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FLASH GENE
Symbol IL12B contributors: mct - updated : 20-09-2015
HGNC name interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40)
HGNC id 5970
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one immunoglobulin-like C2 type domain
  • one fibronectin type III-like domain
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Il12b
    homolog to rattus Il12b
    Homologene
    FAMILY
  • cytokine receptor family
  • type 3 subfamily
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • chemotactic molecule for macrophages
  • can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine- activated killer cells, and stimulate the production of IFN-gamma
  • regulation of the Il12B gene, encoding the shared p40 subcomponent for IL12 and IL23, is critical for innate immune responses and subsequent T cell polarization
  • plays a critical role in enhancing the stability, intracellular trafficking, and export of the p35 subunit
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS immunity/defense
    text
  • IL12 is a signal of the innate immune system
  • growth factor for activated T and NK cells
  • PATHWAY
    metabolism
    signaling
    a component
  • dimerizing with IL12A
  • heterodimeric cytokine composed of p40 and p35 subunits to yield IL-12p70
  • binary complex of a four-helix bundle cytokine (p19) and a soluble class I cytokine receptor p40
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • potent inducer of IFN gamma production
  • interacting with NFKBIZ (NFKBIZ is critical for activation of NK cells in response to IL12B and IL18)
  • NFIL3 is an IL12B transcriptional inhibitor
  • is negatively regulated at the transcriptional level by the STAT3 (signal transducer and activator of transcription 3)-activating anti-inflammatory cytokine IL10
  • HDAC3 is involved in histone deacetylation of the IL12B promoter by IL10
  • enhancement of SIRT1 activity in response to phagocytic stimuli may reduce the accessibility of REL to the IL12A promoter and its transcriptional activation, thus regulating the IL12 p70/IL12B balance and modulating the ongoing immune response
  • KLF10 is a transcription factor that regulates the expression of IL12B in bone marrow-derived macrophages (M-BMMs)
  • secretion of IL1A, IL1B, IL12B, and CCL4 occurs during gelatinase degranulation, a process controlled by STX3
  • cell & other
  • driving development of Th1 cells
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD29
    Susceptibility
  • to asthma
  • late onset of type 1 diabetes
  • to psoriasis
  • to cerebral malaria (CM)
  • to cervical cancer
  • to Takayasu arteritis
  • to inflammatory bowel disease (IBD)
  • to Tuberculosis
  • Variant & Polymorphism other
  • polymorphism in the promoter associated with severity of atopic asthma and non atopic in children
  • allele C of the 3'UTR associate with late onset of type 1 diabetes
  • highly significant association with an IL12B 3-untranslated-region SNP in psoriasis
  • heterozygous genotype corresponding to reduced IL-12p40 transcription and IL-12p70 production associated to cerebral malaria (low levels of IL12 production are associated with an increased risk of CM)
  • association of IL-12beta (1188A/C) gene polymorphism with the risk of cervical cancer
  • IL12B SNP rs6887695 modulates the susceptibility and the phenotype of IBD
  • genetic association between IL12B and Takayasu arteritis (rs56167332)
  • locus conferring strong resistance to Tuberculosis
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    antibodies specific as therapeutic targets in rheumatoid arthritis
    immunologyautoimmune 
    attractive targets for therapy of autoimmune diseases
    ANIMAL & CELL MODELS
    Il12b knock-out mice