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) is a protein subunit 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; OMA:IL12B - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q33.3 Start 159,314,780 bp End 159,330,863 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 B1.1|11 25.94 cM Start 44,290,890 bp End 44,304,860 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad lymph node Pituitary Gland appendix tibialis anterior muscle anterior pituitary rectum gallbladder human kidney olfactory zone of nasal mucosa Top expressed in embryo lumbar subsegment of spinal cord thymus tracheobronchial tree tibiofemoral joint spleen trachea right kidney gastrula carotid body More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cytokine activity interleukin-23 receptor binding protein homodimerization activity interleukin-12 receptor binding 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 space 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 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 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 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 sensory perception of pain 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 cell population proliferation regulation of signaling receptor activity 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 ENSMUSG00000004296 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 Chr 11: 44.29 – 44.3 Mb PubMed search
Wikidata
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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 kDa cytokine receptor like subunit encoded by this gene, and a 35 kDa 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.

Role as IL-23 subunit

Interleukin-12 p40 also serves as a subunit of interleukin 23.

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. S2CID 18488948.
• 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. doi:10.4049/jimmunol.146.9.3074. PMID 1673147. S2CID 23838991.
• 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. S2CID 41634801.
• 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. doi:10.4049/jimmunol.153.12.5366. PMID 7527439. S2CID 36737679.
• 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. doi:10.4049/jimmunol.154.1.116. PMID 7527811. S2CID 31733259.
• 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. S2CID 41702014.
• 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.