Q9EQ14 (IL23A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-23 subunit alpha
Short name=IL-23 subunit alpha
Short name=IL-23-A

Alternative name(s):
Interleukin-23 subunit p19
Short name=IL-23p19

Gene names

Name:

Il23a

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	196 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.1 Ref.3 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15
Subunit structure	Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-23.
Subcellular location	Secreted. Note: Secreted upon association with IL12B. Ref.1
Tissue specificity	Secreted by activated dendritic cells (at protein level). Detected in various tissues with higher expression in polarized Th1 cells and activated macrophages. Ref.1
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. Ref.4 Ref.5 Ref.8 Ref.12
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. Ref.6 Ref.9 Ref.10 Ref.11 Ref.13
Sequence similarities	Belongs to the IL-6 superfamily.

Ontologies

Keywords
Biological process	Antiviral defense Immunity Inflammatory response Innate immunity Tissue remodeling
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell proliferation Inferred from direct assay PubMed 16982811. Source: MGI defense response to Gram-negative bacterium Inferred from electronic annotation. Source: Compara defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of interleukin-10 production Inferred from electronic annotation. Source: Compara positive regulation of NK T cell activation Inferred from electronic annotation. Source: Compara positive regulation of NK T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of T cell mediated cytotoxicity Inferred from direct assay PubMed 14688363. Source: BHF-UCL positive regulation of T-helper 1 type immune response Inferred from direct assay PubMed 14688363. Source: BHF-UCL positive regulation of T-helper 17 cell lineage commitment Inferred from direct assay PubMed 19501566. Source: BHF-UCL positive regulation of T-helper 17 type immune response Inferred from direct assay PubMed 19501566. Source: BHF-UCL positive regulation of activated T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of activation of JAK2 kinase activity Inferred from electronic annotation. Source: Compara positive regulation of defense response to virus by host Inferred from direct assay PubMed 14688363. Source: BHF-UCL positive regulation of granulocyte macrophage colony-stimulating factor production Inferred from electronic annotation. Source: Compara positive regulation of interferon-gamma production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-10 production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-12 production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-17 production Inferred from electronic annotation. Source: Compara positive regulation of memory T cell differentiation Inferred from direct assay PubMed 14688363. Source: BHF-UCL positive regulation of natural killer cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of neutrophil chemotaxis Inferred from direct assay PubMed 19289819. Source: BHF-UCL positive regulation of osteoclast differentiation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction PubMed 19666510. Source: MGI positive regulation of tumor necrosis factor production Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat4 protein Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from electronic annotation. Source: Compara regulation of tyrosine phosphorylation of Stat1 protein Inferred from electronic annotation. Source: Compara tissue remodeling Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	interleukin-23 complex Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IL12B	P29460	2	EBI-2481329,EBI-1029614	From a different organism.
Il12b	P43432	3	EBI-2481329,EBI-2481353

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 196	175	Interleukin-23 subunit alpha		PRO_0000259489

Sequences

	Sequence		Length	Mass (Da)
	Q9EQ14 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: DAF4A318A2DD3B7C	FASTA	196	22,071
	10 20 30 40 50 60 MLDCRAVIML WLLPWVTQGL AVPRSSSPDW AQCQQLSRNL CMLAWNAHAP AGHMNLLREE 70 80 90 100 110 120 EDEETKNNVP RIQCEDGCDP QGLKDNSQFC LQRIRQGLAF YKHLLDSDIF KGEPALLPDS 130 140 150 160 170 180 PMEQLHTSLL GLSQLLQPED HPRETQQMPS LSSSQQWQRP LLRSKILRSL QAFLAIAARV 190 FAHGAATLTE PLVPTA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12." 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. Immunity 13:715-725(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH IL12B, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Monocyte.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary tumor.
[3]	"Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death." 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. J. Immunol. 166:7563-7570(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"Mice lacking bioactive IL-12 can generate protective, antigen-specific cellular responses to mycobacterial infection only if the IL-12 p40 subunit is present." Cooper A.M., Kipnis A., Turner J., Magram J., Ferrante J., Orme I.M. J. Immunol. 168:1322-1327(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY MYCOBACTERIAL INFECTION.
[5]	"Herpes simplex virus type 1 infection induces upregulation of interleukin-23 (p19) mRNA expression in trigeminal ganglia of BALB/c mice." Broberg E.K., Setaelae N., Eraelinna J.-P., Salmi A.A., Roeyttae M., Hukkanen V. J. Interferon Cytokine Res. 22:641-651(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY HERPES SIMPLEX VIRUS TYPE 1 INFECTION.
[6]	"Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation." Murphy C.A., Langrish C.L., Chen Y., Blumenschein W., McClanahan T.K., Kastelein R.A., Sedgwick J.D., Cua D.J. J. Exp. Med. 198:1951-1957(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]	"Antitumor and antimetastatic activity of IL-23." 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. J. Immunol. 171:600-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia." Li J., Gran B., Zhang G.-X., Ventura E.S., Siglienti I., Rostami A., Kamoun M. J. Neurol. Sci. 215:95-103(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY LPS AND IFNG.
[9]	"Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain." 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. Nature 421:744-748(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[10]	"Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice." Ghilardi N., Kljavin N., Chen Q., Lucas S., Gurney A.L., de Sauvage F.J. J. Immunol. 172:2827-2833(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[11]	"Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae." 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. J. Exp. Med. 202:761-769(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[12]	"Fas ligand induces cell-autonomous IL-23 production in dendritic cells, a mechanism for Fas ligand-induced IL-17 production." Kidoya H., Umemura M., Kawabe T., Matsuzaki G., Yahagi A., Imamura R., Suda T. J. Immunol. 175:8024-8031(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY FASLG.
[13]	"IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6." 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. J. Clin. Invest. 116:1310-1316(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[14]	"Transforming growth factor-beta induces development of the T(H)17 lineage." 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. Nature 441:231-234(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"IL-23 promotes tumour incidence and growth." Langowski J.L., Zhang X., Wu L., Mattson J.D., Chen T., Smith K., Basham B., McClanahan T.K., Kastelein R.A., Oft M. Nature 442:461-465(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF301619 mRNA. Translation: AAG37231.1. BC019953 mRNA. Translation: AAH19953.1.
IPI	IPI00110260.
RefSeq	NP_112542.1. NM_031252.2.
UniGene	Mm.125482.
3D structure databases
ProteinModelPortal	Q9EQ14.
SMR	Q9EQ14. Positions 21-188.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9EQ14. 2 interactions.
STRING	10090.ENSMUSP00000026449.
Proteomic databases
PRIDE	Q9EQ14.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000026449; ENSMUSP00000026449; ENSMUSG00000025383.
GeneID	83430.
KEGG	mmu:83430.
UCSC	uc007hmc.1. mouse.
Organism-specific databases
CTD	51561.
MGI	MGI:1932410. Il23a.
Phylogenomic databases
eggNOG	NOG42887.
GeneTree	ENSGT00390000006482.
HOGENOM	HOG000048728.
HOVERGEN	HBG081786.
InParanoid	Q9EQ14.
KO	K05426.
OMA	IHQGLVF.
OrthoDB	EOG43BMQ2.
Gene expression databases
Bgee	Q9EQ14.
CleanEx	MM_IL23A.
Genevestigator	Q9EQ14.
GermOnline	ENSMUSG00000025383. Mus musculus.
Family and domain databases
Gene3D	1.20.1250.10. 1 hit.
InterPro	IPR009079. 4_helix_cytokine-like_core. IPR012351. 4_helix_cytokine_core. IPR010831. IL23A. IPR003573. IL6_MGF_GCSF. [Graphical view]
PANTHER	PTHR15947. PTHR15947. 1 hit.
Pfam	PF00489. IL6. 1 hit. [Graphical view]
SUPFAM	SSF47266. 4_helix_cytokine. 1 hit.
ProtoNet	Search...
Other
NextBio	350550.
SOURCE	Search...

Entry information

Entry name

IL23A_MOUSE

Accession

Primary (citable) accession number: Q9EQ14

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	March 1, 2001
Last modified:	April 3, 2013
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program