IL12A

Interleukin-12 subunit alpha (IL-12 p35) is a protein that in humans is encoded by the IL12A gene.[5]

IL12A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1F45, 3HMX
Identifiers
Aliases	IL12A, CLMF, IL-12A, NFSK, NKSF1, P35, interleukin 12A
External IDs	OMIM: 161560 MGI: 96539 HomoloGene: 681 GeneCards: IL12A
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q25.33 Start 159,988,835 bp[1] End 159,996,019 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 E1|3 31.92 cM Start 68,690,644 bp[2] End 68,698,547 bp[2]
Gene ontology Molecular function • cytokine activity • interleukin-27 binding • interleukin-12 beta subunit binding • GO:0001948 protein binding • protein heterodimerization activity • growth factor activity • interleukin-12 receptor binding Cellular component • cytoplasm • interleukin-12 complex • extracellular region • extracellular • endoplasmic reticulum lumen • late endosome lumen • cell surface Biological process • positive regulation of T cell differentiation • negative regulation of smooth muscle cell proliferation • extrinsic apoptotic signaling pathway • positive regulation of smooth muscle cell apoptotic process • response to virus • positive regulation of T cell mediated cytotoxicity • positive regulation of interferon-gamma production • positive regulation of natural killer cell activation • positive regulation of NK T cell activation • response to lipopolysaccharide • positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target • cell cycle arrest • immune response • response to UV-B • cellular response to lipopolysaccharide • negative regulation of interleukin-17 production • cell migration • positive regulation of natural killer cell mediated cytotoxicity • positive regulation of lymphocyte proliferation • positive regulation of dendritic cell chemotaxis • positive regulation of mononuclear cell proliferation • positive regulation of cell adhesion • defense response to protozoan • defense response to Gram-positive bacterium • positive regulation of T cell proliferation • 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-35-mediated signaling pathway • T-helper 1 cell activation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3592	16159
Ensembl	ENSG00000168811	ENSMUSG00000027776
UniProt	P29459	P43431
RefSeq (mRNA)	NM_000882 NM_001354582 NM_001354583	NM_001159424 NM_008351
RefSeq (protein)	NP_000873 NP_001341511 NP_001341512	NP_001152896 NP_032377
Location (UCSC)	Chr 3: 159.99 – 160 Mb	Chr 3: 68.69 – 68.7 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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-dependent 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.[6]

References

1. GRCh38: Ensembl release 89: ENSG00000168811 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027776 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "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. doi:10.3748/wjg.v12.i35.5606. PMC 4088159. 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.