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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002187 8 - 2347 NP_002178 - 328 - 1991 1673147

EXPRESSION

Type

expressed in	(based on citations)
organ(s)

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune macrophage

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
	System Type Disorder Pubmed immunology autoimmune   antibodies specific as therapeutic targets in rheumatoid arthritis immunology autoimmune   attractive targets for therapy of autoimmune diseases

ANIMAL & CELL MODELS

Il12b knock-out mice