IL12A_MOUSE
ID IL12A_MOUSE Reviewed; 215 AA.
AC P43431;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 157.
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 Flags: Precursor;
GN Name=Il12a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=C57BL/6J; TISSUE=Spleen;
RX PubMed=1350290;
RA Schoenhaut D.S., Chua A.O., Wolitzky A.G., Quinn P.M., Dwyer C.M.,
RA Gately M.K., Gubler U.;
RT "Cloning and expression of murine IL-12.";
RL J. Immunol. 148:3433-3440(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8647196; DOI=10.1002/eji.1830260606;
RA Tone Y., Thompson S.A., Babik J.M., Nolan K.F., Tone M., Raven C.,
RA Waldmann H.;
RT "Structure and chromosomal location of the mouse interleukin-12 p35 and p40
RT subunit genes.";
RL Eur. J. Immunol. 26:1222-1227(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-5.
RC STRAIN=129/Sv;
RX PubMed=8557982;
RA Yoshimoto T., Kojima K., Funakoshi T., Endo Y., Fujita T., Nariuchi H.;
RT "Molecular cloning and characterization of murine IL-12 genes.";
RL J. Immunol. 156:1082-1088(1996).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8766560; DOI=10.1002/eji.1830260722;
RA Mattner F., Magram J., Ferrante J., Launois P., Di Padova K., Behin R.,
RA Gately M.K., Louis J.A., Alber G.;
RT "Genetically resistant mice lacking interleukin-12 are susceptible to
RT infection with Leishmania major and mount a polarized Th2 cell response.";
RL Eur. J. Immunol. 26:1553-1559(1996).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18033300; DOI=10.1038/nature06306;
RA Collison L.W., Workman C.J., Kuo T.T., Boyd K., Wang Y., Vignali K.M.,
RA Cross R., Sehy D., Blumberg R.S., Vignali D.A.;
RT "The inhibitory cytokine IL-35 contributes to regulatory T-cell function.";
RL Nature 450:566-569(2007).
RN [6]
RP FUNCTION.
RX PubMed=30197594; DOI=10.3389/fphar.2018.00959;
RA Zheng X.F., Hu X.Y., Ma B., Fang H., Zhang F., Mao Y.F., Yang F.Y.,
RA Xiao S.C., Xia Z.F.;
RT "Interleukin-35 attenuates D-Galactosamine/Lipopolysaccharide-induced liver
RT injury via enhancing interleukin-10 production in Kupffer cells.";
RL Front. Pharmacol. 9:959-959(2018).
CC -!- FUNCTION: Heterodimerizes with IL12B to form the IL-12 cytokine or with
CC EBI3/IL27B to form the IL-35 cytokine. IL-12 is primarily produced by
CC professional antigen-presenting cells (APCs) such as B-cells and
CC dendritic cells (DCs) as well as macrophages and granulocytes and
CC regulates T-cell and natural killer-cell responses, induces the
CC production of interferon-gamma (IFN-gamma), favors the differentiation
CC of T-helper 1 (Th1) cells and is an important link between innate
CC resistance and adaptive immunity (PubMed:8766560). Mechanistically,
CC exerts its biological effects through a receptor composed of IL12R1 and
CC IL12R2 subunits. Binding to the receptor results in the rapid tyrosine
CC phosphorylation of a number of cellular substrates including the JAK
CC family kinases TYK2 and JAK2. In turn, recruited STAT4 gets
CC phosphorylated and translocates to the nucleus where it regulates
CC cytokine/growth factor responsive genes (By similarity). As part of IL-
CC 35, plays essential roles in maintaining the immune homeostasis of the
CC liver microenvironment and functions also as an immune-suppressive
CC cytokine (PubMed:18033300,PubMed:30197594). Mediates biological events
CC through unconventional receptors composed of IL12RB2 and gp130/IL6ST
CC heterodimers or homodimers. Signaling requires the transcription
CC factors STAT1 and STAT4, which form a unique heterodimer that binds to
CC distinct DNA sites (By similarity). {ECO:0000250|UniProtKB:P29459,
CC ECO:0000269|PubMed:18033300, ECO:0000269|PubMed:30197594,
CC ECO:0000269|PubMed:8766560}.
CC -!- SUBUNIT: Heterodimer with IL12B; disulfide-linked (PubMed:1350290).
CC This heterodimer is known as interleukin IL-12 (PubMed:1350290).
CC Heterodimer with EBI3/IL27B; not disulfide-linked (By similarity). This
CC heterodimer is known as interleukin IL-35 (By similarity).
CC {ECO:0000250|UniProtKB:P29459, ECO:0000269|PubMed:1350290}.
CC -!- INTERACTION:
CC P43431; O35228: Ebi3; NbExp=2; IntAct=EBI-3862959, EBI-3862967;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1350290}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutant mice display normal development
CC (PubMed:8766560). However, they are unable to restrict the progression
CC of Leishmania major infection with strong parasite load in lymphoid
CC tissues observed (PubMed:8766560). In addition, regulatory T-cells are
CC functionally defective and mice are unable to control colitis
CC (resembling inflammatory bowel disease, IBD)(PubMed:18033300).
CC {ECO:0000269|PubMed:18033300, ECO:0000269|PubMed:8766560}.
CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
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DR EMBL; M86672; AAA39292.1; -; mRNA.
DR EMBL; S82419; AAB37382.1; -; Genomic_DNA.
DR EMBL; S82412; AAB37382.1; JOINED; Genomic_DNA.
DR EMBL; S82414; AAB37382.1; JOINED; Genomic_DNA.
DR EMBL; S82417; AAB37382.1; JOINED; Genomic_DNA.
DR EMBL; S82418; AAB37382.1; JOINED; Genomic_DNA.
DR EMBL; D63334; BAA09647.1; -; Genomic_DNA.
DR CCDS; CCDS17400.1; -.
DR PIR; I56135; I56135.
DR RefSeq; NP_001152896.1; NM_001159424.2.
DR RefSeq; NP_032377.1; NM_008351.3.
DR AlphaFoldDB; P43431; -.
DR SMR; P43431; -.
DR ComplexPortal; CPX-387; Interleukin-12 complex.
DR ComplexPortal; CPX-388; Interleukin-12-receptor complex.
DR DIP; DIP-60363N; -.
DR IntAct; P43431; 1.
DR STRING; 10090.ENSMUSP00000029345; -.
DR GlyGen; P43431; 1 site.
DR PhosphoSitePlus; P43431; -.
DR PaxDb; P43431; -.
DR PRIDE; P43431; -.
DR Antibodypedia; 853; 1001 antibodies from 45 providers.
DR DNASU; 16159; -.
DR Ensembl; ENSMUST00000107816; ENSMUSP00000103446; ENSMUSG00000027776.
DR GeneID; 16159; -.
DR KEGG; mmu:16159; -.
DR UCSC; uc008plv.3; mouse.
DR CTD; 3592; -.
DR MGI; MGI:96539; Il12a.
DR VEuPathDB; HostDB:ENSMUSG00000027776; -.
DR eggNOG; ENOG502S8JN; Eukaryota.
DR GeneTree; ENSGT00390000016906; -.
DR HOGENOM; CLU_108538_0_0_1; -.
DR InParanoid; P43431; -.
DR OMA; MNESCLA; -.
DR OrthoDB; 1409826at2759; -.
DR PhylomeDB; P43431; -.
DR BioGRID-ORCS; 16159; 3 hits in 74 CRISPR screens.
DR PRO; PR:P43431; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P43431; protein.
DR Bgee; ENSMUSG00000027776; Expressed in hindlimb stylopod muscle and 40 other tissues.
DR ExpressionAtlas; P43431; baseline and differential.
DR Genevisible; P43431; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0031904; C:endosome lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0043514; C:interleukin-12 complex; IDA:MGI.
DR GO; GO:0042022; C:interleukin-12 receptor complex; IC:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0008083; F:growth factor activity; ISO:MGI.
DR GO; GO:0042163; F:interleukin-12 beta subunit binding; IPI:MGI.
DR GO; GO:0005143; F:interleukin-12 receptor binding; IEA:InterPro.
DR GO; GO:0045513; F:interleukin-27 binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0016477; P:cell migration; ISO:MGI.
DR GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0098586; P:cellular response to virus; ISO:MGI.
DR GO; GO:0042832; P:defense response to protozoan; IDA:MGI.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0006955; P:immune response; IC:ComplexPortal.
DR GO; GO:1903588; P:negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISO:MGI.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; ISO:MGI.
DR GO; GO:0050709; P:negative regulation of protein secretion; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; ISO:MGI.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; ISO:MGI.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:MGI.
DR GO; GO:0050671; P:positive regulation of lymphocyte proliferation; ISO:MGI.
DR GO; GO:0032946; P:positive regulation of mononuclear cell proliferation; ISO:MGI.
DR GO; GO:0032816; P:positive regulation of natural killer cell activation; ISO:MGI.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISO:MGI.
DR GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; ISO:MGI.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; ISO:MGI.
DR GO; GO:0051135; P:positive regulation of NK T cell activation; ISO:MGI.
DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; ISO:MGI.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IGI:MGI.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0010224; P:response to UV-B; ISO:MGI.
DR GO; GO:0042098; P:T cell proliferation; IDA:MGI.
DR GO; GO:0035711; P:T-helper 1 cell activation; IDA:MGI.
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 Cytokine; Disulfide bond; Glycoprotein; Growth factor; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..215
FT /note="Interleukin-12 subunit alpha"
FT /id="PRO_0000015608"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 60..192
FT /evidence="ECO:0000250"
FT DISULFID 81..119
FT /evidence="ECO:0000250"
FT DISULFID 92
FT /note="Interchain (with C-197 in IL12B)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 215 AA; 24179 MW; 56845B9B66D35A53 CRC64;
MCQSRYLLFL ATLALLNHLS LARVIPVSGP ARCLSQSRNL LKTTDDMVKT AREKLKHYSC
TAEDIDHEDI TRDQTSTLKT CLPLELHKNE SCLATRETSS TTRGSCLPPQ KTSLMMTLCL
GSIYEDLKMY QTEFQAINAA LQNHNHQQII LDKGMLVAID ELMQSLNHNG ETLRQKPPVG
EADPYRVKMK LCILLHAFST RVVTINRVMG YLSSA
