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Q8K3I6 (IL27A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 82. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length234 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18

Subunit structure

Heterodimer with EBI3; not disulfide-linked. This heterodimer is known as interleukin IL-27. Ref.1

Subcellular location

Secreted. Note: Poorly secreted without coexpression of EBI3. Ref.1

Tissue specificity

Expressed in macrophages and dendritic cells. Ref.1

Induction

By LPS and Interferon gamma in primary astrocytes and microglia. Induced by Toll-like receptor ligand in dendritic cells. Inhibited by PPAR-alpha agonist such as fenofibrate and produced by TNF-alpha in microglia. Ref.8 Ref.17 Ref.19 Ref.20 Ref.22

Post-translational modification

O-glycosylated By similarity.

Miscellaneous

In mouse models of experimental autoimmune encephalitis (EAE) induced by Toxoplasma Gondi infection, brain levels of IL-27 are massively increased. Deficiency of IL-27 receptors in this mouse model with EAE induces development of a more severe neuroinflammation than in wild-type mice with EAE. This excessive neuroinflammation is associated with increased numbers of TH17 cells in the central nervous system (CNS). Continuous administration of IL-27 to EAE mice produces a strong suppressive effect on active EAE, with reduced CNS infiltration of TH17 cells and TH17 cells activity.

Mice injected with B16F10 tumor cells develop tumors and lung metastasis. In mice injected with B16F10 tumor cells stably transfected with IL-27, tumor cells grow much more slowly and the number of pulmonary metastasis is markedly reduced. IL-27 exhibits a strong antitumor activity as well as antiangiogenic activity with massive decreased of microvessels density in lung metastasis. Similarly, mice injected with C26 colon tumor cells transfected with IL-27 acquire tumor-specific protective activity and exhibit minimal tumor growth with enhanced IFN-gamma production. This antitumor activity is abolished in TBX21-deficient mice. Neuroblastoma cells overexpressing IL-27 also demonstrate markedly delayed growth; This tumor regression appears to be dependent on CD8 cells.

Sequence similarities

Belongs to the IL-6 superfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 234206Interleukin-27 subunit alpha
PRO_0000320140

Regions

Compositional bias161 – 17515Glu-rich

Amino acid modifications

Glycosylation851N-linked (GlcNAc...) Potential

Sequences

Sequence LengthMass (Da)Tools
Q8K3I6 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: DB33E7EC8AB4D0DA

FASTA23426,542
        10         20         30         40         50         60 
MGQVTGDLGW RLSLLLLPLL LVQAGSWGFP TDPLSLQELR REFTVSLYLA RKLLSEVQGY 

        70         80         90        100        110        120 
VHSFAESRLP GVNLDLLPLG YHLPNVSLTF QAWHHLSDSE RLCFLATTLR PFPAMLGGLG 

       130        140        150        160        170        180 
TQGTWTSSER EQLWAMRLDL RDLHRHLRFQ VLAAGFKCSK EEEDKEEEEE EEEEEKKLPL 

       190        200        210        220        230 
GALGGPNQVS SQVSWPQLLY TYQLLHSLEL VLSRAVRDLL LLSLPRRPGS AWDS 

« 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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, SUBUNIT.
Strain: NZB.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Bone marrow.
[3]"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].
Tissue: Brain.
[4]"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.
[5]"IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms."
Lucas S., Ghilardi N., Li J., de Sauvage F.J.
Proc. Natl. Acad. Sci. U.S.A. 100:15047-15052(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Potent antitumor activity of interleukin-27."
Hisada M., Kamiya S., Fujita K., Belladonna M.L., Aoki T., Koyanagi Y., Mizuguchi J., Yoshimoto T.
Cancer Res. 64:1152-1156(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"IL-27 mediates complete regression of orthotopic primary and metastatic murine neuroblastoma tumors: role for CD8+ T cells."
Salcedo R., Stauffer J.K., Lincoln E., Back T.C., Hixon J.A., Hahn C., Shafer-Weaver K., Malyguine A., Kastelein R., Wigginton J.M.
J. Immunol. 173:7170-7182(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Production of IL-27 and other IL-12 family cytokines by microglia and their subpopulations."
Sonobe Y., Yawata I., Kawanokuchi J., Takeuchi H., Mizuno T., Suzumura A.
Brain Res. 1040:202-207(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[9]"Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals."
Chiyo M., Shimozato O., Yu L., Kawamura K., Iizasa T., Fujisawa T., Tagawa M.
Int. J. Cancer 115:437-442(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Augmentation of effector CD8+ T cell generation with enhanced granzyme B expression by IL-27."
Morishima N., Owaki T., Asakawa M., Kamiya S., Mizuguchi J., Yoshimoto T.
J. Immunol. 175:1686-1693(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"IL-27 limits IL-2 production during Th1 differentiation."
Villarino A.V., Stumhofer J.S., Saris C.J.M., Kastelein R.A., de Sauvage F.J., Hunter C.A.
J. Immunol. 176:237-247(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"IL-27 suppresses CD28-mediated IL-2 production through suppressor of cytokine signaling 3."
Owaki T., Asakawa M., Kamiya S., Takeda K., Fukai F., Mizuguchi J., Yoshimoto T.
J. Immunol. 176:2773-2780(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Antiangiogenic and antitumor activities of IL-27."
Shimizu M., Shimamura M., Owaki T., Asakawa M., Fujita K., Kudo M., Iwakura Y., Takeda Y., Luster A.D., Mizuguchi J., Yoshimoto T.
J. Immunol. 176:7317-7324(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Two-sided roles of IL-27: induction of Th1 differentiation on naive CD4+ T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4+ T cells partially through STAT3-dependent mechanism."
Yoshimura T., Takeda A., Hamano S., Miyazaki Y., Kinjyo I., Ishibashi T., Yoshimura A., Yoshida H.
J. Immunol. 177:5377-5385(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"IL-27 induces Th1 differentiation via p38 MAPK/T-bet- and intercellular adhesion molecule-1/LFA-1/ERK1/2-dependent pathways."
Owaki T., Asakawa M., Fukai F., Mizuguchi J., Yoshimoto T.
J. Immunol. 177:7579-7587(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells."
Batten M., Li J., Yi S., Kljavin N.M., Danilenko D.M., Lucas S., Lee J., de Sauvage F.J., Ghilardi N.
Nat. Immunol. 7:929-936(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: MOUSE MODEL OF EXPERIMENTAL AUTOIMMUNE ENCEPHALITIS, FUNCTION.
[17]"Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system."
Stumhofer J.S., Laurence A., Wilson E.H., Huang E., Tato C.M., Johnson L.M., Villarino A.V., Huang Q., Yoshimura A., Sehy D., Saris C.J.M., O'Shea J.J., Hennighausen L., Ernst M., Hunter C.A.
Nat. Immunol. 7:937-945(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: MOUSE MODEL OF EXPERIMENTAL AUTOIMMUNE ENCEPHALITIS, FUNCTION, INDUCTION.
[18]"IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1."
Neufert C., Becker C., Wirtz S., Fantini M.C., Weigmann B., Galle P.R., Neurath M.F.
Eur. J. Immunol. 37:1809-1816(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3."
Molle C., Nguyen M., Flamand V., Renneson J., Trottein F., De Wit D., Willems F., Goldman M., Goriely S.
J. Immunol. 178:7607-7615(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[20]"Suppressive effect of IL-27 on encephalitogenic Th17 cells and the effector phase of experimental autoimmune encephalomyelitis."
Fitzgerald D.C., Ciric B., Touil T., Harle H., Grammatikopolou J., Das Sarma J., Gran B., Zhang G.-X., Rostami A.
J. Immunol. 179:3268-3275(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: MOUSE MODEL OF EXPERIMENTAL AUTOIMMUNE ENCEPHALITIS, INDUCTION.
[21]"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.
[22]"Peroxisome proliferator-activated receptor-alpha agonist fenofibrate regulates IL-12 family cytokine expression in the CNS: relevance to multiple sclerosis."
Xu J., Racke M.K., Drew P.D.
J. Neurochem. 103:1801-1810(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY099297 mRNA. Translation: AAM34499.1.
AK152114 mRNA. Translation: BAE30958.1.
AK153466 mRNA. Translation: BAE32017.1.
BC119402 mRNA. Translation: AAI19403.1.
CCDSCCDS21835.1.
RefSeqNP_663611.1. NM_145636.1.
UniGeneMm.222632.

3D structure databases

ProteinModelPortalQ8K3I6.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8K3I6. 1 interaction.
STRING10090.ENSMUSP00000054637.

PTM databases

PhosphoSiteQ8K3I6.

Proteomic databases

PRIDEQ8K3I6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000058429; ENSMUSP00000054637; ENSMUSG00000044701.
GeneID246779.
KEGGmmu:246779.
UCSCuc009jsc.1. mouse.

Organism-specific databases

CTD246778.
MGIMGI:2384409. Il27.

Phylogenomic databases

eggNOGNOG45660.
GeneTreeENSGT00390000018206.
HOGENOMHOG000113043.
HOVERGENHBG097312.
InParanoidQ8K3I6.
OMAHLRFQVL.
OrthoDBEOG70ZZQ3.
PhylomeDBQ8K3I6.
TreeFamTF337498.

Gene expression databases

BgeeQ8K3I6.
CleanExMM_IL27.
GenevestigatorQ8K3I6.

Family and domain databases

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

Other

NextBio387308.
PROQ8K3I6.
SOURCESearch...

Entry information

Entry nameIL27A_MOUSE
AccessionPrimary (citable) accession number: Q8K3I6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: October 1, 2002
Last modified: July 9, 2014
This is version 82 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot