The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

NFAT5  -  nuclear factor of activated T-cells 5,...

Homo sapiens

Synonyms: KIAA0827, NF-AT5, NFATL1, NFATZ, Nuclear factor of activated T-cells 5, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of NFAT5


High impact information on NFAT5

  • We suggest that NFAT5 participates in specific aspects of host defense by upregulating TNF family genes and other target genes in T cells [3].
  • Like Rel/NF-kappaB proteins but unlike the calcium-regulated NFAT proteins, NFAT5 is constitutively dimeric, and dimerization is essential for DNA binding and transcriptional activity [3].
  • Using dominant-negative proteins that inhibit NFAT5 dimerization, we show that NFAT5 regulates expression of the TNFalpha and lymphotoxin-beta genes in osmotically stressed T cells [3].
  • In addition, the transcriptional activity of NFAT5 is induced by alpha(6)beta(4) clustering in the presence of chemo-attractants, resulting in enhanced cell migration [1].
  • Several kinases are known to contribute to signaling activation of TonEBP/OREBP, including ATM, which is a member of the phosphatidylinositol 3-kinase (PI3K)-like kinase family and is activated by DNA double-strand breaks [4].

Biological context of NFAT5

  • Here we demonstrate that NFAT5 is necessary for optimal T cell development in vivo and allows for optimal cell growth ex vivo under conditions associated with osmotic stress [5].
  • Recently, we mapped the human NFAT5 gene to chromosome 16 by PCR using DNA from hybrid cell lines [6].
  • Genomic organization of the human NFAT5 gene: exon-intron structure of the 14-kb transcript and CpG-island analysis of the promoter region [7].
  • Unlike NFAT1-4, whose nuclear import is tightly regulated by calcineurin-mediated dephosphorylation, NFAT5 is a constitutively nuclear phosphoprotein regardless of calcineurin activation [8].
  • PCR based expression analyses detected NFAT5 transcripts with alternative splicing in 27 fetal and adult human tissues [2].

Anatomical context of NFAT5


Associations of NFAT5 with chemical compounds


Physical interactions of NFAT5

  • TonEBP/OREBP reciprocally coimmunoprecipitates with ATM kinase, demonstrating physical association [12].
  • TonEBP [TonE (tonicity-responsive enhancer)-binding protein] is a transcriptional activator of the Rel family like NF-kappaB (nuclear factor kappaB) and NFAT (nuclear factor of activated T-cells) [13].
  • The N- and C-termini of RHA bound the E'F loop of the DNA-binding domain of TonEBP [13].
  • In hypertonic media there was activation of TauT and heat shock protein-70 (HSP-70) reporter activity and increased binding of TonEBP to the TonE motif [14].

Regulatory relationships of NFAT5

  • The purpose of the present studies was to test whether ATM is also involved in high NaCl-induced TonEBP/OREBP nuclear translocation [10].
  • Overexpression of RHA inhibited the activity of TonEBP; however, catalytic activity of RHA was dispensable for the inhibition [13].
  • In conclusion, these results show that aldose reductase is upregulated by the transcriptional factor NFAT5 under high-glucose conditions in both PBMCs and HMCs [15].
  • TonEBP protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters [16].
  • TonEBP stimulates genes whose products drive cellular accumulation of organic osmolytes and HSP70, which protect cells from the deleterious effects of hypertonicity and urea, respectively [17].

Other interactions of NFAT5


Analytical, diagnostic and therapeutic context of NFAT5


  1. The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Jauliac, S., López-Rodriguez, C., Shaw, L.M., Brown, L.F., Rao, A., Toker, A. Nat. Cell Biol. (2002) [Pubmed]
  2. Quantitative PCR analysis of different splice forms of NFAT5 revealed specific gene expression in fetal and adult brain. Dalski, A., Wagner, H.J., Schwinger, E., Zühlke, C. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  3. Bridging the NFAT and NF-kappaB families: NFAT5 dimerization regulates cytokine gene transcription in response to osmotic stress. López-Rodríguez, C., Aramburu, J., Jin, L., Rakeman, A.S., Michino, M., Rao, A. Immunity (2001) [Pubmed]
  4. Phosphatidylinositol 3-kinase mediates activation of ATM by high NaCl and by ionizing radiation: Role in osmoprotective transcriptional regulation. Irarrazabal, C.E., Burg, M.B., Ward, S.G., Ferraris, J.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. The osmoprotective function of the NFAT5 transcription factor in T cell development and activation. Trama, J., Go, W.Y., Ho, S.N. J. Immunol. (2002) [Pubmed]
  6. Assignment of transcription factor NFAT5 to human chromosome 16q22.1, murine chromosome 8D and porcine chromosome 6p1.4 and comparison of the polyglutamine domains. Hebinck, A., Dalski, A., Engel, H., Mattei, M., Hawken, R., Schwinger, E., Zühlke, C. Cytogenet. Cell Genet. (2000) [Pubmed]
  7. Genomic organization of the human NFAT5 gene: exon-intron structure of the 14-kb transcript and CpG-island analysis of the promoter region. Dalski, A., Schwinger, E., Zühlke, C. Cytogenet. Cell Genet. (2001) [Pubmed]
  8. NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun. Lopez-Rodríguez, C., Aramburu, J., Rakeman, A.S., Rao, A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. The NFAT-related protein NFATL1 (TonEBP/NFAT5) is induced upon T cell activation in a calcineurin-dependent manner. Trama, J., Lu, Q., Hawley, R.G., Ho, S.N. J. Immunol. (2000) [Pubmed]
  10. Ataxia telangiectasia-mutated, a DNA damage-inducible kinase, contributes to high NaCl-induced nuclear localization of transcription factor TonEBP/OREBP. Zhang, Z., Ferraris, J.D., Irarrazabal, C.E., Dmitrieva, N.I., Park, J.H., Burg, M.B. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  11. Degradation of NFAT5, a Transcriptional Regulator of Osmotic Stress-related Genes, Is a Critical Event for Doxorubicin-induced Cytotoxicity in Cardiac Myocytes. Ito, T., Fujio, Y., Takahashi, K., Azuma, J. J. Biol. Chem. (2007) [Pubmed]
  12. ATM, a DNA damage-inducible kinase, contributes to activation by high NaCl of the transcription factor TonEBP/OREBP. Irarrazabal, C.E., Liu, J.C., Burg, M.B., Ferraris, J.D. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  13. TonEBP is inhibited by RNA helicase A via interaction involving the E'F loop. Colla, E., Lee, S.D., Sheen, M.R., Woo, S.K., Kwon, H.M. Biochem. J. (2006) [Pubmed]
  14. TonEBP/OREBP is a regulator of nucleus pulposus cell function and survival in the intervertebral disc. Tsai, T.T., Danielson, K.G., Guttapalli, A., Oguz, E., Albert, T.J., Shapiro, I.M., Risbud, M.V. J. Biol. Chem. (2006) [Pubmed]
  15. Elevated activity of transcription factor nuclear factor of activated T-cells 5 (NFAT5) and diabetic nephropathy. Yang, B., Hodgkinson, A.D., Oates, P.J., Kwon, H.M., Millward, B.A., Demaine, A.G. Diabetes (2006) [Pubmed]
  16. Downregulation of renal sodium transporters and tonicity-responsive enhancer binding protein by long-term treatment with cyclosporin a. Lim, S.W., Ahn, K.O., Sheen, M.R., Jeon, U.S., Kim, J., Yang, C.W., Kwon, H.M. J. Am. Soc. Nephrol. (2007) [Pubmed]
  17. How tonicity regulates genes: story of TonEBP transcriptional activator. Jeon, U.S., Kim, J.A., Sheen, M.R., Kwon, H.M. Acta physiologica (Oxford, England) (2006) [Pubmed]
  18. Calcineurin inhibitor effects on growth and phenotype of human airway epithelial cells in vitro. Neuringer, I.P., Sloan, J., Budd, S., Chalermskulrat, W., Park, R.C., Stonebraker, J.R., O'Neal, W.K., Aris, R.M., Randell, S.H. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2005) [Pubmed]
  19. Partners in transcription: NFAT and AP-1. Macián, F., López-Rodríguez, C., Rao, A. Oncogene (2001) [Pubmed]
  20. Regulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5. Tong, E.H., Guo, J.J., Huang, A.L., Liu, H., Hu, C.D., Chung, S.S., Ko, B.C. J. Biol. Chem. (2006) [Pubmed]
  21. Regulation of ROMK (Kir 1.1) channel expression in kidney thick ascending limb by hypertonicity: role of TonEBP and MAPK pathways. Gallazzini, M., Karim, Z., Bichara, M. Nephron. Physiology (2006) [Pubmed]
WikiGenes - Universities