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Interleukin-27 subunit alpha (IL-27 subunit alpha) (IL-27-A) (IL27-A) (Interleukin-30) (p28)

 IL27A_HUMAN             Reviewed;         243 AA.
Q8NEV9; A0N0L2; Q6P676;
26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
26-FEB-2008, sequence version 2.
23-MAY-2018, entry version 100.
RecName: Full=Interleukin-27 subunit alpha;
Short=IL-27 subunit alpha;
Short=IL-27-A;
Short=IL27-A;
AltName: Full=Interleukin-30;
AltName: Full=p28;
Flags: Precursor;
Name=IL27; Synonyms=IL27A, IL30;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, GLYCOSYLATION, SUBCELLULAR
LOCATION, TISSUE SPECIFICITY, INDUCTION, SUBUNIT, AND VARIANT PRO-119.
PubMed=12121660; DOI=10.1016/S1074-7613(02)00324-2;
Pflanz S., Timans J.C., Cheung J., Rosales R., Kanzler H., Gilbert J.,
Hibbert L., Churakova T., Travis M., Vaisberg E., Blumenschein W.M.,
Mattson J.D., Wagner J.L., To W., Zurawski S., McClanahan T.K.,
Gorman D.M., Bazan J.F., de Waal Malefyt R., Rennick D.,
Kastelein R.A.;
"IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein,
induces proliferation of naive CD4(+) T cells.";
Immunity 16:779-790(2002).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
Nickerson D.A.;
Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-59.
TISSUE=Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
FUNCTION.
PubMed=14565860; DOI=10.1089/10799900360708632;
Hibbert L., Pflanz S., De Waal Malefyt R., Kastelein R.A.;
"IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and
IL-12Rbeta2 in naive T cells.";
J. Interferon Cytokine Res. 23:513-522(2003).
[6]
FUNCTION.
PubMed=17068156; DOI=10.1182/blood-2006-02-001578;
Fakruddin J.M., Lempicki R.A., Gorelick R.J., Yang J.,
Adelsberger J.W., Garcia-Pineres A.J., Pinto L.A., Lane H.C.,
Imamichi T.;
"Noninfectious papilloma virus-like particles inhibit HIV-1
replication: implications for immune control of HIV-1 infection by IL-
27.";
Blood 109:1841-1849(2007).
[7]
FUNCTION.
PubMed=18191724; DOI=10.1016/j.humimm.2007.10.004;
Feng X.M., Chen X.L., Liu N., Chen Z., Zhou Y.L., Han Z.B., Zhang L.,
Han Z.C.;
"Interleukin-27 upregulates major histocompatibility complex class II
expression in primary human endothelial cells through induction of
major histocompatibility complex class II transactivator.";
Hum. Immunol. 68:965-972(2007).
[8]
REVIEW.
PubMed=17294231; DOI=10.1007/s00109-007-0164-7;
Batten M., Ghilardi N.;
"The biology and therapeutic potential of interleukin 27.";
J. Mol. Med. 85:661-672(2007).
[9]
VARIANTS ALA-59 AND PRO-119.
PubMed=17318299; DOI=10.1007/s10038-007-0123-8;
Chae S.-C., Li C.-S., Kim K.M., Yang J.Y., Zhang Q., Lee Y.-C.,
Yang Y.-S., Chung H.-T.;
"Identification of polymorphisms in human interleukin-27 and their
association with asthma in a Korean population.";
J. Hum. Genet. 52:355-361(2007).
-!- FUNCTION: Associates with EBI3 to form the IL-27 interleukin, a
heterodimeric cytokine which functions in innate immunity. IL-27
has pro- and anti-inflammatory properties, that can regulate T-
helper cell development, suppress T-cell proliferation, stimulate
cytotoxic T-cell activity, induce isotype switching in B-cells,
and that has diverse effects on innate immune cells. Among its
target cells are CD4 T-helper cells which can differentiate in
type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17
producing helper T-cells (TH17). It drives rapid clonal expansion
of naive but not memory CD4 T-cells. It also strongly synergizes
with IL-12 to trigger interferon-gamma/IFN-gamma production of
naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR which
appears to be required but not sufficient for IL-27-mediated
signal transduction. IL-27 potentiate the early phase of TH1
response and suppress TH2 and TH17 differentiation. It induces the
differentiation of TH1 cells via two distinct pathways, p38
MAPK/TBX21- and ICAM1/ITGAL/ERK-dependent pathways. It also
induces STAT1, STAT3, STAT4 and STAT5 phosphorylation and
activates TBX21/T-Bet via STAT1 with resulting IL12RB2 up-
regulation, an event crucial to TH1 cell commitment. It suppresses
the expression of GATA3, the inhibitor TH1 cells development. In
CD8 T-cells, it activates STATs as well as GZMB. IL-27 reveals to
be a potent inhibitor of TH17 cell development and of IL-17
production. Indeed IL27 alone is also able to inhibit the
production of IL17 by CD4 and CD8 T-cells. While IL-27 suppressed
the development of proinflammatory Th17 cells via STAT1, it
inhibits the development of anti-inflammatory inducible regulatory
T-cells, iTreg, independently of STAT1. IL-27 has also an effect
on cytokine production, it suppresses proinflammatory cytokine
production such as IL2, IL4, IL5 and IL6 and activates suppressors
of cytokine signaling such as SOCS1 and SOCS3. Apart from
suppression of cytokine production, IL-27 also antagonizes the
effects of some cytokines such as IL6 through direct effects on T-
cells. Another important role of IL-27 is its antitumor activity
as well as its antiangiogenic activity with activation of
production of antiangiogenic chemokines such as IP-10/CXCL10 and
MIG/CXCL9. In vein endothelial cells, it induces IRF1/interferon
regulatory factor 1 and increase the expression of MHC class II
transactivator/CIITA with resulting up-regulation of major
histocompatibility complex class II. IL-27 also demonstrates
antiviral activity with inhibitory properties on HIV-1
replication. {ECO:0000269|PubMed:12121660,
ECO:0000269|PubMed:14565860, ECO:0000269|PubMed:17068156,
ECO:0000269|PubMed:18191724}.
-!- SUBUNIT: Heterodimer with EBI3; not disulfide-linked. This
heterodimer is known as interleukin IL-27.
{ECO:0000269|PubMed:12121660}.
-!- INTERACTION:
Q14213:EBI3; NbExp=2; IntAct=EBI-15887997, EBI-742959;
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12121660}.
Note=Does not seem to be secreted without coexpression of EBI3.
-!- TISSUE SPECIFICITY: Expressed in monocytes and in placenta.
{ECO:0000269|PubMed:12121660}.
-!- INDUCTION: Transiently induced by bacterial lipopolysaccharides
(LPS) stimulation in monocytes. {ECO:0000269|PubMed:12121660}.
-!- PTM: O-glycosylated. {ECO:0000305|PubMed:12121660}.
-!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
-!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-27 entry;
URL="https://en.wikipedia.org/wiki/Interleukin_27";
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; AY099296; AAM34498.1; -; mRNA.
EMBL; EF064720; ABK41903.1; -; Genomic_DNA.
EMBL; CH471279; EAW52277.1; -; Genomic_DNA.
EMBL; BC062422; AAH62422.1; -; mRNA.
CCDS; CCDS10633.1; -.
RefSeq; NP_663634.2; NM_145659.3.
UniGene; Hs.528111; -.
ProteinModelPortal; Q8NEV9; -.
SMR; Q8NEV9; -.
BioGrid; 128924; 2.
DIP; DIP-59473N; -.
IntAct; Q8NEV9; 1.
STRING; 9606.ENSP00000349365; -.
iPTMnet; Q8NEV9; -.
PhosphoSitePlus; Q8NEV9; -.
BioMuta; IL27; -.
DMDM; 182701368; -.
PaxDb; Q8NEV9; -.
PeptideAtlas; Q8NEV9; -.
PRIDE; Q8NEV9; -.
DNASU; 246778; -.
Ensembl; ENST00000356897; ENSP00000349365; ENSG00000197272.
GeneID; 246778; -.
KEGG; hsa:246778; -.
UCSC; uc002dqc.3; human.
CTD; 246778; -.
DisGeNET; 246778; -.
EuPathDB; HostDB:ENSG00000197272.2; -.
GeneCards; IL27; -.
H-InvDB; HIX0038580; -.
HGNC; HGNC:19157; IL27.
HPA; CAB024722; -.
MIM; 608273; gene.
neXtProt; NX_Q8NEV9; -.
OpenTargets; ENSG00000197272; -.
PharmGKB; PA134870478; -.
eggNOG; ENOG410IKKP; Eukaryota.
eggNOG; ENOG4111579; LUCA.
GeneTree; ENSGT00390000018206; -.
HOGENOM; HOG000113043; -.
HOVERGEN; HBG097312; -.
InParanoid; Q8NEV9; -.
OMA; GQAHRFA; -.
OrthoDB; EOG091G0R0C; -.
PhylomeDB; Q8NEV9; -.
TreeFam; TF337498; -.
Reactome; R-HSA-9020956; Interleukin-27 signaling.
SignaLink; Q8NEV9; -.
SIGNOR; Q8NEV9; -.
GenomeRNAi; 246778; -.
PRO; PR:Q8NEV9; -.
Proteomes; UP000005640; Chromosome 16.
Bgee; ENSG00000197272; -.
CleanEx; HS_IL27; -.
ExpressionAtlas; Q8NEV9; baseline and differential.
Genevisible; Q8NEV9; HS.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
GO; GO:0045523; F:interleukin-27 receptor binding; ISS:UniProtKB.
GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB.
GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0070106; P:interleukin-27-mediated signaling pathway; TAS:Reactome.
GO; GO:0002230; P:positive regulation of defense response to virus by host; IEA:Ensembl.
GO; GO:0045078; P:positive regulation of interferon-gamma biosynthetic process; IDA:UniProtKB.
GO; GO:0042129; P:regulation of T cell proliferation; ISS:UniProtKB.
GO; GO:0045625; P:regulation of T-helper 1 cell differentiation; IDA:UniProtKB.
GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
InterPro; IPR026207; IL-27_alpha.
PANTHER; PTHR20879; PTHR20879; 1.
1: Evidence at protein level;
Antiviral protein; Complete proteome; Cytokine; Glycoprotein;
Immunity; Inflammatory response; Innate immunity; Polymorphism;
Reference proteome; Secreted; Signal.
SIGNAL 1 28 {ECO:0000255}.
CHAIN 29 243 Interleukin-27 subunit alpha.
/FTId=PRO_0000320139.
COMPBIAS 164 176 Glu-rich.
VARIANT 59 59 S -> A (in dbSNP:rs17855750).
{ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:17318299}.
/FTId=VAR_039140.
VARIANT 119 119 L -> P (in dbSNP:rs181206).
{ECO:0000269|PubMed:12121660,
ECO:0000269|PubMed:17318299}.
/FTId=VAR_039141.
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


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