Property Summary

NCBI Gene PubMed Count 83
PubMed Score 196.52
PubTator Score 127.51

Knowledge Summary


No data available



  Differential Expression (15)

Disease log2 FC p
Rheumatoid Arthritis 2.300 1.5e-02
interstitial lung disease 1.100 6.0e-04
osteosarcoma 4.822 5.7e-13
medulloblastoma -1.100 1.9e-03
medulloblastoma, large-cell -1.500 3.3e-04
tuberculosis -1.100 4.9e-07
intraductal papillary-mucinous neoplasm ... 1.300 7.6e-03
adult high grade glioma -1.100 9.8e-03
acute myeloid leukemia 1.800 1.2e-02
psoriasis -1.700 2.2e-11
breast carcinoma -1.400 2.6e-19
Alzheimer's disease 1.300 4.9e-02
Pick disease 2.800 7.0e-07
Breast cancer -1.600 4.7e-10
ovarian cancer 1.300 1.1e-03

Gene RIF (66)

26912969 Our data demonstrates the involvement of TonEBP in the mechanisms responsible for osmoadaptation to hyperosmolar stress in retinal pigment epithelium cells.
26506053 Results suggest that the NFAT5 gene, which is upregulated a few hours after cocaine exposure, may be involved in the genetic predisposition to cocaine dependence.
26495302 Additionally, in peritoneal dialysis the cells of the peritoneal cavity are repeatedly exposed to a rise and fall in osmotic concentrations. Here we review the current information about NFAT5 in uremic patients and patients on peritoneal dialysis.
26299924 These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy.
25995271 Real-time PCR and Western blot analysis confirmed up-regulation of NFAT5 mRNA and NFAT5 nuclear content in human preeclamptic placentas
25928084 NFAT5 pathway activation might have a relevant role in inflammatory breast cancer pathogenesis
25878490 The hyperosmotic induction of AQP5 and VEGF in retinal pigment epithelial cells was in part dependent on activation of NFAT5.
25834072 Upregulation of NFAT5 in peritoneal dialysis patients is associated with NFkappaB induction, potentially resulting in the recruitment of macrophages
25728138 HIV-1 Vpu downregulates NRON levels but HIV-1 Nef upregulates NRON levels in Jurkat cells, leading to reciprocal regulation in NFAT activity through NRON by Vpu and Nef
25391900 PKC-alpha contributes to high NaCl-dependent activation of NFAT5 through ERK1/2.
25311085 NFAT5 is directly targeted by miR-568, which is in turn suppressed by the long non-coding RNA, Hotair.
25057011 NFAT5 participates in the regulation of intestinal homeostasis via the suppression of mTORC1/Notch signaling pathway.
25044064 these data support a novel function of the XO-NFAT5 axis in macrophage activation and TLR-induced arthritis
24614757 Suggest that biomechanical stretch is sufficient to activate NFAT5 both in native and cultured VSMCs where it regulates the expression of tenascin-C.
24355664 Data indicate that nuclear factor of activated T cells 5 (NFAT5) is a direct target of miR-568.
23764852 NFAT5 regulation of intestinal cell differentiation may be through inhibition of Wnt/beta-catenin signaling.
23219947 Nfat5 may be involved in regulating chondrogenic differentiation of these cells under both normal and increased osmolarities and might regulate chondrogenic differentiation through influencing early Sox9 expression
22992674 It was concluded that specific DNA binding of NFAT5 contributes to its nuclear localization, by mechanisms as yet undetermined, but independent of ones previously described.
22768306 NFAT5 is induced by hypoxia and could be a protective factor against ischemic damage.
22619484 NFAT5 contributes to osmolality-induced MCP-1 expression in mesothelial cells
22497815 These data indicate that NS5A modulates Hsp72 via NFAT5 and reactive oxygen species activation for hepatitis C virus propagation.
22496647 the innate immune response to MTb infection induces NFAT5 gene and protein expression, and NFAT5 plays a crucial role in MTb regulation of HIV-1 replication via a direct interaction with the viral promoter.
22266867 Data indicate that transcriptional coregulator ddx5/ddx17 RNA helicases can simultaneously regulate the transcriptional activity and alternative splicing of NFAT5 transcription factor.
22190034 HIV-1 Vpu downregulates NRON levels but HIV-1 Nef upregulates NRON levels in Jurkat cells, leading to reciprocal regulation in NFAT activity through NRON by Vpu and Nef
22071693 The nuclear transport of NFAT5a involves reversible palmitoylation.
21982764 These results suggested that TonEBP played an important role in the epithelial cells of renal proximal tubule upon hypertonic stress by enhancing AAD expression, which could promote dopamine secretion to negative regulate Na+/K+-ATPase activity.
21757659 Identify NFAT5 as a novel regulator of vascular smooth muscle cell phenotypic modulation.
21749466 Non-invasive imaging of nuclear factor of activated T-cell 5 (NFAT5) activation follows middle cerebral artery occlusion (MCAO) in NFAT5-luciferase-expressing mice.
21717420 NF-AT5 regulates synovial proliferation and angiogenesis in chronic arthritis.
21418859 Compared with control group, the levels of OREBP, HSP70-2 and MUC5AC in supernatant significantly increased after HBE16 cells were exposed to hypertonic media.
21289293 this study demonstrates that hyperosmotic stress induces S100A4 through NFAT5, and Src and chromatin remodeling are involved.
21209322 High NaCl-induced increase of the overall abundance of TonEBP/OREBP, by itself, eventually raises its effective level in the nucleus, but its rapid CDK5-dependent nuclear localization accelerates the process.
21037089 NFAT5-null mice have constitutive, pronounced hypernatremia and suffer severe immunodeficiency with T cell lymphopenia, altered CD8 naive/memory homeostasis, and inability to reject allogeneic tumors.
20685965 These findings reveal a novel role for TonEBP and Akt in NF-kappaB activation on the onset of hypertonic challenge.
20677014 Observational study of gene-disease association. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20585028 c-Abl is the kinase responsible for high NaCl-induced phosphorylation of TonEBP/OREBP-Y143
20351292 TonEBP/OREBP is extensively regulated by phosphatases, including SHP-1, whose inhibition by high NaCl increases phosphorylation of TonEBP/OREBP at Y143, contributing to the nuclear localization and activation of TonEBP/OREBP
20237496 Observational study of gene-disease association. (HuGE Navigator)
20080774 TonEBP/OREBP becomes phosphorylated at Y143, resulting in binding of PLC-gamma1 to that site, which contributes to TonEBP/OREBP transcriptional activity.
20041176 The loss of nucleosome(s) was found to be initiated by an OREBP-independent mechanism, but was significantly potentiated in the presence of OREBP.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19886771 present in placenta at RNA and protein levels
19750013 NFAT5 exclusion from mitotic chromatin resets its nucleo-cytoplasmic distribution in interphase
19138132 Results of these studies suggest that, in nucleus pulposus cells, osmotic pressure and calcium modulate AQP2 expression through TonEBP and are independent of the calcineurin-NFAT pathway
18606815 Nup88 is up-regulated in response to hypertonic stress and acts to retain TonEBP in the nucleus, activating transcription of critical osmoprotective genes.
18411282 Ser-155 and Ser-158 have important roles in the nucleocytoplasmic trafficking of OREBP/TonEBP and CK1 plays a major role in regulating this process
18367666 activation of p38 isoforms by hypertonicity does not contribute to activation of TonEBP/OREBP because of opposing effects of p38alpha and p38delta.
17440116 the level of CYP2E1 is induced by hypertonic condition via TonEBP transactivation. The present study suggests that osmotic status may influence individual responses to the substrate of CYP2E1.
17173480 Our results define a novel host factor-viral enhancer interaction that reveals a new regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV-1 subtypes and representative simian immunodeficiency viruses.
17148781 PARP-1 and Hsp90 bind to TonEBP; PARP-1 expression reduces TonEBP transcriptional activity and the activity of its transactivating domain and Hsp90 enhances those activities.
16782704 Three protein motifs in OREBP/TonEBP control its proper subcellular localization under different extracellular osmolality, one of which is the nuclear localization signal motif.
16644704 Aldose reductase is upregulated by the transcriptional factor NFAT5 under high-glucose conditions in both mononuclar leukocytes and mesangial cells.
15840767 activation of ATM contributes to high NaCl-induced nuclear translocation of TonEBP/OREBP
15173573 signaling via ATM is necessary for full activation of TonEBP/OREBP
12538727 Sodium/myo-inositol cotransproter, aldose reductase, and HSP70 genes are targets of TonEBP. (tonicity-responsive enhancer binding protein)
12482947 PKA plays an important role in TonEBP/OREBP activation of tonicity-dependent gene expression.
12379312 nuclear expression of NFAT in B-CLL cells leads to enhanced activation of CD23b promoter and increased expression of CD23b isoform
12359721 hypertonic activation by fyn and p38 signaling
12080349 transcriptional activity of NFAT5 is induced by alpha(6)beta(4) clustering in the presence of chemo-attractants, resulting in enhanced cell migration
11936849 modulates the glutathione peroxidase gene in response to oxygen tension
11877454 Recent data implicate NFAT in the control of gene expression influencing the development and adaptation of numerous mammalian cell types
11792870 Activity of the TonEBP/OREBP transactivation domain varies directly with extracellular NaCl concentration
11780147 adopts a NF-kappaB-like structure upon binding to DNA; also encircles its DNA target which may lead to increased kinetic stability of the TonEBP-DNA complex
11528118 cloning of the complete 14-kb cDNA sequence and genomic organization of NFAT5 gene
11046013 Induced upon T cell activation in a calcineurin-dependent manner, which contrasts with the calcineurin-independent induction mediated by hyperosmotic stress.

AA Sequence


Text Mined References (93)

PMID Year Title
26912969 2016 Involvement of TonEBP/NFAT5 in osmoadaptative response of human retinal pigmented epithelial cells to hyperosmolar stress.
26506053 2015 Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence.
26495302 2015 The potential role of NFAT5 and osmolarity in peritoneal injury.
26299924 2015 NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression.
25995271 2015 NFAT5 Is Up-Regulated by Hypoxia: Possible Implications in Preeclampsia and Intrauterine Growth Restriction.
25928084 2015 Systems biology analysis reveals NFAT5 as a novel biomarker and master regulator of inflammatory breast cancer.
25878490 2015 Regulation of the hyperosmotic induction of aquaporin 5 and VEGF in retinal pigment epithelial cells: involvement of NFAT5.
25834072 2015 Activation of nuclear factor of activated T cells 5 in the peritoneal membrane of uremic patients.
25772364 2015 SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage.
25755297 2015 System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability.
25391900 2015 PKC-? contributes to high NaCl-induced activation of NFAT5 (TonEBP/OREBP) through MAPK ERK1/2.
25311085 2014 Nuclear factor of activated T cells 5 maintained by Hotair suppression of miR-568 upregulates S100 calcium binding protein A4 to promote breast cancer metastasis.
25231870 2014 Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
25218447 2014 Uncovering global SUMOylation signaling networks in a site-specific manner.
25114211 2014 Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli.
25057011 2014 Nuclear factor of activated T-cells 5 increases intestinal goblet cell differentiation through an mTOR/Notch signaling pathway.
25044064 2014 The xanthine oxidase-NFAT5 pathway regulates macrophage activation and TLR-induced inflammatory arthritis.
24614757 2014 Arterial wall stress controls NFAT5 activity in vascular smooth muscle cells.
24355664 2014 MiR-568 inhibits the activation and function of CD4? T cells and Treg cells by targeting NFAT5.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24204828 2013 Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits.
23764852 2013 NFAT5 represses canonical Wnt signaling via inhibition of ?-catenin acetylation and participates in regulating intestinal cell differentiation.
23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
23219947 2013 Osmolarity determines the in vitro chondrogenic differentiation capacity of progenitor cells via nuclear factor of activated T-cells 5.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22992674 2012 Mutations that reduce its specific DNA binding inhibit high NaCl-induced nuclear localization of the osmoprotective transcription factor NFAT5.
22768306 2012 NFAT5 is activated by hypoxia: role in ischemia and reperfusion in the rat kidney.
22619484 2012 NFAT5 contributes to osmolality-induced MCP-1 expression in mesothelial cells.
22497815 2012 Nonstructural 5A protein of hepatitis C virus regulates heat shock protein 72 for its own propagation.
22496647 2012 Regulation of Mycobacterium tuberculosis-dependent HIV-1 transcription reveals a new role for NFAT5 in the toll-like receptor pathway.
22266867 2012 Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor.
22071693 2011 Nuclear import of a lipid-modified transcription factor: mobilization of NFAT5 isoform a by osmotic stress.
21982764 2011 The role of TonEBP in regulation of AAD expression and dopamine production in renal proximal tubule cells upon hypertonic challenge.
21757659 2011 Nuclear factor of activated T cells 5 regulates vascular smooth muscle cell phenotypic modulation.
21749466 2012 Non-invasive detection of spatio-temporal activation of SBE and NFAT5 promoters in transgenic reporter mice following stroke.
21717420 2011 NF-AT5 is a critical regulator of inflammatory arthritis.
21418859 2011 [Effect of osmotic response element binding protein on mucus secretion with hypertonicity in human airway epithelial cells].
21289293 2011 Src kinase pathway is involved in NFAT5-mediated S100A4 induction by hyperosmotic stress in colon cancer cells.
21209322 2011 High NaCl-induced activation of CDK5 increases phosphorylation of the osmoprotective transcription factor TonEBP/OREBP at threonine 135, which contributes to its rapid nuclear localization.
21102462 2010 Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.
21037089 2010 NFAT5 regulates T lymphocyte homeostasis and CD24-dependent T cell expansion under pathologic hypernatremia.
20685965 2010 Osmoprotective transcription factor NFAT5/TonEBP modulates nuclear factor-kappaB activity.
20677014 2010 An approach based on a genome-wide association study reveals candidate loci for narcolepsy.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20585028 2010 c-Abl mediates high NaCl-induced phosphorylation and activation of the transcription factor TonEBP/OREBP.
20351292 2010 Contribution of SHP-1 protein tyrosine phosphatase to osmotic regulation of the transcription factor TonEBP/OREBP.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20080774 2010 Phospholipase C-gamma1 is involved in signaling the activation by high NaCl of the osmoprotective transcription factor TonEBP/OREBP.
20041176 2009 Inducible nucleosome depletion at OREBP-binding-sites by hypertonic stress.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19886771 2009 Determination of the NFAT5/TonEBP transcription factor in the human and ovine placenta.
19750013 2009 Exclusion of NFAT5 from mitotic chromatin resets its nucleo-cytoplasmic distribution in interphase.
19138132 2009 Osmolarity and intracellular calcium regulate aquaporin2 expression through TonEBP in nucleus pulposus cells of the intervertebral disc.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18606815 2008 Nucleoporin 88 (Nup88) is regulated by hypertonic stress in kidney cells to retain the transcription factor tonicity enhancer-binding protein (TonEBP) in the nucleus.
18411282 2008 Phosphorylation by casein kinase 1 regulates tonicity-induced osmotic response element-binding protein/tonicity enhancer-binding protein nucleocytoplasmic trafficking.
18367666 2008 MKP-1 inhibits high NaCl-induced activation of p38 but does not inhibit the activation of TonEBP/OREBP: opposite roles of p38alpha and p38delta.
17440116 2007 Regulation of cytochrome P450 2E1 under hypertonic environment through TonEBP in human hepatocytes.
17173480 2006 NFAT5 regulates HIV-1 in primary monocytes via a highly conserved long terminal repeat site.
17148781 2007 Proteomic identification of proteins associated with the osmoregulatory transcription factor TonEBP/OREBP: functional effects of Hsp90 and PARP-1.
16782704 2006 Regulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5.
16644704 2006 Elevated activity of transcription factor nuclear factor of activated T-cells 5 (NFAT5) and diabetic nephropathy.
15840767 2005 Ataxia telangiectasia-mutated, a DNA damage-inducible kinase, contributes to high NaCl-induced nuclear localization of transcription factor TonEBP/OREBP.
15790681 2005 Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells.
15616553 2004 The sequence and analysis of duplication-rich human chromosome 16.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15173573 2004 ATM, a DNA damage-inducible kinase, contributes to activation by high NaCl of the transcription factor TonEBP/OREBP.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12538727 2003 Silencing of TonEBP/NFAT5 transcriptional activator by RNA interference.
12482947 2002 cAMP-independent role of PKA in tonicity-induced transactivation of tonicity-responsive enhancer/ osmotic response element-binding protein.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12421765 2002 Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs.
12379312 2002 The CD23b promoter is a target for NF-AT transcription factors in B-CLL cells.
12370307 2002 Targeted disruption of NFATc3, but not NFATc4, reveals an intrinsic defect in calcineurin-mediated cardiac hypertrophic growth.
12359721 2002 Fyn and p38 signaling are both required for maximal hypertonic activation of the osmotic response element-binding protein/tonicity-responsive enhancer-binding protein (OREBP/TonEBP).
12080349 2002 The role of NFAT transcription factors in integrin-mediated carcinoma invasion.
11936849 2002 The characterization and purification of a human transcription factor modulating the glutathione peroxidase gene in response to oxygen tension.
11934689 2002 Mouse TonEBP-NFAT5: expression in early development and alternative splicing.
11877454 2002 NFAT: ubiquitous regulator of cell differentiation and adaptation.
11780147 2002 Structure of a TonEBP-DNA complex reveals DNA encircled by a transcription factor.
11528118 2001 Genomic organization of the human NFAT5 gene: exon-intron structure of the 14-kb transcript and CpG-island analysis of the promoter region.
11485737 2001 Bridging the NFAT and NF-kappaB families: NFAT5 dimerization regulates cytokine gene transcription in response to osmotic stress.
11233530 1999 NF-AT5: the NF-AT family of transcription factors expands in a new direction.
11072102 2000 Quantitative PCR analysis of different splice forms of NFAT5 revealed specific gene expression in fetal and adult brain.
11060450 2000 Assignment of transcription factor NFAT5 to human chromosome 16q22.1, murine chromosome 8D and porcine chromosome 6p1.4 and comparison of the polyglutamine domains.
11046013 2000 The NFAT-related protein NFATL1 (TonEBP/NFAT5) is induced upon T cell activation in a calcineurin-dependent manner.
10733904 2000 Purification, identification, and characterization of an osmotic response element binding protein.
10565538 1999 Isolation and characterization of novel CAG repeat containing genes expressed in human brain.
10377394 1999 NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun.
10051678 1999 Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity.
10048485 1998 Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.
8889549 1996 Generation and analysis of 280,000 human expressed sequence tags.
8401585 1993 Rapid cDNA sequencing (expressed sequence tags) from a directionally cloned human infant brain cDNA library.