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Q8IZI9

- IFNL3_HUMAN

UniProt

Q8IZI9 - IFNL3_HUMAN

Protein

Interferon lambda-3

Gene

IFNL3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 86 (01 Oct 2014)
      Sequence version 2 (13 Jul 2010)
      Previous versions | rss
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    Functioni

    Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression.2 Publications

    GO - Biological processi

    1. defense response to virus Source: UniProtKB
    2. JAK-STAT cascade Source: InterPro
    3. negative regulation of viral genome replication Source: UniProtKB
    4. positive regulation of immune response Source: InterPro

    Keywords - Molecular functioni

    Cytokine

    Keywords - Biological processi

    Antiviral defense

    Enzyme and pathway databases

    SignaLinkiQ8IZI9.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interferon lambda-3
    Short name:
    IFN-lambda-3
    Alternative name(s):
    Cytokine Zcyto22
    Interleukin-28B
    Short name:
    IL-28B
    Interleukin-28C
    Short name:
    IL-28C
    Gene namesi
    Name:IFNL3
    Synonyms:IL28B, IL28C, ZCYTO22
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:18365. IFNL3.

    Subcellular locationi

    Secreted 1 Publication

    GO - Cellular componenti

    1. extracellular space Source: UniProtKB-KW

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi57 – 571K → A: 51 fold decrease in antiviral activity. 1 Publication
    Mutagenesisi58 – 581D → A: 43 fold decrease in antiviral activity. 1 Publication
    Mutagenesisi118 – 1181V → A: 68 fold decrease in antiviral activity. 1 Publication
    Mutagenesisi121 – 1211Q → A: 46 fold decrease in antiviral activity. 1 Publication
    Mutagenesisi176 – 1761F → A: 40 fold decrease in antiviral activity. 1 Publication
    Mutagenesisi179 – 1791F → A: 650 fold decrease in antiviral activity. 1 Publication

    Organism-specific databases

    Orphaneti284102. Response to polyethylene glycol/interferon-ribavirin in hepatitis C.
    PharmGKBiPA134952671.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2121Sequence AnalysisAdd
    BLAST
    Chaini22 – 196175Interferon lambda-3PRO_0000015510Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi37 ↔ 1361 Publication
    Disulfide bondi71 ↔ 1691 Publication
    Disulfide bondi188 ↔ 1951 Publication

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiQ8IZI9.
    PRIDEiQ8IZI9.

    Expressioni

    Inductioni

    By viral infections or double-stranded RNA.2 Publications

    Gene expression databases

    CleanExiHS_IL28B.
    GenevestigatoriQ8IZI9.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000347165.

    Structurei

    Secondary structure

    1
    196
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi40 – 423
    Helixi47 – 6519
    Beta strandi71 – 733
    Helixi82 – 843
    Helixi87 – 893
    Helixi90 – 11122
    Helixi113 – 13422
    Helixi150 – 15910
    Helixi161 – 1633
    Helixi167 – 17610
    Helixi178 – 1825
    Helixi184 – 1907
    Helixi191 – 1944

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3HHCX-ray2.80A/B/C/D1-196[»]
    ProteinModelPortaliQ8IZI9.
    SMRiQ8IZI9. Positions 37-196.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8IZI9.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the lambda interferon family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG40189.
    HOGENOMiHOG000232074.
    HOVERGENiHBG052108.
    InParanoidiQ8IZI9.
    KOiK05447.
    OMAiRTWDLQQ.
    OrthoDBiEOG7F24V6.
    PhylomeDBiQ8IZI9.
    TreeFamiTF336172.

    Family and domain databases

    InterProiIPR029177. INF_lambda.
    [Graphical view]
    PfamiPF15177. IL28A. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q8IZI9-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTGDCMPVLV LMAAVLTVTG AVPVARLRGA LPDARGCHIA QFKSLSPQEL    50
    QAFKRAKDAL EESLLLKDCK CRSRLFPRTW DLRQLQVRER PVALEAELAL 100
    TLKVLEATAD TDPALGDVLD QPLHTLHHIL SQLRACIQPQ PTAGPRTRGR 150
    LHHWLHRLQE APKKESPGCL EASVTFNLFR LLTRDLNCVA SGDLCV 196
    Length:196
    Mass (Da):21,706
    Last modified:July 13, 2010 - v2
    Checksum:iF2322E10C887184B
    GO

    Sequence cautioni

    The sequence AAN28264.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti108 – 1081T → S in AAN86127. (PubMed:12483210)Curated
    Sequence conflicti120 – 1201D → G in AAQ01561. (PubMed:16539846)Curated
    Sequence conflicti155 – 1551L → P in AAQ01561. (PubMed:16539846)Curated
    Sequence conflicti156 – 1561H → Y in AAN86127. (PubMed:12483210)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti28 – 281R → H.
    Corresponds to variant rs629976 [ dbSNP | Ensembl ].
    VAR_063419
    Natural varianti70 – 701K → R.1 Publication
    Corresponds to variant rs8103142 [ dbSNP | Ensembl ].
    VAR_063420

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY129149 mRNA. Translation: AAN28264.1. Different initiation.
    AY184374 mRNA. Translation: AAN86127.1.
    AY336714 mRNA. Translation: AAR24509.1.
    AY336717 mRNA. Translation: AAQ01561.1.
    AC011445 Genomic DNA. No translation available.
    BC130314 mRNA. Translation: AAI30315.1.
    BC130316 mRNA. Translation: AAI30317.1.
    CCDSiCCDS12530.1.
    RefSeqiNP_742151.2. NM_172139.2.
    XP_005258822.1. XM_005258765.2.
    UniGeneiHs.406744.

    Genome annotation databases

    EnsembliENST00000413851; ENSP00000409000; ENSG00000197110.
    GeneIDi282617.
    KEGGihsa:282617.
    UCSCiuc010xut.2. human.

    Polymorphism databases

    DMDMi300669648.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY129149 mRNA. Translation: AAN28264.1 . Different initiation.
    AY184374 mRNA. Translation: AAN86127.1 .
    AY336714 mRNA. Translation: AAR24509.1 .
    AY336717 mRNA. Translation: AAQ01561.1 .
    AC011445 Genomic DNA. No translation available.
    BC130314 mRNA. Translation: AAI30315.1 .
    BC130316 mRNA. Translation: AAI30317.1 .
    CCDSi CCDS12530.1.
    RefSeqi NP_742151.2. NM_172139.2.
    XP_005258822.1. XM_005258765.2.
    UniGenei Hs.406744.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3HHC X-ray 2.80 A/B/C/D 1-196 [» ]
    ProteinModelPortali Q8IZI9.
    SMRi Q8IZI9. Positions 37-196.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000347165.

    Polymorphism databases

    DMDMi 300669648.

    Proteomic databases

    PaxDbi Q8IZI9.
    PRIDEi Q8IZI9.

    Protocols and materials databases

    DNASUi 282617.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000413851 ; ENSP00000409000 ; ENSG00000197110 .
    GeneIDi 282617.
    KEGGi hsa:282617.
    UCSCi uc010xut.2. human.

    Organism-specific databases

    CTDi 282617.
    GeneCardsi GC19M039735.
    HGNCi HGNC:18365. IFNL3.
    MIMi 607402. gene.
    neXtProti NX_Q8IZI9.
    Orphaneti 284102. Response to polyethylene glycol/interferon-ribavirin in hepatitis C.
    PharmGKBi PA134952671.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG40189.
    HOGENOMi HOG000232074.
    HOVERGENi HBG052108.
    InParanoidi Q8IZI9.
    KOi K05447.
    OMAi RTWDLQQ.
    OrthoDBi EOG7F24V6.
    PhylomeDBi Q8IZI9.
    TreeFami TF336172.

    Enzyme and pathway databases

    SignaLinki Q8IZI9.

    Miscellaneous databases

    EvolutionaryTracei Q8IZI9.
    GeneWikii Interleukin_28B.
    GenomeRNAii 282617.
    NextBioi 93470.
    PROi Q8IZI9.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_IL28B.
    Genevestigatori Q8IZI9.

    Family and domain databases

    InterProi IPR029177. INF_lambda.
    [Graphical view ]
    Pfami PF15177. IL28A. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION.
    2. "IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex."
      Kotenko S.V., Gallagher G., Baurin V.V., Lewis-Antes A., Shen M., Shah N.K., Langer J.A., Sheikh F., Dickensheets H., Donnelly R.P.
      Nat. Immunol. 4:69-77(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
    3. "Liposome-mediated IL-28 and IL-29 expression in A549 cells and anti-viral effect of IL-28 and IL-29 on WISH cells."
      Li M.C., Wang H.Y., Wang H.Y., Li T., He S.H.
      Acta Pharmacol. Sin. 27:453-459(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-70.
      Tissue: Peripheral blood leukocyte.
    4. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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].
    6. "Interferon-lambda: a new addition to an old family."
      Donnelly R.P., Kotenko S.V.
      J. Interferon Cytokine Res. 30:555-564(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    7. "Interferon-lambda in the context of viral infections: production, response and therapeutic implications."
      Hermant P., Michiels T.
      J. Innate Immun. 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    8. "Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family."
      Gad H.H., Dellgren C., Hamming O.J., Vends S., Paludan S.R., Hartmann R.
      J. Biol. Chem. 284:20869-20875(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), DISULFIDE BONDS, MUTAGENESIS OF LYS-57; ASP-58; VAL-118; GLN-121; PHE-176 AND PHE-179.

    Entry informationi

    Entry nameiIFNL3_HUMAN
    AccessioniPrimary (citable) accession number: Q8IZI9
    Secondary accession number(s): A2BDE1
    , Q6VN56, Q7Z4J3, Q8IWL6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 23, 2004
    Last sequence update: July 13, 2010
    Last modified: October 1, 2014
    This is version 86 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3