Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol NFATC4 contributors: mct/npt - updated : 15-05-2017
HGNC name nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4
HGNC id 7778
Location 14q12      Physical location : 24.836.144 - 24.848.808
Synonym name
  • T cell transcription factor NFAT3
  • cytoplasmic nuclear factor of activated T-cells 4
  • Synonym symbol(s) NFAT3, NF-ATc4, NF-AT3
    DNA
    TYPE functioning gene
    STRUCTURE 12.69 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    PSME2 14q11.2 proteasome (prosome, macropain) activator subunit 2 (PA28 beta) RNF31 14q11.2 ring finger protein 31 ISGF3G 14q11.2 interferon-stimulated transcription factor 3, gamma 48kDa REC8L1 14q11.2-q12 REC8-like 1 (yeast) IPO4 14q11.2 importin 4 TM9SF1 14q11.2 transmembrane 9 superfamily member 1 C14orf20 14q11.2 chromosome 14 open reading frame 20 C14orf123 14q11.2 chromosome 14 open reading frame 123 MGC5987 14q11.2 hypothetical protein MGC5987 NEDD8 14q11.2 neural precursor cell expressed, developmentally down-regulated 8 GMPR2 14q11.2 guanosine monophosphate reductase 2 TINF2 14q11.2 TERF1 (TRF1)-interacting nuclear factor 2 TGM1 14q11.2 transglutaminase 1 (K polypeptide epidermal type I, protein-glutamine-gamma-glutamyltransferase) RABGGTA 14q11.2 Rab geranylgeranyltransferase, alpha subunit DHRS1 14q11.2 dehydrogenase/reductase (SDR family) member 1 C14orf21 14q11.2 chromosome 14 open reading frame 21 CIDEB 14q11.2 cell death-inducing DFFA-like effector b LTB4R2 14q11.2-q12 leukotriene B4 receptor 2 LTB4R 14q11.2-q12 leukotriene B4 receptor ADCY4 14q11.2 adenylate cyclase 4 RIPK3 14q11.2 receptor-interacting serine-threonine kinase 3 NFATC4 14q11.2 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 KIAA1305 14q11.2 KIAA1305 HCDI CMA1 14q11.2 chymase 1, mast cell
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 5672 101.4 964 - 2008 18675896
  • variant IA-IXL
  • 10 splicing 4976 95.3 902 - 2008 18675896
  • variant ID-IXL
  • using an in-frame downstream AUG, translation termination at a downstream stop codon
  • 10 splicing - - 857 - 2008 18675896
    9 splicing - - 964 - 2008 18675896
    10 splicing - - 915 - 2008 18675896
    10 splicing - - 807 - 2008 18675896
    9 splicing - - 914 - 2008 18675896
    10 splicing - - 934 - 2008 18675896
    10 splicing - - 826 - 2008 18675896
    9 splicing - - 933 - 2008 18675896
    9 splicing - - 901 - 2008 18675896
    10 splicing - - 890 - 2008 18675896
    10 splicing - - 782 - 2008 18675896
    9 splicing - - 724 - 2008 18675896
    8 splicing - - 831 - 2008 18675896
    7 splicing - - 437 - 2008 18675896
    7 splicing - - 329 - 2008 18675896
    6 splicing - - 436 - 2008 18675896
    5 splicing - - 190 - 2008 18675896
    5 splicing - - 82 - 2008 18675896
    4 splicing - - 189 - 2008 18675896
    11 - 4988 - 965 - 2008 18675896
    11 - 4664 - 857 - 2008 18675896
    10 - 4652 - 794 - 2008 18675896
  • variant ID-IXS
  • 10 - 4630 - 832 - 2008 18675896
  • variant IEi-IXL
  • 9 - 5538 - 889 - 2008 18675896
  • variant IE-IXi
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemovary   
     female systemuterus   
     male systemtestis   
    Urinarykidney    
    Visualeyeanterior segmentiris  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines specifically expressed in ERA positive breast cancer cells
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text neural tube, somites, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a RHD (Rel-like) domain
  • a Ca2+ sensor/translocation domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to rattus Nfatc4 (92.9 pc)
    homolog to murine Nfatc4 (92.7 pc)
    Homologene
    FAMILY
  • activated T-cell (NFAT) family of transcription factors
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text
  • 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
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    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
    INTERACTION
    DNA binding as a monomer
    RNA
    small molecule
    protein
  • 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
  • direct binding of NFATC4 to specific DNA sequences within BACE1 promoter region
  • cell & other
    REGULATION
    activated by neurotrophins and netrins for nuclear localization and stimulation of NFAT-gene transcription and outgrowth of embryonic axons
    calcineurin
    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
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism other G160A increases the risk of cardiac hypertrophy
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS