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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
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoietic    
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunemacrophage
cell lineage
cell lines PDBu-activated EBV-B cell lines secrete IL12A and IL12B
fluid/secretion
at STAGE
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