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Gene Review

NFATC1  -  nuclear factor of activated T-cells,...

Homo sapiens

Synonyms: NF-ATC, NF-ATc, NF-ATc1, NFAT transcription complex cytosolic component, NFAT2, ...
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Disease relevance of NFATC1


High impact information on NFATC1

  • Sculpting heart valves with NFATc and VEGF [7].
  • Calcium signaling activates the phosphatase calcineurin and induces movement of NFATc proteins into the nucleus, where they cooperate with other proteins to form complexes on DNA [8].
  • Here we report the solution structure of the binary complex formed between the core DNA-binding domain of human NFATC1 and the ARRE2 DNA site from the interleukin-2 promoter [9].
  • T cells therefore can become competent for HIV-1 replication by control of regulated host factors such as the NFATc transcription factor [10].
  • NFATc overcame a blockade at reverse transcription and permitted active HIV-1 replication [10].

Chemical compound and disease context of NFATC1


Biological context of NFATC1


Anatomical context of NFATC1


Associations of NFATC1 with chemical compounds


Physical interactions of NFATC1

  • Electrophoretic mobility shift assays reveal that recombinant EGR-1 and NFATc bind independently to their target sites within the IL-2 promoter, and the presence of both sites on the same DNA molecule is required for EGR-1.NFATc.DNA complex formation [21].
  • Although NF-ATp copurifies with NF-ATc, there is as yet no understanding of how NF-ATp is functioning in vivo [22].
  • Although the overall fold of the NFATc DNA-binding domain is related to that of NF-kappaB p50 (refs 2, 3), the two proteins use significantly different strategies for DNA recognition [23].
  • Using immunoprecipitation Western blotting, we showed that NFATc1 interacted with GATA-6 [24].

Regulatory relationships of NFATC1


Other interactions of NFATC1


Analytical, diagnostic and therapeutic context of NFATC1


  1. MCP-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, NFATc1, and calcitonin receptor-positive but require receptor activator of NFkappaB ligand for bone resorption. Kim, M.S., Day, C.J., Selinger, C.I., Magno, C.L., Stephens, S.R., Morrison, N.A. J. Biol. Chem. (2006) [Pubmed]
  2. The T cell activation factor NF-ATc positively regulates HIV-1 replication and gene expression in T cells. Kinoshita, S., Su, L., Amano, M., Timmerman, L.A., Kaneshima, H., Nolan, G.P. Immunity (1997) [Pubmed]
  3. NFATc1 mediates vascular endothelial growth factor-induced proliferation of human pulmonary valve endothelial cells. Johnson, E.N., Lee, Y.M., Sander, T.L., Rabkin, E., Schoen, F.J., Kaushal, S., Bischoff, J. J. Biol. Chem. (2003) [Pubmed]
  4. Gene expression patterns in cell lines from patients with 18q- syndrome. Wang, Z., Cody, J.D., Leach, R.J., O'Connell, P. Hum. Genet. (1999) [Pubmed]
  5. Overexpression of c-myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway. Buchholz, M., Schatz, A., Wagner, M., Michl, P., Linhart, T., Adler, G., Gress, T.M., Ellenrieder, V. EMBO J. (2006) [Pubmed]
  6. Epigenetic changes and suppression of the nuclear factor of activated T cell 1 (NFATC1) promoter in human lymphomas with defects in immunoreceptor signaling. Akimzhanov, A., Krenacs, L., Schlegel, T., Klein-Hessling, S., Bagdi, E., Stelkovics, E., Kondo, E., Chuvpilo, S., Wilke, P., Avots, A., Gattenlöhner, S., Müller-Hermelink, H.K., Palmetshofer, A., Serfling, E. Am. J. Pathol. (2008) [Pubmed]
  7. Sculpting heart valves with NFATc and VEGF. Lambrechts, D., Carmeliet, P. Cell (2004) [Pubmed]
  8. NFAT signaling: choreographing the social lives of cells. Crabtree, G.R., Olson, E.N. Cell (2002) [Pubmed]
  9. Solution structure of the core NFATC1/DNA complex. Zhou, P., Sun, L.J., Dötsch, V., Wagner, G., Verdine, G.L. Cell (1998) [Pubmed]
  10. Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells. Kinoshita, S., Chen, B.K., Kaneshima, H., Nolan, G.P. Cell (1998) [Pubmed]
  11. Expression of NFAT-family proteins in normal human T cells. Lyakh, L., Ghosh, P., Rice, N.R. Mol. Cell. Biol. (1997) [Pubmed]
  12. NFATc1 with AP-3 site binding specificity mediates gene expression of prostate-specific-membrane-antigen. Lee, S.J., Lee, K., Yang, X., Jung, C., Gardner, T., Kim, H.S., Jeng, M.H., Kao, C. J. Mol. Biol. (2003) [Pubmed]
  13. Kinetics of cytokine and NFAT gene expression in human interleukin-2-dependent T lymphoblasts stimulated via T-cell receptor. Sareneva, T., Matikainen, S., Vanhatalo, J., Melén, K., Pelkonen, J., Julkunen, I. Immunology (1998) [Pubmed]
  14. Expression and function of the nuclear factor of activated T cells in colon carcinoma cells: involvement in the regulation of cyclooxygenase-2. Duque, J., Fresno, M., Iñiguez, M.A. J. Biol. Chem. (2005) [Pubmed]
  15. Selective expression of nuclear factor of activated T cells 2/c1 in human basophils: evidence for involvement in IgE-mediated IL-4 generation. Schroeder, J.T., Miura, K., Kim, H.H., Sin, A., Cianferoni, A., Casolaro, V. J. Allergy Clin. Immunol. (2002) [Pubmed]
  16. NF-AT components define a family of transcription factors targeted in T-cell activation. Northrop, J.P., Ho, S.N., Chen, L., Thomas, D.J., Timmerman, L.A., Nolan, G.P., Admon, A., Crabtree, G.R. Nature (1994) [Pubmed]
  17. NFATc1 directly induces the human beta3 integrin gene in osteoclast differentiation. Crotti, T.N., Flannery, M., Walsh, N.C., Fleming, J.D., Goldring, S.R., McHugh, K.P. Journal of musculoskeletal & neuronal interactions. (2005) [Pubmed]
  18. Vav-Rac1-mediated activation of the c-Jun N-terminal kinase/c-Jun/AP-1 pathway plays a major role in stimulation of the distal NFAT site in the interleukin-2 gene promoter. Kaminuma, O., Deckert, M., Elly, C., Liu, Y.C., Altman, A. Mol. Cell. Biol. (2001) [Pubmed]
  19. Characterization of a new isoform of the NFAT (nuclear factor of activated T cells) gene family member NFATc. Park, J., Takeuchi, A., Sharma, S. J. Biol. Chem. (1996) [Pubmed]
  20. Activity- and calcineurin-independent nuclear shuttling of NFATc1, but not NFATc3, in adult skeletal muscle fibers. Shen, T., Liu, Y., Cseresnyés, Z., Hawkins, A., Randall, W.R., Schneider, M.F. Mol. Biol. Cell (2006) [Pubmed]
  21. The early growth response protein (EGR-1) regulates interleukin-2 transcription by synergistic interaction with the nuclear factor of activated T cells. Decker, E.L., Skerka, C., Zipfel, P.F. J. Biol. Chem. (1998) [Pubmed]
  22. Cloning and characterization of NF-ATc and NF-ATp: the cytoplasmic components of NF-AT. Ho, S., Timmerman, L., Northrop, J., Crabtree, G.R. Adv. Exp. Med. Biol. (1994) [Pubmed]
  23. Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc. Wolfe, S.A., Zhou, P., Dötsch, V., Chen, L., You, A., Ho, S.N., Crabtree, G.R., Wagner, G., Verdine, G.L. Nature (1997) [Pubmed]
  24. Calcineurin-GATA-6 pathway is involved in smooth muscle-specific transcription. Wada, H., Hasegawa, K., Morimoto, T., Kakita, T., Yanazume, T., Abe, M., Sasayama, S. J. Cell Biol. (2002) [Pubmed]
  25. Protein kinase Czeta phosphorylates nuclear factor of activated T cells and regulates its transactivating activity. San-Antonio, B., Iñiguez, M.A., Fresno, M. J. Biol. Chem. (2002) [Pubmed]
  26. Rosiglitazone antagonizes vascular endothelial growth factor signaling and nuclear factor of activated T cells activation in cardiac valve endothelium. Sander, T.L., Noll, L., Klinkner, D.B., Weihrauch, D., He, B.J., Kaul, S., Zangwill, S.D., Tweddell, J.S., Pritchard, K.A., Oldham, K.T. Endothelium (2006) [Pubmed]
  27. Grb3-3 is up-regulated in HIV-1-infected T-cells and can potentiate cell activation through NFATc. Li, X., Multon, M.C., Henin, Y., Schweighoffer, F., Venot, C., Josef, J., Zhou, C., LaVecchio, J., Stuckert, P., Raab, M., Mhashilkar, A., Tocque, B., Marasco, W.A. J. Biol. Chem. (2000) [Pubmed]
  28. Human eosinophils constitutively express nuclear factor of activated T cells p and c. Seminario, M.C., Guo, J., Bochner, B.S., Beck, L.A., Georas, S.N. J. Allergy Clin. Immunol. (2001) [Pubmed]
  29. Vascular endothelial growth factor- and thrombin-induced termination factor, Down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis. Minami, T., Horiuchi, K., Miura, M., Abid, M.R., Takabe, W., Noguchi, N., Kohro, T., Ge, X., Aburatani, H., Hamakubo, T., Kodama, T., Aird, W.C. J. Biol. Chem. (2004) [Pubmed]
  30. Restricted epithelial proliferation by lacritin via PKCalpha-dependent NFAT and mTOR pathways. Wang, J., Wang, N., Xie, J., Walton, S.C., McKown, R.L., Raab, R.W., Ma, P., Beck, S.L., Coffman, G.L., Hussaini, I.M., Laurie, G.W. J. Cell Biol. (2006) [Pubmed]
  31. Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells. Martínez-Martínez, S., Gómez del Arco, P., Armesilla, A.L., Aramburu, J., Luo, C., Rao, A., Redondo, J.M. Mol. Cell. Biol. (1997) [Pubmed]
  32. Thrombin-induced autoinhibitory factor, Down syndrome critical region-1, attenuates NFAT-dependent vascular cell adhesion molecule-1 expression and inflammation in the endothelium. Minami, T., Miura, M., Aird, W.C., Kodama, T. J. Biol. Chem. (2006) [Pubmed]
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