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Gene Review

Itch  -  itchy, E3 ubiquitin protein ligase

Mus musculus

Synonyms: 6720481N21Rik, 8030492O04Rik, A130065M08, AIP4, C230047C07Rik, ...
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Disease relevance of Itch


High impact information on Itch


Biological context of Itch

  • Itch promotes ubiquitination of Smad2 and augments Smad2 phosphorylation that requires an intact ligase activity of Itch [8].
  • Allergic symptoms consist of rashes where animals are in contact with the skin, nasal congestion and sneezing, itchy eyes, and asthma (cough, wheezing, and chest tightness) [9].

Anatomical context of Itch

  • Since Notch proteins have many important functions in the immune system, we determined whether Itch regulates Notch signaling in vivo [10].
  • Itchy, a Nedd4 ubiquitin ligase, downregulates latent membrane protein 2A activity in B-cell signaling [11].
  • Allergic rhinitis exerts inflammatory response and irritation of the nasal mucosal membranes leading to sneezing; stuffy/runny nose; nasal congestion; and itchy, watery and swollen eyes [12].
  • Ultraviolet B reduces itchy sensation of uraemic patients by leading to depletion of cutaneous mast cells [13].

Associations of Itch with chemical compounds

  • On cantharidin blister base experiments in humans, SP (10(-3) g/ml) produced slight pain and an itchy sensation [14].
  • As compared with placebo supplementation, supplementation with extract of Perilla frutescens enriched for rosmarinic acid resulted in a significant increase in responder rates for itchy nose, watery eyes, itchy eyes, and total symptoms (P<0.05) [15].

Physical interactions of Itch


Other interactions of Itch


  1. Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis. Hansson, L., Bäckman, A., Ny, A., Edlund, M., Ekholm, E., Ekstrand Hammarström, B., Törnell, J., Wallbrandt, P., Wennbo, H., Egelrud, T. J. Invest. Dermatol. (2002) [Pubmed]
  2. In chronic idiopathic urticaria autoantibodies against Fc epsilonRII/CD23 induce histamine release via eosinophil activation. Puccetti, A., Bason, C., Simeoni, S., Millo, E., Tinazzi, E., Beri, R., Peterlana, D., Zanoni, G., Senna, G., Corrocher, R., Lunardi, C. Clin. Exp. Allergy (2005) [Pubmed]
  3. Expression of nerve growth factor in itchy skins of atopic NC/NgaTnd mice. Tanaka, A., Matsuda, H. J. Vet. Med. Sci. (2005) [Pubmed]
  4. Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation. Oliver, P.M., Cao, X., Worthen, G.S., Shi, P., Briones, N., Macleod, M., White, J., Kirby, P., Kappler, J., Marrack, P., Yang, B. Immunity (2006) [Pubmed]
  5. Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Heissmeyer, V., Macián, F., Im, S.H., Varma, R., Feske, S., Venuprasad, K., Gu, H., Liu, Y.C., Dustin, M.L., Rao, A. Nat. Immunol. (2004) [Pubmed]
  6. Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation. Fang, D., Elly, C., Gao, B., Fang, N., Altman, Y., Joazeiro, C., Hunter, T., Copeland, N., Jenkins, N., Liu, Y.C. Nat. Immunol. (2002) [Pubmed]
  7. Negative regulation of the E3 ubiquitin ligase itch via Fyn-mediated tyrosine phosphorylation. Yang, C., Zhou, W., Jeon, M.S., Demydenko, D., Harada, Y., Zhou, H., Liu, Y.C. Mol. Cell (2006) [Pubmed]
  8. Itch E3 ligase-mediated regulation of TGF-beta signaling by modulating smad2 phosphorylation. Bai, Y., Yang, C., Hu, K., Elly, C., Liu, Y.C. Mol. Cell (2004) [Pubmed]
  9. Laboratory animal allergy: an update. Bush, R.K., Stave, G.M. ILAR journal / National Research Council, Institute of Laboratory Animal Resources. (2003) [Pubmed]
  10. Itch genetically interacts with Notch1 in a mouse autoimmune disease model. Matesic, L.E., Haines, D.C., Copeland, N.G., Jenkins, N.A. Hum. Mol. Genet. (2006) [Pubmed]
  11. Itchy, a Nedd4 ubiquitin ligase, downregulates latent membrane protein 2A activity in B-cell signaling. Ikeda, A., Caldwell, R.G., Longnecker, R., Ikeda, M. J. Virol. (2003) [Pubmed]
  12. Antioxidant properties of Aller-7, a novel polyherbal formulation for allergic rhinitis. D'Souza, P., Amit, A., Saxena, V.S., Bagchi, D., Bagchi, M., Stohs, S.J. Drugs under experimental and clinical research. (2004) [Pubmed]
  13. Ultraviolet B induces mast cell apoptosis: a hypothetical mechanism of ultraviolet B treatment for uraemic pruritus. Szepietowski, J.C., Morita, A., Tsuji, T. Med. Hypotheses (2002) [Pubmed]
  14. Algesiogenic and analgesic activities of synthetic substance P. Kotani, Y., Oka, M., Yonehara, N., Kudo, T., Inoki, R. Jpn. J. Pharmacol. (1981) [Pubmed]
  15. Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. Takano, H., Osakabe, N., Sanbongi, C., Yanagisawa, R., Inoue, K., Yasuda, A., Natsume, M., Baba, S., Ichiishi, E., Yoshikawa, T. Exp. Biol. Med. (Maywood) (2004) [Pubmed]
  16. The Tyrosine Kinase c-Abl Protects c-Jun from Ubiquitination-mediated Degradation in T Cells. Gao, B., Lee, S.M., Fang, D. J. Biol. Chem. (2006) [Pubmed]
  17. Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch. Gao, M., Labuda, T., Xia, Y., Gallagher, E., Fang, D., Liu, Y.C., Karin, M. Science (2004) [Pubmed]
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