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Protein

Interleukin-27 subunit alpha

Gene

IL27

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAntiviral protein, Cytokine
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-447115. Interleukin-12 family signaling.
SignaLinkiQ8NEV9.
SIGNORiQ8NEV9.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-27 subunit alpha
Short name:
IL-27 subunit alpha
Short name:
IL-27-A
Short name:
IL27-A
Alternative name(s):
Interleukin-30
p28
Gene namesi
Name:IL27
Synonyms:IL27A, IL30
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000197272.2.
HGNCiHGNC:19157. IL27.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi246778.
OpenTargetsiENSG00000197272.
PharmGKBiPA134870478.

Polymorphism and mutation databases

BioMutaiIL27.
DMDMi182701368.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000032013929 – 243Interleukin-27 subunit alphaAdd BLAST215

Post-translational modificationi

O-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8NEV9.
PeptideAtlasiQ8NEV9.
PRIDEiQ8NEV9.

PTM databases

iPTMnetiQ8NEV9.
PhosphoSitePlusiQ8NEV9.

Expressioni

Tissue specificityi

Expressed in monocytes and in placenta.1 Publication

Inductioni

Transiently induced by bacterial lipopolysaccharides (LPS) stimulation in monocytes.1 Publication

Gene expression databases

BgeeiENSG00000197272.
CleanExiHS_IL27.
ExpressionAtlasiQ8NEV9. baseline and differential.
GenevisibleiQ8NEV9. HS.

Organism-specific databases

HPAiCAB024722.

Interactioni

Subunit structurei

Heterodimer with EBI3; not disulfide-linked. This heterodimer is known as interleukin IL-27.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi128924. 2 interactors.
DIPiDIP-59473N.
STRINGi9606.ENSP00000349365.

Structurei

3D structure databases

ProteinModelPortaliQ8NEV9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi164 – 176Glu-richAdd BLAST13

Sequence similaritiesi

Belongs to the IL-6 superfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IKKP. Eukaryota.
ENOG4111579. LUCA.
GeneTreeiENSGT00390000018206.
HOGENOMiHOG000113043.
HOVERGENiHBG097312.
InParanoidiQ8NEV9.
OMAiGQAHRFA.
OrthoDBiEOG091G0R0C.
PhylomeDBiQ8NEV9.
TreeFamiTF337498.

Family and domain databases

InterProiView protein in InterPro
IPR026207. IL-27_alpha.
PANTHERiPTHR20879. PTHR20879. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q8NEV9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGQTAGDLGW RLSLLLLPLL LVQAGVWGFP RPPGRPQLSL QELRREFTVS
60 70 80 90 100
LHLARKLLSE VRGQAHRFAE SHLPGVNLYL LPLGEQLPDV SLTFQAWRRL
110 120 130 140 150
SDPERLCFIS TTLQPFHALL GGLGTQGRWT NMERMQLWAM RLDLRDLQRH
160 170 180 190 200
LRFQVLAAGF NLPEEEEEEE EEEEEERKGL LPGALGSALQ GPAQVSWPQL
210 220 230 240
LSTYRLLHSL ELVLSRAVRE LLLLSKAGHS VWPLGFPTLS PQP
Length:243
Mass (Da):27,493
Last modified:February 26, 2008 - v2
Checksum:i2FA8B8AB60B606E8
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03914059S → A2 PublicationsCorresponds to variant dbSNP:rs17855750Ensembl.1
Natural variantiVAR_039141119L → P2 PublicationsCorresponds to variant dbSNP:rs181206Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY099296 mRNA. Translation: AAM34498.1.
EF064720 Genomic DNA. Translation: ABK41903.1.
CH471279 Genomic DNA. Translation: EAW52277.1.
BC062422 mRNA. Translation: AAH62422.1.
CCDSiCCDS10633.1.
RefSeqiNP_663634.2. NM_145659.3.
UniGeneiHs.528111.

Genome annotation databases

EnsembliENST00000356897; ENSP00000349365; ENSG00000197272.
GeneIDi246778.
KEGGihsa:246778.
UCSCiuc002dqc.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIL27A_HUMAN
AccessioniPrimary (citable) accession number: Q8NEV9
Secondary accession number(s): A0N0L2, Q6P676
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: September 27, 2017
This is version 96 of the entry and version 2 of the sequence. See 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families