ID   IFNL3_MOUSE             Reviewed;         193 AA.
AC   Q8CGK6; Q4VK73;
DT   23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   24-JAN-2024, entry version 119.
DE   RecName: Full=Interferon lambda-3;
DE            Short=IFN-lambda-3;
DE   AltName: Full=Interleukin-28B;
DE            Short=IL-28B;
DE   Flags: Precursor;
GN   Name=Ifnl3; Synonyms=Il28, Il28b;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J;
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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC   STRAIN=129/Sv;
RX   PubMed=15914836; DOI=10.1099/vir.0.80904-0;
RA   Bartlett N.W., Buttigieg K., Kotenko S.V., Smith G.L.;
RT   "Murine interferon lambdas (type III interferons) exhibit potent antiviral
RT   activity in vivo in a poxvirus infection model.";
RL   J. Gen. Virol. 86:1589-1596(2005).
RN   [3]
RP   FUNCTION.
RX   PubMed=16618774; DOI=10.1158/0008-5472.can-05-3653;
RA   Lasfar A., Lewis-Antes A., Smirnov S.V., Anantha S., Abushahba W., Tian B.,
RA   Reuhl K., Dickensheets H., Sheikh F., Donnelly R.P., Raveche E.,
RA   Kotenko S.V.;
RT   "Characterization of the mouse IFN-lambda ligand-receptor system: IFN-
RT   lambdas exhibit antitumor activity against B16 melanoma.";
RL   Cancer Res. 66:4468-4477(2006).
RN   [4]
RP   FUNCTION.
RX   PubMed=18250457; DOI=10.4049/jimmunol.180.4.2474;
RA   Ank N., Iversen M.B., Bartholdy C., Staeheli P., Hartmann R., Jensen U.B.,
RA   Dagnaes-Hansen F., Thomsen A.R., Chen Z., Haugen H., Klucher K.,
RA   Paludan S.R.;
RT   "An important role for type III interferon (IFN-lambda/IL-28) in TLR-
RT   induced antiviral activity.";
RL   J. Immunol. 180:2474-2485(2008).
RN   [5]
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   [6]
RP   FUNCTION.
RX   PubMed=21518880; DOI=10.1073/pnas.1100552108;
RA   Pott J., Mahlakoiv T., Mordstein M., Duerr C.U., Michiels T.,
RA   Stockinger S., Staeheli P., Hornef M.W.;
RT   "IFN-lambda determines the intestinal epithelial antiviral host defense.";
RL   Proc. Natl. Acad. Sci. U.S.A. 108:7944-7949(2011).
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).
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:15914836, ECO:0000269|PubMed:16618774,
CC       ECO:0000269|PubMed:18250457, ECO:0000269|PubMed:21518880}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the lambda interferon family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AY184375; AAN86128.1; -; mRNA.
DR   EMBL; AY869696; AAX58715.1; -; mRNA.
DR   CCDS; CCDS21047.1; -.
DR   RefSeq; NP_796370.1; NM_177396.1.
DR   AlphaFoldDB; Q8CGK6; -.
DR   SMR; Q8CGK6; -.
DR   STRING; 10090.ENSMUSP00000077473; -.
DR   PhosphoSitePlus; Q8CGK6; -.
DR   EPD; Q8CGK6; -.
DR   PaxDb; 10090-ENSMUSP00000077473; -.
DR   DNASU; 338374; -.
DR   Ensembl; ENSMUST00000078364.4; ENSMUSP00000077473.4; ENSMUSG00000060747.4.
DR   GeneID; 338374; -.
DR   KEGG; mmu:338374; -.
DR   UCSC; uc009fze.1; mouse.
DR   AGR; MGI:2450574; -.
DR   CTD; 282617; -.
DR   MGI; MGI:2450574; Ifnl3.
DR   VEuPathDB; HostDB:ENSMUSG00000060747; -.
DR   eggNOG; ENOG502SSDC; Eukaryota.
DR   GeneTree; ENSGT00390000014310; -.
DR   HOGENOM; CLU_120266_0_0_1; -.
DR   InParanoid; Q8CGK6; -.
DR   OMA; KAWSCRP; -.
DR   OrthoDB; 4612062at2759; -.
DR   PhylomeDB; Q8CGK6; -.
DR   TreeFam; TF336172; -.
DR   Reactome; R-MMU-8854691; Interleukin-20 family signaling.
DR   BioGRID-ORCS; 338374; 0 hits in 75 CRISPR screens.
DR   ChiTaRS; Ifnl3; mouse.
DR   PRO; PR:Q8CGK6; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q8CGK6; Protein.
DR   Bgee; ENSMUSG00000060747; Expressed in thymus and 1 other cell type or tissue.
DR   GO; GO:0005576; C:extracellular region; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0032002; C:interleukin-28 receptor complex; ISO:MGI.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0032003; F:interleukin-28 receptor binding; ISO:MGI.
DR   GO; GO:0005102; F:signaling receptor binding; ISA:MGI.
DR   GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; IDA:MGI.
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   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.
PE   2: Evidence at transcript level;
KW   Antiviral defense; Cytokine; Disulfide bond; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..193
FT                   /note="Interferon lambda-3"
FT                   /id="PRO_0000015512"
FT   DISULFID        35..132
FT                   /evidence="ECO:0000250"
FT   DISULFID        69..166
FT                   /evidence="ECO:0000250"
FT   DISULFID        185..192
FT                   /evidence="ECO:0000250"
FT   CONFLICT        56
FT                   /note="G -> D (in Ref. 2; AAX58715)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        67
FT                   /note="M -> V (in Ref. 2; AAX58715)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   193 AA;  21664 MW;  357A00AACAA9BC61 CRC64;
     MLLLLLPLLL AAVLTRTQAD PVPRATRLPV EAKDCHIAQF KSLSPKELQA FKKAKGAIEK
     RLLEKDMRCS SHLISRAWDL KQLQVQERPK ALQAEVALTL KVWENINDSA LTTILGQPLH
     TLSHIHSQLQ TCTQLQATAE PKPPSRRLSR WLHRLQEAQS KETPGCLEDS VTSNLFQLLL
     RDLKCVASGD QCV
//