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Q9NPF7 (IL23A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·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
Synonyms:SGRF
ORF Names:UNQ2498/PRO5798
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length189 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.5 Ref.11

Subunit structure

Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-23. Ref.14

Subcellular location

Secreted. Note: Secreted upon association with IL12B. Ref.1

Tissue specificity

Secreted by activated dendritic and phagocytic cells and keratinocytes. Also expressed by dermal Langerhans cells (at protein level). Ref.1 Ref.11

Developmental stage

Expressed by newborns dendritic cells. Ref.10

Induction

Up-regulated by a wide array of pathogens and pathogen-products together with self-signals for danger or injury. Up-regulated in psoriatic dermal tissues, in dendritic cells of multiple sclerosis patients and in tumors. Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 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 term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell proliferation

Inferred from electronic annotation. Source: Ensembl

defense response to Gram-negative bacterium

Inferred from direct assay Ref.7PubMed 20027291. Source: BHF-UCL

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 mutant phenotype Ref.12. Source: BHF-UCL

positive regulation of NF-kappaB import into nucleus

Traceable author statement PubMed 20428758. Source: BHF-UCL

positive regulation of NK T cell activation

Inferred from direct assay PubMed 19088061. Source: BHF-UCL

positive regulation of NK T cell proliferation

Inferred from direct assay PubMed 19088061. Source: BHF-UCL

positive regulation of T cell mediated cytotoxicity

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of T cell proliferation

Inferred from direct assay Ref.5. Source: BHF-UCL

positive regulation of T-helper 1 type immune response

Inferred from direct assay Ref.7. Source: BHF-UCL

positive regulation of T-helper 17 cell lineage commitment

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of T-helper 17 type immune response

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of activated T cell proliferation

Inferred from direct assay Ref.1. Source: BHF-UCL

positive regulation of activation of JAK2 kinase activity

Inferred from direct assay Ref.5. Source: BHF-UCL

positive regulation of defense response to virus by host

Inferred from direct assay Ref.6. Source: BHF-UCL

positive regulation of granulocyte macrophage colony-stimulating factor production

Inferred from direct assay PubMed 20027291. Source: BHF-UCL

positive regulation of inflammatory response

Inferred by curator PubMed 16482511. Source: BHF-UCL

positive regulation of interferon-gamma production

Inferred from direct assay Ref.1PubMed 17888176PubMed 20027291. Source: BHF-UCL

positive regulation of interleukin-10 production

Inferred from direct assay PubMed 15265908. Source: BHF-UCL

positive regulation of interleukin-12 production

Inferred from direct assay PubMed 20027291. Source: BHF-UCL

positive regulation of interleukin-17 production

Inferred from direct assay PubMed 16482511Ref.12PubMed 17888176. Source: BHF-UCL

positive regulation of memory T cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of natural killer cell activation

Inferred by curator PubMed 20027291. Source: BHF-UCL

positive regulation of natural killer cell proliferation

Inferred from direct assay PubMed 19088061. Source: BHF-UCL

positive regulation of neutrophil chemotaxis

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoclast differentiation

Inferred from direct assay PubMed 17888176. Source: BHF-UCL

positive regulation of tissue remodeling

Inferred by curator PubMed 16482511. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of tumor necrosis factor production

Inferred from mutant phenotype Ref.12. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from direct assay Ref.5PubMed 19088061. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat4 protein

Inferred from direct assay Ref.1Ref.5PubMed 19088061. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from direct assay Ref.5. Source: BHF-UCL

regulation of tyrosine phosphorylation of Stat1 protein

Inferred from direct assay Ref.5. Source: BHF-UCL

tissue remodeling

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentinterleukin-23 complex

Inferred from direct assay Ref.1. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 189170Interleukin-23 subunit alpha
PRO_0000259488

Experimental info

Sequence conflict1221G → A in AAG37232. Ref.1
Sequence conflict1471I → M in AAH66267. Ref.4
Sequence conflict1681S → N in AAH66267. Ref.4
Sequence conflict1731V → A in AAH66269. Ref.4
Sequence conflict1891P → L in AAH66269. Ref.4

Secondary structure

.................... 189
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9NPF7 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 51B5C0F188EC1B9F

FASTA18920,730
        10         20         30         40         50         60 
MLGSRAVMLL LLLPWTAQGR AVPGGSSPAW TQCQQLSQKL CTLAWSAHPL VGHMDLREEG 

        70         80         90        100        110        120 
DEETTNDVPH IQCGDGCDPQ GLRDNSQFCL QRIHQGLIFY EKLLGSDIFT GEPSLLPDSP 

       130        140        150        160        170        180 
VGQLHASLLG LSQLLQPEGH HWETQQIPSL SPSQPWQRLL LRFKILRSLQ AFVAVAARVF 


AHGAATLSP 

« 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.
[2]"SGRF; a novel member of the IL-6/G-CSF family."
Hirata Y., Kosuge Y.
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Tissue: Spleen.
[3]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"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].
[5]"A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R."
Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., Rennick D.M. expand/collapse author list , Kastelein R.A., de Waal Malefyt R., Moore K.W.
J. Immunol. 168:5699-5708(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IL12RB1 AND IL23R.
[6]"Regulation of virus-induced IL-12 and IL-23 expression in human macrophages."
Pirhonen J., Matikainen S., Julkunen I.
J. Immunol. 169:5673-5678(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[7]"Commensal Gram-negative bacteria prime human dendritic cells for enhanced IL-23 and IL-27 expression and enhanced Th1 development."
Smits H.H., van Beelen A.J., Hessle C., Westland R., de Jong E., Soeteman E., Wold A., Wierenga E.A., Kapsenberg M.L.
Eur. J. Immunol. 34:1371-1380(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[8]"Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway."
Schnurr M., Toy T., Shin A., Wagner M., Cebon J., Maraskovsky E.
Blood 105:1582-1589(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[9]"Bordetella pertussis-infected human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization and interleukin-23 expression."
Fedele G., Stefanelli P., Spensieri F., Fazio C., Mastrantonio P., Ausiello C.M.
Infect. Immun. 73:1590-1597(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[10]"Preferential production of the IL-12(p40)/IL-23(p19) heterodimer by dendritic cells from human newborns."
Vanden Eijnden S., Goriely S., De Wit D., Goldman M., Willems F.
Eur. J. Immunol. 36:21-26(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[11]"In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin."
Piskin G., Sylva-Steenland R.M.R., Bos J.D., Teunissen M.B.M.
J. Immunol. 176:1908-1915(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[12]"IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production."
Vaknin-Dembinsky A., Balashov K., Weiner H.L.
J. Immunol. 176:7768-7774(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[13]"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: INDUCTION.
[14]"The structure of interleukin-23 reveals the molecular basis of p40 subunit sharing with interleukin-12."
Lupardus P.J., Garcia K.C.
J. Mol. Biol. 382:931-941(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 20-189 IN COMPLEX WITH IL12B, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF301620 mRNA. Translation: AAG37232.1.
AB030000 mRNA. Translation: BAA93686.1.
AB030001 Genomic DNA. Translation: BAA93687.1.
AY359083 mRNA. Translation: AAQ89442.1.
BC066267 mRNA. Translation: AAH66267.1.
BC066268 mRNA. Translation: AAH66268.1.
BC066269 mRNA. Translation: AAH66269.1.
BC067511 mRNA. Translation: AAH67511.1.
BC067512 mRNA. Translation: AAH67512.1.
BC067513 mRNA. Translation: AAH67513.1.
RefSeqNP_057668.1. NM_016584.2.
UniGeneHs.382212.
Hs.98309.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3D85X-ray1.90C20-189[»]
3D87X-ray2.90A/C20-189[»]
3DUHX-ray2.30C/D20-189[»]
3QWRX-ray3.25B20-189[»]
4GRWX-ray2.55A/C1-189[»]
ProteinModelPortalQ9NPF7.
SMRQ9NPF7. Positions 20-187.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119611. 4 interactions.
IntActQ9NPF7. 1 interaction.
STRING9606.ENSP00000228534.

Chemistry

ChEMBLCHEMBL2364154.

Polymorphism databases

DMDM74761641.

Proteomic databases

PaxDbQ9NPF7.
PRIDEQ9NPF7.

Protocols and materials databases

DNASU51561.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000228534; ENSP00000228534; ENSG00000110944.
GeneID51561.
KEGGhsa:51561.
UCSCuc001sla.3. human.

Organism-specific databases

CTD51561.
GeneCardsGC12P056732.
HGNCHGNC:15488. IL23A.
HPAHPA001554.
MIM605580. gene.
neXtProtNX_Q9NPF7.
PharmGKBPA29824.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42887.
HOGENOMHOG000048728.
HOVERGENHBG081786.
InParanoidQ9NPF7.
KOK05426.
OMAIHQGLVF.
OrthoDBEOG76HQ32.
PhylomeDBQ9NPF7.
TreeFamTF337234.

Enzyme and pathway databases

SignaLinkQ9NPF7.

Gene expression databases

BgeeQ9NPF7.
CleanExHS_IL23A.
GenevestigatorQ9NPF7.

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

EvolutionaryTraceQ9NPF7.
GeneWikiInterleukin_23.
GenomeRNAi51561.
NextBio55362.
PROQ9NPF7.
SOURCESearch...

Entry information

Entry nameIL23A_HUMAN
AccessionPrimary (citable) accession number: Q9NPF7
Secondary accession number(s): Q6NZ80, Q6NZ82, Q9H2A5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM