ID IL12B_HUMAN Reviewed; 328 AA. AC P29460; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 27-MAR-2024, entry version 239. DE RecName: Full=Interleukin-12 subunit beta; DE Short=IL-12B; DE AltName: Full=Cytotoxic lymphocyte maturation factor 40 kDa subunit; DE Short=CLMF p40; DE AltName: Full=IL-12 subunit p40; DE AltName: Full=NK cell stimulatory factor chain 2; DE Short=NKSF2; DE Flags: Precursor; GN Name=IL12B; Synonyms=NKSF2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1674604; DOI=10.1073/pnas.88.10.4143; RA Gubler U., Chua A.O., Schoenhaut D.S., Dwyer C.M., McComas W., Motyka R., RA Nabavi N., Wolitzky A.G., Quinn P.M., Familletti P.C., Gately M.K.; RT "Coexpression of two distinct genes is required to generate secreted RT bioactive cytotoxic lymphocyte maturation factor."; RL Proc. Natl. Acad. Sci. U.S.A. 88:4143-4147(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1673147; RA Wolf S.F., Temple P.A., Kobayashi M., Young D., Dicig M., Lowe L., RA Dzialo R., Fitz L., Ferenz C., Hewick R.M., Kelleher K., Herrmann S.H., RA Clark S.C., Azzoni L., Chan S.H., Trinchieri G., Perussia B.; RT "Cloning of cDNA for natural killer cell stimulatory factor, a RT heterodimeric cytokine with multiple biologic effects on T and natural RT killer cells."; RL J. Immunol. 146:3074-3081(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11197695; DOI=10.1038/sj.gene.6363720; RA Huang D., Cancilla M.R., Morahan G.; RT "Complete primary structure, chromosomal localization, and definition of RT polymorphisms of the gene encoding the human interleukin 12 p40 subunit."; RL Genes Immun. 1:515-520(2000). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Hongyuan J., Meiyun Z.; RT "Cloning and sequence analysis of IL-12 cDNA from Chinese."; RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-33 AND PHE-298. RG SeattleSNPs variation discovery resource; RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 23-45. RX PubMed=2204066; DOI=10.1073/pnas.87.17.6808; RA Stern A.S., Podlaski F.J., Hulmes J.D., Pan Y.C.E., Quinn P.M., RA Wolitzky A.G., Familletti P.C., Stremlo D.L., Truitt T., Chizzonite R., RA Gately M.K.; RT "Purification to homogeneity and partial characterization of cytotoxic RT lymphocyte maturation factor from human B-lymphoblastoid cells."; RL Proc. Natl. Acad. Sci. U.S.A. 87:6808-6812(1990). RN [8] RP SIMILARITY TO IL-6 RECEPTOR. RX PubMed=2070420; DOI=10.1016/0092-8674(91)90131-h; RA Gearing D.P., Cosman D.; RT "Homology of the p40 subunit of natural killer cell stimulatory factor RT (NKSF) with the extracellular domain of the interleukin-6 receptor."; RL Cell 66:9-10(1991). RN [9] RP SUBUNIT. RX PubMed=7836910; DOI=10.1084/jem.181.2.537; RA D'Andrea A., Ma X., Aste-Amezaga M., Paganin C., Trinchieri G.; RT "Stimulatory and inhibitory effects of interleukin (IL)-4 and IL-13 on the RT production of cytokines by human peripheral blood mononuclear cells: RT priming for IL-12 and tumor necrosis factor alpha production."; RL J. Exp. Med. 181:537-546(1995). RN [10] RP GLYCOSYLATION AT TRP-319. RX PubMed=10207176; DOI=10.1093/glycob/9.5.435; RA Doucey M.A., Hess D., Blommers M.J., Hofsteenge J.; RT "Recombinant human interleukin-12 is the second example of a C-mannosylated RT protein."; RL Glycobiology 9:435-441(1999). RN [11] RP INVOLVEMENT IN IMD29. RX PubMed=9854038; DOI=10.1172/jci4950; RA Altare F., Lammas D., Revy P., Jouanguy E., Doeffinger R., RA Lamhamedi-Cherradi S.-E., Drysdale P., Scheel-Toellner D., Girdlestone J., RA Darbyshire P., Wadhwa M., Dockrell H., Salmon M., Fischer A., Durandy A., RA Casanova J.-L., Kumararatne D.S.; RT "Inherited interleukin 12 deficiency in a child with bacille Calmette- RT Guerin and Salmonella enteritidis disseminated infection."; RL J. Clin. Invest. 102:2035-2040(1998). RN [12] RP FUNCTION, AND INTERACTION WITH IL23A. RX PubMed=11114383; DOI=10.1016/s1074-7613(00)00070-4; RA Oppmann B., Lesley R., Blom B., Timans J.C., Xu Y., Hunte B., Vega F., RA Yu N., Wang J., Singh K.P., Zonin F., Vaisberg E., Churakova T., Liu M.-R., RA Gorman D., Wagner J., Zurawski S., Liu Y.-J., Abrams J.S., Moore K.W., RA Rennick D.M., de Waal-Malefyt R., Hannum C., Bazan J.F., Kastelein R.A.; RT "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with RT biological activities similar as well as distinct from IL-12."; RL Immunity 13:715-725(2000). RN [13] RP INVOLVEMENT IN IMD29. RX PubMed=11753820; DOI=10.1086/338625; RA Picard C., Fieschi C., Altare F., Al-Jumaah S., Al-Hajjar S., Feinberg J., RA Dupuis S., Soudais C., Al-Mohsen I.Z., Genin E., Lammas D., RA Kumararatne D.S., Leclerc T., Rafii A., Frayha H., Murugasu B., Wah L.B., RA Sinniah R., Loubser M., Okamoto E., Al-Ghonaium A., Tufenkeji H., Abel L., RA Casanova J.-L.; RT "Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype RT of 13 patients from six kindreds."; RL Am. J. Hum. Genet. 70:336-348(2002). RN [14] RP ASSOCIATION WITH PSORIASIS. RX PubMed=17587057; DOI=10.1007/s00439-007-0397-0; RA Capon F., Di Meglio P., Szaub J., Prescott N.J., Dunster C., Baumber L., RA Timms K., Gutin A., Abkevic V., Burden A.D., Lanchbury J., Barker J.N., RA Trembath R.C., Nestle F.O.; RT "Sequence variants in the genes for the interleukin-23 receptor (IL23R) and RT its ligand (IL12B) confer protection against psoriasis."; RL Hum. Genet. 122:201-206(2007). RN [15] RP ASSOCIATION WITH PSORIASIS. RX PubMed=18800148; DOI=10.1038/jid.2008.233; RA Huffmeier U., Lascorz J., Bohm B., Lohmann J., Wendler J., Mossner R., RA Reich K., Traupe H., Kurrat W., Burkhardt H., Reis A.; RT "Genetic variants of the IL-23R pathway: association with psoriatic RT arthritis and psoriasis vulgaris, but no specific risk factor for RT arthritis."; RL J. Invest. Dermatol. 129:355-358(2009). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-328 ALONE AND IN COMPLEX WITH RP IL12A, GLYCOSYLATION AT ASN-222, AND DISULFIDE BONDS. RX PubMed=10899108; DOI=10.1093/emboj/19.14.3530; RA Yoon C., Johnston S.C., Tang J., Stahl M., Tobin J.F., Somers W.S.; RT "Charged residues dominate a unique interlocking topography in the RT heterodimeric cytokine interleukin-12."; RL EMBO J. 19:3530-3541(2000). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 23-328 IN COMPLEX WITH IL23A AND RP ANTIBODY. RX PubMed=18708069; DOI=10.1016/j.jmb.2008.08.001; RA Beyer B.M., Ingram R., Ramanathan L., Reichert P., Le H.V., Madison V., RA Orth P.; RT "Crystal structures of the pro-inflammatory cytokine interleukin-23 and its RT complex with a high-affinity neutralizing antibody."; RL J. Mol. Biol. 382:942-955(2008). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 23-328 IN COMPLEX WITH IL23A, AND RP SUBUNIT. RX PubMed=18680750; DOI=10.1016/j.jmb.2008.07.051; RA Lupardus P.J., Garcia K.C.; RT "The structure of interleukin-23 reveals the molecular basis of p40 subunit RT sharing with interleukin-12."; RL J. Mol. Biol. 382:931-941(2008). CC -!- FUNCTION: Cytokine that can act as a growth factor for activated T and CC NK cells, enhance the lytic activity of NK/lymphokine-activated killer CC cells, and stimulate the production of IFN-gamma by resting PBMC. CC {ECO:0000269|PubMed:11114383}. CC -!- FUNCTION: Associates with IL23A to form the IL-23 interleukin, a CC heterodimeric cytokine which functions in innate and adaptive immunity. CC IL-23 may constitute with IL-17 an acute response to infection in CC peripheral tissues. IL-23 binds to a heterodimeric receptor complex CC composed of IL12RB1 and IL23R, activates the Jak-Stat signaling CC cascade, stimulates memory rather than naive T-cells and promotes CC production of pro-inflammatory cytokines. IL-23 induces autoimmune CC inflammation and thus may be responsible for autoimmune inflammatory CC diseases and may be important for tumorigenesis. CC {ECO:0000269|PubMed:11114383}. CC -!- SUBUNIT: Heterodimer with IL12A; disulfide-linked. The heterodimer is CC known as interleukin IL-12. Heterodimer with IL23A; disulfide-linked. CC The heterodimer is known as interleukin IL-23. Also secreted as a CC monomer. Interacts with NBR1; this interaction promotes IL-12 secretion CC (By similarity). {ECO:0000250|UniProtKB:P43432, CC ECO:0000269|PubMed:10899108, ECO:0000269|PubMed:18680750, CC ECO:0000269|PubMed:18708069, ECO:0000269|PubMed:7836910}. CC -!- INTERACTION: CC P29460; P29459: IL12A; NbExp=2; IntAct=EBI-1029614, EBI-1029636; CC P29460; P29460: IL12B; NbExp=2; IntAct=EBI-1029614, EBI-1029614; CC P29460; Q9NPF7: IL23A; NbExp=6; IntAct=EBI-1029614, EBI-2481154; CC P29460; Q9EQ14: Il23a; Xeno; NbExp=2; IntAct=EBI-1029614, EBI-2481329; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- PTM: Known to be C-mannosylated in the recombinant protein; it is not CC yet known for sure if the wild-type protein is also modified. CC -!- DISEASE: Immunodeficiency 29 (IMD29) [MIM:614890]: A form of Mendelian CC susceptibility to mycobacterial disease, a rare condition caused by CC impairment of interferon-gamma mediated immunity. It is characterized CC by predisposition to illness caused by moderately virulent CC mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, CC environmental non-tuberculous mycobacteria, and by the more virulent CC Mycobacterium tuberculosis. Other microorganisms rarely cause severe CC clinical disease in individuals with susceptibility to mycobacterial CC infections, with the exception of Salmonella which infects less than CC 50% of these individuals. Clinical outcome severity depends on the CC degree of impairment of interferon-gamma mediated immunity. Some CC patients die of overwhelming mycobacterial disease with lepromatous- CC like lesions in early childhood, whereas others develop, later in life, CC disseminated but curable infections with tuberculoid granulomas. IMD29 CC is characterized by undetectable IL12B secretion from leukocytes. CC Affected individuals generally present with BCG disease after CC vaccination in childhood, and at least half also have Salmonella CC infection. Disease phenotype is relatively mild, and patients have a CC good prognosis. {ECO:0000269|PubMed:11753820, CC ECO:0000269|PubMed:9854038}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Psoriasis 11 (PSORS11) [MIM:612599]: A common, chronic CC inflammatory disease of the skin with multifactorial etiology. It is CC characterized by red, scaly plaques usually found on the scalp, elbows CC and knees. These lesions are caused by abnormal keratinocyte CC proliferation and infiltration of inflammatory cells into the dermis CC and epidermis. Note=Disease susceptibility is associated with variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the IL-12B family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=IL12Bbase; Note=IL12B mutation db; CC URL="http://structure.bmc.lu.se/idbase/IL12Bbase/"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/il12b/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M65272; AAA35695.1; -; mRNA. DR EMBL; M65290; AAA59938.1; -; mRNA. DR EMBL; AY008847; AAG32620.1; -; Genomic_DNA. DR EMBL; AF180563; AAD56386.1; -; mRNA. DR EMBL; AF512686; AAM34792.1; -; Genomic_DNA. DR EMBL; BC067498; AAH67498.1; -; mRNA. DR EMBL; BC067499; AAH67499.1; -; mRNA. DR EMBL; BC067500; AAH67500.1; -; mRNA. DR EMBL; BC067501; AAH67501.1; -; mRNA. DR EMBL; BC067502; AAH67502.1; -; mRNA. DR EMBL; BC074723; AAH74723.1; -; mRNA. DR CCDS; CCDS4346.1; -. DR PIR; A38957; A38957. DR RefSeq; NP_002178.2; NM_002187.2. DR PDB; 1F42; X-ray; 2.50 A; A=23-328. DR PDB; 1F45; X-ray; 2.80 A; A=23-328. DR PDB; 3D85; X-ray; 1.90 A; D=23-328. DR PDB; 3D87; X-ray; 2.90 A; B/D=23-328. DR PDB; 3DUH; X-ray; 2.30 A; A/B=23-328. DR PDB; 3HMX; X-ray; 3.00 A; A=23-328. DR PDB; 3QWR; X-ray; 3.25 A; A=23-328. DR PDB; 4GRW; X-ray; 2.55 A; B/D=1-328. DR PDB; 5MJ3; X-ray; 1.74 A; A=23-328. DR PDB; 5MJ4; X-ray; 3.40 A; A=23-328. DR PDB; 5MXA; X-ray; 2.50 A; A=1-328. DR PDB; 5MZV; X-ray; 2.80 A; A=1-328. DR PDB; 5NJD; X-ray; 3.90 A; A/C/E/G/I/K=1-328. DR PDB; 6UIB; X-ray; 2.74 A; B=23-328. DR PDB; 6WDQ; X-ray; 3.40 A; A=21-328. DR PDBsum; 1F42; -. DR PDBsum; 1F45; -. DR PDBsum; 3D85; -. DR PDBsum; 3D87; -. DR PDBsum; 3DUH; -. DR PDBsum; 3HMX; -. DR PDBsum; 3QWR; -. DR PDBsum; 4GRW; -. DR PDBsum; 5MJ3; -. DR PDBsum; 5MJ4; -. DR PDBsum; 5MXA; -. DR PDBsum; 5MZV; -. DR PDBsum; 5NJD; -. DR PDBsum; 6UIB; -. DR PDBsum; 6WDQ; -. DR AlphaFoldDB; P29460; -. DR SMR; P29460; -. DR BioGRID; 109807; 3. DR ComplexPortal; CPX-3290; Interleukin-23 complex. DR ComplexPortal; CPX-381; Interleukin-12 complex. DR ComplexPortal; CPX-382; Interleukin-12-receptor complex. DR ComplexPortal; CPX-383; Interleukin-23-receptor complex. DR CORUM; P29460; -. DR DIP; DIP-3774N; -. DR ELM; P29460; -. DR IntAct; P29460; 4. DR STRING; 9606.ENSP00000231228; -. DR ChEMBL; CHEMBL3580484; -. DR DrugBank; DB02763; 5-Mercapto-2-Nitro-Benzoic Acid. DR DrugBank; DB05459; Briakinumab. DR DrugBank; DB05848; humanized SMART Anti-IL-12 Antibody. DR DrugBank; DB14762; Risankizumab. DR DrugBank; DB14004; Tildrakizumab. DR DrugBank; DB05679; Ustekinumab. DR DrugCentral; P29460; -. DR GlyCosmos; P29460; 3 sites, 1 glycan. DR GlyGen; P29460; 3 sites, 1 C-linked glycan (1 site). DR iPTMnet; P29460; -. DR PhosphoSitePlus; P29460; -. DR BioMuta; IL12B; -. DR DMDM; 266320; -. DR MassIVE; P29460; -. DR PaxDb; 9606-ENSP00000231228; -. DR PeptideAtlas; P29460; -. DR ProteomicsDB; 54570; -. DR ABCD; P29460; 23 sequenced antibodies. DR Antibodypedia; 16629; 1156 antibodies from 48 providers. DR DNASU; 3593; -. DR Ensembl; ENST00000231228.3; ENSP00000231228.2; ENSG00000113302.6. DR GeneID; 3593; -. DR KEGG; hsa:3593; -. DR MANE-Select; ENST00000231228.3; ENSP00000231228.2; NM_002187.3; NP_002178.2. DR UCSC; uc003lxr.2; human. DR AGR; HGNC:5970; -. DR CTD; 3593; -. DR DisGeNET; 3593; -. DR GeneCards; IL12B; -. DR HGNC; HGNC:5970; IL12B. DR HPA; ENSG00000113302; Tissue enhanced (lymphoid). DR MalaCards; IL12B; -. DR MIM; 161561; gene. DR MIM; 612599; phenotype. DR MIM; 614890; phenotype. DR neXtProt; NX_P29460; -. DR OpenTargets; ENSG00000113302; -. DR Orphanet; 319558; Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency. DR Orphanet; 3287; Takayasu arteritis. DR PharmGKB; PA29785; -. DR VEuPathDB; HostDB:ENSG00000113302; -. DR eggNOG; ENOG502RZMA; Eukaryota. DR GeneTree; ENSGT00390000012630; -. DR HOGENOM; CLU_071206_1_0_1; -. DR InParanoid; P29460; -. DR OMA; VAIWELK; -. DR OrthoDB; 4006511at2759; -. DR PhylomeDB; P29460; -. DR TreeFam; TF334829; -. DR PathwayCommons; P29460; -. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-9020591; Interleukin-12 signaling. DR Reactome; R-HSA-9020933; Interleukin-23 signaling. DR SignaLink; P29460; -. DR SIGNOR; P29460; -. DR BioGRID-ORCS; 3593; 16 hits in 1155 CRISPR screens. DR EvolutionaryTrace; P29460; -. DR GeneWiki; Interleukin-12_subunit_beta; -. DR GenomeRNAi; 3593; -. DR Pharos; P29460; Tclin. DR PRO; PR:P29460; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P29460; Protein. DR Bgee; ENSG00000113302; Expressed in primordial germ cell in gonad and 29 other cell types or tissues. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProt. DR GO; GO:0043514; C:interleukin-12 complex; IDA:UniProtKB. DR GO; GO:0070743; C:interleukin-23 complex; IDA:BHF-UCL. DR GO; GO:0031906; C:late endosome lumen; TAS:Reactome. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0005125; F:cytokine activity; IDA:UniProt. DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central. DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0042164; F:interleukin-12 alpha subunit binding; IPI:AgBase. DR GO; GO:0005143; F:interleukin-12 receptor binding; TAS:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0016477; P:cell migration; IDA:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0071346; P:cellular response to type II interferon; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:BHF-UCL. DR GO; GO:0042832; P:defense response to protozoan; IEA:Ensembl. DR GO; GO:0051607; P:defense response to virus; IEA:Ensembl. DR GO; GO:0035722; P:interleukin-12-mediated signaling pathway; IDA:UniProt. DR GO; GO:0030101; P:natural killer cell activation; IDA:UniProtKB. DR GO; GO:0002323; P:natural killer cell activation involved in immune response; IEA:Ensembl. DR GO; GO:1903588; P:negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IGI:ARUK-UCL. DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; IEA:Ensembl. DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IMP:BHF-UCL. DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IDA:BHF-UCL. DR GO; GO:0050709; P:negative regulation of protein secretion; IGI:ARUK-UCL. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IDA:BHF-UCL. DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; IGI:ARUK-UCL. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:UniProtKB. DR GO; GO:0010536; P:positive regulation of activation of Janus kinase activity; IDA:BHF-UCL. DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:BHF-UCL. DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IDA:BHF-UCL. DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:BHF-UCL. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:BHF-UCL. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:BHF-UCL. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:BHF-UCL. DR GO; GO:0050671; P:positive regulation of lymphocyte proliferation; IDA:UniProtKB. DR GO; GO:0043382; P:positive regulation of memory T cell differentiation; ISS:BHF-UCL. DR GO; GO:0032946; P:positive regulation of mononuclear cell proliferation; IMP:AgBase. DR GO; GO:0032816; P:positive regulation of natural killer cell activation; IDA:UniProtKB. DR GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IDA:UniProtKB. DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IDA:BHF-UCL. DR GO; GO:0051135; P:positive regulation of NK T cell activation; IDA:BHF-UCL. DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; IDA:BHF-UCL. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; TAS:BHF-UCL. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:BHF-UCL. DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; IDA:BHF-UCL. DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; ISS:BHF-UCL. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:BHF-UCL. DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IDA:BHF-UCL. DR GO; GO:2000330; P:positive regulation of T-helper 17 cell lineage commitment; ISS:BHF-UCL. DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; ISS:BHF-UCL. DR GO; GO:0034105; P:positive regulation of tissue remodeling; IC:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:BHF-UCL. DR GO; GO:0032729; P:positive regulation of type II interferon production; IDA:UniProtKB. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL. DR GO; GO:0001817; P:regulation of cytokine production; TAS:UniProtKB. DR GO; GO:0042509; P:regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL. DR GO; GO:0010224; P:response to UV-B; IDA:UniProtKB. DR GO; GO:0019953; P:sexual reproduction; TAS:BHF-UCL. DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl. DR GO; GO:0042088; P:T-helper 1 type immune response; TAS:UniProtKB. DR GO; GO:0042093; P:T-helper cell differentiation; IDA:UniProtKB. DR CDD; cd00063; FN3; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 3. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR003530; Hematopoietin_rcpt_L_F3_CS. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR015528; IL-12_beta. DR InterPro; IPR019482; IL-12_beta_cen-dom. DR PANTHER; PTHR48397:SF1; INTERLEUKIN-12 SUBUNIT BETA; 1. DR PANTHER; PTHR48397; INTERLEUKIN-12 SUBUNIT BETA-RELATED; 1. DR Pfam; PF10420; IL12p40_C; 1. DR PIRSF; PIRSF038007; IL_12_beta; 1. DR PRINTS; PR01928; INTRLEUKN12B. DR SMART; SM00408; IGc2; 1. DR SUPFAM; SSF49265; Fibronectin type III; 2. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR PROSITE; PS50853; FN3; 1. DR PROSITE; PS01354; HEMATOPO_REC_L_F3; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR Genevisible; P29460; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytokine; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Immunoglobulin domain; Reference proteome; Secreted; Signal. FT SIGNAL 1..22 FT /evidence="ECO:0000269|PubMed:2204066" FT CHAIN 23..328 FT /note="Interleukin-12 subunit beta" FT /id="PRO_0000010930" FT DOMAIN 23..106 FT /note="Ig-like C2-type" FT DOMAIN 237..328 FT /note="Fibronectin type-III" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT CARBOHYD 135 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 222 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:10899108" FT CARBOHYD 319 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000269|PubMed:10207176" FT /id="CAR_000187" FT DISULFID 50..90 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:10899108" FT DISULFID 131..142 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:10899108" FT DISULFID 170..193 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:10899108" FT DISULFID 199 FT /note="Interchain (with C-96 in IL12A and C-73 in IL23A)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:10899108, ECO:0000269|PubMed:18800148" FT DISULFID 300..327 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:10899108" FT VARIANT 33 FT /note="V -> I (in dbSNP:rs3213096)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_020001" FT VARIANT 298 FT /note="V -> F (in dbSNP:rs3213119)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_049170" FT CONFLICT 239 FT /note="K -> N (in Ref. 2; AAA59938)" FT /evidence="ECO:0000305" FT STRAND 24..27 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 30..36 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 44..49 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 51..53 FT /evidence="ECO:0007829|PDB:3D85" FT STRAND 59..62 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 70..79 FT /evidence="ECO:0007829|PDB:5MJ3" FT HELIX 82..84 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 86..92 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 95..108 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:3D87" FT STRAND 122..126 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 130..147 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 150..160 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 166..170 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 174..181 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 184..197 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 200..202 FT /evidence="ECO:0007829|PDB:3D87" FT STRAND 208..216 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 219..227 FT /evidence="ECO:0007829|PDB:5MJ3" FT HELIX 229..232 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 239..245 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 249..257 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:3HMX" FT TURN 266..268 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 271..278 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 287..299 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 302..304 FT /evidence="ECO:0007829|PDB:5MJ4" FT STRAND 305..315 FT /evidence="ECO:0007829|PDB:5MJ3" FT STRAND 323..326 FT /evidence="ECO:0007829|PDB:5MJ3" SQ SEQUENCE 328 AA; 37169 MW; 118FA801B8F5BB2F CRC64; MCHQQLVISW FSLVFLASPL VAIWELKKDV YVVELDWYPD APGEMVVLTC DTPEEDGITW TLDQSSEVLG SGKTLTIQVK EFGDAGQYTC HKGGEVLSHS LLLLHKKEDG IWSTDILKDQ KEPKNKTFLR CEAKNYSGRF TCWWLTTIST DLTFSVKSSR GSSDPQGVTC GAATLSAERV RGDNKEYEYS VECQEDSACP AAEESLPIEV MVDAVHKLKY ENYTSSFFIR DIIKPDPPKN LQLKPLKNSR QVEVSWEYPD TWSTPHSYFS LTFCVQVQGK SKREKKDRVF TDKTSATVIC RKNASISVRA QDRYYSSSWS EWASVPCS //