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Q8NEV9 (IL27A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 71. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-27 subunit alpha

Short name=IL-27 subunit alpha
Short name=IL-27-A
Short name=IL27-A
Alternative name(s):
p28
Gene names
Name:IL27
Synonyms:IL27A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length243 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cytokine with 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 IL-27 subunit p28 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 replivation. Ref.1 Ref.5 Ref.6 Ref.7

Subunit structure

Heterodimer with IL27B/EBI3. IL-27 is a heterodimer composed IL27 and EBI3. EBI3 is also a component of the IL-12 heterodimer. Ref.1

Subcellular location

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

Tissue specificity

Expressed in monocytes and in placenta. Ref.1

Induction

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

Post-translational modification

O-glycosylated Probable. Ref.1

Sequence similarities

Belongs to the IL-6 superfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 243215Interleukin-27 subunit alpha
PRO_0000320139

Regions

Compositional bias164 – 17613Glu-rich

Natural variations

Natural variant591S → A. Ref.4 Ref.9
Corresponds to variant rs17855750 [ dbSNP | Ensembl ].
VAR_039140
Natural variant1191L → P. Ref.1 Ref.9
Corresponds to variant rs181206 [ dbSNP | Ensembl ].
VAR_039141

Sequences

Sequence LengthMass (Da)Tools
Q8NEV9 [UniParc].

Last modified February 26, 2008. Version 2.
Checksum: 2FA8B8AB60B606E8

FASTA24327,493
        10         20         30         40         50         60 
MGQTAGDLGW RLSLLLLPLL LVQAGVWGFP RPPGRPQLSL QELRREFTVS LHLARKLLSE 

        70         80         90        100        110        120 
VRGQAHRFAE SHLPGVNLYL LPLGEQLPDV SLTFQAWRRL SDPERLCFIS TTLQPFHALL 

       130        140        150        160        170        180 
GGLGTQGRWT NMERMQLWAM RLDLRDLQRH LRFQVLAAGF NLPEEEEEEE EEEEEERKGL 

       190        200        210        220        230        240 
LPGALGSALQ GPAQVSWPQL LSTYRLLHSL ELVLSRAVRE LLLLSKAGHS VWPLGFPTLS 


PQP 

« Hide

References

« Hide 'large scale' references
[1]"IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells."
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. expand/collapse author list , de Waal Malefyt R., Rennick D., Kastelein R.A.
Immunity 16:779-790(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, GLYCOSYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, SUBUNIT, VARIANT PRO-119.
[2]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
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]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. expand/collapse author list , 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
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.
+Additional computationally mapped references.

Web resources

Wikipedia

Interleukin-27 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY099296 mRNA. Translation: AAM34498.1.
EF064720 Genomic DNA. Translation: ABK41903.1.
CH471279 Genomic DNA. Translation: EAW52277.1.
BC062422 mRNA. Translation: AAH62422.1.
RefSeqNP_663634.2. NM_145659.3.
UniGeneHs.528111.

3D structure databases

ProteinModelPortalQ8NEV9.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59473N.
STRING9606.ENSP00000349365.

PTM databases

PhosphoSiteQ8NEV9.

Polymorphism databases

DMDM182701368.

Proteomic databases

PaxDbQ8NEV9.
PRIDEQ8NEV9.

Protocols and materials databases

DNASU246778.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356897; ENSP00000349365; ENSG00000197272.
GeneID246778.
KEGGhsa:246778.
UCSCuc002dqc.3. human.

Organism-specific databases

CTD246778.
GeneCardsGC16M028511.
H-InvDBHIX0038580.
HGNCHGNC:19157. IL27.
HPACAB024722.
MIM608273. gene.
neXtProtNX_Q8NEV9.
PharmGKBPA134870478.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG45660.
HOGENOMHOG000113043.
HOVERGENHBG097312.
InParanoidQ8NEV9.
OMAHLRFQVL.
OrthoDBEOG70ZZQ3.
PhylomeDBQ8NEV9.
TreeFamTF337498.

Enzyme and pathway databases

SignaLinkQ8NEV9.

Gene expression databases

ArrayExpressQ8NEV9.
BgeeQ8NEV9.
CleanExHS_IL27.
GenevestigatorQ8NEV9.

Family and domain databases

InterProIPR026207. IL-27_alpha.
[Graphical view]
PANTHERPTHR20879. PTHR20879. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi246778.
NextBio91980.
PROQ8NEV9.
SOURCESearch...

Entry information

Entry nameIL27A_HUMAN
AccessionPrimary (citable) accession number: Q8NEV9
Secondary accession number(s): A0N0L2, Q6P676
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: February 19, 2014
This is version 71 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM