ID IL12A_HUMAN Reviewed; 219 AA. AC P29459; Q96QZ1; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2002, sequence version 2. DT 23-FEB-2022, entry version 187. DE RecName: Full=Interleukin-12 subunit alpha; DE Short=IL-12A; DE AltName: Full=Cytotoxic lymphocyte maturation factor 35 kDa subunit; DE Short=CLMF p35; DE AltName: Full=IL-12 subunit p35; DE AltName: Full=NK cell stimulatory factor chain 1; DE Short=NKSF1; DE Flags: Precursor; GN Name=IL12A; Synonyms=NKSF1; 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], AND FUNCTION. 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. 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 [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [5] RP PROTEIN SEQUENCE OF 23-48, AND FUNCTION. 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 [6] RP SIMILARITY TO IL-6. RX PubMed=1374259; DOI=10.1016/0167-5699(92)90140-3; RA Merberg D.M., Wolf S.F., Clark S.C.; RT "Sequence similarity between NKSF and the IL-6/G-CSF family."; RL Immunol. Today 13:77-78(1992). RN [7] RP SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=9342359; DOI=10.1073/pnas.94.22.12041; RA Devergne O., Birkenbach M., Kieff E.; RT "Epstein-Barr virus-induced gene 3 and the p35 subunit of interleukin 12 RT form a novel heterodimeric hematopoietin."; RL Proc. Natl. Acad. Sci. U.S.A. 94:12041-12046(1997). RN [8] RP INDUCTION (MICROBIAL INFECTION), AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16548883; DOI=10.1111/j.1462-5822.2005.00644.x; RA Leong W.F., Chow V.T.; RT "Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal RT differential cellular gene expression in response to enterovirus 71 RT infection."; RL Cell. Microbiol. 8:565-580(2006). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 23-219, SUBUNIT, AND DISULFIDE RP 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). 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:1673147, ECO:0000269|PubMed:1674604, CC ECO:0000269|PubMed:2204066}. CC -!- SUBUNIT: Heterodimer with IL12B; disulfide-linked (PubMed:1674604, CC PubMed:10899108). This heterodimer is known as interleukin IL-12 CC (PubMed:1674604). Heterodimer with EBI3/IL27B; not disulfide-linked CC (PubMed:9342359). This heterodimer is known as interleukin IL-35 CC (PubMed:9342359). {ECO:0000269|PubMed:10899108, CC ECO:0000269|PubMed:1674604, ECO:0000269|PubMed:9342359}. CC -!- INTERACTION: CC P29459; P29460: IL12B; NbExp=2; IntAct=EBI-1029636, EBI-1029614; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1674604, CC ECO:0000269|PubMed:9342359}. CC -!- INDUCTION: (Microbial infection) Down-regulated in response to CC enterovirus 71 (EV71) infection. {ECO:0000269|PubMed:16548883}. CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA59937.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-12 entry; CC URL="https://en.wikipedia.org/wiki/Interleukin_12"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/il12a/"; 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; M65291; AAA59937.1; ALT_INIT; mRNA. DR EMBL; M65271; AAA35694.1; -; mRNA. DR EMBL; AF404773; AAK84425.1; -; Genomic_DNA. DR EMBL; AC010370; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR RefSeq; NP_000873.2; NM_000882.3. DR PDB; 1F45; X-ray; 2.80 A; B=23-219. DR PDB; 3HMX; X-ray; 3.00 A; B=23-219. DR PDBsum; 1F45; -. DR PDBsum; 3HMX; -. DR SMR; P29459; -. DR BioGRID; 109806; 9. DR ComplexPortal; CPX-381; Interleukin-12 complex. DR ComplexPortal; CPX-382; Interleukin-12-receptor complex. DR CORUM; P29459; -. DR DIP; DIP-3772N; -. DR IntAct; P29459; 8. DR STRING; 9606.ENSP00000303231; -. DR ChEMBL; CHEMBL2364153; -. DR DrugCentral; P29459; -. DR GlyGen; P29459; 2 sites. DR iPTMnet; P29459; -. DR PhosphoSitePlus; P29459; -. DR BioMuta; IL12A; -. DR DMDM; 20141534; -. DR PaxDb; P29459; -. DR PeptideAtlas; P29459; -. DR PRIDE; P29459; -. DR ABCD; P29459; 1 sequenced antibody. DR Antibodypedia; 853; 1015 antibodies from 45 providers. DR DNASU; 3592; -. DR Ensembl; ENST00000305579; ENSP00000303231; ENSG00000168811. DR GeneID; 3592; -. DR KEGG; hsa:3592; -. DR UCSC; uc003fcx.4; human. DR CTD; 3592; -. DR DisGeNET; 3592; -. DR GeneCards; IL12A; -. DR HGNC; HGNC:5969; IL12A. DR HPA; ENSG00000168811; Tissue enhanced (esophagus). DR MalaCards; IL12A; -. DR MIM; 161560; gene. DR neXtProt; NX_P29459; -. DR Orphanet; 117; Behcet disease. DR Orphanet; 186; Primary biliary cholangitis. DR PharmGKB; PA29784; -. DR VEuPathDB; HostDB:ENSG00000168811; -. DR eggNOG; ENOG502S8JN; Eukaryota. DR InParanoid; P29459; -. DR OrthoDB; 1409826at2759; -. DR PhylomeDB; P29459; -. DR TreeFam; TF330814; -. DR PathwayCommons; P29459; -. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-8984722; Interleukin-35 Signalling. DR Reactome; R-HSA-9020591; Interleukin-12 signaling. DR SignaLink; P29459; -. DR SIGNOR; P29459; -. DR BioGRID-ORCS; 3592; 10 hits in 1043 CRISPR screens. DR EvolutionaryTrace; P29459; -. DR GeneWiki; IL12A; -. DR GenomeRNAi; 3592; -. DR Pharos; P29459; Tclin. DR PRO; PR:P29459; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P29459; protein. DR Bgee; ENSG00000168811; Expressed in lower esophagus mucosa and 104 other tissues. DR ExpressionAtlas; P29459; baseline and differential. DR Genevisible; P29459; HS. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. 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:0031906; C:late endosome lumen; TAS:Reactome. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0042163; F:interleukin-12 beta subunit binding; IPI:AgBase. DR GO; GO:0005143; F:interleukin-12 receptor binding; NAS:UniProtKB. DR GO; GO:0045513; F:interleukin-27 binding; IPI:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB. DR GO; GO:0016477; P:cell migration; IDA:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; IMP:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEP:UniProtKB. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:BHF-UCL. DR GO; GO:0006955; P:immune response; TAS:UniProtKB. DR GO; GO:1903588; P:negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IGI:ARUK-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:0045785; P:positive regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; IMP:UniProtKB. DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:ComplexPortal. DR GO; GO:0050671; P:positive regulation of lymphocyte proliferation; IDA:UniProtKB. 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:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; 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:ComplexPortal. 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:ComplexPortal. 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; IDA:UniProtKB. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:ComplexPortal. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:UniProtKB. DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:UniProtKB. DR GO; GO:0010224; P:response to UV-B; IDA:UniProtKB. DR GO; GO:0009615; P:response to virus; IEP:UniProtKB. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR004281; IL-12_alpha. DR Pfam; PF03039; IL12; 1. DR SUPFAM; SSF47266; SSF47266; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytokine; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Growth factor; Host-virus interaction; Reference proteome; KW Secreted; Signal. FT SIGNAL 1..22 FT /evidence="ECO:0000269|PubMed:2204066" FT CHAIN 23..219 FT /note="Interleukin-12 subunit alpha" FT /id="PRO_0000015604" FT CARBOHYD 93 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 107 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 64..196 FT /evidence="ECO:0000269|PubMed:10899108" FT DISULFID 85..123 FT /evidence="ECO:0000269|PubMed:10899108" FT DISULFID 96 FT /note="Interchain (with C-199 in IL12B)" FT /evidence="ECO:0000269|PubMed:10899108" FT CONFLICT 213 FT /note="M -> T (in Ref. 2; AAA35694)" FT /evidence="ECO:0000305" FT HELIX 43..58 FT /evidence="ECO:0007829|PDB:1F45" FT HELIX 59..61 FT /evidence="ECO:0007829|PDB:1F45" FT TURN 74..78 FT /evidence="ECO:0007829|PDB:3HMX" FT HELIX 81..84 FT /evidence="ECO:0007829|PDB:1F45" FT HELIX 88..92 FT /evidence="ECO:0007829|PDB:1F45" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:3HMX" FT TURN 114..116 FT /evidence="ECO:0007829|PDB:3HMX" FT HELIX 118..145 FT /evidence="ECO:0007829|PDB:1F45" FT HELIX 155..169 FT /evidence="ECO:0007829|PDB:1F45" FT HELIX 190..217 FT /evidence="ECO:0007829|PDB:1F45" SQ SEQUENCE 219 AA; 24874 MW; 7C658AB7716112B2 CRC64; MCPARSLLLV ATLVLLDHLS LARNLPVATP DPGMFPCLHH SQNLLRAVSN MLQKARQTLE FYPCTSEEID HEDITKDKTS TVEACLPLEL TKNESCLNSR ETSFITNGSC LASRKTSFMM ALCLSSIYED LKMYQVEFKT MNAKLLMDPK RQIFLDQNML AVIDELMQAL NFNSETVPQK SSLEEPDFYK TKIKLCILLH AFRIRAVTID RVMSYLNAS //