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FLASH GENE
Symbol NFIL3 contributors: mct - updated : 02-02-2016
HGNC name nuclear factor, interleukin 3 regulated
HGNC id 7787
Location 9q22.31      Physical location : 94.171.328 - 94.186.144
Synonym name
  • nuclear factor regulate by IL3/adenovirus E4 promoter binding protein
  • interleukin-3 promoter transcriptional activator
  • E4 promoter-binding protein 4
  • Synonym symbol(s) E4BP4, NFIL3A, IL3BP1, NF-IL3A, NF-IL3AA
    DNA
    TYPE functioning gene
    STRUCTURE 15.58 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • an E-box for BMAL1-CLOCK
  • MAPPING cloned Y linked N status provisional
    Map see HSN1
    Physical map
    LOC389771 9 LOC389771 LOC157916 9q22.31 interleukin 6 receptor pseudogene LOC392365 9 similar to putative taste receptor HTR2 LOC392366 9 similar to seven transmembrane helix receptor DIRAS2 9q22.32 DIRAS family, GTP-binding RAS-like 2 LOC392367 9 similar to putative taste receptor HTR2 LOC283493 9q22.31 similar to seven transmembrane helix receptor SYK 9q22.1-q22.3 spleen tyrosine kinase AUH 9q22 AU RNA binding protein/enoyl-Coenzyme A hydratase NFIL3 9q22 nuclear factor, interleukin 3 regulated ROR2 9q22.3 receptor tyrosine kinase-like orphan receptor 2 LOC347318 9q22.31 similar to 60S ribosomal protein L21 SPTLC1 9q22.1-q22.2 serine palmitoyltransferase, long chain base subunit 1 LOC389772 9 similar to Osteotesticular phosphatase; protein tyrosine phosphatase, receptor type, V LOC392368 9 similar to KIAA1553 protein LOC138652 9q22.32 similar to bA62C3.1 (similar to testicular serine protease) IARS 9q21 isoleucine-tRNA synthetase C9orf34 9q22.32 chromosome 9 open reading frame 34 OGN 9q22.3 osteoglycin (osteoinductive factor, mimecan) OMD 9p22.3 osteomodulin ASPN 9q22-q31 asporin (LRR class 1) ECM2 9q22.3 extracellular matrix protein 2, female organ and adipocyte specific C9orf12 9q21.33-q22.31 chromosome 9 open reading frame 12 BICD2 9q22.1-q22.3 chromosome 9 open reading frame 12 ANKRD19 9q22.32 ankyrin repeat domain 19 BA526D8.4 9q22.32 KRAB box containing C2H2 type zinc finger bA526D8.4 LOC389773 9 LOC389773 LOC340518 9q22.32 similar to Alox15 protein FGD3 9q22 FGD1 family, member 3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2104 - 462 - 2009 19749763
    2 - 2099 - 462 - 2009 19749763
    2 - 2247 - 462 - 2009 19749763
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Endocrineneuroendocrinepituitary  highly
    Nervousbrain   lowly
     nervecranial nerve  highly
     spinal cord   highly
    Reproductivefemale systemvagina   
    Respiratorylung   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal   Homo sapiens
    Nervouscentral   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
  • a linked basic DNA binding domain
  • a leucine zipper domain
  • mono polymer dimer
    HOMOLOGY
    interspecies homolog to C.elegans neural specification protein CES2
    homolog to murine Nfil3
    Homologene
    FAMILY basic leucine zipper family (BZIP)
    CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • survival of early B-cell progenitors
  • activating IL3 gene expression and repressing also transcription
  • negative regulator of the cyclooxygenase-2 (PTGS2) pathway that drives the expression of both RUNX2 and Osterix
  • osteoblast transcriptional repressor in inhibiting both RUNX2 and SP7 in myeloma bone disease (effect correlated with the increased PTHRP activity)
  • specific and essential requirement for the development of cells of the NK lineage
  • survival factor in pro-B lymphocytes
  • plays as a survival factor in heart and E4BP4 is essential for proper embryonic heart development
  • is potentially a critical regulator for IgE production and airway hyper-responsiveness
  • strongly suppresses FGF21 transcription by binding to a D-box element in the distal promoter region
  • novel insulin-responsive repressor of FGF21 expression during circadian cycles and feeding
  • important for maintaining a repressive state of the FGF21 gene during feeding and in response to insulin in hepatocytes
  • regulatory transcription factor in macrophages, controlling IL12B production induced by bacterial products and the enteric microbiota
  • plays an essential role in the development of CD8A(+) conventional dendritic cells
  • regulates cytokine production and effector function by T(H)2 cells
  • key regulator of T(H)2 responses
  • DBP and NFIL3 proteins are critical for determining the period length of the circadian oscillator
  • STAT3-dependent expression of NFIL3 is a key component of a negative feedback pathway in myeloid cells that suppresses proinflammatory responses
  • drives the formation of mature NK cells by inducing EOMES expression, revealing the differential requirements of NK cell subsets for NFIL3
  • may contribute to the process of dexamethasone-induced osteoblast apoptosis
  • is a key regulator of the development of Innate lymphoid cell (ILC) subsets essential for immune protection in the lung and gut
  • plays a critical role in the development of other mucosal tissue-associated innate lymphocytes
  • is crucial for development of innate lymphoid cells and host protection against intestinal pathogens
  • is an important negative transcription factor, which through binding to the promoter of IGF2R, suppresses the apoptosis induced by IGF2R signaling in cardiomyoblast cells under hypoxic conditions
  • circadian protein indispensable for NK cell development
  • is a critical regulator of the common helper-like innate lymphoid cell progenitor (CHILP)
  • is a key regulator of common helper-like innate lymphoid cells (ILCs) progenitors as they emerge during early lymphopoiesis
  • when NFIL3 function was inhibited specifically in dorsal root ganglia prior to sciatic nerve injury, decrease in regenerative axon growth into the distal nerve segment rather than an increase
  • CELLULAR PROCESS cell life, antiapoptosis
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS circadian , immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • being a component of the negative regulator complex of mammalian circadian clocks
  • INTERACTION
    DNA binding specifically to adenovirus E4, IFNG and IL3 promoters (regulatory sequences)
    RNA
    small molecule
    protein
  • interacting with LAMC1
  • binds a D-box cis-element of the promoter region of target genes to repress transcription
  • interacting with FGF21 (NFIL3-mediated repression of FGF21 is downstream of the insulin-induced AKT signaling and correlated to the fasting-feeding cycling)
  • EHMT2 mediates NFIL3-dependent suppression of hepatic FGF21 by enhancing histone methylation (H3K9me2) of the FGF21 promoter
  • MYSM1 and its interaction with NFIL3 are critical for the stable association of NFIL3 at the ID2 locus during NK cell development
  • transcription factor NFIL3 suppresses T(H)17 cell development by directly binding and repressing the RORC promoter
  • binds directly to the regulatory regions of both EOMES and ID2, promoting their transcription
  • NFIL3 binds directly to the IGF2R promoter region and repress IGF2R gene promoter activity
  • PDKP1, a kinase upstream of MTOR, connects IL15 signaling to NFIL3
  • IL27/NFIL3 signalling axis is a key regulator of effector T-cell responses via induction of HAVCR2, IL10 and T-cell dysfunction
  • cell & other
    REGULATION
    induced by IL4 stimulation in a STAT6-dependent manner
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in ovarian tumor
    constitutional     --over  
    was sufficient to increase NK cell production from hematopoietic progenitor cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • NFIL3-deficient mice showed greatly impaired IgE production in response to antigen