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Q8K3I6

- IL27A_MOUSE

UniProt

Q8K3I6 - IL27A_MOUSE

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Protein

Interleukin-27 subunit alpha

Gene

Il27

Organism
Mus musculus (Mouse)
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/CXCL9.15 Publications

GO - Molecular functioni

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

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: Ensembl
  4. regulation of T cell proliferation Source: MGI
  5. regulation of T-helper 1 cell differentiation Source: Ensembl
  6. response to bacterium Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

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):
p28
Gene namesi
Name:Il27
Synonyms:Il27a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:2384409. Il27.

Subcellular locationi

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

GO - Cellular componenti

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

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828Sequence AnalysisAdd
BLAST
Chaini29 – 234206Interleukin-27 subunit alphaPRO_0000320140Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi85 – 851N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

O-glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PRIDEiQ8K3I6.

PTM databases

PhosphoSiteiQ8K3I6.

Expressioni

Tissue specificityi

Expressed in macrophages and dendritic cells.1 Publication

Inductioni

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.5 Publications

Gene expression databases

BgeeiQ8K3I6.
CleanExiMM_IL27.
GenevestigatoriQ8K3I6.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

IntActiQ8K3I6. 1 interaction.
STRINGi10090.ENSMUSP00000054637.

Structurei

3D structure databases

ProteinModelPortaliQ8K3I6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi161 – 17515Glu-richAdd
BLAST

Sequence similaritiesi

Belongs to the IL-6 superfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG45660.
GeneTreeiENSGT00390000018206.
HOGENOMiHOG000113043.
HOVERGENiHBG097312.
InParanoidiQ8K3I6.
OMAiHLRFQVL.
OrthoDBiEOG70ZZQ3.
PhylomeDBiQ8K3I6.
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.

Q8K3I6-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGQVTGDLGW RLSLLLLPLL LVQAGSWGFP TDPLSLQELR REFTVSLYLA
60 70 80 90 100
RKLLSEVQGY VHSFAESRLP GVNLDLLPLG YHLPNVSLTF QAWHHLSDSE
110 120 130 140 150
RLCFLATTLR PFPAMLGGLG TQGTWTSSER EQLWAMRLDL RDLHRHLRFQ
160 170 180 190 200
VLAAGFKCSK EEEDKEEEEE EEEEEKKLPL GALGGPNQVS SQVSWPQLLY
210 220 230
TYQLLHSLEL VLSRAVRDLL LLSLPRRPGS AWDS
Length:234
Mass (Da):26,542
Last modified:October 1, 2002 - v1
Checksum:iDB33E7EC8AB4D0DA
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY099297 mRNA. Translation: AAM34499.1.
AK152114 mRNA. Translation: BAE30958.1.
AK153466 mRNA. Translation: BAE32017.1.
BC119402 mRNA. Translation: AAI19403.1.
CCDSiCCDS21835.1.
RefSeqiNP_663611.1. NM_145636.1.
UniGeneiMm.222632.

Genome annotation databases

EnsembliENSMUST00000058429; ENSMUSP00000054637; ENSMUSG00000044701.
GeneIDi246779.
KEGGimmu:246779.
UCSCiuc009jsc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY099297 mRNA. Translation: AAM34499.1 .
AK152114 mRNA. Translation: BAE30958.1 .
AK153466 mRNA. Translation: BAE32017.1 .
BC119402 mRNA. Translation: AAI19403.1 .
CCDSi CCDS21835.1.
RefSeqi NP_663611.1. NM_145636.1.
UniGenei Mm.222632.

3D structure databases

ProteinModelPortali Q8K3I6.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q8K3I6. 1 interaction.
STRINGi 10090.ENSMUSP00000054637.

PTM databases

PhosphoSitei Q8K3I6.

Proteomic databases

PRIDEi Q8K3I6.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000058429 ; ENSMUSP00000054637 ; ENSMUSG00000044701 .
GeneIDi 246779.
KEGGi mmu:246779.
UCSCi uc009jsc.1. mouse.

Organism-specific databases

CTDi 246778.
MGIi MGI:2384409. Il27.

Phylogenomic databases

eggNOGi NOG45660.
GeneTreei ENSGT00390000018206.
HOGENOMi HOG000113043.
HOVERGENi HBG097312.
InParanoidi Q8K3I6.
OMAi HLRFQVL.
OrthoDBi EOG70ZZQ3.
PhylomeDBi Q8K3I6.
TreeFami TF337498.

Miscellaneous databases

NextBioi 387308.
PROi Q8K3I6.
SOURCEi Search...

Gene expression databases

Bgeei Q8K3I6.
CleanExi MM_IL27.
Genevestigatori Q8K3I6.

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, 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.
    , 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. 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. 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. 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.

Entry informationi

Entry nameiIL27A_MOUSE
AccessioniPrimary (citable) accession number: Q8K3I6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: October 1, 2002
Last modified: October 29, 2014
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3