ID IL23A_HUMAN Reviewed; 189 AA. AC Q9NPF7; Q6NZ80; Q6NZ82; Q9H2A5; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 25-JAN-2012, entry version 81. DE RecName: Full=Interleukin-23 subunit alpha; DE Short=IL-23 subunit alpha; DE Short=IL-23-A; DE AltName: Full=Interleukin-23 subunit p19; DE Short=IL-23p19; DE Flags: Precursor; GN Name=IL23A; Synonyms=SGRF; ORFNames=UNQ2498/PRO5798; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH IL12B, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX MEDLINE=20567322; PubMed=11114383; DOI=10.1016/S1074-7613(00)00070-4; RA Oppmann B., Lesley R., Blom B., Timans J.C., Xu Y., Hunte B., Vega F., RA Yu N., Wang J., Singh K.P., Zonin F., Vaisberg E., Churakova T., RA Liu M.-R., Gorman D., Wagner J., Zurawski S., Liu Y.-J., Abrams J.S., RA Moore K.W., Rennick D.M., de Waal-Malefyt R., Hannum C., Bazan J.F., RA Kastelein R.A.; RT "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with RT biological activities similar as well as distinct from IL-12."; RL Immunity 13:715-725(2000). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RC TISSUE=Spleen; RA Hirata Y., Kosuge Y.; RT "SGRF; a novel member of the IL-6/G-CSF family."; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX MEDLINE=22887296; PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, AND INTERACTION WITH IL12RB1 AND IL23R. RX MEDLINE=22018152; PubMed=12023369; RA Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., RA Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., RA O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., RA Rennick D.M., Kastelein R.A., de Waal Malefyt R., Moore K.W.; RT "A receptor for the heterodimeric cytokine IL-23 is composed of IL- RT 12Rbeta1 and a novel cytokine receptor subunit, IL-23R."; RL J. Immunol. 168:5699-5708(2002). RN [6] RP INDUCTION. RX PubMed=12421946; RA Pirhonen J., Matikainen S., Julkunen I.; RT "Regulation of virus-induced IL-12 and IL-23 expression in human RT macrophages."; RL J. Immunol. 169:5673-5678(2002). RN [7] RP INDUCTION. RX PubMed=15114670; DOI=10.1002/eji.200324815; RA Smits H.H., van Beelen A.J., Hessle C., Westland R., de Jong E., RA Soeteman E., Wold A., Wierenga E.A., Kapsenberg M.L.; RT "Commensal Gram-negative bacteria prime human dendritic cells for RT enhanced IL-23 and IL-27 expression and enhanced Th1 development."; RL Eur. J. Immunol. 34:1371-1380(2004). RN [8] RP INDUCTION. RX PubMed=15486065; DOI=10.1182/blood-2004-05-1718; RA Schnurr M., Toy T., Shin A., Wagner M., Cebon J., Maraskovsky E.; RT "Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and RT enhances IL-23 expression in human dendritic cells: a novel role for RT the cAMP pathway."; RL Blood 105:1582-1589(2005). RN [9] RP INDUCTION. RX PubMed=15731058; DOI=10.1128/IAI.73.3.1590-1597.2005; RA Fedele G., Stefanelli P., Spensieri F., Fazio C., Mastrantonio P., RA Ausiello C.M.; RT "Bordetella pertussis-infected human monocyte-derived dendritic cells RT undergo maturation and induce Th1 polarization and interleukin-23 RT expression."; RL Infect. Immun. 73:1590-1597(2005). RN [10] RP DEVELOPMENTAL STAGE. RX PubMed=16342235; DOI=10.1002/eji.200535467; RA Vanden Eijnden S., Goriely S., De Wit D., Goldman M., Willems F.; RT "Preferential production of the IL-12(p40)/IL-23(p19) heterodimer by RT dendritic cells from human newborns."; RL Eur. J. Immunol. 36:21-26(2006). RN [11] RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY. RX PubMed=16424222; RA Piskin G., Sylva-Steenland R.M.R., Bos J.D., Teunissen M.B.M.; RT "In vitro and in situ expression of IL-23 by keratinocytes in healthy RT skin and psoriasis lesions: enhanced expression in psoriatic skin."; RL J. Immunol. 176:1908-1915(2006). RN [12] RP INDUCTION. RX PubMed=16751425; RA Vaknin-Dembinsky A., Balashov K., Weiner H.L.; RT "IL-23 is increased in dendritic cells in multiple sclerosis and down- RT regulation of IL-23 by antisense oligos increases dendritic cell IL-10 RT production."; RL J. Immunol. 176:7768-7774(2006). RN [13] RP INDUCTION. RX PubMed=16688182; DOI=10.1038/nature04808; RA Langowski J.L., Zhang X., Wu L., Mattson J.D., Chen T., Smith K., RA Basham B., McClanahan T.K., Kastelein R.A., Oft M.; RT "IL-23 promotes tumour incidence and growth."; RL Nature 442:461-465(2006). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 20-189 IN COMPLEX WITH IL12B, RP AND SUBUNIT. RX PubMed=18680750; DOI=10.1016/j.jmb.2008.07.051; RA Lupardus P.J., Garcia K.C.; RT "The structure of interleukin-23 reveals the molecular basis of p40 RT subunit sharing with interleukin-12."; RL J. Mol. Biol. 382:931-941(2008). CC -!- FUNCTION: Associates with IL12B to form the IL-23 interleukin, an CC heterodimeric cytokine which functions in innate and adaptive CC immunity. IL-23 may constitute with IL-17 an acute response to CC infection in peripheral tissues. IL-23 binds to an heterodimeric CC receptor complex composed of IL12RB1 and IL23R, activates the Jak- CC Stat signaling cascade, stimulates memory rather than naive T- CC cells and promotes production of proinflammatory cytokines. IL-23 CC induces autoimmune inflammation and thus may be responsible for CC autoimmune inflammatory diseases and may be important for CC tumorigenesis. CC -!- SUBUNIT: Heterodimer with IL12B; disulfide-linked. The heterodimer CC is known as interleukin IL-23. CC -!- SUBCELLULAR LOCATION: Secreted. Note=Secreted upon association CC with IL12B. CC -!- TISSUE SPECIFICITY: Secreted by activated dendritic and phagocytic CC cells and keratinocytes. Also expressed by dermal Langerhans cells CC (at protein level). CC -!- DEVELOPMENTAL STAGE: Expressed by newborns dendritic cells. CC -!- INDUCTION: Up-regulated by a wide array of pathogens and pathogen- CC products together with self-signals for danger or injury. Up- CC regulated in psoriatic dermal tissues, in dendritic cells of CC multiple sclerosis patients and in tumors. CC -!- SIMILARITY: Belongs to the IL-6 superfamily. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF301620; AAG37232.1; -; mRNA. DR EMBL; AB030000; BAA93686.1; -; mRNA. DR EMBL; AB030001; BAA93687.1; -; Genomic_DNA. DR EMBL; AY359083; AAQ89442.1; -; mRNA. DR EMBL; BC066267; AAH66267.1; -; mRNA. DR EMBL; BC066268; AAH66268.1; -; mRNA. DR EMBL; BC066269; AAH66269.1; -; mRNA. DR EMBL; BC067511; AAH67511.1; -; mRNA. DR EMBL; BC067512; AAH67512.1; -; mRNA. DR EMBL; BC067513; AAH67513.1; -; mRNA. DR IPI; IPI00300835; -. DR RefSeq; NP_057668.1; NM_016584.2. DR UniGene; Hs.382212; -. DR UniGene; Hs.98309; -. DR PDB; 3D85; X-ray; 1.90 A; C=20-189. DR PDB; 3D87; X-ray; 2.90 A; A/C=20-189. DR PDB; 3DUH; X-ray; 2.30 A; C/D=20-189. DR PDBsum; 3D85; -. DR PDBsum; 3D87; -. DR PDBsum; 3DUH; -. DR ProteinModelPortal; Q9NPF7; -. DR SMR; Q9NPF7; 20-187. DR IntAct; Q9NPF7; 1. DR STRING; Q9NPF7; -. DR DMDM; 74761641; -. DR PRIDE; Q9NPF7; -. DR Ensembl; ENST00000228534; ENSP00000228534; ENSG00000110944. DR GeneID; 51561; -. DR KEGG; hsa:51561; -. DR UCSC; uc001sla.1; human. DR CTD; 51561; -. DR GeneCards; GC12P056732; -. DR H-InvDB; HIX0036667; -. DR HGNC; HGNC:15488; IL23A. DR HPA; HPA001554; -. DR MIM; 605580; gene. DR neXtProt; NX_Q9NPF7; -. DR PharmGKB; PA29824; -. DR eggNOG; prNOG12216; -. DR GeneTree; ENSGT00390000006482; -. DR HOGENOM; HBG127275; -. DR HOVERGEN; HBG081786; -. DR InParanoid; Q9NPF7; -. DR OMA; RIHQGLV; -. DR OrthoDB; EOG43BMQ2; -. DR Pathway_Interaction_DB; il23pathway; IL23-mediated signaling events. DR NextBio; 55362; -. DR ArrayExpress; Q9NPF7; -. DR Bgee; Q9NPF7; -. DR CleanEx; HS_IL23A; -. DR Genevestigator; Q9NPF7; -. DR GermOnline; ENSG00000110944; Homo sapiens. DR GO; GO:0070743; C:interleukin-23 complex; IDA:BHF-UCL. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IMP:BHF-UCL. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:BHF-UCL. DR GO; GO:0010535; P:positive regulation of activation of JAK2 kinase activity; IDA:BHF-UCL. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:BHF-UCL. DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IDA:BHF-UCL. DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:BHF-UCL. DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:BHF-UCL. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:BHF-UCL. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:BHF-UCL. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:BHF-UCL. DR GO; GO:0043382; P:positive regulation of memory T cell differentiation; ISS:BHF-UCL. DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IDA:BHF-UCL. DR GO; GO:0042346; P:positive regulation of NF-kappaB import into nucleus; TAS:BHF-UCL. DR GO; GO:0051135; P:positive regulation of NK T cell activation; IDA:BHF-UCL. DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; IDA:BHF-UCL. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:BHF-UCL. DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; ISS:BHF-UCL. DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IDA:BHF-UCL. DR GO; GO:2000330; P:positive regulation of T-helper 17 cell lineage commitment; ISS:BHF-UCL. DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; ISS:BHF-UCL. DR GO; GO:0034105; P:positive regulation of tissue remodeling; IC:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:BHF-UCL. DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IDA:BHF-UCL. DR GO; GO:0042520; P:positive regulation of tyrosine phosphorylation of Stat4 protein; IDA:BHF-UCL. DR GO; GO:0042523; P:positive regulation of tyrosine phosphorylation of Stat5 protein; IDA:BHF-UCL. DR GO; GO:0042510; P:regulation of tyrosine phosphorylation of Stat1 protein; IDA:BHF-UCL. DR GO; GO:0009615; P:response to virus; IEA:UniProtKB-KW. DR GO; GO:0048771; P:tissue remodeling; IEA:UniProtKB-KW. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR012351; 4_helix_cytokine_core. DR InterPro; IPR010831; IL23A. DR InterPro; IPR003573; IL6_MGF_GCSF. DR Gene3D; G3DSA:1.20.1250.10; 4_helix_cytokine_core; 1. DR KO; K05426; -. DR PANTHER; PTHR15947; IL23A; 1. DR Pfam; PF00489; IL6; 1. DR SUPFAM; SSF47266; 4_helix_cytokine; 1. PE 1: Evidence at protein level; KW 3D-structure; Antiviral defense; Complete proteome; Cytokine; KW Disulfide bond; Immunity; Inflammatory response; Innate immunity; KW Reference proteome; Secreted; Signal; Tissue remodeling. FT SIGNAL 1 19 Potential. FT CHAIN 20 189 Interleukin-23 subunit alpha. FT /FTId=PRO_0000259488. FT CONFLICT 122 122 G -> A (in Ref. 1; AAG37232). FT CONFLICT 147 147 I -> M (in Ref. 4; AAH66267). FT CONFLICT 168 168 S -> N (in Ref. 4; AAH66267). FT CONFLICT 173 173 V -> A (in Ref. 4; AAH66269). FT CONFLICT 189 189 P -> L (in Ref. 4; AAH66269). FT HELIX 30 45 FT HELIX 87 94 FT HELIX 98 103 FT TURN 107 109 FT HELIX 124 128 FT HELIX 132 135 FT HELIX 155 157 FT HELIX 158 181 SQ SEQUENCE 189 AA; 20730 MW; 51B5C0F188EC1B9F CRC64; MLGSRAVMLL LLLPWTAQGR AVPGGSSPAW TQCQQLSQKL CTLAWSAHPL VGHMDLREEG DEETTNDVPH IQCGDGCDPQ GLRDNSQFCL QRIHQGLIFY EKLLGSDIFT GEPSLLPDSP VGQLHASLLG LSQLLQPEGH HWETQQIPSL SPSQPWQRLL LRFKILRSLQ AFVAVAARVF AHGAATLSP //