Q8NEV9 (IL27A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	243 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Antiviral protein Cytokine
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of interferon-gamma biosynthetic process Inferred from direct assay PubMed 12734330. Source: UniProtKB regulation of T cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB regulation of T-helper 1 cell differentiation Inferred from direct assay PubMed 12734330. Source: UniProtKB regulation of defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW response to bacterium Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	interleukin-27 receptor binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	Potential
	Chain	29 – 243	215	Interleukin-27 subunit alpha		PRO_0000320139
Regions
	Compositional bias	164 – 176	13	Glu-rich
Natural variations
	Natural variant	59	1	S → A. Ref.4 Ref.9 Corresponds to variant rs17855750 [ dbSNP | Ensembl ].		VAR_039140
	Natural variant	119	1	L → P. Ref.1 Ref.9 Corresponds to variant rs181206 [ dbSNP | Ensembl ].		VAR_039141

Sequences

	Sequence		Length	Mass (Da)
	Q8NEV9 [UniParc]. Last modified February 26, 2008. Version 2. Checksum: 2FA8B8AB60B606E8	FASTA	243	27,493
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00302598.
RefSeq	NP_663634.2. NM_145659.3.
UniGene	Hs.528111.
3D structure databases
ProteinModelPortal	Q8NEV9.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-59473N.
STRING	9606.ENSP00000349365.
PTM databases
PhosphoSite	Q8NEV9.
Polymorphism databases
DMDM	182701368.
Proteomic databases
PaxDb	Q8NEV9.
PRIDE	Q8NEV9.
Protocols and materials databases
DNASU	246778.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000356897; ENSP00000349365; ENSG00000197272.
GeneID	246778.
KEGG	hsa:246778.
UCSC	uc002dqc.3. human.
Organism-specific databases
CTD	246778.
GeneCards	GC16M028511.
H-InvDB	HIX0038580.
HGNC	HGNC:19157. IL27.
HPA	CAB024722.
MIM	608273. gene.
neXtProt	NX_Q8NEV9.
PharmGKB	PA134870478.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG45660.
HOGENOM	HOG000113043.
HOVERGEN	HBG097312.
InParanoid	Q8NEV9.
OMA	PAQVSWP.
OrthoDB	EOG42NJ1B.
PhylomeDB	Q8NEV9.
Enzyme and pathway databases
Pathway_Interaction_DB	il27pathway. IL27-mediated signaling events.
Gene expression databases
ArrayExpress	Q8NEV9.
Bgee	Q8NEV9.
CleanEx	HS_IL27.
Genevestigator	Q8NEV9.
Family and domain databases
InterPro	IPR026207. IL27-A. [Graphical view]
PANTHER	PTHR20879. PTHR20879. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	246778.
NextBio	91980.
SOURCE	Search...

Entry information

Entry name

IL27A_HUMAN

Accession

Primary (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:	April 3, 2013
This is version 65 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.