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FLASH GENE
Symbol IL12B contributors: mct - updated : 20-09-2014
HGNC name interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40)
HGNC id 5970
Corresponding disease
IL12B susceptibility to BCG, non tuberculous mycobacterial and salmonella infections
Location 5q33.3      Physical location : 158.741.790 - 158.757.481
Synonym name
  • natural killer cell stimulatory factor, 40kDa subunit
  • natural killer cell stimulatory factor-2
  • cytotoxic lymphocyte maturation factor 2
  • IL12, subunit p40
  • interleukin-12 beta chain
  • CLMF p40
  • Synonym symbol(s) CLMF2, CLMF, NKSF, NKSF2, IL23, IL-12B, IMD28, IMD29, p40
    DNA
    TYPE functioning gene
    STRUCTURE 15.70 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • promoter has a putative DNA-binding element for NFIL3
  • MAPPING cloned Y linked N status confirmed
    Map cen - D5S487 - D5S379 - D5S2912 - D5S2913 - D5S378 - ITK - IL12B IL12B - D5S2914 - D5S2915 - D5S412 - D5S2916 - qter
    Physical map
    LOC153743 5q33.3 similar to protein phosphatase 1, regulatory (inhibitor) subunit 2 LOC91937 5q33.3 hypothetical protein BC008988 HAVCR1 5q33.2 hepatitis A virus cellular receptor 1 HAVCR2 5q34 hepatitis A virus cellular receptor 2 CRSP9 5q33.2 cofactor required for Sp1 transcriptional activation, subunit 9, 33kDa MGC26988 5q33.3 hypothetical protein MGC26988 ITK 5q33.1 IL2-inducible T-cell kinase CYFIP2 5q34 cytoplasmic FMR1 interacting protein 2 LOC348938 5q33.3 hypothetical protein LOC348938 ADAM19 5q32-q33 a disintegrin and metalloproteinase domain 19 (meltrin beta) SOX30 5q33 a disintegrin and metalloproteinase domain 19 (meltrin beta) LOC389341 5 similar to RIKEN cDNA 4921536K21 FLJ20546 5q33.3 hypothetical protein FLJ20546 LSM11 5q33.3 U7 snRNA-associated Sm-like protein ENTH 5q23.1-q33.3 U7 snRNA-associated Sm-like protein LOC391843 5 similar to 60S acidic ribosomal protein P2 LOC345471 5q33.3 similar to Hsp90 co-chaperone Cdc37 (Hsp90 chaperone protein kinase-targeting subunit) (p50Cdc37) LOC285721 5q33.3 hypothetical LOC285721 EBF 5q34 early B-cell factor FLJ31951 5q33.3 hypothetical protein FLJ31951 MGC10067 5q33.3 hypothetical protein MGC10067 IL12B 5q31.1-q33.1 interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) ADRA1B 5q33.1 adrenergic, alpha-1B-, receptor TTC1 5q32-q33.2 tetratricopeptide repeat domain 1 KIAA1935 5q34 KIAA1935 protein FABP6 5q23-q35 fatty acid binding protein 6, ileal (gastrotropin) FLJ14166 5q34 hypothetical protein FLJ14166 C1QTNF2 5q33.3 C1q and tumor necrosis factor related protein 2 LOC63920 5q34 transposon-derived Buster3 transposase-like SLU7 5q34 step II splicing factor SLU7 PTTG1 5q35.1 pituitary tumor-transforming 1 FLJ21477 5q34 hypothetical protein FLJ21477 GABRB2 5q33.1-q34 gamma-aminobutyric acid (GABA) A receptor, beta 2 GABRA6 5q33.1-q33.2 gamma-aminobutyric acid (GABA) A receptor, alpha 6 GABRA1 5q33.2 gamma-aminobutyric acid (GABA) A receptor, alpha 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2347 - 328 - 1991 1673147
    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
  • KLF10 is a transcription factor that regulates the expression of IL12B in bone marrow-derived macrophages (M-BMMs)
  • cell & other
  • driving development of Th1 cells
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) IL12B
    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)
  • 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)
  • 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