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Protein

Interferon lambda-3

Gene

IFNL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression.2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Antiviral defense

Enzyme and pathway databases

SignaLinkiQ8IZI9.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon lambda-3
Short name:
IFN-lambda-3
Alternative name(s):
Cytokine Zcyto22
Interleukin-28B
Short name:
IL-28B
Interleukin-28C
Short name:
IL-28C
Gene namesi
Name:IFNL3
Synonyms:IL28B, IL28C, ZCYTO22
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:18365. IFNL3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi57 – 571K → A: 51 fold decrease in antiviral activity. 1 Publication
Mutagenesisi58 – 581D → A: 43 fold decrease in antiviral activity. 1 Publication
Mutagenesisi118 – 1181V → A: 68 fold decrease in antiviral activity. 1 Publication
Mutagenesisi121 – 1211Q → A: 46 fold decrease in antiviral activity. 1 Publication
Mutagenesisi176 – 1761F → A: 40 fold decrease in antiviral activity. 1 Publication
Mutagenesisi179 – 1791F → A: 650 fold decrease in antiviral activity. 1 Publication

Organism-specific databases

Orphaneti284102. Response to antiviral treatment in hepatitis C.
PharmGKBiPA134952671.

Polymorphism and mutation databases

BioMutaiIFNL3.
DMDMi300669648.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 196175Interferon lambda-3PRO_0000015510Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi37 ↔ 1361 Publication
Disulfide bondi71 ↔ 1691 Publication
Disulfide bondi188 ↔ 1951 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiQ8IZI9.
PRIDEiQ8IZI9.

Expressioni

Inductioni

By viral infections or double-stranded RNA.2 Publications

Gene expression databases

CleanExiHS_IL28B.
GenevisibleiQ8IZI9. HS.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000409000.

Structurei

Secondary structure

1
196
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi40 – 423Combined sources
Helixi47 – 6519Combined sources
Beta strandi71 – 733Combined sources
Helixi82 – 843Combined sources
Helixi87 – 893Combined sources
Helixi90 – 11122Combined sources
Helixi113 – 13422Combined sources
Helixi150 – 15910Combined sources
Helixi161 – 1633Combined sources
Helixi167 – 17610Combined sources
Helixi178 – 1825Combined sources
Helixi184 – 1907Combined sources
Helixi191 – 1944Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3HHCX-ray2.80A/B/C/D1-196[»]
ProteinModelPortaliQ8IZI9.
SMRiQ8IZI9. Positions 37-196.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IZI9.

Family & Domainsi

Sequence similaritiesi

Belongs to the lambda interferon family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG40189.
GeneTreeiENSGT00390000014310.
HOGENOMiHOG000232074.
HOVERGENiHBG052108.
InParanoidiQ8IZI9.
KOiK05447.
OMAiRTWDLQQ.
OrthoDBiEOG7F24V6.
PhylomeDBiQ8IZI9.
TreeFamiTF336172.

Family and domain databases

InterProiIPR029177. INF_lambda.
[Graphical view]
PfamiPF15177. IL28A. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8IZI9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTGDCMPVLV LMAAVLTVTG AVPVARLRGA LPDARGCHIA QFKSLSPQEL
60 70 80 90 100
QAFKRAKDAL EESLLLKDCK CRSRLFPRTW DLRQLQVRER PVALEAELAL
110 120 130 140 150
TLKVLEATAD TDPALGDVLD QPLHTLHHIL SQLRACIQPQ PTAGPRTRGR
160 170 180 190
LHHWLHRLQE APKKESPGCL EASVTFNLFR LLTRDLNCVA SGDLCV
Length:196
Mass (Da):21,706
Last modified:July 13, 2010 - v2
Checksum:iF2322E10C887184B
GO

Sequence cautioni

The sequence AAN28264.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti108 – 1081T → S in AAN86127 (PubMed:12483210).Curated
Sequence conflicti120 – 1201D → G in AAQ01561 (PubMed:16539846).Curated
Sequence conflicti155 – 1551L → P in AAQ01561 (PubMed:16539846).Curated
Sequence conflicti156 – 1561H → Y in AAN86127 (PubMed:12483210).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti28 – 281R → H.
Corresponds to variant rs629976 [ dbSNP | Ensembl ].
VAR_063419
Natural varianti70 – 701K → R.1 Publication
Corresponds to variant rs8103142 [ dbSNP | Ensembl ].
VAR_063420

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY129149 mRNA. Translation: AAN28264.1. Different initiation.
AY184374 mRNA. Translation: AAN86127.1.
AY336714 mRNA. Translation: AAR24509.1.
AY336717 mRNA. Translation: AAQ01561.1.
AC011445 Genomic DNA. No translation available.
BC130314 mRNA. Translation: AAI30315.1.
BC130316 mRNA. Translation: AAI30317.1.
CCDSiCCDS12530.1.
RefSeqiNP_742151.2. NM_172139.2.
XP_005258822.1. XM_005258765.3.
UniGeneiHs.406744.

Genome annotation databases

EnsembliENST00000413851; ENSP00000409000; ENSG00000197110.
GeneIDi282617.
KEGGihsa:282617.
UCSCiuc010xut.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY129149 mRNA. Translation: AAN28264.1. Different initiation.
AY184374 mRNA. Translation: AAN86127.1.
AY336714 mRNA. Translation: AAR24509.1.
AY336717 mRNA. Translation: AAQ01561.1.
AC011445 Genomic DNA. No translation available.
BC130314 mRNA. Translation: AAI30315.1.
BC130316 mRNA. Translation: AAI30317.1.
CCDSiCCDS12530.1.
RefSeqiNP_742151.2. NM_172139.2.
XP_005258822.1. XM_005258765.3.
UniGeneiHs.406744.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3HHCX-ray2.80A/B/C/D1-196[»]
ProteinModelPortaliQ8IZI9.
SMRiQ8IZI9. Positions 37-196.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000409000.

Polymorphism and mutation databases

BioMutaiIFNL3.
DMDMi300669648.

Proteomic databases

PaxDbiQ8IZI9.
PRIDEiQ8IZI9.

Protocols and materials databases

DNASUi282617.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000413851; ENSP00000409000; ENSG00000197110.
GeneIDi282617.
KEGGihsa:282617.
UCSCiuc010xut.2. human.

Organism-specific databases

CTDi282617.
GeneCardsiGC19M039735.
HGNCiHGNC:18365. IFNL3.
MIMi607402. gene.
neXtProtiNX_Q8IZI9.
Orphaneti284102. Response to antiviral treatment in hepatitis C.
PharmGKBiPA134952671.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG40189.
GeneTreeiENSGT00390000014310.
HOGENOMiHOG000232074.
HOVERGENiHBG052108.
InParanoidiQ8IZI9.
KOiK05447.
OMAiRTWDLQQ.
OrthoDBiEOG7F24V6.
PhylomeDBiQ8IZI9.
TreeFamiTF336172.

Enzyme and pathway databases

SignaLinkiQ8IZI9.

Miscellaneous databases

EvolutionaryTraceiQ8IZI9.
GeneWikiiInterleukin_28B.
GenomeRNAii282617.
NextBioi93470.
PROiQ8IZI9.
SOURCEiSearch...

Gene expression databases

CleanExiHS_IL28B.
GenevisibleiQ8IZI9. HS.

Family and domain databases

InterProiIPR029177. INF_lambda.
[Graphical view]
PfamiPF15177. IL28A. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION.
  2. "IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex."
    Kotenko S.V., Gallagher G., Baurin V.V., Lewis-Antes A., Shen M., Shah N.K., Langer J.A., Sheikh F., Dickensheets H., Donnelly R.P.
    Nat. Immunol. 4:69-77(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
  3. "Liposome-mediated IL-28 and IL-29 expression in A549 cells and anti-viral effect of IL-28 and IL-29 on WISH cells."
    Li M.C., Wang H.Y., Wang H.Y., Li T., He S.H.
    Acta Pharmacol. Sin. 27:453-459(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-70.
    Tissue: Peripheral blood leukocyte.
  4. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  6. "Interferon-lambda: a new addition to an old family."
    Donnelly R.P., Kotenko S.V.
    J. Interferon Cytokine Res. 30:555-564(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  7. "Interferon-lambda in the context of viral infections: production, response and therapeutic implications."
    Hermant P., Michiels T.
    J. Innate Immun. 6:563-574(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  8. "Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family."
    Gad H.H., Dellgren C., Hamming O.J., Vends S., Paludan S.R., Hartmann R.
    J. Biol. Chem. 284:20869-20875(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), DISULFIDE BONDS, MUTAGENESIS OF LYS-57; ASP-58; VAL-118; GLN-121; PHE-176 AND PHE-179.

Entry informationi

Entry nameiIFNL3_HUMAN
AccessioniPrimary (citable) accession number: Q8IZI9
Secondary accession number(s): A2BDE1
, Q6VN56, Q7Z4J3, Q8IWL6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: July 13, 2010
Last modified: June 24, 2015
This is version 93 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.