Interleukin-12 subunit beta

Details

Name
Interleukin-12 subunit beta
Synonyms
  • CLMF p40
  • Cytotoxic lymphocyte maturation factor 40 kDa subunit
  • IL-12 subunit p40
  • IL-12B
  • NK cell stimulatory factor chain 2
  • NKSF2
Gene Name
IL12B
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016273|Interleukin-12 subunit beta
MCHQQLVISWFSLVFLASPLVAIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITW
TLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQ
KEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERV
RGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKN
LQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVIC
RKNASISVRAQDRYYSSSWSEWASVPCS
Number of residues
328
Molecular Weight
37168.645
Theoretical pI
5.47
GO Classification
Functions
cytokine receptor activity / identical protein binding / interleukin-12 alpha subunit binding / interleukin-12 receptor binding / protein heterodimerization activity
Processes
cell cycle arrest / cell migration / cellular response to interferon-gamma / cellular response to lipopolysaccharide / defense response to Gram-negative bacterium / defense response to protozoan / defense response to virus / interferon-gamma biosynthetic process / natural killer cell activation / natural killer cell activation involved in immune response / negative regulation of growth of symbiont in host / negative regulation of inflammatory response to antigenic stimulus / negative regulation of interleukin-10 production / negative regulation of interleukin-17 production / negative regulation of smooth muscle cell proliferation / positive regulation of activated T cell proliferation / positive regulation of activation of JAK2 kinase activity / positive regulation of cell adhesion / positive regulation of defense response to virus by host / positive regulation of granulocyte macrophage colony-stimulating factor production / positive regulation of inflammatory response / positive regulation of interferon-gamma biosynthetic process / positive regulation of interferon-gamma production / positive regulation of interleukin-10 production / positive regulation of interleukin-12 production / positive regulation of interleukin-17 production / positive regulation of lymphocyte proliferation / positive regulation of memory T cell differentiation / positive regulation of mononuclear cell proliferation / positive regulation of natural killer cell activation / positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / positive regulation of natural killer cell proliferation / positive regulation of NF-kappaB import into nucleus / positive regulation of NK T cell activation / positive regulation of NK T cell proliferation / positive regulation of osteoclast differentiation / positive regulation of smooth muscle cell apoptotic process / positive regulation of T cell mediated cytotoxicity / positive regulation of T cell proliferation / positive regulation of T-helper 1 type immune response / positive regulation of T-helper 17 cell lineage commitment / positive regulation of T-helper 17 type immune response / positive regulation of tissue remodeling / positive regulation of tumor necrosis factor production / positive regulation of tyrosine phosphorylation of Stat3 protein / positive regulation of tyrosine phosphorylation of Stat4 protein / positive regulation of tyrosine phosphorylation of Stat5 protein / regulation of cytokine biosynthetic process / regulation of tyrosine phosphorylation of Stat1 protein / response to UV-B / sensory perception of pain / sexual reproduction / T-helper 1 type immune response / T-helper cell differentiation
Components
cytoplasm / extracellular space / interleukin-12 complex / interleukin-23 complex / membrane
General Function
Protein heterodimerization activity
Specific 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.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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0016274|Interleukin-12 subunit beta (IL12B)
ATGTGTCACCAGCAGTTGGTCATCTCTTGGTTTTCCCTGGTTTTTCTGGCATCTCCCCTC
GTGGCCATATGGGAACTGAAGAAAGATGTTTATGTCGTAGAATTGGATTGGTATCCGGAT
GCCCCTGGAGAAATGGTGGTCCTCACCTGTGACACCCCTGAAGAAGATGGTATCACCTGG
ACCTTGGACCAGAGCAGTGAGGTCTTAGGCTCTGGCAAAACCCTGACCATCCAAGTCAAA
GAGTTTGGAGATGCTGGCCAGTACACCTGTCACAAAGGAGGCGAGGTTCTAAGCCATTCG
CTCCTGCTGCTTCACAAAAAGGAAGATGGAATTTGGTCCACTGATATTTTAAAGGACCAG
AAAGAACCCAAAAATAAGACCTTTCTAAGATGCGAGGCCAAGAATTATTCTGGACGTTTC
ACCTGCTGGTGGCTGACGACAATCAGTACTGATTTGACATTCAGTGTCAAAAGCAGCAGA
GGCTCTTCTGACCCCCAAGGGGTGACGTGCGGAGCTGCTACACTCTCTGCAGAGAGAGTC
AGAGGGGACAACAAGGAGTATGAGTACTCAGTGGAGTGCCAGGAGGACAGTGCCTGCCCA
GCTGCTGAGGAGAGTCTGCCCATTGAGGTCATGGTGGATGCCGTTCACAAGCTCAAGTAT
GAAAACTACACCAGCAGCTTCTTCATCAGGGACATCATCAAACCTGACCCACCCAAGAAC
TTGCAGCTGAAGCCATTAAAGAATTCTCGGCAGGTGGAGGTCAGCTGGGAGTACCCTGAC
ACCTGGAGTACTCCACATTCCTACTTCTCCCTGACATTCTGCGTTCAGGTCCAGGGCAAG
AGCAAGAGAGAAAAGAAAGATAGAGTCTTCACGGACAAGACCTCAGCCACGGTCATCTGC
CGCAAAAATGCCAGCATTAGCGTGCGGGCCCAGGACCGCTACTATAGCTCATCTTGGAGC
GAATGGGCATCTGTGCCCTGCAGTTAG
Chromosome Location
5
Locus
5q31.1-q33.1
External Identifiers
ResourceLink
UniProtKB IDP29460
UniProtKB Entry NameIL12B_HUMAN
GenBank Protein ID180626
GenBank Gene IDM65272
GenAtlas IDIL12B
HGNC IDHGNC:5970
General References
  1. Gubler U, Chua AO, Schoenhaut DS, Dwyer CM, McComas W, Motyka R, Nabavi N, Wolitzky AG, Quinn PM, Familletti PC, et al.: Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4143-7. [PubMed:1674604]
  2. Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, Dzialo R, Fitz L, Ferenz C, Hewick RM, et al.: Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol. 1991 May 1;146(9):3074-81. [PubMed:1673147]
  3. Huang D, Cancilla MR, Morahan G: Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit. Genes Immun. 2000 Dec;1(8):515-20. [PubMed:11197695]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  5. Stern AS, Podlaski FJ, Hulmes JD, Pan YC, Quinn PM, Wolitzky AG, Familletti PC, Stremlo DL, Truitt T, Chizzonite R, et al.: Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6808-12. [PubMed:2204066]
  6. Gearing DP, Cosman D: Homology of the p40 subunit of natural killer cell stimulatory factor (NKSF) with the extracellular domain of the interleukin-6 receptor. Cell. 1991 Jul 12;66(1):9-10. [PubMed:2070420]
  7. D'Andrea A, Ma X, Aste-Amezaga M, Paganin C, Trinchieri G: 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. 1995 Feb 1;181(2):537-46. [PubMed:7836910]
  8. Doucey MA, Hess D, Blommers MJ, Hofsteenge J: Recombinant human interleukin-12 is the second example of a C-mannosylated protein. Glycobiology. 1999 May;9(5):435-41. [PubMed:10207176]
  9. Altare F, Lammas D, Revy P, Jouanguy E, Doffinger R, Lamhamedi S, Drysdale P, Scheel-Toellner D, Girdlestone J, Darbyshire P, Wadhwa M, Dockrell H, Salmon M, Fischer A, Durandy A, Casanova JL, Kumararatne DS: Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J Clin Invest. 1998 Dec 15;102(12):2035-40. [PubMed:9854038]
  10. 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: Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000 Nov;13(5):715-25. [PubMed:11114383]
  11. Picard C, Fieschi C, Altare F, Al-Jumaah S, Al-Hajjar S, Feinberg J, Dupuis S, Soudais C, Al-Mohsen IZ, Genin E, Lammas D, Kumararatne DS, Leclerc T, Rafii A, Frayha H, Murugasu B, Wah LB, Sinniah R, Loubser M, Okamoto E, Al-Ghonaium A, Tufenkeji H, Abel L, Casanova JL: Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. Am J Hum Genet. 2002 Feb;70(2):336-48. Epub 2001 Dec 17. [PubMed:11753820]
  12. Capon F, Di Meglio P, Szaub J, Prescott NJ, Dunster C, Baumber L, Timms K, Gutin A, Abkevic V, Burden AD, Lanchbury J, Barker JN, Trembath RC, Nestle FO: Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis. Hum Genet. 2007 Sep;122(2):201-6. Epub 2007 Jun 22. [PubMed:17587057]
  13. Huffmeier U, Lascorz J, Bohm B, Lohmann J, Wendler J, Mossner R, Reich K, Traupe H, Kurrat W, Burkhardt H, Reis A: Genetic variants of the IL-23R pathway: association with psoriatic arthritis and psoriasis vulgaris, but no specific risk factor for arthritis. J Invest Dermatol. 2009 Feb;129(2):355-8. doi: 10.1038/jid.2008.233. Epub 2008 Sep 18. [PubMed:18800148]
  14. Yoon C, Johnston SC, Tang J, Stahl M, Tobin JF, Somers WS: Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12. EMBO J. 2000 Jul 17;19(14):3530-41. [PubMed:10899108]
  15. Beyer BM, Ingram R, Ramanathan L, Reichert P, Le HV, Madison V, Orth P: Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody. J Mol Biol. 2008 Oct 17;382(4):942-55. doi: 10.1016/j.jmb.2008.08.001. Epub 2008 Aug 7. [PubMed:18708069]
  16. Lupardus PJ, Garcia KC: The structure of interleukin-23 reveals the molecular basis of p40 subunit sharing with interleukin-12. J Mol Biol. 2008 Oct 17;382(4):931-41. doi: 10.1016/j.jmb.2008.07.051. Epub 2008 Jul 25. [PubMed:18680750]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB027635-Mercapto-2-Nitro-Benzoic AcidexperimentalunknownDetails
DB05679Ustekinumabapproved, investigationalyesinhibitorDetails
DB05459BriakinumabinvestigationalunknownDetails
DB05848humanized SMART Anti-IL-12 AntibodyinvestigationalunknownDetails
DB06083TapinarofinvestigationalunknownDetails
DB05679Ustekinumabapproved, investigationalyesinhibitorDetails
DB14004Tildrakizumabapproved, investigationalyesantagonistDetails
DB14762Risankizumabapproved, investigationalyesinhibitorDetails