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FLASH GENE
Symbol NFATC2 contributors: mct/npt/pgu - updated : 25-04-2012
HGNC name nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
HGNC id 7776
Location 20q13.2      Physical location : 50.007.765 - 50.179.168
Synonym name
  • preexisting component of NFAT transcription complex, calcineurin dependent
  • T cell transcription factor NFAT1
  • NFAT pre-existing subunit
  • calcineurin-dependent 2
    • Synonym symbol(s) NFATP, NFAT1, KIAA0611, RP5-1009H6.1, NF-ATP
    DNA
    TYPE functioning gene
    STRUCTURE 151.49 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure putative binding sites for the Runx family of transcription factors
    MAPPING cloned Y linked N status confirmed
    Map cen - D20S869 - D20S196 - NFATC2 - D20S857 - NFATC2 - D20S185 - D20S845 - qter
    Authors UCSC 2009
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 splicing 3254 99.7 921 - 2008 18675896
    also called variant IB-IIL-Xa or variant B
    10 splicing 3166 100 925 - 2008 18675896
  • also called variant C or variant IB-IIL-deltaXa
  • lacking an exon in the coding region, which results in a frameshift, compared to variant 1
    • 11 splicing 2974 97.6 901 - 2008 18675896
    also called variant D or variant IA-IIL-Xa
    11 splicing - - 702 - 2008 18675896
    11 splicing - - 702 - 2008 18675896
    10 splicing - - 905 - 2008 18675896
    10 splicing - - 706 - 2008 18675896
    10 splicing - - 706 - 2008 18675896
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   predominantly
    Digestivestomach   highly
    Lymphoid/Immunelymph node   highly
     spleen   highly Homo sapiens
     thymus    
    Reproductivemale systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte Homo sapiens
    Lymphoid/ImmuneT cell Homo sapiens
    not specificadipocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a calcineurin binding motif (targeting motif, PxIxIT) near the N terminus of the regulatory domain, which also contains a nuclear localization signal (NLS)
  • a serine-rich region
  • three SP motifs and a second calcineurin binding motif
  • a central Rel-like, DNA binding domain
  • a C terminal transactivation domain, with a region of the DNA binding domain necessary and sufficient for interaction with JUN in the absence of DNA, and this same region of NFATC2 was required for the synergistic activation of IL2 transcription in T cells
    • conjugated PhosphoP
    mono polymer complex
    HOMOLOGY
    interspecies homolog to rattus Nfatc2 (90.7 pc)
    homolog to murine Nfatc2 (90.1 pc)
    intraspecies homolog to NFKB/REL proteins
    Homologene
    FAMILY
  • nuclear factor of activated T cells (NFAT) family
    • CATEGORY immunity/defense , transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text
  • translocated to nucleus after activation controlled by calcineurin-mediated dephosphorylation
  • cytoplasmic phosphorylated form
    • basic FUNCTION
  • acting as a putative regulator of cytokine genes expression in T cells and immature thymocytes and positive regulator of IL-4 gene transcription
  • participating in the transcriptional control of genes involved in adipocyte metabolism and lipolysis, in mature adipocytes
  • having a critical role in the adipocyte differentiation process and in the regulation of genes in newly differentiated adipocytes prompted us to look for the regulatory involvement of NFAT proteins
  • playing an important role downstream of calcineurin and calcineurin mediates myocyte hypertrophy through activation of NFAT transcription factors
  • having a major role in pathological cardiac remodeling and being a necessary mediator of calcineurin-dependent cardiac hypertrophy and heart failure
  • functioning as a repressor of cartilage cell growth and differentiation
  • activating MEF2D in synergy with the coactivator p300 (CITED1, CITED2) for the transcription of NR4A1
  • transcriptionally active in fast muscles, i.e., in response to less frequent calcium transients and, presumably, lower Calcineurin activity
  • NFATC1 and NFATC2 are expressed in T cells at various stages of development and states of activation and have been implicated in several essential regulatory mechanisms that exhibit a cell type specificity
  • can modulate cellular transformation intrinsically
  • is potentially an essential transcriptional regulator of chondrocyte homeostasis in adult articular cartilage
  • likely plays an important role in NELL1-mediated osteochondral differentiation
  • may play a role in the maintenance of steady-state hematopoiesis and bone remodeling in adult organisms
  • positively regulates transcription of a large number of inducible cytokine genes including IL2, IL4, IL5 and other cytokines, and disruption of NFATC2 results in an unexpected increase of IL4
  • NFATC2, NFATC3 possess distinct nuclear localization dynamics in response to cell stimulation
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling
    a component
  • pre-existing component of nuclear factor activated T cells
  • forming cooperative complexes with the inducible component NFATC1, NFATCX, FOS and JUN on DNA, involved in expression of genes collectively coordinating immune response
    • INTERACTION
    DNA binding to promoters of cytokine genes
  • binding as monomers
    • RNA
    small molecule
    protein
  • interacting with NFATC2IP
  • interacting with XPO1 by phosphorylated form
  • mediates PlGF-induced myelomonocytic cell recruitment via the induction of TNF
  • IRF2BP2 is a negative regulator of the NFATC2 transcription factor, suggesting that NFATC2 repression occurs at the transcriptional level
  • primary response gene of NELL1
  • GPC6 is a novel NFATC1, NFATC2, NFATC3, NFATC4 target gene in breast cancer cells that promotes invasive migration through WNT5A signalling
  • NFATC2 and JUNB cooperatively regulate IL31 gene expression in CD4+ T cells in health and disease
    • cell & other
    REGULATION
    activated by calcineurin
    RUNX2 (potential downstream target of RUNX2)
    induced by activated T cell receptors
    inhibited by cyclosporin A,FK506
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    not only protects the heart from pathological hypertrophy but also efficiently counteracts myocardial functional deterioration following biomechanical stress
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquiredheart failure
    targeting either NFATc2 activation or its immediate downstream target genes provide a suitable approach for future drug design to treat forms of pathological cardiac hypertrophy and heart failure
    cancerdigestivepancreas
    inactivation of oncogenic NFATc2 might be an attractive strategy in treatment of pancreatic cancer
    ANIMAL & CELL MODELS