IL12B_HUMAN
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 03-AUG-2022, entry version 230.
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. {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/";
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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; 5.
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; DB06083; Tapinarof.
DR DrugBank; DB14004; Tildrakizumab.
DR DrugBank; DB05679; Ustekinumab.
DR DrugCentral; P29460; -.
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; P29460; -.
DR PeptideAtlas; P29460; -.
DR PRIDE; P29460; -.
DR ABCD; P29460; 23 sequenced antibodies.
DR Antibodypedia; 16629; 979 antibodies from 48 providers.
DR DNASU; 3593; -.
DR Ensembl; ENST00000231228.3; ENSP00000231228.2; ENSG00000113302.5.
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 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; 1179405at2759; -.
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 1071 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 lymph node and 28 other tissues.
DR Genevisible; P29460; HS.
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:ComplexPortal.
DR GO; GO:0043514; C:interleukin-12 complex; IDA:UniProtKB.
DR GO; GO:0042022; C:interleukin-12 receptor complex; IC:ComplexPortal.
DR GO; GO:0070743; C:interleukin-23 complex; IDA:BHF-UCL.
DR GO; GO:0072536; C:interleukin-23 receptor complex; IC:ComplexPortal.
DR GO; GO:0031906; C:late endosome lumen; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
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:0071346; P:cellular response to interferon-gamma; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; 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:0006955; P:immune response; IC:ComplexPortal.
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:0032729; P:positive regulation of interferon-gamma production; IDA:ComplexPortal.
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:1901224; P:positive regulation of NIK/NF-kappaB signaling; TAS: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:0045672; P:positive regulation of osteoclast differentiation; IDA:BHF-UCL.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:ComplexPortal.
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; IDA:ComplexPortal.
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: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:0019233; P:sensory perception of pain; IEA:Ensembl.
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; -; 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; PTHR23036:SF156; PTHR23036:SF156; 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; SSF48726; SSF48726; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS01354; HEMATOPO_REC_L_F3; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
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
