IL12A

Interleukin 12A
PDB rendering based on 1f45.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1F45​, 3HMX​
Identifiers
Symbols	IL12A ; CLMF; IL-12A; NFSK; NKSF1; P35
External IDs	OMIM: 161560 MGI: 96539 HomoloGene: 681 GeneCards: IL12A Gene
Gene ontology Molecular function • cytokine activity • interleukin-12 receptor binding • protein binding • growth factor activity • interleukin-12 beta subunit binding • interleukin-27 binding • protein heterodimerization activity Cellular component • extracellular space • cytoplasm • interleukin-12 complex Biological process • positive regulation of T cell mediated cytotoxicity • positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target • immune response • cell cycle arrest • response to virus • response to UV-B • cell migration • response to lipopolysaccharide • negative regulation of interleukin-17 production • positive regulation of interferon-gamma production • positive regulation of natural killer cell activation • positive regulation of mononuclear cell proliferation • positive regulation of smooth muscle cell apoptotic process • positive regulation of T cell proliferation • positive regulation of tyrosine phosphorylation of Stat4 protein • defense response to protozoan • positive regulation of T cell differentiation • positive regulation of cell adhesion • positive regulation of natural killer cell mediated cytotoxicity • negative regulation of smooth muscle cell proliferation • positive regulation of lymphocyte proliferation • defense response to Gram-positive bacterium • positive regulation of NK T cell activation • cellular response to lipopolysaccharide • extrinsic apoptotic signaling pathway • cellular response to virus • positive regulation of dendritic cell chemotaxis Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3592	16159
Ensembl	ENSG00000168811	ENSMUSG00000027776
UniProt	P29459	P43431
RefSeq (mRNA)	NM_000882	NM_001159424
RefSeq (protein)	NP_000873	NP_001152896
Location (UCSC)	Chr 3: 159.99 – 160 Mb	Chr 3: 68.69 – 68.7 Mb
PubMed search

Interleukin-12 subunit alpha is a protein that in humans is encoded by the IL12A gene.^[1]

Function

This gene encodes a subunit of the cytokine Interleukin 12 (IL-12) that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon gamma (INF-γ), and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity.^[2]

References

1. Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, Dzialo R, Fitz L, Ferenz C, Hewick RM (May 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.
2. "Entrez Gene: IL12A interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35)".

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.
• Muthumani K, Desai BM, Hwang DS, Choo AY, Laddy DJ, Thieu KP, Rao RG, Weiner DB (2004). "HIV-1 Vpr and anti-inflammatory activity.". DNA Cell Biol. 23 (4): 239–47. doi:10.1089/104454904773819824. PMID 15142381.
• Zhao RY, Elder RT (2005). "Viral infections and cell cycle G2/M regulation.". Cell Res. 15 (3): 143–9. doi:10.1038/sj.cr.7290279. PMID 15780175.
• Zhao RY, Bukrinsky M, Elder RT (2005). "HIV-1 viral protein R (Vpr) & host cellular responses.". Indian J. Med. Res. 121 (4): 270–86. PMID 15817944.
• Peluso I, Pallone F, Monteleone G (2006). "Interleukin-12 and Th1 immune response in Crohn's disease: pathogenetic relevance and therapeutic implication.". World J. Gastroenterol. 12 (35): 5606–10. PMID 17007011.
• Quaranta MG, Mattioli B, Giordani L, Viora M (2006). "The immunoregulatory effects of HIV-1 Nef on dendritic cells and the pathogenesis of AIDS.". FASEB J. 20 (13): 2198–208. doi:10.1096/fj.06-6260rev. PMID 17077296.
• Small RD (1976). "Letter: Statistical analysis of respiratory sensitivity to CO₂.". N. Engl. J. Med. 295 (7): 397. doi:10.1056/NEJM197608122950720. PMID 934235.
• Schoenhaut DS, Chua AO, Wolitzky AG, Quinn PM, Dwyer CM, McComas W, Familletti PC, Gately MK, Gubler U (1992). "Cloning and expression of murine IL-12.". J. Immunol. 148 (11): 3433–40. PMID 1350290.
• 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.
• 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. doi:10.1073/pnas.88.10.4143. PMC 51614. PMID 1674604.
• Kubin M, Kamoun M, Trinchieri G (1994). "Interleukin 12 synergizes with B7/CD28 interaction in inducing efficient proliferation and cytokine production of human T cells.". J. Exp. Med. 180 (1): 211–22. doi:10.1084/jem.180.1.211. PMC 2191554. PMID 7516408.
• 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.
• 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.
• 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.
• 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. PMC 190299. PMID 8648753.
• Thierfelder WE, van Deursen JM, Yamamoto K, Tripp RA, Sarawar SR, Carson RT, Sangster MY, Vignali DA, Doherty PC, Grosveld GC, Ihle JN (1996). "Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells.". Nature 382 (6587): 171–4. doi:10.1038/382171a0. PMID 8700208.
• 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.
• 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. PMID 9108403.
• Kim JH, Loveland JE, Sitz KV, Ratto Kim S, Mclinden RJ, Tencer K, Davis K, Burke DS, Boswell RN, Redfield RR, Birx DL (1997). "Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1.". Clin. Exp. Immunol. 108 (2): 243–50. doi:10.1046/j.1365-2249.1997.d01-1006.x. PMC 1904649. PMID 9158092.