ID:IL12B_HUMAN DESCRIPTION: RecName: Full=Interleukin-12 subunit beta; Short=IL-12B; AltName: Full=Cytotoxic lymphocyte maturation factor 40 kDa subunit; Short=CLMF p40; AltName: Full=IL-12 subunit p40; AltName: Full=NK cell stimulatory factor chain 2; Short=NKSF2; Flags: Precursor; 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. FUNCTION: 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. SUBUNIT: Heterodimer with IL12A; disulfide-linked. The heterodimer is known as interleukin IL-12. Heterodimer with IL23A; disulfide- linked. The heterodimer is known as interleukin IL-23. Also secreted as a monomer. INTERACTION: Self; NbExp=2; IntAct=EBI-1029614, EBI-1029614; P29459:IL12A; NbExp=2; IntAct=EBI-1029614, EBI-1029636; Q9EQ14:Il23a (xeno); NbExp=2; IntAct=EBI-1029614, EBI-2481329; SUBCELLULAR LOCATION: Secreted. PTM: Known to be C-mannosylated in the recombinant protein; it is not yet known for sure if the wild-type protein is also modified. DISEASE: Defects in IL12B are a cause of mendelian susceptibility to mycobacterial disease (MSMD) [MIM:209950]; also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity, whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. DISEASE: Genetic variations in IL12B are a cause of susceptibility to psoriasis type 11 (PSORS11) [MIM:612599]. Psoriasis is a common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. SIMILARITY: Belongs to the type I cytokine receptor family. Type 3 subfamily. SIMILARITY: Contains 1 fibronectin type-III domain. SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like) domain. WEB RESOURCE: Name=IL12Bbase; Note=IL12B mutation db; URL="http://bioinf.uta.fi/IL12Bbase/"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/IL12B"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/il12b/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P29460
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001916 positive regulation of T cell mediated cytotoxicity GO:0002230 positive regulation of defense response to virus by host GO:0002323 natural killer cell activation involved in immune response GO:0002827 positive regulation of T-helper 1 type immune response GO:0002860 positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target GO:0002862 negative regulation of inflammatory response to antigenic stimulus GO:0007050 cell cycle arrest GO:0007166 cell surface receptor signaling pathway GO:0008283 cell proliferation GO:0010033 response to organic substance GO:0010224 response to UV-B GO:0010469 regulation of receptor activity GO:0010536 positive regulation of activation of Janus kinase activity GO:0016477 cell migration GO:0019221 cytokine-mediated signaling pathway GO:0019233 sensory perception of pain GO:0019953 sexual reproduction GO:0030101 natural killer cell activation GO:0032609 interferon-gamma production GO:0032693 negative regulation of interleukin-10 production GO:0032700 negative regulation of interleukin-17 production GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor production GO:0032729 positive regulation of interferon-gamma production GO:0032733 positive regulation of interleukin-10 production GO:0032735 positive regulation of interleukin-12 production GO:0032740 positive regulation of interleukin-17 production GO:0032760 positive regulation of tumor necrosis factor production GO:0032816 positive regulation of natural killer cell activation GO:0032819 positive regulation of natural killer cell proliferation GO:0032946 positive regulation of mononuclear cell proliferation GO:0034105 positive regulation of tissue remodeling GO:0034393 positive regulation of smooth muscle cell apoptotic process GO:0035722 interleukin-12-mediated signaling pathway GO:0035744 T-helper 1 cell cytokine production GO:0038155 interleukin-23-mediated signaling pathway GO:0042035 regulation of cytokine biosynthetic process GO:0042088 T-helper 1 type immune response GO:0042093 T-helper cell differentiation GO:0042095 interferon-gamma biosynthetic process GO:0042102 positive regulation of T cell proliferation GO:0042104 positive regulation of activated T cell proliferation GO:0042509 regulation of tyrosine phosphorylation of STAT protein GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein GO:0042832 defense response to protozoan GO:0043382 positive regulation of memory T cell differentiation GO:0044130 negative regulation of growth of symbiont in host GO:0045078 positive regulation of interferon-gamma biosynthetic process GO:0045672 positive regulation of osteoclast differentiation GO:0045785 positive regulation of cell adhesion GO:0048662 negative regulation of smooth muscle cell proliferation GO:0050671 positive regulation of lymphocyte proliferation GO:0050729 positive regulation of inflammatory response GO:0050829 defense response to Gram-negative bacterium GO:0051135 positive regulation of NK T cell activation GO:0051142 positive regulation of NK T cell proliferation GO:0051607 defense response to virus GO:0071222 cellular response to lipopolysaccharide GO:0071346 cellular response to interferon-gamma GO:1901224 positive regulation of NIK/NF-kappaB signaling GO:2000318 positive regulation of T-helper 17 type immune response GO:2000330 positive regulation of T-helper 17 cell lineage commitment
M65290 - Human natural killer cell stimulatory factor (NKSF) mRNA, complete cds, clone p40. JD499497 - Sequence 480521 from Patent EP1572962. AY046592 - Homo sapiens interleukin 12 p40 mutant mRNA, partial cds. AY046593 - Homo sapiens interleukin 12 p40 mRNA, partial cds. JD116269 - Sequence 97293 from Patent EP1572962. JD319258 - Sequence 300282 from Patent EP1572962. JD110209 - Sequence 91233 from Patent EP1572962. JD105008 - Sequence 86032 from Patent EP1572962. JD517196 - Sequence 498220 from Patent EP1572962. JD189823 - Sequence 170847 from Patent EP1572962. JD230114 - Sequence 211138 from Patent EP1572962. JD282008 - Sequence 263032 from Patent EP1572962. JD561440 - Sequence 542464 from Patent EP1572962. JD093086 - Sequence 74110 from Patent EP1572962. JD184204 - Sequence 165228 from Patent EP1572962. JD268505 - Sequence 249529 from Patent EP1572962. JD143903 - Sequence 124927 from Patent EP1572962. JD045083 - Sequence 26107 from Patent EP1572962. JD532243 - Sequence 513267 from Patent EP1572962. JD558755 - Sequence 539779 from Patent EP1572962. JD452793 - Sequence 433817 from Patent EP1572962. JD533120 - Sequence 514144 from Patent EP1572962. JD361913 - Sequence 342937 from Patent EP1572962. JD533121 - Sequence 514145 from Patent EP1572962. JD471585 - Sequence 452609 from Patent EP1572962. JD533119 - Sequence 514143 from Patent EP1572962. JD199502 - Sequence 180526 from Patent EP1572962. JD250045 - Sequence 231069 from Patent EP1572962. JD119118 - Sequence 100142 from Patent EP1572962. JD276677 - Sequence 257701 from Patent EP1572962. JD160024 - Sequence 141048 from Patent EP1572962. JD548467 - Sequence 529491 from Patent EP1572962. JD137087 - Sequence 118111 from Patent EP1572962. JD296317 - Sequence 277341 from Patent EP1572962. JD375224 - Sequence 356248 from Patent EP1572962. M65272 - Human cytotoxic lymphocyte maturation factor 40 kDa subunit mRNA, complete cds. JD042975 - Sequence 23999 from Patent EP1572962. BC067498 - Homo sapiens interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40), mRNA (cDNA clone MGC:79355 IMAGE:6971868), complete cds. BC067499 - Homo sapiens interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40), mRNA (cDNA clone MGC:79356 IMAGE:6971869), complete cds. BC067500 - Homo sapiens interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40), mRNA (cDNA clone MGC:79358 IMAGE:6971872), complete cds. BC067501 - Homo sapiens interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40), mRNA (cDNA clone MGC:79359 IMAGE:6971873), complete cds. BC067502 - Homo sapiens interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40), mRNA (cDNA clone MGC:79360 IMAGE:6971874), complete cds. JD539304 - Sequence 520328 from Patent EP1572962. BC074723 - Homo sapiens interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40), mRNA (cDNA clone MGC:103792 IMAGE:30915173), complete cds. AF180563 - Homo sapiens interleukin 12, P40 mRNA, complete cds. HQ447568 - Synthetic construct Homo sapiens clone IMAGE:100070909; CCSB014586_01 interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, (IL12B) gene, encodes complete protein. KJ897050 - Synthetic construct Homo sapiens clone ccsbBroadEn_06444 IL12B gene, encodes complete protein. CU688308 - Synthetic construct Homo sapiens gateway clone IMAGE:100022944 5' read IL12B mRNA. AB590700 - Synthetic construct DNA, clone: pFN21AE1812, Homo sapiens IL12B gene for interleukin 12B, without stop codon, in Flexi system. EF173865 - Homo sapiens interleukin 12 mRNA, partial cds. JD396554 - Sequence 377578 from Patent EP1572962. MB420117 - JP 2019519517-A/125: COMBINATIONS OF MRNAS ENCODING IMMUNE MODULATING POLYPEPTIDES AND USES THEREOF. MB420118 - JP 2019519517-A/126: COMBINATIONS OF MRNAS ENCODING IMMUNE MODULATING POLYPEPTIDES AND USES THEREOF. MP517998 - Sequence 17 from Patent WO2020041655.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_th1th2Pathway - Th1/Th2 Differentiation
Reactome (by CSHL, EBI, and GO)
Protein P29460 (Reactome details) participates in the following event(s):
R-HSA-8950183 IL12B binds IL23A R-HSA-8950456 IL12B dimerizes R-HSA-447226 Interleukin-12 binds Interleukin-12 receptor R-HSA-8950128 Interleukin-12 dissociates from Interleukin-12 receptor R-HSA-8950347 IL12A:IL12B translocates from late endosome lumen to extracellular region R-HSA-8950752 IL12A:IL12B translocates from Golgi lumen to late endosome lumen R-HSA-8950423 JAK2, TYK2 in IL12A:IL12RB1:TYK2:IL12B:IL12RB2:JAK2 are phosphorylated R-HSA-8950448 STAT4 binds to IL12RB2 in Interleukin-12 receptor complex R-HSA-8950364 IL23R in IL23:IL23 receptor complex is phosphorylated R-HSA-9020591 Interleukin-12 signaling R-HSA-9020933 Interleukin-23 signaling R-HSA-6783783 Interleukin-10 signaling R-HSA-447115 Interleukin-12 family signaling R-HSA-6785807 Interleukin-4 and 13 signaling R-HSA-449147 Signaling by Interleukins R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-168256 Immune System
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
