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Q9EQ14 (IL23A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length196 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processAntiviral defense
Immunity
Inflammatory response
Innate immunity
Tissue remodeling
   Cellular componentSecreted
   DomainSignal
   Molecular functionCytokine
   PTMDisulfide bond
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell proliferation

Inferred from direct assay PubMed 16982811. Source: MGI

defense response to Gram-negative bacterium

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

positive regulation of NK T cell activation

Inferred from electronic annotation. Source: Ensembl

positive regulation of NK T cell proliferation

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

positive regulation of activation of JAK2 kinase activity

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

positive regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-10 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-12 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-17 production

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

positive regulation of neutrophil chemotaxis

Inferred from direct assay PubMed 19289819. Source: BHF-UCL

positive regulation of osteoclast differentiation

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from electronic annotation. Source: Ensembl

positive regulation of tyrosine phosphorylation of Stat4 protein

Inferred from electronic annotation. Source: Ensembl

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from electronic annotation. Source: Ensembl

regulation of tyrosine phosphorylation of Stat1 protein

Inferred from electronic annotation. Source: Ensembl

tissue remodeling

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentextracellular space

Inferred from direct assay PubMed 21148126. Source: MGI

interleukin-23 complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionprotein binding

Inferred from physical interaction Ref.1. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IL12BP294602EBI-2481329,EBI-1029614From a different organism.
Il12bP434323EBI-2481329,EBI-2481353

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 196175Interleukin-23 subunit alpha
PRO_0000259489

Sequences

Sequence LengthMass (Da)Tools
Q9EQ14 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: DAF4A318A2DD3B7C

FASTA19622,071
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
CCDSCCDS24270.1.
RefSeqNP_112542.1. NM_031252.2.
UniGeneMm.125482.

3D structure databases

ProteinModelPortalQ9EQ14.
SMRQ9EQ14. Positions 21-188.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9EQ14. 2 interactions.
STRING10090.ENSMUSP00000026449.

Proteomic databases

PRIDEQ9EQ14.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026449; ENSMUSP00000026449; ENSMUSG00000025383.
GeneID83430.
KEGGmmu:83430.
UCSCuc007hmc.1. mouse.

Organism-specific databases

CTD51561.
MGIMGI:1932410. Il23a.

Phylogenomic databases

eggNOGNOG42887.
GeneTreeENSGT00390000006482.
HOGENOMHOG000048728.
HOVERGENHBG081786.
InParanoidQ9EQ14.
KOK05426.
OMAIHQGLVF.
OrthoDBEOG76HQ32.
PhylomeDBQ9EQ14.
TreeFamTF337234.

Gene expression databases

BgeeQ9EQ14.
CleanExMM_IL23A.
GenevestigatorQ9EQ14.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR010831. IL-23_alpha.
IPR003573. IL-6/IL-23/GCSF/MGF.
[Graphical view]
PANTHERPTHR15947. PTHR15947. 1 hit.
PfamPF00489. IL6. 1 hit.
[Graphical view]
SUPFAMSSF47266. SSF47266. 1 hit.
ProtoNetSearch...

Other

NextBio350550.
PROQ9EQ14.
SOURCESearch...

Entry information

Entry nameIL23A_MOUSE
AccessionPrimary (citable) accession number: Q9EQ14
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot