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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
Location 16q22.1      Physical location : 68.119.374 - 68.260.837
Synonym name
  • nuclear factor of activated T-cells, cytoplasmic 3
  • T cell transcription factor NFAT4
  • cytoplasmic nuclear factor of activated T-cells 3
  • Synonym symbol(s) NFAT4, NFATX, NFC3
    DNA
    TYPE functioning gene
    STRUCTURE 141.46 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D16S3031 - CBFB - CDH5 - HSD11B2 - CDH11 - LCAT LCAT - NFATC3 - E2F4 - AARS - CDH3 - D16S3095 - NQO1 - HP HP - qter
    Authors Gene Map (98)
    Physical map
    TSNAXIP1 16q22.2 translin-associated factor X interacting protein 1 FLJ13111 16q22.1 hypothetical protein FLJ13111 THAP11 16q22.1 THAP domain containing 11 NUTF2 16q22.2 nuclear transport factor 2 RCD-8 16q22.1 autoantigen UNQ2446 16q22.1 MRCC2446 PSKH1 16q22.1 protein serine kinase H1 CTRL 16q22.1 chymotrypsin-like PSMB10 16q22.1 proteasome (prosome, macropain) subunit, beta type, 10 LCAT 16q22.1 lecithin-cholesterol acyltransferase SLC12A4 16q22.1 solute carrier family 12 (potassium/chloride transporters), member 4 DPEP3 16q22.1 dipeptidase 3 DPEP2 16q22.1 dipeptidase 2 LOC339065 16q22.1 similar to putative membrane-bound dipeptidase-2 DDX28 16q22.2 DEAD (Asp-Glu-Ala-Asp) box polypeptide 28 FLJ20399 16q22.1 hypothetical protein FLJ20399 NFATC3 16q22.1 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 splicing 3901 115.5 1075 - 2008 18675896
    also called variant IB-deltaXa or variant 1
    11 splicing 4005 115.1 1068 skeletal muscle, thymus, kidney, small intestine, heart, ovary, prostate, placenta, pancreas 2008 18675896
  • also called variant IB-Xa or variant 2
  • containing an additional segment in the coding region, which causes a frameshift, compared to variant 1
  • 11 splicing 3990 114.9 1065 thymus, kidney, testis, spleen 2008 18675896
  • also called variant 3
  • containing an additional segment in the coding region, which causes a frameshift, compared to variant 1
  • 9 splicing 3769 112.5 1045 thymus, skeletal muscle 2008 18675896
  • also called variant IB-IX or variant 4
  • having a distinct 3' UTR and 3' coding region compared to variant 1
  • 11 splicing - - 589 - 2008 18675896
    also called IAL-Xa
    10 splicing - - 596 - 2008 18675896
    also called IAL-deltaXa
    9 splicing - - 566 - 2008 18675896
    also called IAL-IX
    11 splicing - - 589 - 2008 18675896
    also called IAS-Xa
    10 splicing - - 596 - 2008 18675896
    also called IAS-deltaXa
    9 splicing - - 566 - 2008 18675896
    also called IAS-IX
    11 splicing - - 589 - 2008 18675896
    also called variant IC-Xa
    10 splicing - - 596 - 2008 18675896
    also called IC-deltaXa
    9 splicing - - 566 - 2008 18675896
    also called variant IC-IX
    11 splicing - - 589 - 2008 18675896
    also called variant ID-Xa
    10 splicing - - 596 - 2008 18675896
    also called variant ID-deltaXa
    9 splicing - - 566 - 2008 18675896
    also called variant ID-IX
    11 splicing - - 589 - 2008 18675896
    also called variant IE-Xa
    10 splicing - - 596 - 2008 18675896
    also called variant IE-deltaXa
    9 splicing - - 566 - 2008 18675896
    also called variant IE-IX
    11 splicing - - 589 - 2008 18675896
    also called variant IF-Xa
    10 splicing - - 596 - 2008 18675896
    also called variant IF-deltaXa
    9 splicing - - 566 - 2008 18675896
    also called variant IF-IX
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvesselartery    Homo sapiens
    Lymphoid/Immunelymph node   highly
     thymus   highly
     tonsils   highly
    Reproductivemale system    
    Respiratoryrespiratory tractlarynx  highly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmoothvessel highly Homo sapiens
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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
  • 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