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Q8NEV9

- IL27A_HUMAN

UniProt

Q8NEV9 - IL27A_HUMAN

Protein

Interleukin-27 subunit alpha

Gene

IL27

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 75 (01 Oct 2014)
      Sequence version 2 (26 Feb 2008)
      Previous versions | rss
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    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 defense response to virus Source: UniProtKB-KW
    5. regulation of T cell proliferation Source: UniProtKB
    6. regulation of T-helper 1 cell differentiation Source: UniProtKB
    7. response to bacterium Source: Ensembl

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

    GO - Cellular componenti

    1. extracellular space Source: UniProtKB

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134870478.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2828Sequence AnalysisAdd
    BLAST
    Chaini29 – 243215Interleukin-27 subunit alphaPRO_0000320139Add
    BLAST

    Post-translational modificationi

    O-glycosylated.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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

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

    Sequence similaritiesi

    Belongs to the IL-6 superfamily.Curated

    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

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    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

    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: October 1, 2014
    This is version 75 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