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Symbol NFATC4 contributors: mct/npt - updated : 15-05-2017
HGNC name nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4
HGNC id 7778
  • a RHD (Rel-like) domain
  • a Ca2+ sensor/translocation domain
  • conjugated PhosphoP
    interspecies homolog to rattus Nfatc4 (92.9 pc)
    homolog to murine Nfatc4 (92.7 pc)
  • activated T-cell (NFAT) family of transcription factors
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
  • cytoplasmic phosphorylated form
  • nuclear after activation controlled by calcineurin-mediated dephosphorylation
  • nuclear in skeletal muscle, but a predominantly cytosolic localization in other tissues
  • remains phosphorylated and localized to the cytosol, only exhibiting nuclear localization following prolonged (1-3 h) depolarization
  • basic FUNCTION
  • regulate cytokine gene expression in T cells (to suppress local aberrant growth of vessels)
  • required for cardiac development and mitochondrial function
  • involved in adipocyte differentiation
  • playing a role in learning and memory
  • mediating myotube differentiation after activation by RPS6KA3
  • implicated as a critical regulator of the cardiac development and hypertrophy
  • having an unexpected role as a direct transcriptional repressor of GAP43 expression and may be a more general role in the control of the neuronal outgrowth program
  • negative and not a positive regulator of GAP43 during neuronal outgrowth and maturation
  • occupies the GAP43 promoter and neurotrophin stimulation reduces promoter occupancy
  • may be having the potential to regulate the expression of other genes involved in neuronal outgrowth and maturation
  • may plays a role in axonal regeneration after axotomy by controlling the gene expression of neuronal outgrowth genes
  • transcriptionally active in fast muscles, i.e., in response to less frequent calcium transients and, presumably, lower Calcineurin activity
  • inhibits breast cancer cell motility by targeting the LCN2 gene
  • opposing transcriptional activities of FOXP1 and NFATC4 maintaining cardiomyocyte homeostasis
  • NFATC4 calcineurin-dependent activity is required selectively for survival of adult-born neurons in response to BDNF signaling (pMID: 22586092)
  • is essential in the regulation of adult hippocampal neurogenesis and is a central player of BDNF–driven prosurvival signaling in hippocampal adult-born neurons
  • may play a role in promoting the brain secondary damage following intracerebral hemorrhage (ICH)
  • NFATC4 might exert its pro-apoptotic function in neuronal apoptosis through extrinsic pathway
  • is a key activity-dependent transcriptional regulator of GABA signaling in hippocampal progenitor cells
  • CELLULAR PROCESS nucleotide, transcription
    signaling signal transduction
  • signaling axis between BDNF and NFATC4 in adult hippocampal neural progenitor cells
  • integration of MAPK7 with NFATC4 nucleo-cytoplasmic shuttling and PKA activation in adipocyte signaling
  • calcineurin-NFATC4 signaling axis acts as a major regulator of Neural stem cells (NSCs)self-renewal and proliferation by promoting the expression of transcription factors (TFs), including ID2, that contribute to the maintenance of the NSC state
  • a component
    DNA binding as a monomer
    small molecule
  • interacting with ESR1 and ESR2
  • functional interaction between lipin 1 (LPIN1) and the nuclear factor of activated T cells c4 (NFATC4) (represses NFATC4 transcriptional activity through protein-protein interaction, and LPIN1 is present at the promoters of NFATC4 transcriptional targets)
  • GPC6 is a novel NFATC1, NFATC2, NFATC3, NFATC4 target gene in breast cancer cells that promotes invasive migration through WNT5A signalling
  • critical role of CITED2 in cardiomyocyte differentiation by affecting the expression of NFATC4 leading to down-regulation of NKX2.5 and beta-MHC cardiomyocyte genes
  • following cyclic stretch, NFATC4 was activated in cardiac fibroblasts in a SDC4- and calcineurin-dependent manner
  • TRIM17 also inhibited NFATC4 nuclear translocation and activity
  • direct binding of NFATC4 to specific DNA sequences within BACE1 promoter region
  • cell & other
    activated by neurotrophins and netrins for nuclear localization and stimulation of NFAT-gene transcription and outgrowth of embryonic axons
    repressed by ESR1 and ESR2 (ESR may play a critical role in regulation of NFAT3 transcriptional activity)
    Other phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217)
    phosphorylated by RPS6KA3
    regulated by the ubiquitin
    proteasome system that plays an important role in regulating NFATC4 stability and transactivation
    regulated by the calcium/calmodulin-dependent phosphatase calcineurin
    corresponding disease(s)
    Variant & Polymorphism other G160A increases the risk of cardiac hypertrophy
    Candidate gene
    Therapy target