IFNL2_HUMAN
ID IFNL2_HUMAN Reviewed; 200 AA.
AC Q8IZJ0; Q45KQ8; Q6VN55; Q8IWL7;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Interferon lambda-2;
DE Short=IFN-lambda-2;
DE AltName: Full=Cytokine Zcyto20;
DE AltName: Full=Interleukin-28A;
DE Short=IL-28A;
DE Flags: Precursor;
GN Name=IFNL2; Synonyms=IL28A, ZCYTO20;
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].
RX PubMed=16146571; DOI=10.1186/1743-422x-2-80;
RA Zhu H., Butera M., Nelson D., Liu C.;
RT "Novel type I interferon IL-28A suppresses hepatitis C viral RNA
RT replication.";
RL Virol. J. 2:80-80(2005).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-200, FUNCTION, SUBCELLULAR LOCATION, AND
RP 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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-200, AND FUNCTION.
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 [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).
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 ECO:0000269|PubMed:16539846}.
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 -!- CAUTION: It is uncertain whether Met-1 or Met-5 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAR24510.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-28 entry;
CC URL="https://en.wikipedia.org/wiki/Interleukin_28";
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DR EMBL; AY129148; AAN28263.1; -; mRNA.
DR EMBL; DQ126336; AAZ38827.1; -; Genomic_DNA.
DR EMBL; DQ126337; AAZ38828.1; -; mRNA.
DR EMBL; BC113581; AAI13582.1; -; mRNA.
DR EMBL; BC113583; AAI13584.1; -; mRNA.
DR EMBL; AY184373; AAN86126.1; -; mRNA.
DR EMBL; AY336715; AAR24510.1; ALT_INIT; mRNA.
DR CCDS; CCDS42567.1; -.
DR RefSeq; NP_742150.1; NM_172138.1.
DR AlphaFoldDB; Q8IZJ0; -.
DR SMR; Q8IZJ0; -.
DR BioGRID; 129394; 2.
DR ComplexPortal; CPX-6012; Interferon lambda receptor-ligand complex, IFNL2 variant.
DR IntAct; Q8IZJ0; 1.
DR STRING; 9606.ENSP00000333639; -.
DR iPTMnet; Q8IZJ0; -.
DR PhosphoSitePlus; Q8IZJ0; -.
DR BioMuta; IFNL2; -.
DR DMDM; 55976531; -.
DR MassIVE; Q8IZJ0; -.
DR PaxDb; Q8IZJ0; -.
DR PRIDE; Q8IZJ0; -.
DR Antibodypedia; 30284; 367 antibodies from 30 providers.
DR DNASU; 282616; -.
DR Ensembl; ENST00000331982.6; ENSP00000333639.5; ENSG00000183709.8.
DR GeneID; 282616; -.
DR KEGG; hsa:282616; -.
DR MANE-Select; ENST00000331982.6; ENSP00000333639.5; NM_172138.2; NP_742150.1.
DR UCSC; uc002oku.2; human.
DR CTD; 282616; -.
DR DisGeNET; 282616; -.
DR GeneCards; IFNL2; -.
DR HGNC; HGNC:18364; IFNL2.
DR HPA; ENSG00000183709; Not detected.
DR MIM; 607401; gene.
DR neXtProt; NX_Q8IZJ0; -.
DR OpenTargets; ENSG00000183709; -.
DR PharmGKB; PA134934396; -.
DR VEuPathDB; HostDB:ENSG00000183709; -.
DR eggNOG; ENOG502SSDC; Eukaryota.
DR GeneTree; ENSGT00390000014310; -.
DR HOGENOM; CLU_120266_0_0_1; -.
DR InParanoid; Q8IZJ0; -.
DR OMA; ISAQHEC; -.
DR OrthoDB; 1429532at2759; -.
DR PhylomeDB; Q8IZJ0; -.
DR TreeFam; TF336172; -.
DR PathwayCommons; Q8IZJ0; -.
DR Reactome; R-HSA-8854691; Interleukin-20 family signaling.
DR SignaLink; Q8IZJ0; -.
DR SIGNOR; Q8IZJ0; -.
DR BioGRID-ORCS; 282616; 93 hits in 988 CRISPR screens.
DR GenomeRNAi; 282616; -.
DR Pharos; Q8IZJ0; Tbio.
DR PRO; PR:Q8IZJ0; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8IZJ0; protein.
DR Bgee; ENSG00000183709; Expressed in mucosa of transverse colon and 7 other tissues.
DR Genevisible; Q8IZJ0; 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:0002385; P:mucosal immune response; 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 2: Evidence at transcript level;
KW Antiviral defense; Cytokine; Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..200
FT /note="Interferon lambda-2"
FT /id="PRO_0000015509"
FT VARIANT 10
FT /note="T -> M (in dbSNP:rs554971)"
FT /id="VAR_053384"
FT VARIANT 112
FT /note="T -> A (in dbSNP:rs8103362)"
FT /id="VAR_053385"
FT CONFLICT 151
FT /note="T -> A (in Ref. 4; AAN86126)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 200 AA; 22288 MW; DFC7B49F31BF488E CRC64;
MKLDMTGDCT PVLVLMAAVL TVTGAVPVAR LHGALPDARG CHIAQFKSLS PQELQAFKRA
KDALEESLLL KDCRCHSRLF PRTWDLRQLQ VRERPMALEA ELALTLKVLE ATADTDPALV
DVLDQPLHTL HHILSQFRAC IQPQPTAGPR TRGRLHHWLY RLQEAPKKES PGCLEASVTF
NLFRLLTRDL NCVASGDLCV
