IL23A_MOUSE
ID IL23A_MOUSE Reviewed; 196 AA.
AC Q9EQ14;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Interleukin-23 subunit alpha;
DE Short=IL-23 subunit alpha;
DE Short=IL-23-A;
DE AltName: Full=Interleukin-23 subunit p19;
DE Short=IL-23p19;
DE Flags: Precursor;
GN Name=Il23a;
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], FUNCTION, INTERACTION WITH IL12B, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Monocyte;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP FUNCTION.
RX PubMed=11390512; DOI=10.4049/jimmunol.166.12.7563;
RA Wiekowski M.T., Leach M.W., Evans E.W., Sullivan L., Chen S.-C.,
RA Vassileva G., Bazan J.F., Gorman D.M., Kastelein R.A., Narula S.,
RA Lira S.A.;
RT "Ubiquitous transgenic expression of the IL-23 subunit p19 induces
RT multiorgan inflammation, runting, infertility, and premature death.";
RL J. Immunol. 166:7563-7570(2001).
RN [4]
RP INDUCTION BY MYCOBACTERIAL INFECTION.
RX PubMed=11801672; DOI=10.4049/jimmunol.168.3.1322;
RA Cooper A.M., Kipnis A., Turner J., Magram J., Ferrante J., Orme I.M.;
RT "Mice lacking bioactive IL-12 can generate protective, antigen-specific
RT cellular responses to mycobacterial infection only if the IL-12 p40 subunit
RT is present.";
RL J. Immunol. 168:1322-1327(2002).
RN [5]
RP INDUCTION BY HERPES SIMPLEX VIRUS TYPE 1 INFECTION.
RX PubMed=12162874; DOI=10.1089/10799900260100123;
RA Broberg E.K., Setaelae N., Eraelinna J.-P., Salmi A.A., Roeyttae M.,
RA Hukkanen V.;
RT "Herpes simplex virus type 1 infection induces upregulation of interleukin-
RT 23 (p19) mRNA expression in trigeminal ganglia of BALB/c mice.";
RL J. Interferon Cytokine Res. 22:641-651(2002).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14662908; DOI=10.1084/jem.20030896;
RA Murphy C.A., Langrish C.L., Chen Y., Blumenschein W., McClanahan T.K.,
RA Kastelein R.A., Sedgwick J.D., Cua D.J.;
RT "Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint
RT autoimmune inflammation.";
RL J. Exp. Med. 198:1951-1957(2003).
RN [7]
RP FUNCTION.
RX PubMed=12847224; DOI=10.4049/jimmunol.171.2.600;
RA Lo C.-H., Lee S.-C., Wu P.-Y., Pan W.-Y., Su J., Cheng C.-W., Roffler S.R.,
RA Chiang B.-L., Lee C.-N., Wu C.-W., Tao M.-H.;
RT "Antitumor and antimetastatic activity of IL-23.";
RL J. Immunol. 171:600-607(2003).
RN [8]
RP INDUCTION BY LPS AND IFNG.
RX PubMed=14568135; DOI=10.1016/s0022-510x(03)00203-x;
RA Li J., Gran B., Zhang G.-X., Ventura E.S., Siglienti I., Rostami A.,
RA Kamoun M.;
RT "Differential expression and regulation of IL-23 and IL-12 subunits and
RT receptors in adult mouse microglia.";
RL J. Neurol. Sci. 215:95-103(2003).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12610626; DOI=10.1038/nature01355;
RA Cua D.J., Sherlock J., Chen Y., Murphy C.A., Joyce B., Seymour B.,
RA Lucian L., To W., Kwan S., Churakova T., Zurawski S., Wiekowski M.T.,
RA Lira S.A., Gorman D., Kastelein R.A., Sedgwick J.D.;
RT "Interleukin-23 rather than interleukin-12 is the critical cytokine for
RT autoimmune inflammation of the brain.";
RL Nature 421:744-748(2003).
RN [10]
RP FUNCTION.
RX PubMed=12417590; DOI=10.1074/jbc.m207577200;
RA Aggarwal S., Ghilardi N., Xie M.H., de Sauvage F.J., Gurney A.L.;
RT "Interleukin-23 promotes a distinct CD4 T cell activation state
RT characterized by the production of interleukin-17.";
RL J. Biol. Chem. 278:1910-1914(2003).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14978083; DOI=10.4049/jimmunol.172.5.2827;
RA Ghilardi N., Kljavin N., Chen Q., Lucas S., Gurney A.L., de Sauvage F.J.;
RT "Compromised humoral and delayed-type hypersensitivity responses in IL-23-
RT deficient mice.";
RL J. Immunol. 172:2827-2833(2004).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16157683; DOI=10.1084/jem.20050193;
RA Happel K.I., Dubin P.J., Zheng M., Ghilardi N., Lockhart C., Quinton L.J.,
RA Odden A.R., Shellito J.E., Bagby G.J., Nelson S., Kolls J.K.;
RT "Divergent roles of IL-23 and IL-12 in host defense against Klebsiella
RT pneumoniae.";
RL J. Exp. Med. 202:761-769(2005).
RN [13]
RP INDUCTION BY FASLG.
RX PubMed=16339539; DOI=10.4049/jimmunol.175.12.8024;
RA Kidoya H., Umemura M., Kawabe T., Matsuzaki G., Yahagi A., Imamura R.,
RA Suda T.;
RT "Fas ligand induces cell-autonomous IL-23 production in dendritic cells, a
RT mechanism for Fas ligand-induced IL-17 production.";
RL J. Immunol. 175:8024-8031(2005).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16670770; DOI=10.1172/jci21404;
RA Yen D., Cheung J., Scheerens H., Poulet F., McClanahan T.K., McKenzie B.,
RA Kleinschek M.A., Owyang A., Mattson J., Blumenschein W., Murphy E.,
RA Sathe M., Cua D.J., Kastelein R.A., Rennick D.M.;
RT "IL-23 is essential for T cell-mediated colitis and promotes inflammation
RT via IL-17 and IL-6.";
RL J. Clin. Invest. 116:1310-1316(2006).
RN [15]
RP FUNCTION.
RX PubMed=16648837; DOI=10.1038/nature04754;
RA Mangan P.R., Harrington L.E., O'Quinn D.B., Helms W.S., Bullard D.C.,
RA Elson C.O., Hatton R.D., Wahl S.M., Schoeb T.R., Weaver C.T.;
RT "Transforming growth factor-beta induces development of the T(H)17
RT lineage.";
RL Nature 441:231-234(2006).
RN [16]
RP FUNCTION.
RX PubMed=16688182; DOI=10.1038/nature04808;
RA Langowski J.L., Zhang X., Wu L., Mattson J.D., Chen T., Smith K.,
RA Basham B., McClanahan T.K., Kastelein R.A., Oft M.;
RT "IL-23 promotes tumour incidence and growth.";
RL Nature 442:461-465(2006).
RN [17]
RP FUNCTION.
RX PubMed=19900478; DOI=10.1016/j.imlet.2009.10.012;
RA Li X., Kim K.W., Cho M.L., Ju J.H., Kang C.M., Oh H.J., Min J.K., Lee S.H.,
RA Park S.H., Kim H.Y.;
RT "IL-23 induces receptor activator of NF-kappaB ligand expression in
RT fibroblast-like synoviocytes via STAT3 and NF-kappaB signal pathways.";
RL Immunol. Lett. 127:100-107(2010).
CC -!- FUNCTION: Associates with IL12B 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, ECO:0000269|PubMed:11390512,
CC ECO:0000269|PubMed:12610626, ECO:0000269|PubMed:12847224,
CC ECO:0000269|PubMed:14662908, ECO:0000269|PubMed:14978083,
CC ECO:0000269|PubMed:16157683, ECO:0000269|PubMed:16648837,
CC ECO:0000269|PubMed:16670770, ECO:0000269|PubMed:16688182}.
CC -!- FUNCTION: Associates with IL12B to form the pro-inflammatory cytokine
CC IL-23 that plays different roles in innate and adaptive immunity
CC (PubMed:11114383, PubMed:11390512, PubMed:16670770). Released by
CC antigen-presenting cells such as dendritic cells or macrophages, binds
CC to a heterodimeric receptor complex composed of IL12RB1 and IL23R to
CC activate JAK2 and TYK2 which then phosphorylate the receptor to form a
CC docking site leading to the phosphorylation of STAT3 and STAT4 (By
CC similarity). This process leads to activation of several pathways
CC including p38 MAPK or NF-kappa-B and promotes the production of pro-
CC inflammatory cytokines such as interleukin-17A/IL17A (PubMed:19900478).
CC In turn, participates in the early and effective intracellular
CC bacterial clearance (PubMed:16157683). Promotes the expansion and
CC survival of T-helper 17 cells, a CD4-positive helper T-cell subset that
CC produces IL-17, as well as other IL-17-producing cells
CC (PubMed:16648837). {ECO:0000250|UniProtKB:Q9NPF7,
CC ECO:0000269|PubMed:11114383, ECO:0000269|PubMed:11390512,
CC ECO:0000269|PubMed:12610626, ECO:0000269|PubMed:12847224,
CC ECO:0000269|PubMed:14662908, ECO:0000269|PubMed:14978083,
CC ECO:0000269|PubMed:16157683, ECO:0000269|PubMed:16648837,
CC ECO:0000269|PubMed:16670770, ECO:0000269|PubMed:16688182,
CC ECO:0000269|PubMed:19900478}.
CC -!- SUBUNIT: Heterodimer with IL12B; disulfide-linked (PubMed:11114383).
CC The heterodimer is known as interleukin IL-23 (PubMed:11114383).
CC Interacts with IL23R; this interaction enables recruitment of IL12RB1
CC (By similarity). {ECO:0000250|UniProtKB:Q9NPF7,
CC ECO:0000269|PubMed:11114383}.
CC -!- INTERACTION:
CC Q9EQ14; P43432: Il12b; NbExp=3; IntAct=EBI-2481329, EBI-2481353;
CC Q9EQ14; P29460: IL12B; Xeno; NbExp=2; IntAct=EBI-2481329, EBI-1029614;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11114383}.
CC Note=Secreted upon association with IL12B.
CC -!- TISSUE SPECIFICITY: Secreted by activated dendritic cells (at protein
CC level). Detected in various tissues with higher expression in polarized
CC Th1 cells and activated macrophages. {ECO:0000269|PubMed:11114383}.
CC -!- INDUCTION: Up-regulated in trigeminal glanglia after herpes simplex
CC virus type 1 infection, in the lung of mice infected with mycobacteria
CC or Klebsiella pneumoniae. Up-regulated in microglia by combined LPS and
CC IFNG stimulation. Up-regulated by FASLG. {ECO:0000269|PubMed:11801672,
CC ECO:0000269|PubMed:12162874, ECO:0000269|PubMed:14568135,
CC ECO:0000269|PubMed:16339539}.
CC -!- DISRUPTION PHENOTYPE: Mice have no overt phenotype but display
CC compromised humoral and delayed-type hypersensitivity responses. They
CC also have impaired secretion of IL17 and IL17F, higher susceptibility
CC to Klebsiella pneumoniae and Citrobacter rodentium infection, do not
CC develop experimentally-induced autoimmune encephalitis a mouse model of
CC multiple sclerosis, collagen-induced arthritis a rodent model of
CC rheumatoid arthritis and also spontaneous colitis induced by IL10
CC deficiency a rodent model of inflammatory bowel disease. Transgenic
CC mice expressing Il23a ubiquitously display multiorgan inflammation and
CC infertility, express acute phase genes, have impaired growth and dye
CC prematurely. {ECO:0000269|PubMed:12610626, ECO:0000269|PubMed:14662908,
CC ECO:0000269|PubMed:14978083, ECO:0000269|PubMed:16157683,
CC ECO:0000269|PubMed:16670770}.
CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
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DR EMBL; AF301619; AAG37231.1; -; mRNA.
DR EMBL; BC019953; AAH19953.1; -; mRNA.
DR CCDS; CCDS24270.1; -.
DR RefSeq; NP_112542.1; NM_031252.2.
DR AlphaFoldDB; Q9EQ14; -.
DR SMR; Q9EQ14; -.
DR ComplexPortal; CPX-3293; Interleukin-23 complex.
DR ComplexPortal; CPX-389; Interleukin-23-receptor complex.
DR IntAct; Q9EQ14; 2.
DR STRING; 10090.ENSMUSP00000026449; -.
DR PaxDb; Q9EQ14; -.
DR PRIDE; Q9EQ14; -.
DR ProteomicsDB; 267234; -.
DR Antibodypedia; 803; 632 antibodies from 38 providers.
DR DNASU; 83430; -.
DR Ensembl; ENSMUST00000026449; ENSMUSP00000026449; ENSMUSG00000025383.
DR GeneID; 83430; -.
DR KEGG; mmu:83430; -.
DR UCSC; uc007hmc.1; mouse.
DR CTD; 51561; -.
DR MGI; MGI:1932410; Il23a.
DR VEuPathDB; HostDB:ENSMUSG00000025383; -.
DR eggNOG; ENOG502STAQ; Eukaryota.
DR GeneTree; ENSGT00390000006482; -.
DR HOGENOM; CLU_122915_0_0_1; -.
DR InParanoid; Q9EQ14; -.
DR OMA; WARCQQL; -.
DR OrthoDB; 1344829at2759; -.
DR PhylomeDB; Q9EQ14; -.
DR TreeFam; TF337234; -.
DR Reactome; R-MMU-9020933; Interleukin-23 signaling.
DR BioGRID-ORCS; 83430; 2 hits in 74 CRISPR screens.
DR PRO; PR:Q9EQ14; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9EQ14; protein.
DR Bgee; ENSMUSG00000025383; Expressed in secondary oocyte and 18 other tissues.
DR Genevisible; Q9EQ14; MM.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA: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:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0045519; F:interleukin-23 receptor binding; ISO:MGI.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; IC:ComplexPortal.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:MGI.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISO:MGI.
DR GO; GO:0010536; P:positive regulation of activation of Janus kinase activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO:MGI.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:MGI.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI.
DR GO; GO:0043382; P:positive regulation of memory T cell differentiation; IDA:BHF-UCL.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; ISO:MGI.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IDA:BHF-UCL.
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:0045672; P:positive regulation of osteoclast differentiation; ISO:MGI.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IDA:BHF-UCL.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:ComplexPortal.
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; IDA:BHF-UCL.
DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0042509; P:regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0042098; P:T cell proliferation; IDA:MGI.
DR GO; GO:0048771; P:tissue remodeling; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR010831; IL-23_alpha.
DR PANTHER; PTHR15947; PTHR15947; 1.
DR Pfam; PF16649; IL23; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
PE 1: Evidence at protein level;
KW Antiviral defense; Cytokine; Disulfide bond; Immunity;
KW Inflammatory response; Innate immunity; Reference proteome; Secreted;
KW Signal; Tissue remodeling.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..196
FT /note="Interleukin-23 subunit alpha"
FT /id="PRO_0000259489"
SQ SEQUENCE 196 AA; 22071 MW; DAF4A318A2DD3B7C CRC64;
MLDCRAVIML WLLPWVTQGL AVPRSSSPDW AQCQQLSRNL CMLAWNAHAP AGHMNLLREE
EDEETKNNVP RIQCEDGCDP QGLKDNSQFC LQRIRQGLAF YKHLLDSDIF KGEPALLPDS
PMEQLHTSLL GLSQLLQPED HPRETQQMPS LSSSQQWQRP LLRSKILRSL QAFLAIAARV
FAHGAATLTE PLVPTA
