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Q9NPF7

- IL23A_HUMAN

UniProt

Q9NPF7 - IL23A_HUMAN

Protein

Interleukin-23 subunit alpha

Gene

IL23A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 1 (01 Oct 2000)
      Previous versions | rss
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    Functioni

    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.3 Publications

    GO - Biological processi

    1. defense response to Gram-negative bacterium Source: BHF-UCL
    2. defense response to virus Source: UniProtKB-KW
    3. inflammatory response Source: UniProtKB-KW
    4. innate immune response Source: UniProtKB-KW
    5. negative regulation of interleukin-10 production Source: BHF-UCL
    6. positive regulation of activated T cell proliferation Source: BHF-UCL
    7. positive regulation of activation of JAK2 kinase activity Source: BHF-UCL
    8. positive regulation of defense response to virus by host Source: BHF-UCL
    9. positive regulation of granulocyte macrophage colony-stimulating factor production Source: BHF-UCL
    10. positive regulation of inflammatory response Source: BHF-UCL
    11. positive regulation of interferon-gamma production Source: BHF-UCL
    12. positive regulation of interleukin-10 production Source: BHF-UCL
    13. positive regulation of interleukin-12 production Source: BHF-UCL
    14. positive regulation of interleukin-17 production Source: BHF-UCL
    15. positive regulation of memory T cell differentiation Source: BHF-UCL
    16. positive regulation of natural killer cell activation Source: BHF-UCL
    17. positive regulation of natural killer cell proliferation Source: BHF-UCL
    18. positive regulation of neutrophil chemotaxis Source: Ensembl
    19. positive regulation of NF-kappaB import into nucleus Source: BHF-UCL
    20. positive regulation of NK T cell activation Source: BHF-UCL
    21. positive regulation of NK T cell proliferation Source: BHF-UCL
    22. positive regulation of osteoclast differentiation Source: BHF-UCL
    23. positive regulation of T cell mediated cytotoxicity Source: BHF-UCL
    24. positive regulation of T cell proliferation Source: BHF-UCL
    25. positive regulation of T-helper 17 cell lineage commitment Source: BHF-UCL
    26. positive regulation of T-helper 17 type immune response Source: BHF-UCL
    27. positive regulation of T-helper 1 type immune response Source: BHF-UCL
    28. positive regulation of tissue remodeling Source: BHF-UCL
    29. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    30. positive regulation of tumor necrosis factor production Source: BHF-UCL
    31. positive regulation of tyrosine phosphorylation of Stat3 protein Source: BHF-UCL
    32. positive regulation of tyrosine phosphorylation of Stat4 protein Source: BHF-UCL
    33. positive regulation of tyrosine phosphorylation of Stat5 protein Source: BHF-UCL
    34. regulation of tyrosine phosphorylation of Stat1 protein Source: BHF-UCL
    35. T cell proliferation Source: Ensembl
    36. tissue remodeling Source: UniProtKB-KW

    Keywords - Molecular functioni

    Cytokine

    Keywords - Biological processi

    Antiviral defense, Immunity, Inflammatory response, Innate immunity, Tissue remodeling

    Enzyme and pathway databases

    SignaLinkiQ9NPF7.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:IL23A
    Synonyms:SGRF
    ORF Names:UNQ2498/PRO5798
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:15488. IL23A.

    Subcellular locationi

    Secreted 1 Publication
    Note: Secreted upon association with IL12B.

    GO - Cellular componenti

    1. interleukin-23 complex Source: BHF-UCL

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29824.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919Sequence AnalysisAdd
    BLAST
    Chaini20 – 189170Interleukin-23 subunit alphaPRO_0000259488Add
    BLAST

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiQ9NPF7.
    PRIDEiQ9NPF7.

    Expressioni

    Tissue specificityi

    Secreted by activated dendritic and phagocytic cells and keratinocytes. Also expressed by dermal Langerhans cells (at protein level).2 Publications

    Developmental stagei

    Expressed by newborns dendritic cells.1 Publication

    Inductioni

    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.7 Publications

    Gene expression databases

    BgeeiQ9NPF7.
    CleanExiHS_IL23A.
    GenevestigatoriQ9NPF7.

    Organism-specific databases

    HPAiHPA001554.

    Interactioni

    Subunit structurei

    Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-23.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IL12BP294603EBI-2481154,EBI-1029614

    Protein-protein interaction databases

    BioGridi119611. 4 interactions.
    IntActiQ9NPF7. 1 interaction.
    STRINGi9606.ENSP00000228534.

    Structurei

    Secondary structure

    1
    189
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi30 – 4516
    Turni49 – 513
    Helixi73 – 753
    Helixi79 – 846
    Helixi87 – 10418
    Helixi107 – 1104
    Beta strandi111 – 1133
    Helixi121 – 13515
    Beta strandi136 – 1383
    Helixi155 – 1573
    Helixi158 – 18629

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ9NPF7.
    SMRiQ9NPF7. Positions 20-187.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9NPF7.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the IL-6 superfamily.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG42887.
    HOGENOMiHOG000048728.
    HOVERGENiHBG081786.
    InParanoidiQ9NPF7.
    KOiK05426.
    OMAiIHQGLVF.
    OrthoDBiEOG76HQ32.
    PhylomeDBiQ9NPF7.
    TreeFamiTF337234.

    Family and domain databases

    Gene3Di1.20.1250.10. 1 hit.
    InterProiIPR009079. 4_helix_cytokine-like_core.
    IPR012351. 4_helix_cytokine_core.
    IPR010831. IL-23_alpha.
    IPR003573. IL-6/IL-23/GCSF/MGF.
    [Graphical view]
    PANTHERiPTHR15947. PTHR15947. 1 hit.
    PfamiPF00489. IL6. 1 hit.
    [Graphical view]
    SUPFAMiSSF47266. SSF47266. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9NPF7-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLGSRAVMLL LLLPWTAQGR AVPGGSSPAW TQCQQLSQKL CTLAWSAHPL    50
    VGHMDLREEG DEETTNDVPH IQCGDGCDPQ GLRDNSQFCL QRIHQGLIFY 100
    EKLLGSDIFT GEPSLLPDSP VGQLHASLLG LSQLLQPEGH HWETQQIPSL 150
    SPSQPWQRLL LRFKILRSLQ AFVAVAARVF AHGAATLSP 189
    Length:189
    Mass (Da):20,730
    Last modified:October 1, 2000 - v1
    Checksum:i51B5C0F188EC1B9F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti122 – 1221G → A in AAG37232. (PubMed:11114383)Curated
    Sequence conflicti147 – 1471I → M in AAH66267. (PubMed:15489334)Curated
    Sequence conflicti168 – 1681S → N in AAH66267. (PubMed:15489334)Curated
    Sequence conflicti173 – 1731V → A in AAH66269. (PubMed:15489334)Curated
    Sequence conflicti189 – 1891P → L in AAH66269. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS8916.1.
    RefSeqiNP_057668.1. NM_016584.2.
    UniGeneiHs.382212.
    Hs.98309.

    Genome annotation databases

    EnsembliENST00000228534; ENSP00000228534; ENSG00000110944.
    GeneIDi51561.
    KEGGihsa:51561.
    UCSCiuc001sla.3. human.

    Polymorphism databases

    DMDMi74761641.

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS8916.1.
    RefSeqi NP_057668.1. NM_016584.2.
    UniGenei Hs.382212.
    Hs.98309.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3D85 X-ray 1.90 C 20-189 [» ]
    3D87 X-ray 2.90 A/C 20-189 [» ]
    3DUH X-ray 2.30 C/D 20-189 [» ]
    3QWR X-ray 3.25 B 20-189 [» ]
    4GRW X-ray 2.55 A/C 1-189 [» ]
    ProteinModelPortali Q9NPF7.
    SMRi Q9NPF7. Positions 20-187.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 119611. 4 interactions.
    IntActi Q9NPF7. 1 interaction.
    STRINGi 9606.ENSP00000228534.

    Chemistry

    ChEMBLi CHEMBL2364154.

    Polymorphism databases

    DMDMi 74761641.

    Proteomic databases

    PaxDbi Q9NPF7.
    PRIDEi Q9NPF7.

    Protocols and materials databases

    DNASUi 51561.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000228534 ; ENSP00000228534 ; ENSG00000110944 .
    GeneIDi 51561.
    KEGGi hsa:51561.
    UCSCi uc001sla.3. human.

    Organism-specific databases

    CTDi 51561.
    GeneCardsi GC12P056732.
    HGNCi HGNC:15488. IL23A.
    HPAi HPA001554.
    MIMi 605580. gene.
    neXtProti NX_Q9NPF7.
    PharmGKBi PA29824.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG42887.
    HOGENOMi HOG000048728.
    HOVERGENi HBG081786.
    InParanoidi Q9NPF7.
    KOi K05426.
    OMAi IHQGLVF.
    OrthoDBi EOG76HQ32.
    PhylomeDBi Q9NPF7.
    TreeFami TF337234.

    Enzyme and pathway databases

    SignaLinki Q9NPF7.

    Miscellaneous databases

    EvolutionaryTracei Q9NPF7.
    GeneWikii Interleukin_23.
    GenomeRNAii 51561.
    NextBioi 55362.
    PROi Q9NPF7.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9NPF7.
    CleanExi HS_IL23A.
    Genevestigatori Q9NPF7.

    Family and domain databases

    Gene3Di 1.20.1250.10. 1 hit.
    InterProi IPR009079. 4_helix_cytokine-like_core.
    IPR012351. 4_helix_cytokine_core.
    IPR010831. IL-23_alpha.
    IPR003573. IL-6/IL-23/GCSF/MGF.
    [Graphical view ]
    PANTHERi PTHR15947. PTHR15947. 1 hit.
    Pfami PF00489. IL6. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47266. SSF47266. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. 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. 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. 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. 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.

    Entry informationi

    Entry nameiIL23A_HUMAN
    AccessioniPrimary (citable) accession number: Q9NPF7
    Secondary accession number(s): Q6NZ80, Q6NZ82, Q9H2A5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 31, 2006
    Last sequence update: October 1, 2000
    Last modified: October 1, 2014
    This is version 106 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3