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FLASH GENE
Symbol NFATC1 contributors: mct/pgu - updated : 04-08-2015
HGNC name nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
HGNC id 7775
Location 18q23      Physical location : 77.155.771 - 77.289.322
Synonym name
  • NFAT transcription complex cytosolic component
  • nuclear factor of activated T-cells, cytosolic component 1
  • Synonym symbol(s) NFATC, NFAT2, NF-ATC, EVI138, MGC138448
    DNA
    TYPE functioning gene
    STRUCTURE 133.55 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map cen - D18S1141 - NFATC1 - D18S1095 - D18S70 - qter
    Physical map
    LOC284275 18q23 hypothetical LOC284275 KIAA0222 18q23 hypothetical LOC284275 ZNF236 18q22-q23 zinc finger protein 236 MBP 18q23 myelin basic protein LOC388483 18 LOC388483 GALR1 18q23 galanin receptor 1 LOC390864 18 similar to amino acid feature: Rod protein domain, aa 266 .. 468; amino acid feature: globular protein domain, aa 32 .. 265 LOC125595 18q23 hypothetical LOC125595 LOC390865 18 similar to hypothetical protein LOC390866 18 LOC390866 LOC390867 18 similar to Splicing factor 3A subunit 2 (Spliceosome associated protein 62) (SAP 62) (SF3a66) LOC390868 18 similar to hypothetical protein LOC388484 18 LOC388484 SALL3 18q23 sal-like 3 (Drosophila) ATP9B 18q23 ATPase, Class II, type 9B NFATC1 18q23 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 LOC388485 18 LOC388485 LOC390869 18 similar to immediate early protein homolog LOC147294 18q23 similar to immediate early protein homolog FLJ25715 18q23 hypothetical protein FLJ25715 CTDP1 18q23 CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) phosphatase, subunit 1 LOC390870 18 LOC390870 KCNG2 18q22-q23 potassium voltage-gated channel, subfamily G, member 2 FLJ22378 DIM1 FLJ21172 18q23 hypothetical protein FLJ21172 KIAA0863 18q23 KIAA0863 protein PARD6G 18q23 par-6 partitioning defective 6 homolog gamma (C. elegans)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 splicing 3140 77.7 716 - 2008 18675896
  • isoform A
  • 10 splicing 4762 88.6 825 - 2008 18675896
  • using an alternate splice site in the 3' coding region compared to variant 1, which results in a frameshift
  • isoform B
  • 10 splicing 4621 100.2 930 - 2008 18675896
  • differing in the 5' and 3' UTR, and the coding region compared to variant 1
  • isoform C
  • 9 splicing 3671 38.5 353 - 2008 18675896
  • differing in the 3'UTR, using a downstream start codon and an alternate splice site in the 3' coding region
  • having multiple coding region differences compared to variant 1
  • isoform D
  • 10 splicing 4336 87.7 812 - 2008 18675896
  • differing in the 5' and 3' UTR and in the coding region
  • isoform E
  • 11 - - - 943 - 2008 18675896
    9 - - - 713 - 2008 18675896
    9 - - - 700 - 2008 18675896
    8 - - - 703 - 2008 18675896
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrineparathyroid   highly
    Lymphoid/Immunelymph node   highly
     spleen   highly
     thymus   highly
    Nervousbrain    
    Reproductivemale systemprostate   
    Skin/Tegumentskin appendageshair   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Epithelialbarrier liningendocardium  
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Lymphoid/ImmuneT cell Homo sapiens
    Skin/Tegumenthair follicle cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • calcineurin binding motif (targeting motif, PxIxIT) near at the N-terminus of the regulatory domain
  • a nuclear localization signal (NLS)
  • a serine-rich region
  • 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 murine Nfatc1 (86.9 pc)
    intraspecies homolog to NFKB/REL proteins
    Homologene
    FAMILY
  • REL/DORSAL family
  • CATEGORY immunity/defense , regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    text
  • translocated to nucleus after activation controlled by calcineurin-mediated dephosphorylation
  • cytoplasmic phosphorylated form
  • cytosolic in cerebellar granules in the presence of growth factors and KCl
  • basic FUNCTION
  • acting as a putative regulator of gene expression in T cells and immature thymocytes and positive regulator of IL-2 and IL-4 gene transcription
  • playing a critical role in the initiation of epithelial- mesenchymal transformation
  • may be having a major role in fiber type specification in skeletal muscle
  • playing a crucial role for the differentiation of bone-resorbing osteoclasts
  • regulating the beta3 integrin promoter
  • different isoforms of this protein may regulate inducible expression of different cytokine genes
  • controlling gene expression in embryonic cardiac cells
  • may regulate differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells
  • transcription factor required for development of cardiac valves
  • activating the expression of endogenous RCAN1 in the endocardium
  • being required for TGF beta-mediated transcriptional regulation of fibronectin
  • regulating bulge stem cell quiescence, and repressing the expression of CDK4 in hair follicle stem cells
  • required for endocardial expression of TNFSF11 and CTSK during valve formation
  • playing a necessary role for remodeling endocardial cushions into mature heart valve leaflets and being also an essential effector of receptor activator of NFkappaB ligand (RANKL) signaling required for transcriptional activation of bone matrix remodeling enzymes during osteoclast differentiation
  • regulating CTSK promoter activity, after its activation by TNFSF11 via the Ca2+/calmodulin/calcineurin pathway
  • specific determinant of slow muscle gene expression
  • function cooperatively with MITF and MEF2A to transactivate the ATP6V0D2 promoter during RANKL-induced osteoclastogenesis
  • functions as the key regulator of osteoclast differentiation by inducing fusogenic genes such as TM7SF4
  • 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
  • key transcription factor, playing a role in regulating expression of osteoclast-specific downstream target genes such as ACP5 and OSCAR
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling
  • intracellular signaling cascade
  • EDF1/CALM1/PPP3CA/NFATC1 pathway
  • a component
  • component of nuclear factor activated T cells
  • forming cooperative complexes with FOS and JUN on DNA, in expression of cytokine genes collectively coordinating immune response
  • INTERACTION
    DNA
  • binding to promoters of cytokine genes
  • binding as a monomer
  • RNA
    small molecule
    protein
  • interacting with SOX9 in the differentiation of endocardial cushion cells
  • interacting with SP7 to control osteoblastic bone formation
  • direct transcriptional target of RCAN1 within the endocardium during a critical window of heart valve formation
  • interacting with ATP6V0D2 (NFATC1/ATP6V0D2 and dendritic cell-specific transmembrane protein signaling axis plays a key role in the osteoclast multinucleation process, which is essential for efficient bone resorption)
  • OSCAR is an important costimulatory receptor for osteoclast differentiation through activation of NFATC1
  • demethylation of H3K27me3 in the NFATC1 gene locus by KDM6B plays a critical role in TNFSF11-induced osteoclast differentiation
  • GPC6 is a novel NFATC1, NFATC2, NFATC3, NFATC4 target gene in breast cancer cells that promotes invasive migration through WNT5A signalling
  • both FOXP3 and SIVA1 function as negative regulators of IL2 gene expression in Treg cells, via suppression of NFATC1 by FOXP3 and of NFKB1 by both FOXP3 and SIVA1
  • IL2 upregulates CD86 expression on human CD4(+) and CD8(+) T cells via a receptor-dependent mechanism that involves the NFATC1 and mammalian target of rapamycin pathways
  • AKT2 a negative regulator of NFATC1 activation through its ability to inhibit calcium mobilization from the ER
  • KDM8 is a post-translational co-repressor for NFATC1 that attenuates osteoclastogenesis
  • synthesis of FN1 is mediated by a transcriptional complex consisting of NFATC1, SP7 and FOS
  • upon TNFSF11 activation, HDAC7 suppresses NFATC1 and prevents CTNNB1 down-regulation, thereby blocking osteoclast differentiation
  • SERPINA12 likely downregulates osteoclastogenesis in part by inhibiting expression of the transcription factor NFATC1
  • mediates RHOA-induced FN1 upregulation in glomerular podocytes
  • FAM102A plays a critical role in TNFRSF11A-induced osteoclast differentiation, and its role may be closely related to the induction of NFATC1
  • autocrine/paracrine role for RARRES2 in regulating osteoclast differentiation of hematopoietic stem cell (HSC) through modulating intracellular calcium and NFATC1 expression/activation
  • NFATC1 sequestering the SMAD3 prevents the proteasome mediated degradation of SKIL and SKIL has a role on the regulation of MMP2, MMP9 activity
  • ASIC1-mediated calcium entry plays a critical role in osteoclastogenesis by regulating activation of the NFATC1
  • ETS1 promotes the expression of IL2 by modulating the activity of NFATC1
  • NFATC1-mediated transcription regulates UTRN expression and FHL1 which promotes muscle hypertrophy, is a transcriptional activator of NFATC1
  • GRK5-mediated pathological cardiac hypertrophy involves the activation of NFATC1 because GRK5 causes enhancement of NFATC1-mediated hypertrophic gene transcription
  • cell & other
    REGULATION
    activated by calcineurin
    both Ca2+ oscillation/calcineurin-dependent and independent signal pathways and the Ca2+ oscillation-independent pathway depends completely on osteoblasts and is not activated during RANKL/M-CSF-induced osteoclastogenesis
    inhibited by cyclosporin A,FK506
    Other calcineurin dependent
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene potential VSD-susceptibility gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularmyopathy 
    FHL1-NFATC1-UTRN signaling axis that can functionally compensate for dystrophin and treat DMD
    ANIMAL & CELL MODELS