ID   IFNL1_HUMAN             Reviewed;         200 AA.
AC   Q8IU54; A0AV25; Q17R34;
DT   23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   07-APR-2021, entry version 143.
DE   RecName: Full=Interferon lambda-1;
DE            Short=IFN-lambda-1;
DE   AltName: Full=Cytokine Zcyto21;
DE   AltName: Full=Interleukin-29;
DE            Short=IL-29;
DE   Flags: Precursor;
GN   Name=IFNL1; Synonyms=IL29, ZCYTO21;
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].
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].
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].
RA   Li M., He S.;
RT   "Construction of mammalian cell expression vector of human interleukin
RT   (IL)-28A, IL-28B and IL-29 gene from activated peripheral blood mononuclear
RT   cell and analysis of its sequence.";
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
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], AND VARIANT ASP-188.
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 (2.1 ANGSTROMS) OF 21-200 IN COMPLEX WITH IFNLR1, AND
RP   DISULFIDE BOND.
RX   PubMed=20934432; DOI=10.1016/j.jmb.2010.09.068;
RA   Miknis Z.J., Magracheva E., Li W., Zdanov A., Kotenko S.V., Wlodawer A.;
RT   "Crystal structure of human interferon-lambda1 in complex with its high-
RT   affinity receptor interferon-lambdaR1.";
RL   J. Mol. Biol. 404:650-664(2010).
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. Exerts an
CC       immunomodulatory effect by up-regulating MHC class I antigen
CC       expression.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- INDUCTION: By viral infections or double-stranded RNA.
CC   -!- SIMILARITY: Belongs to the lambda interferon family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-29 entry;
CC       URL="https://en.wikipedia.org/wiki/Interleukin_29";
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DR   EMBL; AY129150; AAN28265.1; -; mRNA.
DR   EMBL; AY184372; AAN86125.1; -; mRNA.
DR   EMBL; AY336716; AAR24511.1; -; mRNA.
DR   EMBL; AC011445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC074985; AAH74985.1; -; mRNA.
DR   EMBL; BC126183; AAI26184.1; -; mRNA.
DR   EMBL; BC117482; AAI17483.1; -; mRNA.
DR   CCDS; CCDS12531.1; -.
DR   RefSeq; NP_742152.1; NM_172140.1.
DR   PDB; 3OG4; X-ray; 2.16 A; A=23-200.
DR   PDB; 3OG6; X-ray; 2.10 A; A=20-200.
DR   PDBsum; 3OG4; -.
DR   PDBsum; 3OG6; -.
DR   SMR; Q8IU54; -.
DR   BioGRID; 129396; 6.
DR   ComplexPortal; CPX-6011; Interferon lambda receptor-ligand complex, IFNL1 variant.
DR   IntAct; Q8IU54; 3.
DR   STRING; 9606.ENSP00000329991; -.
DR   GlyGen; Q8IU54; 1 site.
DR   iPTMnet; Q8IU54; -.
DR   PhosphoSitePlus; Q8IU54; -.
DR   BioMuta; IFNL1; -.
DR   MassIVE; Q8IU54; -.
DR   PaxDb; Q8IU54; -.
DR   PeptideAtlas; Q8IU54; -.
DR   PRIDE; Q8IU54; -.
DR   ProteomicsDB; 70504; -.
DR   Antibodypedia; 30288; 281 antibodies.
DR   DNASU; 282618; -.
DR   Ensembl; ENST00000333625; ENSP00000329991; ENSG00000182393.
DR   GeneID; 282618; -.
DR   KEGG; hsa:282618; -.
DR   UCSC; uc002okv.4; human.
DR   CTD; 282618; -.
DR   DisGeNET; 282618; -.
DR   GeneCards; IFNL1; -.
DR   HGNC; HGNC:18363; IFNL1.
DR   HPA; ENSG00000182393; Tissue enhanced (blood).
DR   MIM; 607403; gene.
DR   neXtProt; NX_Q8IU54; -.
DR   OpenTargets; ENSG00000182393; -.
DR   PharmGKB; PA134899000; -.
DR   VEuPathDB; HostDB:ENSG00000182393.2; -.
DR   eggNOG; ENOG502SSDC; Eukaryota.
DR   GeneTree; ENSGT00390000014310; -.
DR   HOGENOM; CLU_120266_0_0_1; -.
DR   InParanoid; Q8IU54; -.
DR   OMA; CNTRLFH; -.
DR   OrthoDB; 1429532at2759; -.
DR   PhylomeDB; Q8IU54; -.
DR   TreeFam; TF336172; -.
DR   PathwayCommons; Q8IU54; -.
DR   Reactome; R-HSA-449836; Other interleukin signaling.
DR   Reactome; R-HSA-8854691; Interleukin-20 family signaling.
DR   SignaLink; Q8IU54; -.
DR   SIGNOR; Q8IU54; -.
DR   BioGRID-ORCS; 282618; 10 hits in 979 CRISPR screens.
DR   GeneWiki; Interleukin_29; -.
DR   GenomeRNAi; 282618; -.
DR   Pharos; Q8IU54; Tbio.
DR   PRO; PR:Q8IU54; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q8IU54; protein.
DR   Bgee; ENSG00000182393; Expressed in granulocyte and 15 other tissues.
DR   Genevisible; Q8IU54; HS.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0032002; C:interleukin-28 receptor complex; IDA:UniProtKB.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0032003; F:interleukin-28 receptor binding; IPI:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR   GO; GO:0032696; P:negative regulation of interleukin-13 production; IDA:UniProtKB.
DR   GO; GO:0032714; P:negative regulation of interleukin-5 production; IDA:UniProtKB.
DR   GO; GO:0043381; P:negative regulation of memory T cell differentiation; IDA:UniProtKB.
DR   GO; GO:0045581; P:negative regulation of T cell differentiation; IDA:UniProtKB.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0002829; P:negative regulation of type 2 immune response; IDA:UniProtKB.
DR   GO; GO:0050778; P:positive regulation of immune response; TAS:UniProtKB.
DR   GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:UniProtKB.
DR   GO; GO:0045345; P:positive regulation of MHC class I biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:UniProtKB.
DR   GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:InterPro.
DR   Gene3D; 1.20.1250.60; -; 1.
DR   InterPro; IPR038326; IFN-lambda_sf.
DR   InterPro; IPR029177; INF_lambda.
DR   PANTHER; PTHR31943; PTHR31943; 1.
DR   Pfam; PF15177; IL28A; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Antiviral defense; Cytokine; Disulfide bond; Glycoprotein;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..200
FT                   /note="Interferon lambda-1"
FT                   /id="PRO_0000015511"
FT   CARBOHYD        65
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        68..164
FT                   /evidence="ECO:0000269|PubMed:20934432"
FT   VARIANT         188
FT                   /note="N -> D (in dbSNP:rs30461)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_024506"
FT   HELIX           44..61
FT                   /evidence="ECO:0007744|PDB:3OG6"
FT   HELIX           79..81
FT                   /evidence="ECO:0007744|PDB:3OG6"
FT   HELIX           84..86
FT                   /evidence="ECO:0007744|PDB:3OG6"
FT   HELIX           87..105
FT                   /evidence="ECO:0007744|PDB:3OG6"
FT   TURN            108..110
FT                   /evidence="ECO:0007744|PDB:3OG6"
FT   HELIX           111..129
FT                   /evidence="ECO:0007744|PDB:3OG6"
FT   HELIX           145..159
FT                   /evidence="ECO:0007744|PDB:3OG6"
FT   HELIX           162..178
FT                   /evidence="ECO:0007744|PDB:3OG6"
FT   HELIX           180..186
FT                   /evidence="ECO:0007744|PDB:3OG6"
SQ   SEQUENCE   200 AA;  21898 MW;  D4433B9462DCB4A1 CRC64;
     MAAAWTVVLV TLVLGLAVAG PVPTSKPTTT GKGCHIGRFK SLSPQELASF KKARDALEES
     LKLKNWSCSS PVFPGNWDLR LLQVRERPVA LEAELALTLK VLEAAAGPAL EDVLDQPLHT
     LHHILSQLQA CIQPQPTAGP RPRGRLHHWL HRLQEAPKKE SAGCLEASVT FNLFRLLTRD
     LKYVADGNLC LRTSTHPEST
//