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Q8NEV9

- IL27A_HUMAN

UniProt

Q8NEV9 - IL27A_HUMAN

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Protein
Interleukin-27 subunit alpha
Gene
IL27, IL27A, IL30
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. interleukin-27 receptor binding Source: UniProtKB
  2. receptor binding Source: UniProtKB

GO - Biological processi

  1. inflammatory response Source: UniProtKB-KW
  2. innate immune response Source: UniProtKB-KW
  3. positive regulation of interferon-gamma biosynthetic process Source: UniProtKB
  4. regulation of T cell proliferation Source: UniProtKB
  5. regulation of T-helper 1 cell differentiation Source: UniProtKB
  6. regulation of defense response to virus Source: UniProtKB-KW
  7. response to bacterium Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Antiviral protein, Cytokine

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

SignaLinkiQ8NEV9.

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
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:19157. IL27.

Subcellular locationi

Secreted
Note: Does not seem to be secreted without coexpression of EBI3.1 Publication

GO - Cellular componenti

  1. extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134870478.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828 Reviewed prediction
Add
BLAST
Chaini29 – 243215Interleukin-27 subunit alpha
PRO_0000320139Add
BLAST

Post-translational modificationi

O-glycosylated Inferred.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8NEV9.
PRIDEiQ8NEV9.

PTM databases

PhosphoSiteiQ8NEV9.

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

ArrayExpressiQ8NEV9.
BgeeiQ8NEV9.
CleanExiHS_IL27.
GenevestigatoriQ8NEV9.

Organism-specific databases

HPAiCAB024722.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

DIPiDIP-59473N.
STRINGi9606.ENSP00000349365.

Structurei

3D structure databases

ProteinModelPortaliQ8NEV9.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi164 – 17613Glu-rich
Add
BLAST

Sequence similaritiesi

Belongs to the IL-6 superfamily.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG45660.
HOGENOMiHOG000113043.
HOVERGENiHBG097312.
InParanoidiQ8NEV9.
OMAiHLRFQVL.
OrthoDBiEOG70ZZQ3.
PhylomeDBiQ8NEV9.
TreeFamiTF337498.

Family and domain databases

InterProiIPR026207. IL-27_alpha.
[Graphical view]
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

MGQTAGDLGW RLSLLLLPLL LVQAGVWGFP RPPGRPQLSL QELRREFTVS    50
LHLARKLLSE VRGQAHRFAE SHLPGVNLYL LPLGEQLPDV SLTFQAWRRL 100
SDPERLCFIS TTLQPFHALL GGLGTQGRWT NMERMQLWAM RLDLRDLQRH 150
LRFQVLAAGF NLPEEEEEEE EEEEEERKGL LPGALGSALQ GPAQVSWPQL 200
LSTYRLLHSL ELVLSRAVRE LLLLSKAGHS VWPLGFPTLS PQP 243
Length:243
Mass (Da):27,493
Last modified:February 26, 2008 - v2
Checksum:i2FA8B8AB60B606E8
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591S → A.2 Publications
Corresponds to variant rs17855750 [ dbSNP | Ensembl ].
VAR_039140
Natural varianti119 – 1191L → P.2 Publications
Corresponds to variant rs181206 [ dbSNP | Ensembl ].
VAR_039141

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi182701368.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Interleukin-27 entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY099296 mRNA. Translation: AAM34498.1 .
EF064720 Genomic DNA. Translation: ABK41903.1 .
CH471279 Genomic DNA. Translation: EAW52277.1 .
BC062422 mRNA. Translation: AAH62422.1 .
CCDSi CCDS10633.1.
RefSeqi NP_663634.2. NM_145659.3.
UniGenei Hs.528111.

3D structure databases

ProteinModelPortali Q8NEV9.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-59473N.
STRINGi 9606.ENSP00000349365.

PTM databases

PhosphoSitei Q8NEV9.

Polymorphism databases

DMDMi 182701368.

Proteomic databases

PaxDbi Q8NEV9.
PRIDEi Q8NEV9.

Protocols and materials databases

DNASUi 246778.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000356897 ; ENSP00000349365 ; ENSG00000197272 .
GeneIDi 246778.
KEGGi hsa:246778.
UCSCi uc002dqc.3. human.

Organism-specific databases

CTDi 246778.
GeneCardsi GC16M028511.
H-InvDB HIX0038580.
HGNCi HGNC:19157. IL27.
HPAi CAB024722.
MIMi 608273. gene.
neXtProti NX_Q8NEV9.
PharmGKBi PA134870478.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG45660.
HOGENOMi HOG000113043.
HOVERGENi HBG097312.
InParanoidi Q8NEV9.
OMAi HLRFQVL.
OrthoDBi EOG70ZZQ3.
PhylomeDBi Q8NEV9.
TreeFami TF337498.

Enzyme and pathway databases

SignaLinki Q8NEV9.

Miscellaneous databases

GenomeRNAii 246778.
NextBioi 91980.
PROi Q8NEV9.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8NEV9.
Bgeei Q8NEV9.
CleanExi HS_IL27.
Genevestigatori Q8NEV9.

Family and domain databases

InterProi IPR026207. IL-27_alpha.
[Graphical view ]
PANTHERi PTHR20879. PTHR20879. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, GLYCOSYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, SUBUNIT, VARIANT PRO-119.
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-59.
    Tissue: Lung.
  5. "IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells."
    Hibbert L., Pflanz S., De Waal Malefyt R., Kastelein R.A.
    J. Interferon Cytokine Res. 23:513-522(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Noninfectious papilloma virus-like particles inhibit HIV-1 replication: implications for immune control of HIV-1 infection by IL-27."
    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.
    Blood 109:1841-1849(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Interleukin-27 upregulates major histocompatibility complex class II expression in primary human endothelial cells through induction of major histocompatibility complex class II transactivator."
    Feng X.M., Chen X.L., Liu N., Chen Z., Zhou Y.L., Han Z.B., Zhang L., Han Z.C.
    Hum. Immunol. 68:965-972(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "The biology and therapeutic potential of interleukin 27."
    Batten M., Ghilardi N.
    J. Mol. Med. 85:661-672(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  9. "Identification of polymorphisms in human interleukin-27 and their association with asthma in a Korean population."
    Chae S.-C., Li C.-S., Kim K.M., Yang J.Y., Zhang Q., Lee Y.-C., Yang Y.-S., Chung H.-T.
    J. Hum. Genet. 52:355-361(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ALA-59 AND PRO-119.

Entry informationi

Entry nameiIL27A_HUMAN
AccessioniPrimary (citable) accession number: Q8NEV9
Secondary accession number(s): A0N0L2, Q6P676
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: July 9, 2014
This is version 74 of the entry and version 2 of the sequence. [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

External Data

Dasty 3

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