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Gene Review

CD9  -  CD9 molecule

Homo sapiens

Synonyms: 5H9 antigen, BA2, BTCC-1, CD9 antigen, Cell growth-inhibiting gene 2 protein, ...
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Disease relevance of CD9

  • Furthermore, ectopic expression of CD9 in fibrosarcoma cells affected adhesion-induced tyrosine phosphorylation of FAK, that correlated with the reorganization of the cortical actin cytoskeleton [1].
  • Anti-CD9 monoclonal antibodies were found to specifically inhibit the transendothelial migration of melanoma cells; the inhibitory effect was likely caused by a strengthening of CD9-mediated heterotypic interactions of TCs to the EC monolayer [2].
  • Coprecipitation of CD36, CD9, and alpha6beta1 was also observed on platelets from a patient with Glanzmann thrombasthenia, indicating that alphaII(b)beta3 is not required for the other proteins to associate [3].
  • These findings complement our earlier studies on MRP-1/CD9, another member of the transmembrane 4 superfamily, whose reduced expression in non-small cell lung cancer appears to be a factor of poor prognosis [4].
  • Our results indicate that several members of the neuroglandular antigen are expressed in melanoma and that low expression of CD9 on primary melanomas might have prognostic significance with respect to the potential for metastasis [5].

Psychiatry related information on CD9


High impact information on CD9

  • The dose of chemoattractants required to induce motility-related functions is generally at least ten-fold smaller than the dose required to initiate secretory and respiratory burst activities [11].
  • COPI-coated vesicle budding from lipid bilayers whose composition resembles mammalian Golgi membranes requires coatomer, ARF, GTP, and cytoplasmic tails of putative cargo receptors (p24 family proteins) or membrane cargo proteins (containing the KKXX retrieval signal) emanating from the bilayer surface [12].
  • Patients who received L-697,661 had rapid, dose-related decreases in plasma p24 antigen levels [13].
  • Of eight cord-blood samples from neonates with proved HIV infection, five were positive for immune-complex-dissociated p24 antigen [14].
  • Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen [15].

Chemical compound and disease context of CD9


Biological context of CD9


Anatomical context of CD9

  • Moreover, PSG17 binding to macrophages from CD9-deficient mice was significantly reduced [26].
  • Ectopic expression of CD9 caused a four- to eightfold increase in RD cell syncytia formation, whereas anti-CD9 and anti-CD81 antibodies markedly delayed RD syncytia formation [21].
  • In summary, TM4SF proteins such as CD9 and CD81 appear to promote muscle cell fusion and support myotube maintenance [21].
  • Finally, anti-CD9 and anti-CD81 monoclonal antibodies triggered apoptotic degeneration of C2C12 cell myotubes after they were formed [21].
  • Others, such as CD9 and CD81, remain diffusely distributed at the cell surface.In conclusion, we show that CD151 is a major component of (pre)-hemidesmosomal structures and that its recruitment into hemidesmosomes is regulated by the integrin alpha6beta4 [27].

Associations of CD9 with chemical compounds

  • On normal resting platelets, immunolabeling for CD9 and PECAM1 was found lining the plasma membrane and the luminal face of the open canalicular system [22].
  • Only CD9 is coprecipitated with CD36 from platelets that were solubilized in Brij 96 [3].
  • Second, CD9 and alpha(3) integrin colocalized with ganglioside GM1 as seen by double staining of fixed cells [28].
  • This association is detected as early as 15 min after metabolic labeling, and the use of Brefeldin A demonstrates that it does not require Golgi modifications of either CD9 or integrin beta1 [29].
  • The association of CD63 with CD9 and alphaIIbbeta3, was not inhibited by preincubation of platelets with RGDS or EGTA [30].
  • Treatment of CD9-nonexpressing 5T33MMvt cells with the clinically relevant histone deacetylase inhibitor LBH589 resulted in a significant increase in CD9 expression [31].

Physical interactions of CD9

  • MHC class II/CD38/CD9: a lipid-raft-dependent signaling complex in human monocytes [25].
  • In support of this conclusion, IL-16 bound to CD9-expressing CHO cell transfectants [24].
  • These data indicate that colligin/Hsp47 is anchored to the cell membrane in a complex with CD9 where it moderates tumor cell invasion and motility possibly by acting as a serpin protein inhibitor or as a receptor for collagen [32].
  • Finally we demonstrated that epithelial cell adhesion molecule and CD9 form a new primary complex in the tetraspanin web [33].
  • We now demonstrate that transmembrane TGF-alpha physically interacts with CD9, a protein with four membrane spanning domains that is frequently coexpressed with TGF-alpha in carcinomas [34].

Co-localisations of CD9

  • The CD9 was colocalized with RA-A47 on the cell surface, where it may have affected integrin signaling [35].

Regulatory relationships of CD9


Other interactions of CD9

  • Co-immunoprecipitation of DRAP27/CD9 with DTR and chemical cross-linking suggest a tight association of these membrane-bound proteins [40].
  • However, circulating TdT+ cells infrequently expressed CD19 (4.5%) and CD9 (2.3%), compared with their marrow counterparts (74% and 47%, respectively) [41].
  • CD34(high)CD38(low)Thy1(+) primitive progenitors are contained in the population with intermediate CD9 expression, thus suggesting that CD9 expression may precede CD38 appearance [23].
  • CD36 associates with CD9 and integrins on human blood platelets [3].
  • Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1 [22].

Analytical, diagnostic and therapeutic context of CD9


  1. Characterization of integrin-tetraspanin adhesion complexes: role of tetraspanins in integrin signaling. Berditchevski, F., Odintsova, E. J. Cell Biol. (1999) [Pubmed]
  2. Regulatory role of tetraspanin CD9 in tumor-endothelial cell interaction during transendothelial invasion of melanoma cells. Longo, N., Yáñez-Mó, M., Mittelbrunn, M., de la Rosa, G., Muñoz, M.L., Sánchez-Madrid, F., Sánchez-Mateos, P. Blood (2001) [Pubmed]
  3. CD36 associates with CD9 and integrins on human blood platelets. Miao, W.M., Vasile, E., Lane, W.S., Lawler, J. Blood (2001) [Pubmed]
  4. Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer. Adachi, M., Taki, T., Ieki, Y., Huang, C.L., Higashiyama, M., Miyake, M. Cancer Res. (1996) [Pubmed]
  5. Expression of the neuroglandular antigen and analogues in melanoma. CD9 expression appears inversely related to metastatic potential of melanoma. Si, Z., Hersey, P. Int. J. Cancer (1993) [Pubmed]
  6. Risk factors and clinical presentation of acute primary HIV infection in India. Bollinger, R.C., Brookmeyer, R.S., Mehendale, S.M., Paranjape, R.S., Shepherd, M.E., Gadkari, D.A., Quinn, T.C. JAMA (1997) [Pubmed]
  7. Cerebrospinal fluid human immunodeficiency virus type 1 (HIV-1) p24 antigen levels in HIV-1-related dementia. Royal, W., Selnes, O.A., Concha, M., Nance-Sproson, T.E., McArthur, J.C. Ann. Neurol. (1994) [Pubmed]
  8. Cerebrospinal fluid HIV-1 p24 antigen and culture: sensitivity and specificity for AIDS-dementia complex. Brew, B.J., Paul, M.O., Nakajima, G., Khan, A., Gallardo, H., Price, R.W. J. Neurol. Neurosurg. Psychiatr. (1994) [Pubmed]
  9. Quantification of human immunodeficiency virus type 1 p24 antigen and antibody rivals human immunodeficiency virus type 1 RNA and CD4+ enumeration for prognosis. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group. Read, J.S., Rich, K.C., Korelitz, J.J., Mofenson, L.M., Harris, R., Moye, J.H., Meyer, W.A., Pahwa, S.G., Bethel, J.W., Nugent, R.P. Pediatr. Infect. Dis. J. (2000) [Pubmed]
  10. Effects of alcohol ingestion on in vitro susceptibility of peripheral blood mononuclear cells to infection with HIV and of selected T-cell functions. Bagasra, O., Kajdacsy-Balla, A., Lischner, H.W. Alcohol. Clin. Exp. Res. (1989) [Pubmed]
  11. Chemoattractant receptors on phagocytic cells. Snyderman, R., Pike, M.C. Annu. Rev. Immunol. (1984) [Pubmed]
  12. Coupling of coat assembly and vesicle budding to packaging of putative cargo receptors. Bremser, M., Nickel, W., Schweikert, M., Ravazzola, M., Amherdt, M., Hughes, C.A., Söllner, T.H., Rothman, J.E., Wieland, F.T. Cell (1999) [Pubmed]
  13. A short-term clinical evaluation of L-697,661, a non-nucleoside inhibitor of HIV-1 reverse transcriptase. L-697,661 Working Group. Saag, M.S., Emini, E.A., Laskin, O.L., Douglas, J., Lapidus, W.I., Schleif, W.A., Whitley, R.J., Hildebrand, C., Byrnes, V.W., Kappes, J.C. N. Engl. J. Med. (1993) [Pubmed]
  14. Rapid serologic testing with immune-complex-dissociated HIV p24 antigen for early detection of HIV infection in neonates. Southern California Pediatric AIDS Consortium. Miles, S.A., Balden, E., Magpantay, L., Wei, L., Leiblein, A., Hofheinz, D., Toedter, G., Stiehm, E.R., Bryson, Y. N. Engl. J. Med. (1993) [Pubmed]
  15. A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study. Hamilton, J.D., Hartigan, P.M., Simberkoff, M.S., Day, P.L., Diamond, G.R., Dickinson, G.M., Drusano, G.L., Egorin, M.J., George, W.L., Gordin, F.M. N. Engl. J. Med. (1992) [Pubmed]
  16. Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer. Murayama, Y., Miyagawa, J., Shinomura, Y., Kanayama, S., Isozaki, K., Yamamori, K., Mizuno, H., Ishiguro, S., Kiyohara, T., Miyazaki, Y., Taniguchi, N., Higashiyama, S., Matsuzawa, Y. Int. J. Cancer (2002) [Pubmed]
  17. CD9 is expressed on human endometrial epithelial cells in association with integrins alpha(6), alpha(3) and beta(1). Park, K.R., Inoue, T., Ueda, M., Hirano, T., Higuchi, T., Maeda, M., Konishi, I., Fujiwara, H., Fujii, S. Mol. Hum. Reprod. (2000) [Pubmed]
  18. Androgens induce CD-9 in human prostate tissue. Chuan, Y., Pang, S.T., Bergh, A., Norstedt, G., Pousette, A. Int. J. Androl. (2005) [Pubmed]
  19. Molecular cloning and characterization of chick CD9. Kobayashi, T. The Kurume medical journal. (2000) [Pubmed]
  20. Intestinal macrophages display reduced permissiveness to human immunodeficiency virus 1 and decreased surface CCR5. Li, L., Meng, G., Graham, M.F., Shaw, G.M., Smith, P.D. Gastroenterology (1999) [Pubmed]
  21. Role of transmembrane 4 superfamily (TM4SF) proteins CD9 and CD81 in muscle cell fusion and myotube maintenance. Tachibana, I., Hemler, M.E. J. Cell Biol. (1999) [Pubmed]
  22. Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1. Cramer, E.M., Berger, G., Berndt, M.C. Blood (1994) [Pubmed]
  23. CD9 and megakaryocyte differentiation. Clay, D., Rubinstein, E., Mishal, Z., Anjo, A., Prenant, M., Jasmin, C., Boucheix, C., Le Bousse-Kerdilès, M.C. Blood (2001) [Pubmed]
  24. Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor. Qi, J.C., Wang, J., Mandadi, S., Tanaka, K., Roufogalis, B.D., Madigan, M.C., Lai, K., Yan, F., Chong, B.H., Stevens, R.L., Krilis, S.A. Blood (2006) [Pubmed]
  25. MHC class II/CD38/CD9: a lipid-raft-dependent signaling complex in human monocytes. Zilber, M.T., Setterblad, N., Vasselon, T., Doliger, C., Charron, D., Mooney, N., Gelin, C. Blood (2005) [Pubmed]
  26. Murine CD9 is the receptor for pregnancy-specific glycoprotein 17. Waterhouse, R., Ha, C., Dveksler, G.S. J. Exp. Med. (2002) [Pubmed]
  27. The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha6beta4 and may regulate the spatial organization of hemidesmosomes. Sterk, L.M., Geuijen, C.A., Oomen, L.C., Calafat, J., Janssen, H., Sonnenberg, A. J. Cell Biol. (2000) [Pubmed]
  28. 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]
  29. CD9, but not other tetraspans, associates with the beta1 integrin precursor. Rubinstein, E., Poindessous-Jazat, V., Le Naour, F., Billard, M., Boucheix, C. Eur. J. Immunol. (1997) [Pubmed]
  30. CD63 associates with the alphaIIb beta3 integrin-CD9 complex on the surface of activated platelets. Israels, S.J., McMillan-Ward, E.M., Easton, J., Robertson, C., McNicol, A. Thromb. Haemost. (2001) [Pubmed]
  31. Epigenetic silencing of the tetraspanin CD9 during disease progression in multiple myeloma cells and correlation with survival. De Bruyne, E., Bos, T.J., Asosingh, K., Vande Broek, I., Menu, E., Van Valckenborgh, E., Atadja, P., Coiteux, V., Leleu, X., Thielemans, K., Van Camp, B., Vanderkerken, K., Van Riet, I. Clin. Cancer Res. (2008) [Pubmed]
  32. Cell surface colligin/Hsp47 associates with tetraspanin protein CD9 in epidermoid carcinoma cell lines. Hebert, C., Norris, K., Della Coletta, R., Reynolds, M., Ordóñez, J., Sauk, J.J. J. Cell. Biochem. (1999) [Pubmed]
  33. Profiling of the tetraspanin web of human colon cancer cells. Le Naour, F., André, M., Greco, C., Billard, M., Sordat, B., Emile, J.F., Lanza, F., Boucheix, C., Rubinstein, E. Mol. Cell Proteomics (2006) [Pubmed]
  34. The tetraspanin CD9 associates with transmembrane TGF-alpha and regulates TGF-alpha-induced EGF receptor activation and cell proliferation. Shi, W., Fan, H., Shum, L., Derynck, R. J. Cell Biol. (2000) [Pubmed]
  35. Downregulation of rheumatoid arthritis-related antigen RA-A47 (HSP47/colligin-2) in chondrocytic cell lines induces apoptosis and cell-surface expression of RA-A47 in association with CD9. Hattori, T., von der Mark, K., Kawaki, H., Yutani, Y., Kubota, S., Nakanishi, T., Eberspaecher, H., de Crombrugghe, B., Takigawa, M. J. Cell. Physiol. (2005) [Pubmed]
  36. Aberrant expression of tetraspanin molecules in B-cell chronic lymphoproliferative disorders and its correlation with normal B-cell maturation. Barrena, S., Almeida, J., Yunta, M., López, A., Fernández-Mosteirín, N., Giralt, M., Romero, M., Perdiguer, L., Delgado, M., Orfao, A., Lazo, P.A. Leukemia (2005) [Pubmed]
  37. 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]
  38. CD9 amino acids critical for upregulation of diphtheria toxin binding. Hasuwa, H., Shishido, Y., Yamazaki, A., Kobayashi, T., Yu, X., Mekada, E. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  39. CD9-regulated adhesion. Anti-CD9 monoclonal antibody induce pre-B cell adhesion to bone marrow fibroblasts through de novo recognition of fibronectin. Masellis-Smith, A., Shaw, A.R. J. Immunol. (1994) [Pubmed]
  40. Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. Iwamoto, R., Higashiyama, S., Mitamura, T., Taniguchi, N., Klagsbrun, M., Mekada, E. EMBO J. (1994) [Pubmed]
  41. Phenotypic heterogeneity of TDT+ cells in the blood and bone marrow: implications for surveillance of residual leukemia. Smith, R.G., Kitchens, R.L. Blood (1989) [Pubmed]
  42. Promoter hypermethylation of tetraspanin members contributes to their silencing in myeloma cell lines. Drucker, L., Tohami, T., Tartakover-Matalon, S., Zismanov, V., Shapiro, H., Radnay, J., Lishner, M. Carcinogenesis (2006) [Pubmed]
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