IFNL3_HUMAN
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 03-AUG-2022, entry version 137.
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.ENSP00000409000; -.
DR iPTMnet; Q8IZI9; -.
DR PhosphoSitePlus; Q8IZI9; -.
DR BioMuta; IFNL3; -.
DR DMDM; 300669648; -.
DR MassIVE; Q8IZI9; -.
DR PaxDb; Q8IZI9; -.
DR PeptideAtlas; Q8IZI9; -.
DR PRIDE; Q8IZI9; -.
DR Antibodypedia; 54997; 371 antibodies from 30 providers.
DR DNASU; 282617; -.
DR Ensembl; ENST00000413851.3; ENSP00000409000.2; ENSG00000197110.10.
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 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 Orphanet; 284102; Prediction of response to antiviral treatment in hepatitis C.
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; 1429532at2759; -.
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 990 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 superior frontal gyrus and 11 other tissues.
DR ExpressionAtlas; Q8IZI9; baseline and differential.
DR Genevisible; Q8IZI9; HS.
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; IC: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 signaling pathway; IC:ComplexPortal.
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;
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
