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Interleukin-23 subunit alpha (IL-23 subunit alpha) (IL-23-A) (Interleukin-23 subunit p19) (IL-23p19)

 IL23A_MOUSE             Reviewed;         196 AA.
Q9EQ14;
31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
01-MAR-2001, sequence version 1.
28-MAR-2018, entry version 113.
RecName: Full=Interleukin-23 subunit alpha;
Short=IL-23 subunit alpha;
Short=IL-23-A;
AltName: Full=Interleukin-23 subunit p19;
Short=IL-23p19;
Flags: Precursor;
Name=Il23a;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH IL12B,
SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
TISSUE=Monocyte;
PubMed=11114383; DOI=10.1016/S1074-7613(00)00070-4;
Oppmann B., Lesley R., Blom B., Timans J.C., Xu Y., Hunte B., Vega F.,
Yu N., Wang J., Singh K.P., Zonin F., Vaisberg E., Churakova T.,
Liu M.-R., Gorman D., Wagner J., Zurawski S., Liu Y.-J., Abrams J.S.,
Moore K.W., Rennick D.M., de Waal-Malefyt R., Hannum C., Bazan J.F.,
Kastelein R.A.;
"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with
biological activities similar as well as distinct from IL-12.";
Immunity 13:715-725(2000).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=FVB/N; TISSUE=Mammary tumor;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
FUNCTION.
PubMed=11390512; DOI=10.4049/jimmunol.166.12.7563;
Wiekowski M.T., Leach M.W., Evans E.W., Sullivan L., Chen S.-C.,
Vassileva G., Bazan J.F., Gorman D.M., Kastelein R.A., Narula S.,
Lira S.A.;
"Ubiquitous transgenic expression of the IL-23 subunit p19 induces
multiorgan inflammation, runting, infertility, and premature death.";
J. Immunol. 166:7563-7570(2001).
[4]
INDUCTION BY MYCOBACTERIAL INFECTION.
PubMed=11801672; DOI=10.4049/jimmunol.168.3.1322;
Cooper A.M., Kipnis A., Turner J., Magram J., Ferrante J., Orme I.M.;
"Mice lacking bioactive IL-12 can generate protective, antigen-
specific cellular responses to mycobacterial infection only if the IL-
12 p40 subunit is present.";
J. Immunol. 168:1322-1327(2002).
[5]
INDUCTION BY HERPES SIMPLEX VIRUS TYPE 1 INFECTION.
PubMed=12162874; DOI=10.1089/10799900260100123;
Broberg E.K., Setaelae N., Eraelinna J.-P., Salmi A.A., Roeyttae M.,
Hukkanen V.;
"Herpes simplex virus type 1 infection induces upregulation of
interleukin-23 (p19) mRNA expression in trigeminal ganglia of BALB/c
mice.";
J. Interferon Cytokine Res. 22:641-651(2002).
[6]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=14662908; DOI=10.1084/jem.20030896;
Murphy C.A., Langrish C.L., Chen Y., Blumenschein W., McClanahan T.K.,
Kastelein R.A., Sedgwick J.D., Cua D.J.;
"Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in
joint autoimmune inflammation.";
J. Exp. Med. 198:1951-1957(2003).
[7]
FUNCTION.
PubMed=12847224; DOI=10.4049/jimmunol.171.2.600;
Lo C.-H., Lee S.-C., Wu P.-Y., Pan W.-Y., Su J., Cheng C.-W.,
Roffler S.R., Chiang B.-L., Lee C.-N., Wu C.-W., Tao M.-H.;
"Antitumor and antimetastatic activity of IL-23.";
J. Immunol. 171:600-607(2003).
[8]
INDUCTION BY LPS AND IFNG.
PubMed=14568135; DOI=10.1016/S0022-510X(03)00203-X;
Li J., Gran B., Zhang G.-X., Ventura E.S., Siglienti I., Rostami A.,
Kamoun M.;
"Differential expression and regulation of IL-23 and IL-12 subunits
and receptors in adult mouse microglia.";
J. Neurol. Sci. 215:95-103(2003).
[9]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=12610626; DOI=10.1038/nature01355;
Cua D.J., Sherlock J., Chen Y., Murphy C.A., Joyce B., Seymour B.,
Lucian L., To W., Kwan S., Churakova T., Zurawski S., Wiekowski M.T.,
Lira S.A., Gorman D., Kastelein R.A., Sedgwick J.D.;
"Interleukin-23 rather than interleukin-12 is the critical cytokine
for autoimmune inflammation of the brain.";
Nature 421:744-748(2003).
[10]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=14978083; DOI=10.4049/jimmunol.172.5.2827;
Ghilardi N., Kljavin N., Chen Q., Lucas S., Gurney A.L.,
de Sauvage F.J.;
"Compromised humoral and delayed-type hypersensitivity responses in
IL-23-deficient mice.";
J. Immunol. 172:2827-2833(2004).
[11]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=16157683; DOI=10.1084/jem.20050193;
Happel K.I., Dubin P.J., Zheng M., Ghilardi N., Lockhart C.,
Quinton L.J., Odden A.R., Shellito J.E., Bagby G.J., Nelson S.,
Kolls J.K.;
"Divergent roles of IL-23 and IL-12 in host defense against Klebsiella
pneumoniae.";
J. Exp. Med. 202:761-769(2005).
[12]
INDUCTION BY FASLG.
PubMed=16339539; DOI=10.4049/jimmunol.175.12.8024;
Kidoya H., Umemura M., Kawabe T., Matsuzaki G., Yahagi A., Imamura R.,
Suda T.;
"Fas ligand induces cell-autonomous IL-23 production in dendritic
cells, a mechanism for Fas ligand-induced IL-17 production.";
J. Immunol. 175:8024-8031(2005).
[13]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=16670770; DOI=10.1172/JCI21404;
Yen D., Cheung J., Scheerens H., Poulet F., McClanahan T.K.,
McKenzie B., Kleinschek M.A., Owyang A., Mattson J., Blumenschein W.,
Murphy E., Sathe M., Cua D.J., Kastelein R.A., Rennick D.M.;
"IL-23 is essential for T cell-mediated colitis and promotes
inflammation via IL-17 and IL-6.";
J. Clin. Invest. 116:1310-1316(2006).
[14]
FUNCTION.
PubMed=16648837; DOI=10.1038/nature04754;
Mangan P.R., Harrington L.E., O'Quinn D.B., Helms W.S., Bullard D.C.,
Elson C.O., Hatton R.D., Wahl S.M., Schoeb T.R., Weaver C.T.;
"Transforming growth factor-beta induces development of the T(H)17
lineage.";
Nature 441:231-234(2006).
[15]
FUNCTION.
PubMed=16688182; DOI=10.1038/nature04808;
Langowski J.L., Zhang X., Wu L., Mattson J.D., Chen T., Smith K.,
Basham B., McClanahan T.K., Kastelein R.A., Oft M.;
"IL-23 promotes tumour incidence and growth.";
Nature 442:461-465(2006).
-!- FUNCTION: Associates with IL12B to form the IL-23 interleukin, a
heterodimeric cytokine which functions in innate and adaptive
immunity. IL-23 may constitute with IL-17 an acute response to
infection in peripheral tissues. IL-23 binds to a heterodimeric
receptor complex composed of IL12RB1 and IL23R, activates the Jak-
Stat signaling cascade, stimulates memory rather than naive T-
cells and promotes production of proinflammatory cytokines. IL-23
induces autoimmune inflammation and thus may be responsible for
autoimmune inflammatory diseases and may be important for
tumorigenesis. {ECO:0000269|PubMed:11114383,
ECO:0000269|PubMed:11390512, ECO:0000269|PubMed:12610626,
ECO:0000269|PubMed:12847224, ECO:0000269|PubMed:14662908,
ECO:0000269|PubMed:14978083, ECO:0000269|PubMed:16157683,
ECO:0000269|PubMed:16648837, ECO:0000269|PubMed:16670770,
ECO:0000269|PubMed:16688182}.
-!- SUBUNIT: Heterodimer with IL12B; disulfide-linked. The heterodimer
is known as interleukin IL-23.
-!- INTERACTION:
P29460:IL12B (xeno); NbExp=2; IntAct=EBI-2481329, EBI-1029614;
P43432:Il12b; NbExp=3; IntAct=EBI-2481329, EBI-2481353;
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11114383}.
Note=Secreted upon association with IL12B.
-!- TISSUE SPECIFICITY: Secreted by activated dendritic cells (at
protein level). Detected in various tissues with higher expression
in polarized Th1 cells and activated macrophages.
{ECO:0000269|PubMed:11114383}.
-!- INDUCTION: Up-regulated in trigeminal glanglia after herpes
simplex virus type 1 infection, in the lung of mice infected with
mycobacteria or Klebsiella pneumoniae. Up-regulated in microglia
by combined LPS and IFNG stimulation. Up-regulated by FASLG.
{ECO:0000269|PubMed:11801672, ECO:0000269|PubMed:12162874,
ECO:0000269|PubMed:14568135, ECO:0000269|PubMed:16339539}.
-!- DISRUPTION PHENOTYPE: Mice have no overt phenotype but display
compromised humoral and delayed-type hypersensitivity responses.
They also have impaired secretion of IL17 and IL17F, higher
succeptibility to Klebsiella pneumoniae and Citrobacter rodentium
infection, do not develop experimentally-induced autoimmune
encephalitis a mouse model of multiple sclerosis, collagen-induced
arthritis a rodent model of rheumatoid arthritis and also
spontaneous colitis induced by IL10 deficiency a rodent model of
inflammatory bowel disease. Transgenic mice expressing Il23a
ubiquitously display multiorgan inflammation and infertility,
express acute phase genes, have impaired growth and dye
prematurely. {ECO:0000269|PubMed:12610626,
ECO:0000269|PubMed:14662908, ECO:0000269|PubMed:14978083,
ECO:0000269|PubMed:16157683, ECO:0000269|PubMed:16670770}.
-!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; AF301619; AAG37231.1; -; mRNA.
EMBL; BC019953; AAH19953.1; -; mRNA.
CCDS; CCDS24270.1; -.
RefSeq; NP_112542.1; NM_031252.2.
UniGene; Mm.125482; -.
ProteinModelPortal; Q9EQ14; -.
SMR; Q9EQ14; -.
IntAct; Q9EQ14; 2.
STRING; 10090.ENSMUSP00000026449; -.
PaxDb; Q9EQ14; -.
PRIDE; Q9EQ14; -.
Ensembl; ENSMUST00000026449; ENSMUSP00000026449; ENSMUSG00000025383.
GeneID; 83430; -.
KEGG; mmu:83430; -.
UCSC; uc007hmc.1; mouse.
CTD; 51561; -.
MGI; MGI:1932410; Il23a.
eggNOG; ENOG410IGBY; Eukaryota.
eggNOG; ENOG411142Q; LUCA.
GeneTree; ENSGT00390000006482; -.
HOGENOM; HOG000048728; -.
HOVERGEN; HBG081786; -.
InParanoid; Q9EQ14; -.
KO; K05426; -.
OMA; PMGHVDL; -.
OrthoDB; EOG091G0Q9J; -.
PhylomeDB; Q9EQ14; -.
TreeFam; TF337234; -.
Reactome; R-MMU-9020933; Interleukin-23 signaling.
PRO; PR:Q9EQ14; -.
Proteomes; UP000000589; Chromosome 10.
Bgee; ENSMUSG00000025383; -.
CleanEx; MM_IL23A; -.
Genevisible; Q9EQ14; MM.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IDA:MGI.
GO; GO:0070743; C:interleukin-23 complex; IDA:BHF-UCL.
GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
GO; GO:0045519; F:interleukin-23 receptor binding; IEA:Ensembl.
GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:MGI.
GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:MGI.
GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISO:MGI.
GO; GO:0010536; P:positive regulation of activation of Janus kinase activity; ISO:MGI.
GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:BHF-UCL.
GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI.
GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO:MGI.
GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI.
GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:MGI.
GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI.
GO; GO:0043382; P:positive regulation of memory T cell differentiation; IDA:BHF-UCL.
GO; GO:0032819; P:positive regulation of natural killer cell proliferation; ISO:MGI.
GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IDA:BHF-UCL.
GO; GO:0051135; P:positive regulation of NK T cell activation; ISO:MGI.
GO; GO:0051142; P:positive regulation of NK T cell proliferation; ISO:MGI.
GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:MGI.
GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IDA:BHF-UCL.
GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:MGI.
GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IDA:BHF-UCL.
GO; GO:2000330; P:positive regulation of T-helper 17 cell lineage commitment; IDA:BHF-UCL.
GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; IDA:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
GO; GO:0042509; P:regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
GO; GO:0042098; P:T cell proliferation; IDA:MGI.
GO; GO:0048771; P:tissue remodeling; IEA:UniProtKB-KW.
InterPro; IPR009079; 4_helix_cytokine-like_core.
InterPro; IPR010831; IL-23_alpha.
PANTHER; PTHR15947; PTHR15947; 1.
Pfam; PF16649; IL23; 1.
SUPFAM; SSF47266; SSF47266; 1.
1: Evidence at protein level;
Antiviral defense; Complete proteome; Cytokine; Disulfide bond;
Immunity; Inflammatory response; Innate immunity; Reference proteome;
Secreted; Signal; Tissue remodeling.
SIGNAL 1 21 {ECO:0000255}.
CHAIN 22 196 Interleukin-23 subunit alpha.
/FTId=PRO_0000259489.
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


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