.A., Luchansky, S.J., Meray, R.K., Ray, S.S., Lansbury, P.T., Ringe, D., Petsko, G.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. High expression of ubiquitin carboxy-terminal hydrolase-L1 and -L3 mRNA predicts early recurrence in patients with invasive breast cancer. Miyoshi, Y., Nakayama, S., Torikoshi, Y., Tanaka, S., Ishihara, H., Taguchi, T., Tamaki, Y., Noguchi, S. Cancer Sci. (2006) [Pubmed]
  3. Molecular profiling of the immune response in colon cancer using protein microarrays: occurrence of autoantibodies to ubiquitin C-terminal hydrolase L3. Nam, M.J., Madoz-Gurpide, J., Wang, H., Lescure, P., Schmalbach, C.E., Zhao, R., Misek, D.E., Kuick, R., Brenner, D.E., Hanash, S.M. Proteomics (2003) [Pubmed]
  4. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Wilkinson, K.D., Lee, K.M., Deshpande, S., Duerksen-Hughes, P., Boss, J.M., Pohl, J. Science (1989) [Pubmed]
  5. Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution. Johnston, S.C., Larsen, C.N., Cook, W.J., Wilkinson, K.D., Hill, C.P. EMBO J. (1997) [Pubmed]
  6. Molecular cloning of chick UCH-6 which shares high similarity with human UCH-L3: its unusual substrate specificity and tissue distribution. Baek, S.H., Yoo, Y.J., Tanaka, K., Chung, C.H. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  7. Nonhydrolyzable diubiquitin analogues are inhibitors of ubiquitin conjugation and deconjugation. Yin, L., Krantz, B., Russell, N.S., Deshpande, S., Wilkinson, K.D. Biochemistry (2000) [Pubmed]
  8. Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies. Barrachina, M., Castaño, E., Dalfó, E., Maes, T., Buesa, C., Ferrer, I. Neurobiol. Dis. (2006) [Pubmed]
  9. Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line. Liu, Y., Lashuel, H.A., Choi, S., Xing, X., Case, A., Ni, J., Yeh, L.A., Cuny, G.D., Stein, R.L., Lansbury, P.T. Chem. Biol. (2003) [Pubmed]
  10. A novel in vitro assay for deubiquitination of I kappa B alpha. Strayhorn, W.D., Wadzinski, B.E. Arch. Biochem. Biophys. (2002) [Pubmed]
  11. Activity profiling of deubiquitinating enzymes in cervical carcinoma biopsies and cell lines. Rolén, U., Kobzeva, V., Gasparjan, N., Ovaa, H., Winberg, G., Kisseljov, F., Masucci, M.G. Mol. Carcinog. (2006) [Pubmed]
  12. Synthesis and characterization of fluorescent ubiquitin derivatives as highly sensitive substrates for the deubiquitinating enzymes UCH-L3 and USP-2. Tirat, A., Schilb, A., Riou, V., Leder, L., Gerhartz, B., Zimmermann, J., Worpenberg, S., Eidhoff, U., Freuler, F., Stettler, T., Mayr, L., Ottl, J., Leuenberger, B., Filipuzzi, I. Anal. Biochem. (2005) [Pubmed]
  13. Substrate profiling of deubiquitin hydrolases with a positional scanning library and mass spectrometry. Mason, D.E., Ek, J., Peters, E.C., Harris, J.L. Biochemistry (2004) [Pubmed]
  14. The binding site for UCH-L3 on ubiquitin: mutagenesis and NMR studies on the complex between ubiquitin and UCH-L3. Wilkinson, K.D., Laleli-Sahin, E., Urbauer, J., Larsen, C.N., Shih, G.H., Haas, A.L., Walsh, S.T., Wand, A.J. J. Mol. Biol. (1999) [Pubmed]
  15. Mechanism-based proteomics tools based on ubiquitin and ubiquitin-like proteins: synthesis of active site-directed probes. Ovaa, H., Galardy, P.J., Ploegh, H.L. Meth. Enzymol. (2005) [Pubmed]
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