ID IL27A_HUMAN Reviewed; 243 AA. AC Q8NEV9; A0N0L2; Q6P676; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 26-FEB-2008, sequence version 2. DT 27-MAR-2024, entry version 132. DE RecName: Full=Interleukin-27 subunit alpha; DE Short=IL-27 subunit alpha; DE Short=IL-27-A; DE Short=IL27-A; DE AltName: Full=Interleukin-30; DE AltName: Full=p28; DE Flags: Precursor; GN Name=IL27; Synonyms=IL27A, IL30; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, GLYCOSYLATION, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, INDUCTION, SUBUNIT, AND VARIANT PRO-119. RX PubMed=12121660; DOI=10.1016/s1074-7613(02)00324-2; RA Pflanz S., Timans J.C., Cheung J., Rosales R., Kanzler H., Gilbert J., RA Hibbert L., Churakova T., Travis M., Vaisberg E., Blumenschein W.M., RA Mattson J.D., Wagner J.L., To W., Zurawski S., McClanahan T.K., RA Gorman D.M., Bazan J.F., de Waal Malefyt R., Rennick D., Kastelein R.A.; RT "IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces RT proliferation of naive CD4(+) T cells."; RL Immunity 16:779-790(2002). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., RA Nickerson D.A.; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-59. RC TISSUE=Lung; 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION. RX PubMed=14565860; DOI=10.1089/10799900360708632; RA Hibbert L., Pflanz S., De Waal Malefyt R., Kastelein R.A.; RT "IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and IL- RT 12Rbeta2 in naive T cells."; RL J. Interferon Cytokine Res. 23:513-522(2003). RN [6] RP FUNCTION. RX PubMed=17068156; DOI=10.1182/blood-2006-02-001578; RA Fakruddin J.M., Lempicki R.A., Gorelick R.J., Yang J., Adelsberger J.W., RA Garcia-Pineres A.J., Pinto L.A., Lane H.C., Imamichi T.; RT "Noninfectious papilloma virus-like particles inhibit HIV-1 replication: RT implications for immune control of HIV-1 infection by IL-27."; RL Blood 109:1841-1849(2007). RN [7] RP FUNCTION. RX PubMed=18191724; DOI=10.1016/j.humimm.2007.10.004; RA Feng X.M., Chen X.L., Liu N., Chen Z., Zhou Y.L., Han Z.B., Zhang L., RA Han Z.C.; RT "Interleukin-27 upregulates major histocompatibility complex class II RT expression in primary human endothelial cells through induction of major RT histocompatibility complex class II transactivator."; RL Hum. Immunol. 68:965-972(2007). RN [8] RP REVIEW. RX PubMed=17294231; DOI=10.1007/s00109-007-0164-7; RA Batten M., Ghilardi N.; RT "The biology and therapeutic potential of interleukin 27."; RL J. Mol. Med. 85:661-672(2007). RN [9] RP VARIANTS ALA-59 AND PRO-119. RX PubMed=17318299; DOI=10.1007/s10038-007-0123-8; RA Chae S.-C., Li C.-S., Kim K.M., Yang J.Y., Zhang Q., Lee Y.-C., Yang Y.-S., RA Chung H.-T.; RT "Identification of polymorphisms in human interleukin-27 and their RT association with asthma in a Korean population."; RL J. Hum. Genet. 52:355-361(2007). CC -!- FUNCTION: Associates with EBI3 to form the IL-27 interleukin, a CC heterodimeric cytokine which functions in innate immunity. IL-27 has CC pro- and anti-inflammatory properties, that can regulate T-helper cell CC development, suppress T-cell proliferation, stimulate cytotoxic T-cell CC activity, induce isotype switching in B-cells, and that has diverse CC effects on innate immune cells. Among its target cells are CD4 T-helper CC cells which can differentiate in type 1 effector cells (TH1), type 2 CC effector cells (TH2) and IL17 producing helper T-cells (TH17). It CC drives rapid clonal expansion of naive but not memory CD4 T-cells. It CC also strongly synergizes with IL-12 to trigger interferon-gamma/IFN- CC gamma production of naive CD4 T-cells, binds to the cytokine receptor CC WSX-1/TCCR which appears to be required but not sufficient for IL-27- CC mediated signal transduction. IL-27 potentiate the early phase of TH1 CC response and suppress TH2 and TH17 differentiation. It induces the CC differentiation of TH1 cells via two distinct pathways, p38 CC MAPK/TBX21- and ICAM1/ITGAL/ERK-dependent pathways. It also induces CC STAT1, STAT3, STAT4 and STAT5 phosphorylation and activates TBX21/T-Bet CC via STAT1 with resulting IL12RB2 up-regulation, an event crucial to TH1 CC cell commitment. It suppresses the expression of GATA3, the inhibitor CC TH1 cells development. In CD8 T-cells, it activates STATs as well as CC GZMB. IL-27 reveals to be a potent inhibitor of TH17 cell development CC and of IL-17 production. Indeed IL27 alone is also able to inhibit the CC production of IL17 by CD4 and CD8 T-cells. While IL-27 suppressed the CC development of pro-inflammatory Th17 cells via STAT1, it inhibits the CC development of anti-inflammatory inducible regulatory T-cells, iTreg, CC independently of STAT1. IL-27 has also an effect on cytokine CC production, it suppresses pro-inflammatory cytokine production such as CC IL2, IL4, IL5 and IL6 and activates suppressors of cytokine signaling CC such as SOCS1 and SOCS3. Apart from suppression of cytokine production, CC IL-27 also antagonizes the effects of some cytokines such as IL6 CC through direct effects on T-cells. Another important role of IL-27 is CC its antitumor activity as well as its antiangiogenic activity with CC activation of production of antiangiogenic chemokines such as IP- CC 10/CXCL10 and MIG/CXCL9. In vein endothelial cells, it induces CC IRF1/interferon regulatory factor 1 and increase the expression of MHC CC class II transactivator/CIITA with resulting up-regulation of major CC histocompatibility complex class II. IL-27 also demonstrates antiviral CC activity with inhibitory properties on HIV-1 replication. CC {ECO:0000269|PubMed:12121660, ECO:0000269|PubMed:14565860, CC ECO:0000269|PubMed:17068156, ECO:0000269|PubMed:18191724}. CC -!- SUBUNIT: Heterodimer with EBI3; not disulfide-linked. This heterodimer CC is known as interleukin IL-27. {ECO:0000269|PubMed:12121660}. CC -!- INTERACTION: CC Q8NEV9; O75462: CRLF1; NbExp=2; IntAct=EBI-15887997, EBI-15587902; CC Q8NEV9; Q14213: EBI3; NbExp=2; IntAct=EBI-15887997, EBI-742959; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12121660}. Note=Does CC not seem to be secreted without coexpression of EBI3. CC -!- TISSUE SPECIFICITY: Expressed in monocytes and in placenta. CC {ECO:0000269|PubMed:12121660}. CC -!- INDUCTION: Transiently induced by bacterial lipopolysaccharides (LPS) CC stimulation in monocytes. {ECO:0000269|PubMed:12121660}. CC -!- PTM: O-glycosylated. {ECO:0000305|PubMed:12121660}. CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-27 entry; CC URL="https://en.wikipedia.org/wiki/Interleukin_27"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY099296; AAM34498.1; -; mRNA. DR EMBL; EF064720; ABK41903.1; -; Genomic_DNA. DR EMBL; CH471279; EAW52277.1; -; Genomic_DNA. DR EMBL; BC062422; AAH62422.1; -; mRNA. DR CCDS; CCDS10633.1; -. DR RefSeq; NP_663634.2; NM_145659.3. DR PDB; 7U7N; EM; 3.47 A; D=29-243. DR PDB; 7ZXK; X-ray; 2.20 A; A/C=29-243. DR PDB; 8D85; EM; 3.81 A; D=29-243. DR PDBsum; 7U7N; -. DR PDBsum; 7ZXK; -. DR PDBsum; 8D85; -. DR AlphaFoldDB; Q8NEV9; -. DR EMDB; EMD-27246; -. DR EMDB; EMD-27247; -. DR SMR; Q8NEV9; -. DR BioGRID; 128924; 5. DR DIP; DIP-59473N; -. DR IntAct; Q8NEV9; 2. DR STRING; 9606.ENSP00000349365; -. DR iPTMnet; Q8NEV9; -. DR PhosphoSitePlus; Q8NEV9; -. DR BioMuta; IL27; -. DR DMDM; 182701368; -. DR jPOST; Q8NEV9; -. DR MassIVE; Q8NEV9; -. DR PaxDb; 9606-ENSP00000349365; -. DR PeptideAtlas; Q8NEV9; -. DR ProteomicsDB; 73223; -. DR Antibodypedia; 13022; 643 antibodies from 39 providers. DR DNASU; 246778; -. DR Ensembl; ENST00000356897.1; ENSP00000349365.1; ENSG00000197272.2. DR GeneID; 246778; -. DR KEGG; hsa:246778; -. DR MANE-Select; ENST00000356897.1; ENSP00000349365.1; NM_145659.3; NP_663634.2. DR UCSC; uc002dqc.3; human. DR AGR; HGNC:19157; -. DR CTD; 246778; -. DR DisGeNET; 246778; -. DR GeneCards; IL27; -. DR HGNC; HGNC:19157; IL27. DR HPA; ENSG00000197272; Tissue enriched (liver). DR MIM; 608273; gene. DR neXtProt; NX_Q8NEV9; -. DR OpenTargets; ENSG00000197272; -. DR PharmGKB; PA134870478; -. DR VEuPathDB; HostDB:ENSG00000197272; -. DR eggNOG; ENOG502SVMM; Eukaryota. DR GeneTree; ENSGT00390000018206; -. DR HOGENOM; CLU_102031_0_0_1; -. DR InParanoid; Q8NEV9; -. DR OMA; LCFLSMM; -. DR OrthoDB; 4628116at2759; -. DR PhylomeDB; Q8NEV9; -. DR TreeFam; TF337498; -. DR PathwayCommons; Q8NEV9; -. DR Reactome; R-HSA-9020956; Interleukin-27 signaling. DR SignaLink; Q8NEV9; -. DR SIGNOR; Q8NEV9; -. DR BioGRID-ORCS; 246778; 12 hits in 1137 CRISPR screens. DR ChiTaRS; IL27; human. DR GenomeRNAi; 246778; -. DR Pharos; Q8NEV9; Tbio. DR PRO; PR:Q8NEV9; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q8NEV9; Protein. DR Bgee; ENSG00000197272; Expressed in right lobe of liver and 95 other cell types or tissues. DR ExpressionAtlas; Q8NEV9; baseline and differential. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW. DR GO; GO:0045523; F:interleukin-27 receptor binding; ISS:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IEA:Ensembl. DR GO; GO:0032729; P:positive regulation of type II interferon production; IDA:UniProtKB. DR GO; GO:0042129; P:regulation of T cell proliferation; ISS:UniProtKB. DR GO; GO:0045625; P:regulation of T-helper 1 cell differentiation; IDA:UniProtKB. DR GO; GO:0140459; P:response to Gram-positive bacterium; IEA:Ensembl. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR026207; IL-27_alpha. DR PANTHER; PTHR20879; INTERLEUKIN-27 SUBUNIT ALPHA; 1. DR PANTHER; PTHR20879:SF1; INTERLEUKIN-27 SUBUNIT ALPHA; 1. DR Genevisible; Q8NEV9; HS. PE 1: Evidence at protein level; KW 3D-structure; Antiviral protein; Cytokine; Glycoprotein; Immunity; KW Inflammatory response; Innate immunity; Reference proteome; Secreted; KW Signal. FT SIGNAL 1..28 FT /evidence="ECO:0000255" FT CHAIN 29..243 FT /note="Interleukin-27 subunit alpha" FT /id="PRO_0000320139" FT VARIANT 59 FT /note="S -> A (in dbSNP:rs17855750)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17318299" FT /id="VAR_039140" FT VARIANT 119 FT /note="L -> P (in dbSNP:rs181206)" FT /evidence="ECO:0000269|PubMed:12121660, FT ECO:0000269|PubMed:17318299" FT /id="VAR_039141" FT TURN 40..43 FT /evidence="ECO:0007829|PDB:7U7N" FT HELIX 44..72 FT /evidence="ECO:0007829|PDB:7U7N" FT HELIX 78..80 FT /evidence="ECO:0007829|PDB:7U7N" FT STRAND 85..87 FT /evidence="ECO:0007829|PDB:7U7N" FT HELIX 94..99 FT /evidence="ECO:0007829|PDB:7U7N" FT HELIX 102..113 FT /evidence="ECO:0007829|PDB:7U7N" FT HELIX 116..124 FT /evidence="ECO:0007829|PDB:7U7N" FT STRAND 126..128 FT /evidence="ECO:0007829|PDB:7U7N" FT HELIX 131..158 FT /evidence="ECO:0007829|PDB:7U7N" FT HELIX 166..178 FT /evidence="ECO:0007829|PDB:7U7N" FT HELIX 197..225 FT /evidence="ECO:0007829|PDB:7U7N" SQ SEQUENCE 243 AA; 27493 MW; 2FA8B8AB60B606E8 CRC64; MGQTAGDLGW RLSLLLLPLL LVQAGVWGFP RPPGRPQLSL QELRREFTVS LHLARKLLSE VRGQAHRFAE SHLPGVNLYL LPLGEQLPDV SLTFQAWRRL SDPERLCFIS TTLQPFHALL GGLGTQGRWT NMERMQLWAM RLDLRDLQRH LRFQVLAAGF NLPEEEEEEE EEEEEERKGL LPGALGSALQ GPAQVSWPQL LSTYRLLHSL ELVLSRAVRE LLLLSKAGHS VWPLGFPTLS PQP //