Interleukin-12 subunit beta

Subunit beta of interleukin 12 (also known as IL-12B, natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor p40, or interleukin-12 subunit p40)[4] is a protein that in humans is encoded by the IL12B gene. IL-12B is a common subunit of interleukin 12 and Interleukin 23.

IL12B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1F42, 1F45, 3D85, 3D87, 3DUH, 3HMX, 3QWR, 4GRW, 4OE8, 4OG9
Identifiers
Aliases	IL12B, CLMF, CLMF2, IL-12B, IMD28, NKSF, NKSF2, IMD29, Interleukin 12 subunit beta, interleukin 12B
External IDs	OMIM: 161561 MGI: 96540 HomoloGene: 1648 GeneCards: IL12B
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q33.3 Start 159,314,780 bp[1] End 159,330,487 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • cytokine activity • interleukin-23 receptor binding • protein homodimerization activity • interleukin-12 receptor binding • GO:0001948 protein binding • identical protein binding • protein heterodimerization activity • interleukin-12 alpha subunit binding • cytokine receptor activity • growth factor activity • cytokine receptor binding • cytokine binding Cellular component • cytoplasm • membrane • interleukin-12 complex • interleukin-23 complex • extracellular region • extracellular • endoplasmic reticulum lumen • cytosol • late endosome lumen • cell surface • external side of plasma membrane • receptor complex Biological process • positive regulation of cell adhesion • negative regulation of interleukin-10 production • negative regulation of smooth muscle cell proliferation • positive regulation of inflammatory response • sexual reproduction • positive regulation of interleukin-12 production • positive regulation of smooth muscle cell apoptotic process • defense response to Gram-negative bacterium • positive regulation of interleukin-10 production • positive regulation of interferon-gamma biosynthetic process • positive regulation of T cell mediated cytotoxicity • natural killer cell activation • positive regulation of natural killer cell activation • positive regulation of interferon-gamma production • positive regulation of osteoclast differentiation • interferon-gamma biosynthetic process • positive regulation of T-helper 17 cell lineage commitment • response to organic substance • positive regulation of NK T cell activation • positive regulation of natural killer cell proliferation • natural killer cell activation involved in immune response • cell surface receptor signaling pathway • positive regulation of NK T cell proliferation • positive regulation of T-helper 17 type immune response • negative regulation of inflammatory response to antigenic stimulus • defense response to virus • positive regulation of tissue remodeling • positive regulation of T-helper 1 type immune response • positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target • cell cycle arrest • positive regulation of granulocyte macrophage colony-stimulating factor production • positive regulation of T cell proliferation • positive regulation of memory T cell differentiation • cellular response to interferon-gamma • positive regulation of tumor necrosis factor production • T-helper 1 type immune response • regulation of cytokine biosynthetic process • nociception • response to UV-B • positive regulation of interleukin-17 production • cellular response to lipopolysaccharide • negative regulation of interleukin-17 production • T-helper cell differentiation • cell migration • positive regulation of lymphocyte proliferation • positive regulation of mononuclear cell proliferation • positive regulation of activated T cell proliferation • defense response to protozoan • positive regulation of defense response to virus by host • positive regulation of activation of Janus kinase activity • regulation of tyrosine phosphorylation of STAT protein • positive regulation of tyrosine phosphorylation of STAT protein • interleukin-12-mediated signaling pathway • cellular proliferation • regulation of receptor activity • interferon-gamma production • T-helper 1 cell cytokine production • cytokine-mediated signaling pathway • interleukin-23-mediated signaling pathway • positive regulation of NIK/NF-kappaB signaling Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3593	16160
Ensembl	ENSG00000113302	n/a
UniProt	P29460	P43432
RefSeq (mRNA)	NM_002187	NM_008352 NM_001303244
RefSeq (protein)	NP_002178	NP_001290173
Location (UCSC)	Chr 5: 159.31 – 159.33 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Function

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 gene polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children.[4]

Role as IL-23 subunit

Interleukin-12 p40 also serves as a subunit of Interleukin 23.[5]

References

1. GRCh38: Ensembl release 89: ENSG00000113302 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Entrez Gene: IL12B interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40)".
5. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (November 2000). "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12". Immunity. 13 (5): 715–25. doi:10.1016/S1074-7613(00)00070-4. PMID 11114383.

Further reading

• Airoldi I, Guglielmino R, Carra G, Corcione A, Gerosa F, Taborelli G, Trinchieri G, Pistoia V (2002). "The interleukin-12 and interleukin-12 receptor system in normal and transformed human B lymphocytes". Haematologica. 87 (4): 434–42. PMID 11940489.
• Abdi K (2002). "IL-12: the role of p40 versus p75". Scand. J. Immunol. 56 (1): 1–11. doi:10.1046/j.1365-3083.2002.01101.x. PMID 12100467.
• Sieburth D, Jabs EW, Warrington JA, Li X, Lasota J, LaForgia S, Kelleher K, Huebner K, Wasmuth JJ, Wolf SF (1992). "Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5". Genomics. 14 (1): 59–62. doi:10.1016/S0888-7543(05)80283-6. PMID 1358798.
• Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, Dzialo R, Fitz L, Ferenz C, Hewick RM (1991). "Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells". J. Immunol. 146 (9): 3074–81. PMID 1673147.
• Gubler U, Chua AO, Schoenhaut DS, Dwyer CM, McComas W, Motyka R, Nabavi N, Wolitzky AG, Quinn PM, Familletti PC (1991). "Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor". Proc. Natl. Acad. Sci. U.S.A. 88 (10): 4143–7. Bibcode:1991PNAS...88.4143G. doi:10.1073/pnas.88.10.4143. PMC 51614. PMID 1674604.
• Gearing DP, Cosman D (1991). "Homology of the p40 subunit of natural killer cell stimulatory factor (NKSF) with the extracellular domain of the interleukin-6 receptor". Cell. 66 (1): 9–10. doi:10.1016/0092-8674(91)90131-H. PMID 2070420.
• Stern AS, Podlaski FJ, Hulmes JD, Pan YC, Quinn PM, Wolitzky AG, Familletti PC, Stremlo DL, Truitt T, Chizzonite R (1990). "Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells". Proc. Natl. Acad. Sci. U.S.A. 87 (17): 6808–12. Bibcode:1990PNAS...87.6808S. doi:10.1073/pnas.87.17.6808. PMC 54627. PMID 2204066.
• Aragane Y, Riemann H, Bhardwaj RS, Schwarz A, Sawada Y, Yamada H, Luger TA, Kubin M, Trinchieri G, Schwarz T (1995). "IL-12 is expressed and released by human keratinocytes and epidermoid carcinoma cell lines". J. Immunol. 153 (12): 5366–72. PMID 7527439.
• Ling P, Gately MK, Gubler U, Stern AS, Lin P, Hollfelder K, Su C, Pan YC, Hakimi J (1995). "Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity". J. Immunol. 154 (1): 116–27. PMID 7527811.
• Murphy TL, Cleveland MG, Kulesza P, Magram J, Murphy KM (1995). "Regulation of interleukin 12 p40 expression through an NF-kappa B half-site". Mol. Cell. Biol. 15 (10): 5258–67. doi:10.1128/MCB.15.10.5258. PMC 230773. PMID 7565674.
• Sharma V, Knobloch TJ, Benjamin D (1995). "Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines". Biochem. Biophys. Res. Commun. 208 (2): 704–13. doi:10.1006/bbrc.1995.1395. PMID 7695626.
• Warrington JA, Bengtsson U (1995). "High-resolution physical mapping of human 5q31-q33 using three methods: radiation hybrid mapping, interphase fluorescence in situ hybridization, and pulsed-field gel electrophoresis". Genomics. 24 (2): 395–8. doi:10.1006/geno.1994.1636. PMID 7698768.
• D'Andrea A, Ma X, Aste-Amezaga M, Paganin C, Trinchieri G (1995). "Stimulatory and inhibitory effects of interleukin (IL)-4 and IL-13 on the production of cytokines by human peripheral blood mononuclear cells: priming for IL-12 and tumor necrosis factor alpha production". J. Exp. Med. 181 (2): 537–46. doi:10.1084/jem.181.2.537. PMC 2191875. PMID 7836910.
• Gillessen S, Carvajal D, Ling P, Podlaski FJ, Stremlo DL, Familletti PC, Gubler U, Presky DH, Stern AS, Gately MK (1995). "Mouse interleukin-12 (IL-12) p40 homodimer: a potent IL-12 antagonist". Eur. J. Immunol. 25 (1): 200–6. doi:10.1002/eji.1830250133. PMID 7843232.
• Radrizzani M, Accornero P, Amidei A, Aiello A, Delia D, Kurrle R, Colombo MP (1995). "IL-12 inhibits apoptosis induced in a human Th1 clone by gp120/CD4 cross-linking and CD3/TCR activation or by IL-2 deprivation". Cell. Immunol. 161 (1): 14–21. doi:10.1006/cimm.1995.1003. PMID 7867080.
• Ma X, Chow JM, Gri G, Carra G, Gerosa F, Wolf SF, Dzialo R, Trinchieri G (1996). "The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells". J. Exp. Med. 183 (1): 147–57. doi:10.1084/jem.183.1.147. PMC 2192398. PMID 8551218.
• Fantuzzi L, Gessani S, Borghi P, Varano B, Conti L, Puddu P, Belardelli F (1996). "Induction of interleukin-12 (IL-12) by recombinant glycoprotein gp120 of human immunodeficiency virus type 1 in human monocytes/macrophages: requirement of gamma interferon for IL-12 secretion". J. Virol. 70 (6): 4121–4. doi:10.1128/JVI.70.6.4121-4124.1996. PMC 190299. PMID 8648753.
• Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G (1996). "Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation". J. Exp. Med. 184 (2): 747–52. doi:10.1084/jem.184.2.747. PMC 2192696. PMID 8760829.
• Kato K, Shimozato O, Hoshi K, Wakimoto H, Hamada H, Yagita H, Okumura K (1996). "Local production of the p40 subunit of interleukin 12 suppresses T-helper 1-mediated immune responses and prevents allogeneic myoblast rejection". Proc. Natl. Acad. Sci. U.S.A. 93 (17): 9085–9. Bibcode:1996PNAS...93.9085K. doi:10.1073/pnas.93.17.9085. PMC 38599. PMID 8799158.
• Taoufik Y, Lantz O, Wallon C, Charles A, Dussaix E, Delfraissy JF (1997). "Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect interleukin-10-mediated effect". Blood. 89 (8): 2842–8. doi:10.1182/blood.V89.8.2842. PMID 9108403.