IL12B (interleukin 12B)

Gene

• Entrez ID: 3593
• Gene name: Interleukin 12B
• Gene symbol: IL12B
• Synonyms: CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF, NKSF2
• Chromosome: 5
• Chromosome location: 5q33.3
• Summary: This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT715151	hsa-miR-4284	HITS-CLIP	19536157
MIRT715152	hsa-miR-6511b-3p	HITS-CLIP	19536157
MIRT715153	hsa-miR-6511a-3p	HITS-CLIP	19536157
MIRT715154	hsa-miR-103b	HITS-CLIP	19536157
MIRT715155	hsa-miR-4705	HITS-CLIP	19536157
MIRT715156	hsa-miR-3614-3p	HITS-CLIP	19536157
MIRT732755	hsa-miR-16-5p	Luciferase reporter assay, qRT-PCR	26073885

Transcription factors

Transcription factor	Regulation	Reference
EP300	Activation	15482860
ETS2	Unknown	10657616
IRF1	Unknown	10657616
JUN	Activation	14688340
KLF1	Unknown	14976188
NFKB1	Activation	14688340;18690006
NFKB1	Unknown	10657616
REL	Unknown	10657616
RELA	Activation	14688340;18690006
RELA	Unknown	10657616;15270850
SPI1	Unknown	11254706
VDR	Repression	21310195

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001817	Process	Regulation of cytokine production	TAS	1673147
GO:0001916	Process	Positive regulation of T cell mediated cytotoxicity	ISS
GO:0002230	Process	Positive regulation of defense response to virus by host	IDA	12421946
GO:0002230	Process	Positive regulation of defense response to virus by host	ISS
GO:0002323	Process	Natural killer cell activation involved in immune response	IEA
GO:0002827	Process	Positive regulation of T-helper 1 type immune response	IDA	15114670
GO:0002827	Process	Positive regulation of T-helper 1 type immune response	ISS
GO:0002860	Process	Positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target	IDA	7903063
GO:0002862	Process	Negative regulation of inflammatory response to antigenic stimulus	IEA
GO:0004896	Function	Cytokine receptor activity	IBA	21873635
GO:0005125	Function	Cytokine activity	IDA	1674604
GO:0005143	Function	Interleukin-12 receptor binding	TAS	1674604
GO:0005143	Function	Interleukin-12 receptor binding	TAS	9603733
GO:0005515	Function	Protein binding	IPI	7527811, 10899108, 11023671, 11114383, 12023369, 18680750, 29997244
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	TAS	1673147
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005829	Component	Cytosol	TAS
GO:0007050	Process	Cell cycle arrest	IDA	16942485
GO:0008083	Function	Growth factor activity	IDA	1674604
GO:0008283	Process	Cell population proliferation	IEA
GO:0009897	Component	External side of plasma membrane	IBA	21873635
GO:0010224	Process	Response to UV-B	IDA	8992506
GO:0010536	Process	Positive regulation of activation of Janus kinase activity	IDA	12023369
GO:0016477	Process	Cell migration	IDA	7903063
GO:0019221	Process	Cytokine-mediated signaling pathway	IBA	21873635
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019233	Process	Sensory perception of pain	IEA
GO:0019953	Process	Sexual reproduction	TAS	16772281
GO:0019955	Function	Cytokine binding	IBA	21873635
GO:0030101	Process	Natural killer cell activation	IDA	1673147
GO:0031906	Component	Late endosome lumen	TAS
GO:0032609	Process	Interferon-gamma production	TAS	1673147
GO:0032693	Process	Negative regulation of interleukin-10 production	IMP	16751425
GO:0032700	Process	Negative regulation of interleukin-17 production	IDA	16482511
GO:0032725	Process	Positive regulation of granulocyte macrophage colony-stimulating factor production	IDA	20027291
GO:0032729	Process	Positive regulation of interferon-gamma production	IDA	1674604, 11114383, 19088061, 20027291
GO:0032729	Process	Positive regulation of interferon-gamma production	TAS	1673147
GO:0032733	Process	Positive regulation of interleukin-10 production	IDA	15265908
GO:0032733	Process	Positive regulation of interleukin-10 production	TAS	18675459
GO:0032735	Process	Positive regulation of interleukin-12 production	IDA	20027291
GO:0032740	Process	Positive regulation of interleukin-17 production	IDA	16482511, 16751425, 17888176
GO:0032760	Process	Positive regulation of tumor necrosis factor production	IMP	16751425
GO:0032816	Process	Positive regulation of natural killer cell activation	IC	20027291
GO:0032816	Process	Positive regulation of natural killer cell activation	IDA	1674604
GO:0032819	Process	Positive regulation of natural killer cell proliferation	IDA	19088061
GO:0032946	Process	Positive regulation of mononuclear cell proliferation	IMP	11023671
GO:0034105	Process	Positive regulation of tissue remodeling	IC	16482511
GO:0034393	Process	Positive regulation of smooth muscle cell apoptotic process	IDA	16942485
GO:0035722	Process	Interleukin-12-mediated signaling pathway	TAS
GO:0038155	Process	Interleukin-23-mediated signaling pathway	TAS
GO:0042088	Process	T-helper 1 type immune response	TAS	1673147
GO:0042093	Process	T-helper cell differentiation	IDA	1673147
GO:0042102	Process	Positive regulation of T cell proliferation	IDA	12023369
GO:0042104	Process	Positive regulation of activated T cell proliferation	IDA	1674604, 11114383
GO:0042164	Function	Interleukin-12 alpha subunit binding	IBA	21873635
GO:0042164	Function	Interleukin-12 alpha subunit binding	IPI	11023671
GO:0042509	Process	Regulation of tyrosine phosphorylation of STAT protein	IDA	12023369
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	IDA	12023369
GO:0042802	Function	Identical protein binding	IPI	7527811
GO:0042832	Process	Defense response to protozoan	IEA
GO:0043235	Component	Receptor complex	IBA	21873635
GO:0043382	Process	Positive regulation of memory T cell differentiation	ISS
GO:0043514	Component	Interleukin-12 complex	IBA	21873635
GO:0043514	Component	Interleukin-12 complex	IDA	1674604, 11114383
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045519	Function	Interleukin-23 receptor binding	IDA	11114383
GO:0045672	Process	Positive regulation of osteoclast differentiation	IDA	17888176
GO:0045785	Process	Positive regulation of cell adhesion	IDA	7903063
GO:0046982	Function	Protein heterodimerization activity	IPI	1674604, 11023671
GO:0048662	Process	Negative regulation of smooth muscle cell proliferation	IDA	16942485
GO:0050671	Process	Positive regulation of lymphocyte proliferation	IDA	1674604
GO:0050709	Process	Negative regulation of protein secretion	IGI	30106099
GO:0050729	Process	Positive regulation of inflammatory response	IC	16482511
GO:0050829	Process	Defense response to Gram-negative bacterium	IDA	15114670, 20027291
GO:0051135	Process	Positive regulation of NK T cell activation	IC	20027291
GO:0051135	Process	Positive regulation of NK T cell activation	IDA	19088061
GO:0051142	Process	Positive regulation of NK T cell proliferation	IDA	19088061
GO:0051607	Process	Defense response to virus	IEA
GO:0070743	Component	Interleukin-23 complex	IBA	21873635
GO:0070743	Component	Interleukin-23 complex	IDA	11114383
GO:0071222	Process	Cellular response to lipopolysaccharide	IEA
GO:0071346	Process	Cellular response to interferon-gamma	IEA
GO:1900747	Process	Negative regulation of vascular endothelial growth factor signaling pathway	IGI	30106099
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	TAS	20428758
GO:1903588	Process	Negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	IGI	30106099
GO:2000318	Process	Positive regulation of T-helper 17 type immune response	ISS
GO:2000330	Process	Positive regulation of T-helper 17 cell lineage commitment	ISS

Other IDs

• MIM: 161561
• HGNC: 5970
• e!Ensembl: ENSG00000113302

Protein

• UniProt ID: P29460
• Protein name: Interleukin-12 subunit beta (IL-12B) (Cytotoxic lymphocyte maturation factor 40 kDa subunit) (CLMF p40) (IL-12 subunit p40) (NK cell stimulatory factor chain 2) (NKSF2)
• Protein function: Cytokine that 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 by resting PBMC. ; Associates with IL23A to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis.
• PDB: 1F42, 1F45, 3D85, 3D87, 3DUH, 3HMX, 3QWR, 4GRW, 5MJ3, 5MJ4, 5MXA, 5MZV, 5NJD, 6UIB, 6WDQ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10420	IL12p40_C	126 → 216	Cytokine interleukin-12p40 C-terminus	Domain

• Sequence:

  MCHQQLVISWFSLVFLASPLVAIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITW
  TLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQ
  KEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERV
  RGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKN
  LQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVIC
  RKNASISVRAQDRYYSSSWSEWASVPCS

• Sequence length: 328