IL27A_HUMAN
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 03-AUG-2022, entry version 123.
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";
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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 AlphaFoldDB; Q8NEV9; -.
DR SMR; Q8NEV9; -.
DR BioGRID; 128924; 3.
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; Q8NEV9; -.
DR PeptideAtlas; Q8NEV9; -.
DR PRIDE; Q8NEV9; -.
DR ProteomicsDB; 73223; -.
DR Antibodypedia; 13022; 606 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 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; PAQVSWP; -.
DR OrthoDB; 1356544at2759; -.
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; 11 hits in 1059 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 94 other tissues.
DR ExpressionAtlas; Q8NEV9; baseline and differential.
DR Genevisible; Q8NEV9; HS.
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 interferon-gamma 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; PTHR20879; 1.
PE 1: Evidence at protein level;
KW Antiviral protein; Cytokine; Glycoprotein; Immunity; Inflammatory response;
KW Innate immunity; Reference proteome; Secreted; 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"
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
