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Gene Review

CD63  -  CD63 molecule

Homo sapiens

Synonyms: CD63 antigen, Granulophysin, LAMP-3, Lysosomal-associated membrane protein 3, ME491, ...
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Disease relevance of CD63

  • IMPLICATIONS: Our results indicate that the data obtained in studies of these three melanoma antigens may be pooled, and we propose that the molecule recognized by these reagents be classified as CD63 [1].
  • Immunolabeling demonstrated that these compartments contained the late endosomal marker CD63, which was enriched on vesicles within these structures and incorporated into the envelope of budding virions [2].
  • All of the carcinomas were ME491/CD63 positive [3].
  • During studies to identify cellular molecules that could be involved in macrophage infection, we observed inhibition of HIV-1 infection of macrophages by monoclonal antibody (MAb) to the tetraspan transmembrane glycoprotein CD63 [4].
  • Potential role for CD63 in CCR5-mediated human immunodeficiency virus type 1 infection of macrophages [4].

High impact information on CD63

  • Although the lysosomal protein CD63 was mislocalized to the plasma membrane, perforin and granzymes were correctly localized to the lytic granules in AP-3-deficient CTLs [5].
  • The AP-3 deficiency results in increased surface expression of the lysosomal membrane proteins CD63, lamp-1, and lamp-2, but not of nonlysosomal proteins [6].
  • In these structures FasL colocalizes with both melanosomal (i.e., gp100) and lysosomal (i.e., CD63) antigens [7].
  • We additionally show that melanosome-containing multivesicular bodies degranulate extracellularly and release FasL-bearing microvesicles, that coexpress both gp100 and CD63 and retain their functional activity in triggering Fas-dependent apoptosis of lymphoid cells [7].
  • The levels and expression of the proteins CD63 and granulophysin in platelets from control and from a Hermansky-Pudlak syndrome subject (a condition characterized by dense granule and lysosomal deficiencies and the accumulation of ceroid-like material in reticuloendothelial cells) were examined [8].

Chemical compound and disease context of CD63

  • Among genes found differentially expressed, the CD63 tetraspanin, not previously recognized in colon cancer progression, and the alpha3 integrin chain were both up-regulated in low metastatic E2 cells and were analyzed for their functional role using adhesion, migration, and invasion assays [9].
  • In addition, neopterin (r = 0.37, r = 0.44), IL6 (r = 0.37, r = 0.60) and CD63 expression (r = 0.39, r = 0.45) correlated significantly with disease activity as measured by the Birmingham Vasculitis Activity Score and C reactive protein values, respectively [10].
  • CONCLUSION : The current study suggests that serine protein kinase activity associated with CD63 may play a role in signaling by CD63 in melanoma cells [11].
  • Chronic urticaria serum induces histamine release, leukotriene production, and basophil CD63 surface expression--inhibitory effects ofanti-inflammatory drugs [12].
  • In this study, we determined that in HeLa and T cells, the MA mutant Gag proteins that are defective in plasma membrane targeting form virus particles in a CD63-positive compartment, defined as the late endosome or multivesicular body (MVB) [13].

Biological context of CD63


Anatomical context of CD63


Associations of CD63 with chemical compounds

  • ME491 melanoma-associated glycoprotein family: antigenic identity of ME491, NKI/C-3, neuroglandular antigen (NGA), and CD63 proteins [1].
  • Enzymatic and immunochemical assays show a phosphatidylinositol 4-kinase in novel and specific complexes with proteins (CD63 and CD81) of the transmembrane 4 superfamily (TM4SF) and an integrin (alpha3beta1) [18].
  • Strong, tyrosine-dependent interaction of the wild-type carboxyterminal tail of CD63 with the AP-3 adaptor subunit mu 3 was observed using a yeast two-hybrid system [19].
  • Here we show that prototype complexes of CD9 or CD81 (TM4SF proteins) with alpha(3)beta(1) (an integrin) and complexes of CD63 (a TM4SF protein) with phosphatidylinositol 4-kinase (PtdIns 4-K) may indeed localize within lipid raft-like microdomains, as seen by three different criteria [20].
  • CD63 co-immunoprecipitated with a lipid kinase which, on the basis of enzymatic properties(stimulated by nonionic detergents, inhibited by adenosine), is consistent with PI 4-kinase type II [21].
  • Coexpression of CD63 enhanced tyrosine phosphorylation of ROMK1 [22].

Physical interactions of CD63


Regulatory relationships of CD63

  • CD9 was expressed on the plasma membrane of enterocytes in crypts and at the bases of the villi whereas CD63 demonstrated a unique granular appearance concentrated in the apical cytoplasm below the brush border [25].
  • Redistribution of TI-VAMP in the ER of syntaxin-1-expressing cells was microtubule dependent and impaired the trafficking of CD63, a cargo of TI-VAMP-containing vesicles [26].
  • The expression of CD63 in CML-CP platelets was induced by TPO treatment [27].
  • These results suggest that CD63 regulates MT1-MMP by targeting to lysosomes [28].
  • Furthermore, internalization of CD63 was completely blocked in cells expressing a syntenin-1 mutant lacking the first 100 amino acids [29].

Other interactions of CD63

  • Moreover, we assessed the prognostic value of evaluating the expressions of MRP-1, KAI1, and ME491 simultaneously in NSCLCs [30].
  • These included an integrin (alpha6beta1) and three different TM4SF proteins (CD9, CD63, and NAG-2) [31].
  • Also, cross-linking experiments established that alpha 3 beta 1/CD81, alpha 3 beta 1/CD9, and alpha 3 beta 1/CD63 associations occur on the surface of intact cells and suggested that a critical interaction site is located within extracellular domains [32].
  • Particularly in this latter quality CD63 clearly surpasses several other CD28-independent costimulatory pathways previously described [33].
  • CONCLUSION: The rise in CD63 during VIT indicates a partial basophil degranulation with release of stored protein mediators, including IL-4 [34].

Analytical, diagnostic and therapeutic context of CD63


  1. ME491 melanoma-associated glycoprotein family: antigenic identity of ME491, NKI/C-3, neuroglandular antigen (NGA), and CD63 proteins. Demetrick, D.J., Herlyn, D., Tretiak, M., Creasey, D., Clevers, H., Donoso, L.A., Vennegoor, C.J., Dixon, W.T., Jerry, L.M. J. Natl. Cancer Inst. (1992) [Pubmed]
  2. Infectious HIV-1 assembles in late endosomes in primary macrophages. Pelchen-Matthews, A., Kramer, B., Marsh, M. J. Cell Biol. (2003) [Pubmed]
  3. Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients. Huang, C.I., Kohno, N., Ogawa, E., Adachi, M., Taki, T., Miyake, M. Am. J. Pathol. (1998) [Pubmed]
  4. Potential role for CD63 in CCR5-mediated human immunodeficiency virus type 1 infection of macrophages. von Lindern, J.J., Rojo, D., Grovit-Ferbas, K., Yeramian, C., Deng, C., Herbein, G., Ferguson, M.R., Pappas, T.C., Decker, J.M., Singh, A., Collman, R.G., O'Brien, W.A. J. Virol. (2003) [Pubmed]
  5. Adaptor protein 3-dependent microtubule-mediated movement of lytic granules to the immunological synapse. Clark, R.H., Stinchcombe, J.C., Day, A., Blott, E., Booth, S., Bossi, G., Hamblin, T., Davies, E.G., Griffiths, G.M. Nat. Immunol. (2003) [Pubmed]
  6. Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor. Dell'Angelica, E.C., Shotelersuk, V., Aguilar, R.C., Gahl, W.A., Bonifacino, J.S. Mol. Cell (1999) [Pubmed]
  7. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. Andreola, G., Rivoltini, L., Castelli, C., Huber, V., Perego, P., Deho, P., Squarcina, P., Accornero, P., Lozupone, F., Lugini, L., Stringaro, A., Molinari, A., Arancia, G., Gentile, M., Parmiani, G., Fais, S. J. Exp. Med. (2002) [Pubmed]
  8. The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky-Pudlak syndrome, and appears identical to granulophysin. Nishibori, M., Cham, B., McNicol, A., Shalev, A., Jain, N., Gerrard, J.M. J. Clin. Invest. (1993) [Pubmed]
  9. Complementary DNA arrays identify CD63 tetraspanin and alpha3 integrin chain as differentially expressed in low and high metastatic human colon carcinoma cells. Sordat, I., Decraene, C., Silvestre, T., Petermann, O., Auffray, C., Piétu, G., Sordat, B. Lab. Invest. (2002) [Pubmed]
  10. Monocyte activation in patients with Wegener's granulomatosis. Muller Kobold, A.C., Kallenberg, C.G., Tervaert, J.W. Ann. Rheum. Dis. (1999) [Pubmed]
  11. Protein kinase activity is associated with CD63 in melanoma cells. Iida, J., Skubitz, A.P., McCarthy, J.B., Skubitz, K.M. Journal of translational medicine [electronic resource]. (2005) [Pubmed]
  12. Chronic urticaria serum induces histamine release, leukotriene production, and basophil CD63 surface expression--inhibitory effects ofanti-inflammatory drugs. Wedi, B., Novacovic, V., Koerner, M., Kapp, A. J. Allergy Clin. Immunol. (2000) [Pubmed]
  13. Cell-type-dependent targeting of human immunodeficiency virus type 1 assembly to the plasma membrane and the multivesicular body. Ono, A., Freed, E.O. J. Virol. (2004) [Pubmed]
  14. The tetraspanin CD63 enhances the internalization of the H,K-ATPase beta-subunit. Duffield, A., Kamsteeg, E.J., Brown, A.N., Pagel, P., Caplan, M.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  15. CD63/Pltgp40: a platelet activation antigen identical to the stage-specific, melanoma-associated antigen ME491. Azorsa, D.O., Hyman, J.A., Hildreth, J.E. Blood (1991) [Pubmed]
  16. CD63 tetraspanin slows down cell migration and translocates to the endosomal-lysosomal-MIICs route after extracellular stimuli in human immature dendritic cells. Mantegazza, A.R., Barrio, M.M., Moutel, S., Bover, L., Weck, M., Brossart, P., Teillaud, J.L., Mordoh, J. Blood (2004) [Pubmed]
  17. CD63 is a component of Weibel-Palade bodies of human endothelial cells. Vischer, U.M., Wagner, D.D. Blood (1993) [Pubmed]
  18. A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase. Berditchevski, F., Tolias, K.F., Wong, K., Carpenter, C.L., Hemler, M.E. J. Biol. Chem. (1997) [Pubmed]
  19. Role of adaptor complex AP-3 in targeting wild-type and mutated CD63 to lysosomes. Rous, B.A., Reaves, B.J., Ihrke, G., Briggs, J.A., Gray, S.R., Stephens, D.J., Banting, G., Luzio, J.P. Mol. Biol. Cell (2002) [Pubmed]
  20. Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts. Claas, C., Stipp, C.S., Hemler, M.E. J. Biol. Chem. (2001) [Pubmed]
  21. CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen. Israels, S.J., McMillan-Ward, E.M. Thromb. Haemost. (2005) [Pubmed]
  22. Expression of tetraspan protein CD63 activates protein-tyrosine kinase (PTK) and enhances the PTK-induced inhibition of ROMK channels. Lin, D., Kamsteeg, E.J., Zhang, Y., Jin, Y., Sterling, H., Yue, P., Roos, M., Duffield, A., Spencer, J., Caplan, M., Wang, W.H. J. Biol. Chem. (2008) [Pubmed]
  23. Mass, charge, and subcellular localization of a unique secretory product identified by the basophil-specific antibody BB1. McEuen, A.R., Calafat, J., Compton, S.J., Easom, N.J., Buckley, M.G., Knol, E.F., Walls, A.F. J. Allergy Clin. Immunol. (2001) [Pubmed]
  24. Metastatic uveal melanoma: an ocular melanoma associated antigen in the serum of patients with metastatic disease. Donoso, L.A., Felberg, N.T., Edelberg, K., Borlinghaus, P., Herlyn, M. Journal of immunoassay. (1986) [Pubmed]
  25. Localization of the transmembrane 4 superfamily (TM4SF) member PETA-3 (CD151) in normal human tissues: comparison with CD9, CD63, and alpha5beta1 integrin. Sincock, P.M., Mayrhofer, G., Ashman, L.K. J. Histochem. Cytochem. (1997) [Pubmed]
  26. Ectopic expression of syntaxin 1 in the ER redirects TI-VAMP- and cellubrevin-containing vesicles. Martinez-Arca, S., Proux-Gillardeaux, V., Alberts, P., Louvard, D., Galli, T. J. Cell. Sci. (2003) [Pubmed]
  27. Constitutively activated phosphatidylinositol 3-kinase primes platelets from patients with chronic myelogenous leukemia for thrombopoietin-induced aggregation. Kubota, Y., Tanaka, T., Ohnishi, H., Kitanaka, A., Okutani, Y., Taminato, T., Ishida, T., Kamano, H. Leukemia (2004) [Pubmed]
  28. Tetraspanin CD63 promotes targeting and lysosomal proteolysis of membrane-type 1 matrix metalloproteinase. Takino, T., Miyamori, H., Kawaguchi, N., Uekita, T., Seiki, M., Sato, H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  29. Syntenin-1 Is a New Component of Tetraspanin-Enriched Microdomains: Mechanisms and Consequences of the Interaction of Syntenin-1 with CD63. Latysheva, N., Muratov, G., Rajesh, S., Padgett, M., Hotchin, N.A., Overduin, M., Berditchevski, F. Mol. Cell. Biol. (2006) [Pubmed]
  30. Novel staging protocol for non-small-cell lung cancers according to MRP-1/CD9 and KAI1/CD82 gene expression. Adachi, M., Taki, T., Konishi, T., Huang, C.I., Higashiyama, M., Miyake, M. J. Clin. Oncol. (1998) [Pubmed]
  31. NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins. Tachibana, I., Bodorova, J., Berditchevski, F., Zutter, M.M., Hemler, M.E. J. Biol. Chem. (1997) [Pubmed]
  32. Characterization of novel complexes on the cell surface between integrins and proteins with 4 transmembrane domains (TM4 proteins). Berditchevski, F., Zutter, M.M., Hemler, M.E. Mol. Biol. Cell (1996) [Pubmed]
  33. CD63 as an activation-linked T cell costimulatory element. Pfistershammer, K., Majdic, O., Stöckl, J., Zlabinger, G., Kirchberger, S., Steinberger, P., Knapp, W. J. Immunol. (2004) [Pubmed]
  34. Surface membrane antigen alteration on blood basophils in patients with Hymenoptera venom allergy under immunotherapy. Siegmund, R., Vogelsang, H., Machnik, A., Herrmann, D. J. Allergy Clin. Immunol. (2000) [Pubmed]
  35. Increased expression of surface activation markers on neutrophils following migration into the nasal lumen. Kinhult, J., Egesten, A., Benson, M., Uddman, R., Cardell, L.O. Clin. Exp. Allergy (2003) [Pubmed]
  36. Exosomal-like vesicles are present in human blood plasma. Caby, M.P., Lankar, D., Vincendeau-Scherrer, C., Raposo, G., Bonnerot, C. Int. Immunol. (2005) [Pubmed]
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