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FLASH GENE
Symbol NFAT5 contributors: mct/npt/pgu - updated : 20-03-2015
HGNC name nuclear factor of activated T-cells 5, tonicity-responsive
HGNC id 7774
RNA
TRANSCRIPTS type messenger
text five alternative splicing transcripts
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
15 - 14185 - 1455 - 2000 11060450
also called variant 4/isoform a
14 - 14123 165.8 1531 - 2000 11060450
also called variant 3/isoform c
15 - 14177 - 1484 - 2000 11060450
also called variant 2/isoform b
16 - 14239 - 1455 - 2011 22071693
  • also called variant 1/isoform a
  • contribute about half of all endogenous expression of human NFAT5 isoforms in the isotonic state
  • is indeed myristoylated and palmitoylated on its transport to the plasmalemma via the endoplasmic reticulum and the Golgi
  • 15 - 14174 - 1548 - 2000 11060450
    also called variant 6/isoform d
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon  
    Lymphoid/Immunethymus     Homo sapiens
    Nervousbrain   highly
    Reproductivefemale systemplacenta  highly
     male systemprostate   
    Urinarykidneyrenal medulla  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • IP-TIG domain
  • a DNA-binding domain related to both the NFAT and NFKB families
  • the motif-Y143 is in a region (AAs 132
  • 156) previously characterized as an auxiliary export domain (AED), necessary for export from the nucleus under normotonic and hypotonic conditions
    mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • NFAT/Rel family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text present in both the cytoplasm and the nucleus under normotonic conditions
    basic FUNCTION
  • playing a central role as a tonicity-responsive transcription factor required for kidney homeostasis and function
  • only known mammalian transcription factor that regulates hypertonic stress-induced gene transcription
  • initiating loss of nucleosome(s) by an NFAT5-independent mechanism, but significantly potentiated in the presence of NFAT5
  • importance of Ser-155 and Ser-158 in the nucleocytoplasmic trafficking of NFAT5 and CSNK1A1 can plays a major role in regulating this process
  • protects cells from osmotic stress
  • role of NFAT5 and CD24 in the homeostasis of T cells under osmostress
  • novel regulator of smooth muscle cell phenotypic modulation
  • DDX5 and DDX17 have a dual role in the control of the pro-migratory NFAT5 transcription factor
  • is a novel regulator of mammalian anti-pathogen responses
  • role of NFAT5 in cardiac differentiation of stem cells (PMID;
  • regulator of Wnt signaling, and NFAT5 regulation of intestinal cell differentiation may be through inhibition of Wnt/CTNNB signaling
  • has specific functions during T-cell development independent of its role as an osmoprotective transcription factor
  • the specific participation of NFAT5 downstream from the pre-TCR also lends support to the notion that this receptor controls distinct outcomes that are, for the most part, functionally independent
  • transcription factor that protects the kidney from hypertonic stress and also is activated by hypoxia
  • NFAT5 is part of a protective mechanism that limits renal damage induced by ischemia-reperfusion injury (IRI)
  • arterial wall stress controls NFAT5 activity in vascular smooth muscle cells
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • PLCG1 is part of the protein complex that associates with NFAT5 at its DNA binding site
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with PLCG1 (when NaCl is elevated, NFAT5 becomes phosphorylated at Y143, resulting in binding of PLCG1 to that site, which contributes to NFAT5 transcriptional activity, transactivating activity, and nuclear localization)
  • interacting with NUP88 (up-regulated in response to hypertonic stress and acts to retain NFAT5 in the nucleus, activating transcription of critical osmoprotective genes)
  • is necessary for the regulation of AQP1 expression in the inner medulla of the kidney under hypertonic conditions
  • CD24 is a novel NFAT5 target induced by hypertonicity, and required to sustain T cell expansion under osmostress (NFAT5 bound to the CD24 promoter in response to hypertonicity facilitated the local derepression of chromatin and enhanced the expression of CD24 mRNA and protein)
  • WWTR1 modulates cellular responses to hyperosmotic stress through fine-tuning of NFAT5 activity via tyrosine phosphorylation
  • is necessary for the transcriptional regulation of AQP4 expression and for local astrocyte swelling with accompanying restriction of the neuropil extracellular space
  • interaction between CIDEC and NFAT5, and CIDEC not only modulates lipid droplet (LD) homeostasis but also modulates the response to osmotic stress via a physical interaction with NFAT5 at the LD surface
  • is a target of the IKBKB/NFKB pathway in thymocytes and as a downstream effector of the prosurvival role of the pre-T-cell receptor
  • HIF1A positively regulates the induction of NFAT5 and HSPA4 by placental hypoxia
  • cell & other
    REGULATION
    Other extensively regulated by phosphatases, including PTPN6, whose inhibition by high NaCl increases phosphorylation of NFAT5 at Y143, contributing to the nuclear localization and activation of NFAT5
    regulated by the IKBKB pathway in thymocytes and acts as a survival factor downstream from the pre-TCR, independent of its osmoprotective function
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    significantly higher in the preeclamptic compared to normal placentas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyimmunodeficiency 
    long terminal repeat site NFAT5 interaction may thus present a novel therapeutic target to suppress HIV-1 replication and progression of AIDS
    ANIMAL & CELL MODELS
  • TonEBP mutant mice display marked decrement in the expression of AQP1 in the inner medulla
  • Nfat5-deficient mice present severe atrophy of the renal medulla, systemic hypernatremia, and a reduced thymocyte compartment and mature T-cell lymphopenia