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FLASH GENE
Symbol IL4 contributors: mct/pgu - updated : 09-03-2015
HGNC name interleukin 4
HGNC id 6014
Corresponding disease
APY10 predisposition to eczema and asthma, atopy 10
Location 5q31.1      Physical location : 132.009.372 - 132.018.368
Synonym name
  • B-cell stimulatory factor 1
  • lymphocyte stimulatory factor 1
  • B cell growth factor 1
  • binetrakin
  • pitrakinra
  • Synonym symbol(s) BSF1, IL-4, BCGF1, BCGF-1, MGC79402
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 8.70 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure the coordinate regulator (LCR) of IL4, IL3 and IL5 is a 0.4kb sequence which is located in the intergenic region between IL4 and IL13 (Loots 00)
    MAPPING cloned Y linked N status confirmed
    Map see IRF1
    Physical map
    ACTBP4 5q23.3 actin, beta pseudogene 4 FACL6 5q31 fatty-acid-Coenzyme A ligase, long-chain 6 IL3 5q31.1 interleukin 3 (colony-stimulating factor, multiple) CSF2 5q31.1 colony stimulating factor 2 (granulocyte-macrophage) LOC389325 5 LOC389325 P4HA2 5q31.1 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide II RIL 5q31.1 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide II SLC22A4 5q31.2 solute carrier family 22 (organic cation transporter), member 4 SLC22A5 5q31.1-q32 solute carrier family 22 (organic cation transporter), member 5 LOC389326 5 hypothetical gene supported by AK096941; AK128882 IRF1 5q31.1 interferon regulatory factor 1 IL5 5q31.1 interleukin 5 (colony-stimulating factor, eosinophil) RAD50 5q31 RAD50 homolog (S. cerevisiae) IL13 5q31.1 interleukin 13 IL4 5q31.1 interleukin 4 KIF3A 5q31 kinesin family member 3A SEPT8 5q31 kinesin family member 3A LOC134548 5q31.1 hypothetical protein LOC134548 APXL2 5q31.1 hypothetical protein LOC134548 GDF9 5q31.1 growth differentiation factor 9 QP-C 5q31.1 low molecular mass ubiquinone-binding protein (9.5kD) LEAP-2 5q31.1 liver-expressed antimicrobial peptide 2 AF5Q31 5q31 liver-expressed antimicrobial peptide 2 LOC389327 5 hypothetical gene supported by AK129671 LOC391832 5 similar to putative nucleic acid binding protein RY-1 FLJ20094 5q31.1 hypothetical protein FLJ20094 HSPA4 5q31.1-q32 heat shock 70kDa protein 4 KIAA1061 5q31.1 KIAA1061 protein
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 921 17.5 153 - 1995 7806280
    3 splicing 873 15.7 137 - 1995 7806280
    lacking exon 2
    - splicing - - - - 2011 21285395
  • lacking the region encoded by the second exon
  • in contrast to IL4, IL4D2 did not induce eosinophilia or goblet cell hyperplasia
  • promotes lymphocytic inflammation, and the effects of IL4D2 are not mediated by endogenous IL4
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   moderately
     tonsils   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium  
    Epithelialbarrier/lininguroepithelium  
    Epithelialsecretoryglandularexocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 24 aa signal peptide (2,5kDA)
  • conjugated GlycoP
    isoforms Precursor a 129 amino acids mature peptide (15,0 kda)
    HOMOLOGY
    interspecies ortholog to C.elegans y43f8b.12
    Homologene
    FAMILY
  • interleukin, IL-4/IL-13 family
  • CATEGORY immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • important switch factor directing Ig-E synthesis
  • T cell and mast cell growth factor activities
  • potent modulator of ion transport in the bronchial epithelium and of ion composition of airway surface fluid
  • inhibition of matrix metalloproteinas-3 (MMP-3) synthetis in fibroblasts
  • involved in excessive deposition of extracellular matrix (EMC) proteins in giant papillae
  • directing germinal center-B cells to differentiate into memory B cells
  • Th2-promoting cytokine IL4 played a permissive role that superseded Treg function, thereby allowing the development of allergic inflammation
  • with its STAT6-signalling pathway are critical for the expression of Th2 effector immune responses in peripheral tissues such as the skin, lung and gut
  • important immune regulatory protein that possesses potent anti-osteoclastogenic properties, and does so via the transcription factor STAT6
  • IL4 and IL13 prime the migrational response of haemopoietic progenitor cells to CXCL12 by enhancing the incorporation of CXCR4 into lipid rafts
  • plays a critical role in higher functions of the normal brain, such as memory and learning
  • IL13 and IL4 can uniquely affect the expression of particular genes such as DUSP1 and TIMP33 and do so through different Jaks
  • IL4 exerts its proliferative actions via IL4R in hepatocytes, and eosinophil-derived IL4 stimulates hepatocyte proliferation in regenerating liver
  • IL4 and IL4 receptor expression is dispensable for the development and function of natural killer T cells
  • plays a central role in the orchestration of Type 2 immunity
  • during T cell activation in the lymph node, IL4 promotes Th2 differentiation and inhibits Th1 generation
  • attenuates Th1-associated chemokine expression and Th1 trafficking to inflamed tissues and limits pathogen clearance
  • IL4 up-regulation of IL19 in keratinocytes, which may play an important role in AD pathogenesis
  • IL4 and melatonin inhibited inflammation and angiogenesis triggered by high glucose and IL1B
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    text differentiation and proliferation of B cells, T cells and mast cells
    PATHWAY
    metabolism
    signaling
  • IL4 pathway of proliferation may have developed as an alternative to CSF1 to increase resident macrophages numbers without coincident monocyte recruitment
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activating STAT6
  • regulating CCR5 and CD4 expression and HIV1 replication in macrophages and microglia
  • MINA, is an IL4 repressor, controling T helper type 2 bias
  • IL4, IL9, IL13 may increase CLCA1 expression in cystic fibrosis but may not have a significant effect on mucus expression
  • IL4 inhibits osteoclast formation by inhibiting TNFSF11 induction of NFATC1 via STAT6 as an early event, in addition to its suppression of other signaling pathways
  • IRF4 activates IL2 and IL4 promoters in cooperation with REL
  • role of posttranslational modification of MAF in IL4 production and Th cell-mediated autoimmune diseases
  • IL4 downregulated in a STAT6-dependent manner the memory-specific expression of KLRK1, thereby increasing the activation threshold of memory CD8 T cells
  • while IL4 inhibits and activates different sets of lysosomal genes, STAT6 mediates only the activating effects of IL4, by promoting increased expression and by neutralizing undefined inhibitory signals induced by IL4
  • ICOS costimulation-dependent translational control may ensure targeted delivery of IL4 to cognate B cells during T-B collaborations in the germinal center
  • key role for KLF13 in the expression of IL4 in CD4(+) T cells
  • KLF13 cooperates with MAF to regulate IL4 expression in CD4+ T cells
  • IL4 was able to inhibit BCL2L11 upregulation and prevent cell death, and downmodulation of BCL2L11 by IL4 occurred in a posttranscriptional manner
  • IL4 increases the binding of STAT6 to its response elements in the IL19 promoter
  • IL4 is essential for the production of IL31, whereas TGFB1 significantly suppresses IL31 expression at the mRNA and protein levels
  • cell & other
    REGULATION
    activated by JUNB, a transcriptional activator of various cytokine genes, such as IL2, IL4, and IL10
    )
    inhibited by ICAM1 in CD4(+) T cells
    repressed by PTPN6 that is an essential negative regulator of IL4 signaling in T lymphocytes
    Other regulated by MAF a potent transactivator
    of the IL4 gene in Th2 cells
    regulated by MAPK14 (regulates IL4 production by mRNA stabilization, and TCR stimulation phosphorylates MAPK14, partially through the calcium-dependent pathway)
    ASSOCIATED DISORDERS
    corresponding disease(s) APY10
    Susceptibility
  • to thromboembolic strocke
  • to diabetic peripheral neuropathy (DPN)
  • Variant & Polymorphism repeat , other
  • C582T is a predictor of thromboembolic strocke
  • intron 3 VNTR polymorphism of the IL4 gene plays an important role in the occurrence of DPN
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    transgenic mice that inappropriatly expressed IL4 under the direction of the proximal promoter for the lymphocyte-specific protein tyrosine kinase gene (lck/IL4) developed severe osteoporosis