ID   IFNL3_HUMAN             Reviewed;         196 AA.
AC   Q8IZI9; A2BDE1; Q6VN56; Q7Z4J3; Q8IWL6;
DT   23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT   13-JUL-2010, sequence version 2.
DT   24-JAN-2024, entry version 144.
DE   RecName: Full=Interferon lambda-3;
DE            Short=IFN-lambda-3;
DE   AltName: Full=Cytokine Zcyto22;
DE   AltName: Full=Interleukin-28B;
DE            Short=IL-28B;
DE   AltName: Full=Interleukin-28C;
DE            Short=IL-28C;
DE   Flags: Precursor;
GN   Name=IFNL3; Synonyms=IL28B, IL28C, ZCYTO22;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INDUCTION.
RX   PubMed=12469119; DOI=10.1038/ni873;
RA   Sheppard P., Kindsvogel W., Xu W., Henderson K., Schlutsmeyer S.,
RA   Whitmore T.E., Kuestner R., Garrigues U., Birks C., Roraback J.,
RA   Ostrander C., Dong D., Shin J., Presnell S., Fox B., Haldeman B.,
RA   Cooper E., Taft D., Gilbert T., Grant F.J., Tackett M., Krivan W.,
RA   McKnight G., Clegg C., Foster D., Klucher K.M.;
RT   "IL-28, IL-29 and their class II cytokine receptor IL-28R.";
RL   Nat. Immunol. 4:63-68(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX   PubMed=12483210; DOI=10.1038/ni875;
RA   Kotenko S.V., Gallagher G., Baurin V.V., Lewis-Antes A., Shen M.,
RA   Shah N.K., Langer J.A., Sheikh F., Dickensheets H., Donnelly R.P.;
RT   "IFN-lambdas mediate antiviral protection through a distinct class II
RT   cytokine receptor complex.";
RL   Nat. Immunol. 4:69-77(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-70.
RC   TISSUE=Peripheral blood leukocyte;
RX   PubMed=16539846; DOI=10.1111/j.1745-7254.2006.00292.x;
RA   Li M.C., Wang H.Y., Wang H.Y., Li T., He S.H.;
RT   "Liposome-mediated IL-28 and IL-29 expression in A549 cells and anti-viral
RT   effect of IL-28 and IL-29 on WISH cells.";
RL   Acta Pharmacol. Sin. 27:453-459(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   REVIEW.
RX   PubMed=20712453; DOI=10.1089/jir.2010.0078;
RA   Donnelly R.P., Kotenko S.V.;
RT   "Interferon-lambda: a new addition to an old family.";
RL   J. Interferon Cytokine Res. 30:555-564(2010).
RN   [7]
RP   REVIEW.
RX   PubMed=24751921; DOI=10.1159/000360084;
RA   Hermant P., Michiels T.;
RT   "Interferon-lambda in the context of viral infections: production, response
RT   and therapeutic implications.";
RL   J. Innate Immun. 6:563-574(2014).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), DISULFIDE BONDS, AND MUTAGENESIS OF
RP   LYS-57; ASP-58; VAL-118; GLN-121; PHE-176 AND PHE-179.
RX   PubMed=19457860; DOI=10.1074/jbc.m109.002923;
RA   Gad H.H., Dellgren C., Hamming O.J., Vends S., Paludan S.R., Hartmann R.;
RT   "Interferon-lambda is functionally an interferon but structurally related
RT   to the interleukin-10 family.";
RL   J. Biol. Chem. 284:20869-20875(2009).
CC   -!- FUNCTION: Cytokine with antiviral, antitumour and immunomodulatory
CC       activities. Plays a critical role in the antiviral host defense,
CC       predominantly in the epithelial tissues. Acts as a ligand for the
CC       heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1,
CC       and receptor engagement leads to the activation of the JAK/STAT
CC       signaling pathway resulting in the expression of IFN-stimulated genes
CC       (ISG), which mediate the antiviral state. Has a restricted receptor
CC       distribution and therefore restricted targets: is primarily active in
CC       epithelial cells and this cell type-selective action is because of the
CC       epithelial cell-specific expression of its receptor IFNLR1. Seems not
CC       to be essential for early virus-activated host defense in vaginal
CC       infection, but plays an important role in Toll-like receptor (TLR)-
CC       induced antiviral defense. Plays a significant role in the antiviral
CC       immune defense in the intestinal epithelium. Exerts an immunomodulatory
CC       effect by up-regulating MHC class I antigen expression.
CC       {ECO:0000269|PubMed:12469119, ECO:0000269|PubMed:12483210}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12483210}.
CC   -!- INDUCTION: By viral infections or double-stranded RNA.
CC       {ECO:0000269|PubMed:12469119, ECO:0000269|PubMed:12483210}.
CC   -!- SIMILARITY: Belongs to the lambda interferon family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAN28264.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AY129149; AAN28264.1; ALT_INIT; mRNA.
DR   EMBL; AY184374; AAN86127.1; -; mRNA.
DR   EMBL; AY336714; AAR24509.1; -; mRNA.
DR   EMBL; AY336717; AAQ01561.1; -; mRNA.
DR   EMBL; AC011445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC130314; AAI30315.1; -; mRNA.
DR   EMBL; BC130316; AAI30317.1; -; mRNA.
DR   CCDS; CCDS12530.1; -.
DR   RefSeq; NP_001333866.1; NM_001346937.1.
DR   RefSeq; NP_742151.2; NM_172139.3.
DR   PDB; 3HHC; X-ray; 2.80 A; A/B/C/D=1-196.
DR   PDB; 5T5W; X-ray; 2.85 A; C=34-195.
DR   PDBsum; 3HHC; -.
DR   PDBsum; 5T5W; -.
DR   AlphaFoldDB; Q8IZI9; -.
DR   SMR; Q8IZI9; -.
DR   BioGRID; 129395; 10.
DR   ComplexPortal; CPX-6013; Interferon lambda receptor-ligand complex, IFNL3 variant.
DR   IntAct; Q8IZI9; 2.
DR   MINT; Q8IZI9; -.
DR   STRING; 9606.ENSP00000481633; -.
DR   iPTMnet; Q8IZI9; -.
DR   PhosphoSitePlus; Q8IZI9; -.
DR   BioMuta; IFNL3; -.
DR   DMDM; 300669648; -.
DR   MassIVE; Q8IZI9; -.
DR   PaxDb; 9606-ENSP00000409000; -.
DR   PeptideAtlas; Q8IZI9; -.
DR   Antibodypedia; 54997; 393 antibodies from 30 providers.
DR   DNASU; 282617; -.
DR   Ensembl; ENST00000413851.3; ENSP00000409000.2; ENSG00000197110.10.
DR   Ensembl; ENST00000709043.1; ENSP00000517481.1; ENSG00000291876.1.
DR   GeneID; 282617; -.
DR   KEGG; hsa:282617; -.
DR   MANE-Select; ENST00000413851.3; ENSP00000409000.2; NM_172139.4; NP_742151.2.
DR   UCSC; uc010xut.3; human.
DR   AGR; HGNC:18365; -.
DR   CTD; 282617; -.
DR   DisGeNET; 282617; -.
DR   GeneCards; IFNL3; -.
DR   HGNC; HGNC:18365; IFNL3.
DR   HPA; ENSG00000197110; Not detected.
DR   MalaCards; IFNL3; -.
DR   MIM; 607402; gene.
DR   neXtProt; NX_Q8IZI9; -.
DR   OpenTargets; ENSG00000197110; -.
DR   PharmGKB; PA134952671; -.
DR   VEuPathDB; HostDB:ENSG00000197110; -.
DR   eggNOG; ENOG502SSDC; Eukaryota.
DR   GeneTree; ENSGT00390000014310; -.
DR   HOGENOM; CLU_120266_0_0_1; -.
DR   InParanoid; Q8IZI9; -.
DR   OMA; KAWSCRP; -.
DR   OrthoDB; 4612062at2759; -.
DR   PhylomeDB; Q8IZI9; -.
DR   TreeFam; TF336172; -.
DR   PathwayCommons; Q8IZI9; -.
DR   Reactome; R-HSA-8854691; Interleukin-20 family signaling.
DR   SignaLink; Q8IZI9; -.
DR   SIGNOR; Q8IZI9; -.
DR   BioGRID-ORCS; 282617; 11 hits in 1051 CRISPR screens.
DR   EvolutionaryTrace; Q8IZI9; -.
DR   GeneWiki; Interleukin_28B; -.
DR   GenomeRNAi; 282617; -.
DR   Pharos; Q8IZI9; Tbio.
DR   PRO; PR:Q8IZI9; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q8IZI9; Protein.
DR   Bgee; ENSG00000197110; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 13 other cell types or tissues.
DR   ExpressionAtlas; Q8IZI9; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR   GO; GO:0098586; P:cellular response to virus; NAS:ComplexPortal.
DR   GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR   GO; GO:0045071; P:negative regulation of viral genome replication; ISS:UniProtKB.
DR   GO; GO:0050778; P:positive regulation of immune response; IEA:InterPro.
DR   GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:InterPro.
DR   GO; GO:0038196; P:type III interferon-mediated signaling pathway; NAS:ComplexPortal.
DR   Gene3D; 1.20.1250.60; Interferon lambda; 1.
DR   InterPro; IPR038326; IFN-lambda_sf.
DR   InterPro; IPR029177; INF_lambda.
DR   PANTHER; PTHR31943:SF1; INTERFERON LAMBDA-2-RELATED; 1.
DR   PANTHER; PTHR31943; INTERLEUKIN-28 AND 29; 1.
DR   Pfam; PF15177; IL28A; 1.
DR   Genevisible; Q8IZI9; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Antiviral defense; Cytokine; Disulfide bond;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..196
FT                   /note="Interferon lambda-3"
FT                   /id="PRO_0000015510"
FT   DISULFID        37..136
FT                   /evidence="ECO:0000269|PubMed:19457860"
FT   DISULFID        71..169
FT                   /evidence="ECO:0000269|PubMed:19457860"
FT   DISULFID        188..195
FT                   /evidence="ECO:0000269|PubMed:19457860"
FT   VARIANT         28
FT                   /note="R -> H (in dbSNP:rs629976)"
FT                   /id="VAR_063419"
FT   VARIANT         70
FT                   /note="K -> R (in dbSNP:rs8103142)"
FT                   /evidence="ECO:0000269|PubMed:16539846"
FT                   /id="VAR_063420"
FT   MUTAGEN         57
FT                   /note="K->A: 51 fold decrease in antiviral activity."
FT                   /evidence="ECO:0000269|PubMed:19457860"
FT   MUTAGEN         58
FT                   /note="D->A: 43 fold decrease in antiviral activity."
FT                   /evidence="ECO:0000269|PubMed:19457860"
FT   MUTAGEN         118
FT                   /note="V->A: 68 fold decrease in antiviral activity."
FT                   /evidence="ECO:0000269|PubMed:19457860"
FT   MUTAGEN         121
FT                   /note="Q->A: 46 fold decrease in antiviral activity."
FT                   /evidence="ECO:0000269|PubMed:19457860"
FT   MUTAGEN         176
FT                   /note="F->A: 40 fold decrease in antiviral activity."
FT                   /evidence="ECO:0000269|PubMed:19457860"
FT   MUTAGEN         179
FT                   /note="F->A: 650 fold decrease in antiviral activity."
FT                   /evidence="ECO:0000269|PubMed:19457860"
FT   CONFLICT        108
FT                   /note="T -> S (in Ref. 2; AAN86127)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        120
FT                   /note="D -> G (in Ref. 3; AAQ01561)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        155
FT                   /note="L -> P (in Ref. 3; AAQ01561)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        156
FT                   /note="H -> Y (in Ref. 2; AAN86127)"
FT                   /evidence="ECO:0000305"
FT   HELIX           40..42
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           47..65
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   STRAND          71..73
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           82..84
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           87..89
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           90..111
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           113..134
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           150..159
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           161..163
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           167..176
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           178..182
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           184..190
FT                   /evidence="ECO:0007829|PDB:3HHC"
FT   HELIX           191..194
FT                   /evidence="ECO:0007829|PDB:3HHC"
SQ   SEQUENCE   196 AA;  21706 MW;  F2322E10C887184B CRC64;
     MTGDCMPVLV LMAAVLTVTG AVPVARLRGA LPDARGCHIA QFKSLSPQEL QAFKRAKDAL
     EESLLLKDCK CRSRLFPRTW DLRQLQVRER PVALEAELAL TLKVLEATAD TDPALGDVLD
     QPLHTLHHIL SQLRACIQPQ PTAGPRTRGR LHHWLHRLQE APKKESPGCL EASVTFNLFR
     LLTRDLNCVA SGDLCV
//