InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: IL12B

Summary

InnateDB Protein

IDBP-55895.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

IL12B

Protein Name

interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40)

Synonyms

CLMF; CLMF2; IL-12B; IMD28; IMD29; NKSF; NKSF2;

Species

Homo sapiens

Ensembl Protein

ENSP00000231228

InnateDB Gene

IDBG-55893 (IL12B)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:11114383}.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. {ECO:0000269PubMed:11114383}.

Subcellular Localization

Secreted.

Disease Associations

Mendelian susceptibility to mycobacterial disease (MSMD) [MIM:209950]: This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non- tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity, whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. {ECO:0000269PubMed:11753820, ECO:0000269PubMed:9854038}. Note=The disease is caused by mutations affecting the gene represented in this entry.Psoriasis 11 (PSORS11) [MIM:612599]: A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 35 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	36 [view]
Protein-Protein	17 [view]
Protein-DNA	19 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	19 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004896	cytokine receptor activity
GO:0005125	cytokine activity
GO:0005126	cytokine receptor binding
GO:0005143	interleukin-12 receptor binding
GO:0005515	protein binding
GO:0008083	growth factor activity
GO:0042164	interleukin-12 alpha subunit binding
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0045519	interleukin-23 receptor binding
GO:0046982	protein heterodimerization activity

Biological Process

GO:0001916	positive regulation of T cell mediated cytotoxicity
GO:0002230	positive regulation of defense response to virus by host
GO:0002323	natural killer cell activation involved in immune response
GO:0002827	positive regulation of T-helper 1 type immune response
GO:0002860	positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0002862	negative regulation of inflammatory response to antigenic stimulus
GO:0007050	cell cycle arrest
GO:0007166	cell surface receptor signaling pathway
GO:0010224	response to UV-B
GO:0010535	positive regulation of activation of JAK2 kinase activity
GO:0016477	cell migration
GO:0019221	cytokine-mediated signaling pathway
GO:0019233	sensory perception of pain
GO:0019953	sexual reproduction
GO:0030101	natural killer cell activation
GO:0032693	negative regulation of interleukin-10 production
GO:0032700	negative regulation of interleukin-17 production
GO:0032725	positive regulation of granulocyte macrophage colony-stimulating factor production
GO:0032729	positive regulation of interferon-gamma production
GO:0032733	positive regulation of interleukin-10 production
GO:0032735	positive regulation of interleukin-12 production
GO:0032740	positive regulation of interleukin-17 production
GO:0032760	positive regulation of tumor necrosis factor production
GO:0032816	positive regulation of natural killer cell activation
GO:0032819	positive regulation of natural killer cell proliferation
GO:0032946	positive regulation of mononuclear cell proliferation
GO:0034105	positive regulation of tissue remodeling
GO:0034393	positive regulation of smooth muscle cell apoptotic process
GO:0042035	regulation of cytokine biosynthetic process
GO:0042088	T-helper 1 type immune response
GO:0042093	T-helper cell differentiation
GO:0042095	interferon-gamma biosynthetic process
GO:0042102	positive regulation of T cell proliferation
GO:0042104	positive regulation of activated T cell proliferation
GO:0042346	positive regulation of NF-kappaB import into nucleus
GO:0042510	regulation of tyrosine phosphorylation of Stat1 protein
GO:0042517	positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042520	positive regulation of tyrosine phosphorylation of Stat4 protein
GO:0042523	positive regulation of tyrosine phosphorylation of Stat5 protein
GO:0042832	defense response to protozoan
GO:0043382	positive regulation of memory T cell differentiation
GO:0044130	negative regulation of growth of symbiont in host
GO:0045078	positive regulation of interferon-gamma biosynthetic process
GO:0045087	innate immune response (InnateDB)
GO:0045672	positive regulation of osteoclast differentiation
GO:0045785	positive regulation of cell adhesion
GO:0048662	negative regulation of smooth muscle cell proliferation
GO:0050671	positive regulation of lymphocyte proliferation
GO:0050729	positive regulation of inflammatory response
GO:0050829	defense response to Gram-negative bacterium
GO:0051135	positive regulation of NK T cell activation
GO:0051142	positive regulation of NK T cell proliferation
GO:0051607	defense response to virus
GO:0071222	cellular response to lipopolysaccharide
GO:0071346	cellular response to interferon-gamma
GO:2000318	positive regulation of T-helper 17 type immune response
GO:2000330	positive regulation of T-helper 17 cell lineage commitment

Cellular Component

GO:0005615	extracellular space
GO:0005737	cytoplasm
GO:0016020	membrane
GO:0043514	interleukin-12 complex
GO:0070743	interleukin-23 complex

Protein Structure and Domains

PDB ID

InterPro

IPR003598 Immunoglobulin subtype 2
IPR003961 Fibronectin, type III
IPR007110 Immunoglobulin-like domain
IPR015528 Interleukin-12 beta
IPR019482 Interleukin-12 beta, central domain

PFAM

PF00041
PF01108
PF10420

PRINTS

PR01928

PIRSF

PIRSF038007

SMART

SM00408
SM00060

TIGRFAMs

Post-translational Modifications

Modification

Cross-References