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FLASH GENE
Symbol NFATC3 contributors: mct/npt - updated : 05-09-2016
HGNC name nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3
HGNC id 7777
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a calcineurin binding motif (targeting motif, PxIxIT) near at the N terminus of the regulatory domain
  • a nuclear localization signal (NLS)
  • a serine-rich region and three SP motifs
  • a second calcineurin binding domain
  • a central Rel-like, DNA binding domain
  • a C terminal transactivation domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to rattus Nfatc3 (89.7 pc)
    homolog to murine Nfatc3 (89.6 pc)
    Homologene
    FAMILY
  • activated T-cell (NFAT) family of transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • cytoplasmic phosphorylated form
  • nuclear after activation controlled by calcineurin-mediated dephosphorylation
  • undergoes rapid dephosphorylation and nuclear translocation that are essentially complete within 20 min depolarization
  • basic FUNCTION
  • acting as a putative regulator of gene expression in T cells and immature thymocytes and of cytokines to suppress local aberrant growth of vessels
  • inducing chondrogenesis and chondrocyte gene expression
  • required for cardiac development and mitochondrial function
  • calcineurin/NFATC3 signaling pathway regulates the expression of the 1 subunit of Ca2+-activated K+ (BK) channel in arterial smooth muscle and plays a critical role in the development of angiotensin II-induced hypertension
  • translocates to the nucleus in response both to a slow and to a fast-like pattern of activity (Calabria 2009)
  • transcriptionally active in fast muscles, i.e., in response to less frequent calcium transients and, presumably, lower Calcineurin activity (Calabria 2009)
  • transcription factor tightly regulated by the calcium/calmodulin-dependent phosphatase, calcineurin, activated in astrocytes applied with calcium ionophore or APP (
  • positive feedback control between STIM1/SOCE and NFATC3 is required for efficient induction and progression of myoblast differentiation
  • NFATC2, NFATC3 possess distinct nuclear localization dynamics in response to cell stimulation
  • important and novel regulatory mechanisms of NFATC3 activation in in pulmonary arterial smooth muscle cells (PASMC) by ROS
  • transcription factor NFATC3 binds to IRF7 and functions synergistically to enhance IRF7-mediated IFN expression in Plasmacytoid dendritic cells (pDCs)
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA binding to promoters of cytokine genes
    RNA
    small molecule
    protein
  • calcineurin substrate (calcineurin/NFATC3 activates BMP expression)
  • RhoA/Rho kinase (ROK) increases actin polymerization, thus providing structural support for NFATC3 nuclear transport
  • GPC6 is a novel NFATC1, NFATC2, NFATC3, NFATC4 target gene in breast cancer cells that promotes invasive migration through WNT5A signalling
  • NFATC3 promotes BACE1 expression via direct interaction with the BACE1 promoter
  • STIM1 regulates NFATC3 expression and its activity, and myotube formation
  • regulates the expression levels of STIM1 and ORAI1, and the activity of SOCE in C2C12 myoblasts
  • astrocyte MMP3 expression was induced by overexpression of a constitutively active form of NFATC3
  • TRIM17 binds preferentially SUMOylated forms of NFATC3
  • NFATC3 binds to the promoter of the TRIM17 gene together with JUN
  • NR4A1 functionally interacts with NFATC3 and GATA4 and inhibits their transcriptional activities, which are critical for the development of cardiac hypertrophy
  • NFATC3 specifically binds to IRF7 and enhances IRF7-mediated IFN production
  • cell & other
    REGULATION
    activated by calcineurin
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    transiently up-regulated in the early phase of myoblast differentiation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a marker of activation for a specific population of astrocytes in response to brain damage, which may have consequences for neuronal survival
  • Therapy target
    ANIMAL & CELL MODELS