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Gene Review

CD247  -  CD247 molecule

Homo sapiens

Synonyms: CD3-ZETA, CD3H, CD3Q, CD3Z, IMD25, ...
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Disease relevance of CD247


High impact information on CD247

  • In addition, several other internal feedback controls on TCR/CD3 function, by CD4-induced tyrosine-specific phosphorylation of the CD3 zeta subunit, or on the Ca2+ signal, by extracellular Cl- or by GM1 gangliosides, are also postulated [6].
  • Here we show that soluble CD8alphaalpha receptor, despite an extremely low affinity for MHC, inhibits activation of cytotoxic lymphocytes by obstructing CD3 zeta-chain phosphorylation [7].
  • But recent studies indicate that NK cells do express CD3 zeta, co-associated with other membrane proteins [8].
  • These findings indicate that CD3 zeta can co-associate with membrane receptors of diverse cell types and function as a common structure for signal transduction [8].
  • Variants of a murine antigen-specific T cell hybridoma that express normal amounts of CD3-zeta 2 but decreased amounts of CD3-zeta eta were isolated [9].

Chemical compound and disease context of CD247


Biological context of CD247


Anatomical context of CD247


Associations of CD247 with chemical compounds

  • The enzymatically inactive CD45 C828S mutant protein, in which the cysteine residue at the catalytic center was changed to a serine residue, bound tightly to the phosphorylated CD3 zeta chain [16].
  • Here we report an association of type II PtdIns 4-kinase with TCR-CD3 zeta chain upon cross-linking [17].
  • Glycoprotein (GP)Ib-V-IX (CD42) and GPIIb (CD41) are examples of MK-specific proteins having receptor properties essential for platelet adhesion and aggregation [18].
  • The receptor consists of a single-chain antibody (scFv) binding domain specific for carcinoembryonic antigen (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and intracellular CD3 zeta signaling chain [19].
  • Citrulline can preserve proliferation and prevent the loss of CD3 zeta chain under conditions of low arginine [20].

Physical interactions of CD247

  • Taken together, these results suggest that, unlike the non-raft pool, CD38 in rafts is able to initiate and propagate several activating signaling pathways, possibly by facilitating critical associations within other raft subsets, for example, LAT rafts via its capacity to interact with Lck and CD3-zeta [11].
  • We have examined the ability of the CD3-gamma delta epsilon and CD3-zeta signaling modules of the T cell receptor (TCR) to couple CD38 to intracellular signaling pathways [21].
  • These experiments showed that the presence of CD3-zeta 2 in the TCR-CD3 complex is of critical importance for the ability of CD4 to enhance early transducing signals inside the cell [22].

Enzymatic interactions of CD247

  • Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain [16].

Co-localisations of CD247

  • However, when conjugates are formed in the presence of anti-alpha 4 antibodies, VLA-4 colocalizes with the CD3-zeta chain at the center of the synapse [23].

Regulatory relationships of CD247


Other interactions of CD247

  • Northern blot analysis of transcripts coding for CD3/TCR molecules revealed the presence of CD3 zeta, epsilon, and gamma transcripts, while CD3 delta was undetectable [26].
  • CD38 signaling in T cells is initiated within a subset of membrane rafts containing Lck and the CD3-zeta subunit of the T cell antigen receptor [11].
  • In this report, we extended these findings by examining the expression and functional relationship of 1F7 on the CD3 and CD2 pathways of activation of human thymocytes [27].
  • The human OTF1 locus which overlaps the CD3Z gene is located at 1q22-->q23 [28].
  • Thus, the phosphorylated CD3 zeta chain is a specific and high-affinity substrate of the CD45 PTPase [16].

Analytical, diagnostic and therapeutic context of CD247

  • Most importantly, we showed that solid-phase immobilization of anti-1F7 has a comitogenic effect on thymocyte activation induced by anti-CD3 but not anti-CD2 [27].
  • Coculture of parental LC89 cells with PBMC was consistently associated with a downmodulation in the expression of the CD3 zeta chain, as well as of the tyrosine kinases p56ick and ZAP-70 [29].
  • Furthermore, immunoprecipitation with anti-CD3 gamma and anti-CD3 delta antibodies from 1% NP40 and 1% Brij96 cell lysates showed that these subunits form independent partial complexes which are cross-linked through the CD3 zeta homodimer [12].
  • Human natural killer cells and mature T lymphocytes express identical CD3 zeta subunits as defined by cDNA cloning and sequence analysis [13].
  • The inability of rIL-2 to generate tumour-specific CTLs despite restoration of CD3-zeta expression and the presence of an intact lytic mechanism suggests that successful immunotherapy may require the development of strategies to increase the immunogenicity of this tumour [1].


  1. Interleukin 2 restores CD3-zeta chain expression but fails to generate tumour-specific lytic activity in tumour-infiltrating lymphocytes derived from human colorectal hepatic metastases. Yoong, K.F., Adams, D.H. Br. J. Cancer (1998) [Pubmed]
  2. CD3 zeta expression of regional lymph node and peripheral blood lymphocytes in gastric cancer. Ishigami, S., Natsugoe, S., Miyazono, F., Tokuda, K., Nakajo, A., Matsumoto, M., Okumura, H., Nakashima, S., Hokita, S., Maruyama, I., Aikou, T. Anticancer Res. (2004) [Pubmed]
  3. CD3-zetachain expression of intratumoral lymphocytes is closely related to survival in gastric carcinoma patients. Ishigami, S., Natsugoe, S., Tokuda, K., Nakajo, A., Higashi, H., Iwashige, H., Aridome, K., Hokita, S., Aikou, T. Cancer (2002) [Pubmed]
  4. An anti-CD30 chimeric receptor that mediates CD3-zeta-independent T-cell activation against Hodgkin's lymphoma cells in the presence of soluble CD30. Hombach, A., Heuser, C., Sircar, R., Tillmann, T., Diehl, V., Pohl, C., Abken, H. Cancer Res. (1998) [Pubmed]
  5. Expression and activity of signaling molecules in T lymphocytes obtained from patients with metastatic melanoma before and after interleukin 2 therapy. Rabinowich, H., Banks, M., Reichert, T.E., Logan, T.F., Kirkwood, J.M., Whiteside, T.L. Clin. Cancer Res. (1996) [Pubmed]
  6. Calcium and T lymphocyte activation. Gardner, P. Cell (1989) [Pubmed]
  7. Antagonism of cytotoxic T-lymphocyte activation by soluble CD8. Sewell, A.K., Gerth, U.C., Price, D.A., Purbhoo, M.A., Boulter, J.M., Gao, G.F., Bell, J.I., Phillips, R.E., Jakobsen, B.K. Nat. Med. (1999) [Pubmed]
  8. Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. Lanier, L.L., Yu, G., Phillips, J.H. Nature (1989) [Pubmed]
  9. T cell CD3-zeta eta heterodimer expression and coupling to phosphoinositide hydrolysis. Merćep, M., Bonifacino, J.S., Garcia-Morales, P., Samelson, L.E., Klausner, R.D., Ashwell, J.D. Science (1988) [Pubmed]
  10. Decreased Expression of CD3 zeta and Nuclear Transcription Factor kappa B in Patients with Pulmonary Tuberculosis: Potential Mechanisms and Reversibility with Treatment. Zea, A.H., Culotta, K.S., Ali, J., Mason, C., Park, H.J., Zabaleta, J., Garcia, L.F., Ochoa, A.C. J. Infect. Dis. (2006) [Pubmed]
  11. CD38 signaling in T cells is initiated within a subset of membrane rafts containing Lck and the CD3-zeta subunit of the T cell antigen receptor. Muñoz, P., Navarro, M.D., Pavón, E.J., Salmerón, J., Malavasi, F., Sancho, J., Zubiaur, M. J. Biol. Chem. (2003) [Pubmed]
  12. Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 epsilon/gamma dimers associate indistinctly with both TCR alpha and TCR beta chains. Evidence for a double TCR heterodimer model. San José, E., Sahuquillo, A.G., Bragado, R., Alarcón, B. Eur. J. Immunol. (1998) [Pubmed]
  13. Human natural killer cells and mature T lymphocytes express identical CD3 zeta subunits as defined by cDNA cloning and sequence analysis. Moingeon, P., Stebbins, C.C., D'Adamio, L., Lucich, J., Reinherz, E.L. Eur. J. Immunol. (1990) [Pubmed]
  14. Novel leukemic lymphoma with probable derivation from immature stage of natural killer (NK) lineage in an aged patient. Kawano, S., Tatsumi, E., Yoneda, N., Yamaguchi, N., Goji, J., Ito, H., Nagai, T., Nishikori, M., Okamura, A., Koiwai, O. Hematological oncology. (1995) [Pubmed]
  15. T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-zeta complex, recruits intracellular signaling proteins to the plasma membrane. Bruyns, E., Marie-Cardine, A., Kirchgessner, H., Sagolla, K., Shevchenko, A., Mann, M., Autschbach, F., Bensussan, A., Meuer, S., Schraven, B. J. Exp. Med. (1998) [Pubmed]
  16. Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain. Furukawa, T., Itoh, M., Krueger, N.X., Streuli, M., Saito, H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  17. Type II phosphatidylinositol 4-kinase beta associates with TCR-CD3 zeta chain in Jurkat cells. Srivastava, R., Sinha, R.K., Subrahmanyam, G. Mol. Immunol. (2006) [Pubmed]
  18. The alpha(IIb)beta(3) integrin and GPIb-V-IX complex identify distinct stages in the maturation of CD34(+) cord blood cells to megakaryocytes. Lepage, A., Leboeuf, M., Cazenave, J.P., de la Salle, C., Lanza, F., Uzan, G. Blood (2000) [Pubmed]
  19. An entirely humanized CD3 zeta-chain signaling receptor that directs peripheral blood t cells to specific lysis of carcinoembryonic antigen-positive tumor cells. Hombach, A., Schneider, C., Sent, D., Koch, D., Willemsen, R.A., Diehl, V., Kruis, W., Bolhuis, R.L., Pohl, C., Abken, H. Int. J. Cancer (2000) [Pubmed]
  20. Citrulline can preserve proliferation and prevent the loss of CD3 zeta chain under conditions of low arginine. Bansal, V., Rodriguez, P., Wu, G., Eichler, D.C., Zabaleta, J., Taheri, F., Ochoa, J.B. JPEN. Journal of parenteral and enteral nutrition. (2004) [Pubmed]
  21. The CD3-gamma delta epsilon transducing module mediates CD38-induced protein-tyrosine kinase and mitogen-activated protein kinase activation in Jurkat T cells. Zubiaur, M., Guirado, M., Terhorst, C., Malavasi, F., Sancho, J. J. Biol. Chem. (1999) [Pubmed]
  22. CD3-zeta surface expression is required for CD4-p56lck-mediated upregulation of T cell antigen receptor-CD3 signaling in T cells. Sancho, J., Ledbetter, J.A., Choi, M.S., Kanner, S.B., Deans, J.P., Terhorst, C. J. Biol. Chem. (1992) [Pubmed]
  23. VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses. Mittelbrunn, M., Molina, A., Escribese, M.M., Yáñez-Mó, M., Escudero, E., Ursa, A., Tejedor, R., Mampaso, F., Sánchez-Madrid, F. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  24. Targeting Src homology 2 domain-containing tyrosine phosphatase (SHP-1) into lipid rafts inhibits CD3-induced T cell activation. Su, M.W., Yu, C.L., Burakoff, S.J., Jin, Y.J. J. Immunol. (2001) [Pubmed]
  25. HSP-10 in ovarian cancer: expression and suppression of T-cell signaling. Akyol, S., Gercel-Taylor, C., Reynolds, L.C., Taylor, D.D. Gynecol. Oncol. (2006) [Pubmed]
  26. In vitro expansion of CD3/TCR- human thymocyte populations that selectively lack CD3 delta gene expression: a phenotypic and functional analysis. Poggi, A., Biassoni, R., Pella, N., Paolieri, F., Bellomo, R., Bertolini, A., Moretta, L., Mingari, M.C. J. Exp. Med. (1990) [Pubmed]
  27. 1F7 (CD26): a marker of thymic maturation involved in the differential regulation of the CD3 and CD2 pathways of human thymocyte activation. Dang, N.H., Torimoto, Y., Shimamura, K., Tanaka, T., Daley, J.F., Schlossman, S.F., Morimoto, C. J. Immunol. (1991) [Pubmed]
  28. The human OTF1 locus which overlaps the CD3Z gene is located at 1q22-->q23. Sturm, R.A., Eyre, H.J., Baker, E., Sutherland, G.R. Cytogenet. Cell Genet. (1995) [Pubmed]
  29. Transfer of the interleukin-2 gene into human cancer cells induces specific antitumor recognition and restores the expression of CD3/T-cell receptor associated signal transduction molecules. Guarini, A., Riera, L., Cignetti, A., Montacchini, L., Massaia, M., Foa, R. Blood (1997) [Pubmed]
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