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Literature for peptidase C12.003: ubiquitinyl hydrolase-L3

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Pharma

(Topics flags: S Structure, A Assay, P Specificity, K Knockout, I Inhibitor, V Review. To select only the references relevant to a single topic, click the link above. See explanation.)

    2025
  1. D'Amico,F., Ormeno,C.T., Poeran,S., Akkermans,J., Tjokrodirijo,R.T.N., Sampadi,B., van Veelen,P., Sapmaz,A. and Mulder,M.P.C.
    Advancing the Exploration of the Ubiquitin-like Protein FUBI with Synthetic Chemical Tools
    Chembiochem (2025) , e202500321-e202500321. PubMed  Europe PubMed DOI
  2. Kim,M.S. and Kim,M.S.
    Deubiquitination of epidermal growth factor receptor by ubiquitin-specific peptidase 54 enhances drug sensitivity to gefitinib in gefitinib-resistant non-small cell lung cancer cells
    PLoS ONE (2025) 20, e0320668-e0320668. PubMed  Europe PubMed DOI  PMC  EPMC
  3. Liu,J., Hu,S., Xiao,J. and Zhou,J.
    UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression
    Cancer Cell Int (2025) 25, 276-276. PubMed  Europe PubMed DOI  PMC  EPMC
  4. Lou,S., Wang,H., Mo,G., Li,H., Xie,H., Huang,Y., Li,H., Ma,K., Zhang,X., Yan,M., Zhang,J., Pi,Y. and Han,P.
    A TRIM21-UCHL3-ITCH-SIPA1 axis promotes colorectal cancer growth and metastasis
    Cancer Lett (2025) 639, 218221-218221. PubMed  Europe PubMed DOI
  5. Zhang,J., Allen,J., Ward,S.J., Dekker,L.V. and Dreveny,I.
    A versatile fluorescence polarization based deubiquitination assay using an isopeptide bond substrate mimetic (IsoMim)
    J Biol Chem (2025) , 110342-110342. PubMed  Europe PubMed DOI  I
  6. Zheng,R., Yan,J., Wen,Y., Wei,Y., Zhi,W., Tu,C., Tan,Y. and Xu,W.
    DNAH10 interacts with UCHL3-PACRG complex to coordinate sperm head and flagella development during spermiogenesis
    Development (2025) PubMed  Europe PubMed DOI
    7. 2024
  7. Fan,L., You,H., Jiang,X., Niu,Y., Chen,Z., Wang,H., Xu,Y., Zhou,P., Wei,L., Jiang,T., Deng,D., Xue,L., Peng,Y., Xing,W. and Shao,N.
    UCHL3 induces radiation resistance and acquisition of mesenchymal phenotypes by deubiquitinating POLD4 in glioma stem cells
    Cell Mol Life Sci (2024) 81, 247-247. PubMed  Europe PubMed DOI  PMC  EPMC
  8. Lei,H., Xu,H. and Wu,Y.
    Role of UCHL3 in health and disease
    Biochem Biophys Res Commun (2024) 734, 150626-150626. PubMed  Europe PubMed DOI  V
  9. Xu,Z., Zhang,N. and Shi,L.
    Potential roles of UCH family deubiquitinases in tumorigenesis and chemical inhibitors developed against them
    Am J Cancer Res (2024) 14, 2666-2694. PubMed  Europe PubMed DOI  PMC  EPMC  V
    10. 2023
  10. Liu,T., Fan,M.Q., Xie,X.X., Shu,Q.P., Du,X.H., Qi,L.Z., Zhang,X.D., Zhang,M.H., Shan,G., Du,R.L. and Li,S.Z.
    Activation of CTNNB1 by deubiquitinase UCHL3-mediated stabilization facilitates bladder cancer progression
    J Transl Med (2023) 21, 656-656. PubMed  Europe PubMed DOI  PMC  EPMC
    11. 2022
  11. Hafez,N., Modather El-Awadly,Z. and Arafa,R.K.
    UCH-L3 structure and function: Insights about a promising drug target
    Eur J Med Chem (2022) 227, 113970-113970. PubMed  Europe PubMed DOI
    12. 2020
  12. Gui,W., Shen,S. and Zhuang,Z.
    Photocaged Cell-Permeable Ubiquitin Probe for Temporal Profiling of Deubiquitinating Enzymes
    J Am Chem Soc (2020) 142, 19493-19501. PubMed  Europe PubMed DOI
  13. Hewitt,C.S., Krabill,A.D., Das,C. and Flaherty,D.P.
    Development of Ubiquitin Variants with Selectivity for Ubiquitin C-Terminal Hydrolase Deubiquitinases
    Biochemistry (2020) 59, 3447-3462. PubMed  Europe PubMed DOI
  14. Li,J., Zheng,Y., Li,X., Dong,X., Chen,W., Guan,Z. and Zhang,C.
    UCHL3 promotes proliferation of colorectal cancer cells by regulating SOX12 via AKT/mTOR signaling pathway
    Am J Transl Res (2020) 12, 6445-6454. PubMed  Europe PubMed  PMC  EPMC  K
  15. Ouyang,L., Yan,B., Liu,Y., Mao,C., Wang,M., Liu,N., Wang,Z., Liu,S., Shi,Y., Chen,L., Wang,X., Cheng,Y., Cao,Y., Xiao,D., Zhang,L., Liu,S. and Tao,Y.
    The deubiquitylase UCHL3 maintains cancer stem-like properties by stabilizing the aryl hydrocarbon receptor
    Signal Transduct Target Ther (2020) 5, 78-78. PubMed  Europe PubMed DOI  PMC  EPMC
    16. 2019
  16. Song,Z., Tu,X., Zhou,Q., Huang,J., Chen,Y., Liu,J., Lee,S., Kim,W., Nowsheen,S., Luo,K., Yuan,J. and Lou,Z.
    A novel UCHL3 inhibitor, perifosine, enhances PARP inhibitor cytotoxicity through inhibition of homologous recombination-mediated DNA double strand break repair
    Cell Death Dis (2019) 10, 398-398. PubMed  Europe PubMed DOI  I
  17. Song,Z., Li,J., Zhang,L., Deng,J., Fang,Z., Xiang,X. and Xiong,J.
    UCHL3 promotes pancreatic cancer progression and chemo-resistance through FOXM1 stabilization
    Am J Cancer Res (2019) 9, 1970-1981. PubMed  Europe PubMed
    18. 2018
  18. Nishi,R., Wijnhoven,P.W.G., Kimura,Y., Matsui,M., Konietzny,R., Wu,Q., Nakamura,K., Blundell,T.L. and Kessler,B.M.
    The deubiquitylating enzyme UCHL3 regulates Ku80 retention at sites of DNA damage
    Sci Rep (2018) 8, 17891-17891. PubMed  Europe PubMed DOI  PMC  EPMC
    19. 2015
  19. Bett,J.S., Ritorto,M.S., Ewan,R., Jaffray,E.G., Virdee,S., Chin,J.W., Knebel,A., Kurz,T., Trost,M., Tatham,M.H. and Hay,R.T.
    Ubiquitin C-terminal hydrolases cleave isopeptide- and peptide-linked ubiquitin from structured proteins but do not edit ubiquitin homopolymers
    Biochem J (2015) 466, 489-498. PubMed  Europe PubMed DOI
    20. 2014
  20. Navarro,M.F., Carmody,L., Romo-Fewell,O., Lokensgard,M.E. and Love,J.J.
    Characterizing substrate selectivity of ubiquitin C-terminal hydrolase-L3 using engineered alpha-linked ubiquitin substrates
    Biochemistry (2014) 53, 8031-8042. PubMed  Europe PubMed DOI  P
    21. 2012
  21. Iphofer,A., Kummer,A., Nimtz,M., Ritter,A., Arnold,T., Frank,R., van den Heuvel,J., Kessler,B.M., Jansch,L. and Franke,R.
    Profiling ubiquitin linkage specificities of deubiquitinating enzymes with branched ubiquitin isopeptide probes
    Chembiochem (2012) 13, 1416-1420. PubMed  Europe PubMed DOI  P
  22. Issaenko,O.A. and Amerik,A.Y.
    Chalcone-based small-molecule inhibitors attenuate malignant phenotype via targeting deubiquitinating enzymes
    Cell Cycle (2012) 11, 1804-1817. PubMed  Europe PubMed DOI  I
  23. Mtango,N.R., Sutovsky,M., Susor,A., Zhong,Z., Latham,K.E. and Sutovsky,P.
    Essential role of maternal UCHL1 and UCHL3 in fertilization and preimplantation embryo development
    J Cell Physiol (2012) 227, 1592-1603. PubMed  Europe PubMed DOI
  24. Zhou,Z.R., Zhang,Y.H., Liu,S., Song,A.X. and Hu,H.Y.
    Length of the active-site crossover loop defines the substrate specificity of ubiquitin C-terminal hydrolases for ubiquitin chains
    Biochem J (2012) 441, 143-149. PubMed  Europe PubMed DOI
    25. 2011
  25. Dennissen,F.J., Kholod,N., Hermes,D.J., Kemmerling,N., Steinbusch,H.W., Dantuma,N.P. and van Leeuwen,F.W.
    Mutant ubiquitin (UBB+1) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3)
    FEBS Lett (2011) 585, 2568-2574. PubMed  Europe PubMed DOI
  26. Kim,J.Y., Lee,J.M. and Cho,J.Y.
    Ubiquitin C-terminal hydrolase-L3 regulates Smad1 ubiquitination and osteoblast differentiation
    FEBS Lett (2011) 585, 1121-1126. PubMed  Europe PubMed DOI
    27. 2010
  27. Setsuie,R., Suzuki,M., Tsuchiya,Y. and Wada,K.
    Skeletal muscles of Uchl3 knockout mice show polyubiquitinated protein accumulation and stress responses
    Neurochem Int (2010) 56, 911-918. PubMed  Europe PubMed DOI  K
    28. 2009
  28. Andersson,F.I., Pina,D.G., Mallam,A.L., Blaser,G. and Jackson,S.E.
    Untangling the folding mechanism of the 5(2)-knotted protein UCH-L3
    FEBS J (2009) 276, 2625-2635. PubMed  Europe PubMed DOI
  29. Popp,M.W., Artavanis-Tsakonas,K. and Ploegh,H.L.
    Substrate filtering by the active site crossover loop in UCHL3 revealed by sortagging and gain-of-function mutations
    J Biol Chem (2009) 284, 3593-3602. PubMed  Europe PubMed DOI  PMC  EPMC
  30. Setsuie,R., Sakurai,M., Sakaguchi,Y. and Wada,K.
    Ubiquitin dimers control the hydrolase activity of UCH-L3
    Neurochem Int (2009) 54, 314-321. PubMed  Europe PubMed DOI
  31. Setsuie,R., Suzuki,M., Kabuta,T., Fujita,H., Miura,S., Ichihara,N., Yamada,D., Wang,Y.L., Ezaki,O., Suzuki,Y. and Wada,K.
    Ubiquitin C-terminal hydrolase-L3-knockout mice are resistant to diet-induced obesity and show increased activation of AMP-activated protein kinase in skeletal muscle
    FASEB J (2009) 23, 4148-4157. PubMed  Europe PubMed DOI  K
  32. Suzuki,M., Setsuie,R. and Wada,K.
    Ubiquitin carboxyl-terminal hydrolase L3 promotes insulin signaling and adipogenesis
    Endocrinology (2009) 150, 5230-5239. PubMed  Europe PubMed DOI  K
    33. 2008
  33. Drag,M., Mikolajczyk,J., Bekes,M., Reyes-Turcu,F.E., Ellman,J.A., Wilkinson,K.D. and Salvesen,G.S.
    Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes)
    Biochem J (2008) 415, 367-375. PubMed  Europe PubMed DOI  PMC  EPMC  P
    34. 2007
  34. Butterworth,M.B., Edinger,R.S., Ovaa,H., Burg,D., Johnson,J.P. and Frizzell,R.A.
    The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel
    J Biol Chem (2007) 282, 37885-37893. PubMed  Europe PubMed DOI
  35. Hassiepen,U., Eidhoff,U., Meder,G., Bulber,J.F., Hein,A., Bodendorf,U., Lorthiois,E. and Martoglio,B.
    A sensitive fluorescence intensity assay for deubiquitinating proteases using ubiquitin-rhodamine110-glycine as substrate
    Anal Biochem (2007) 371, 201-207. PubMed  Europe PubMed DOI  A
  36. Hirayama,K., Aoki,S., Nishikawa,K., Matsumoto,T. and Wada,K.
    Identification of novel chemical inhibitors for ubiquitin C-terminal hydrolase-L3 by virtual screening
    Bioorg Med Chem (2007) 15, 6810-6818. PubMed  Europe PubMed DOI  I
  37. Kwon,J.
    The new function of two ubiquitin C-terminal hydrolase isozymes as reciprocal modulators of germ cell apoptosis
    Exp Anim (2007) 56, 71-77. PubMed  Europe PubMed DOI  K
    38. 2006
  38. Kwon,J., Sekiguchi,S., Wang,Y.L., Setsuie,R., Yoshikawa,Y. and Wada,K.
    The region-specific functions of two ubiquitin C-terminal hydrolase isozymes along the epididymis
    Exp Anim (2006) 55, 35-43. PubMed  Europe PubMed DOI  K
    39. 2005
  39. [YEAR:5-11-2005]Misaghi,S., Galardy,P.J., Meester,W.J., Ovaa,H., Ploegh,H.L. and Gaudet,R.
    Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate
    J Biol Chem (5-11-2005) 280, 1512-1520. PubMed  Europe PubMed DOI  S  I
  40. 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. and Filipuzzi,I.
    Synthesis and characterization of fluorescent ubiquitin derivatives as highly sensitive substrates for the deubiquitinating enzymes UCH-L3 and USP-2
    Anal Biochem (2005) 343, 244-255. PubMed  Europe PubMed DOI  A
  41. [YEAR:9-5-2005]Wood,M.A., Kaplan,M.P., Brensinger,C.M., Guo,W. and Abel,T.
    Ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory
    Hippocampus (9-5-2005) 15, 610-621. PubMed  Europe PubMed DOI
    42. 2004
  42. Hemelaar,J., Borodovsky,A., Kessler,B.M., Reverter,D., Cook,J., Kolli,N., Gan-Erdene,T., Wilkinson,K.D., Gill,G., Lima,C.D., Ploegh,H.L. and Ovaa,H.
    Specific and covalent targeting of conjugating and deconjugating enzymes of ubiquitin-like proteins
    Mol Cell Biol (2004) 24, 84-95. PubMed  Europe PubMed DOI  PMC  EPMC  I
  43. [YEAR:14-4-2004]Kwon,J., Wang,Y.L., Setsuie,R., Sekiguchi,S., Sakurai,M., Sato,Y., Lee,W.W., Ishii,Y., Kyuwa,S., Noda,M., Wada,K. and Yoshikawa,Y.
    Developmental regulation of ubiquitin C-terminal hydrolase isozyme expression during spermatogenesis in mice
    Biol Reprod (14-4-2004) 71, 515-521. PubMed  Europe PubMed DOI
  44. Kwon,J., Wang,Y.L., Setsuie,R., Sekiguchi,S., Sato,Y., Sakurai,M., Noda,M., Aoki,S., Yoshikawa,Y. and Wada,K.
    Two closely related ubiquitin C-terminal hydrolase isozymes function as reciprocal modulators of germ cell apoptosis in cryptorchid testis
    Am J Pathol (2004) 165, 1367-1374. PubMed  Europe PubMed DOI  PMC  EPMC
  45. [YEAR:1-6-2004]Mason,D.E., Ek,J., Peters,E.C. and Harris,J.L.
    Substrate profiling of deubiquitin hydrolases with a positional scanning library and mass spectrometry
    Biochemistry (1-6-2004) 43, 6535-6544. PubMed  Europe PubMed DOI
  46. Wilkinson,K.D.
    Ubiquitin C-terminal hydrolase
    [ISSN:0-12-079610-4] (2004) 2, 1225-1229.  V
    47. 2003
  47. Nam,M.J., Madoz-Gurpide,J., Wang,H., Lescure,P., Schmalbach,C.E., Zhao,R., Misek,D.E., Kuick,R., Brenner,D.E. and Hanash,S.M.
    Molecular profiling of the immune response in colon cancer using protein microarrays: occurrence of autoantibodies to ubiquitin C-terminal hydrolase L3
    Proteomics (2003) 3, 2108-2115. PubMed  Europe PubMed DOI
    48. 2001
  48. [YEAR:1-9-2001]Kurihara,L.J., Kikuchi,T., Wada,K. and Tilghman,S.M.
    Loss of Uch-L1 and Uch-L3 leads to neurodegeneration, posterior paralysis and dysphagia
    Hum Mol Genet (1-9-2001) 10, 1963-1970. PubMed  Europe PubMed  K
    49. 2000
  49. Kurihara,L.J., Semenova,E., Levorse,J.M. and Tilghman,S.M.
    Expression and functional analysis of Uch-L3 during mouse development
    Mol Cell Biol (2000) 20, 2498-2504. PubMed  Europe PubMed DOI  PMC  EPMC
    50. 1999
  50. [YEAR:3-9-1999]Wilkinson,K.D., Laleli-Sahin,E., Urbauer,J., Larsen,C.N., Shih,G.H., Haas,A.L., Walsh,S.T. and Wand,A.J.
    The binding site for UCH-L3 on ubiquitin: mutagenesis and NMR studies on the complex between ubiquitin and UCH-L3
    J Mol Biol (3-9-1999) 291, 1067-1077. PubMed  Europe PubMed DOI
    51. 1998
  51. [YEAR:17-2-1998]Dang,L.C., Melandri,F.D. and Stein,R.L.
    Kinetic and mechanistic studies on the hydrolysis of ubiquitin C-terminal 7-amido-4-methylcoumarin by deubiquitinating enzymes
    Biochemistry (17-2-1998) 37, 1868-1879. PubMed  Europe PubMed DOI  A  I
  52. [YEAR:10-3-1998]Larsen,C.N., Krantz,B.A. and Wilkinson,K.D.
    Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases
    Biochemistry (10-3-1998) 37, 3358-3368. PubMed  Europe PubMed DOI
  53. [YEAR:29-10-1998]Wada,H., Kito,K., Caskey,L.S., Yeh,E.T. and Kamitani,T.
    Cleavage of the C-terminus of NEDD8 by UCH-L3
    Biochem Biophys Res Commun (29-10-1998) 251, 688-692. PubMed  Europe PubMed DOI
    54. 1997
  54. Johnston,S.C., Larsen,C.N., Cook,W.J., Wilkinson,K.D. and Hill,C.P.
    Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution
    EMBO J (1997) 16, 3787-3796. PubMed  Europe PubMed DOI  PMC  EPMC  S
  55. Pilon,A., Yost,P., Chase,T.E., Lohnas,G., Burkett,T., Roberts,S. and Bentley,W.E.
    Ubiquitin fusion technology: bioprocessing of peptides
    Biotechnol Prog (1997) 13, 374-379. PubMed  Europe PubMed DOI
    56. 1996
  56. Larsen,C.N., Price,J.S. and Wilkinson,K.D.
    Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues
    Biochemistry (1996) 35, 6735-6744. PubMed  Europe PubMed DOI
    57. 1995
  57. Potempa,J., Pavloff,N. and Travis,J.
    Porphyromonas gingivalis: a proteinase/gene accounting audit
    Trends Microbiol (1995) 3, 430-434. PubMed  Europe PubMed DOI

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