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Q8IZI9

- IFNL3_HUMAN

UniProt

Q8IZI9 - IFNL3_HUMAN

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Protein
Interferon lambda-3
Gene
IFNL3, IL28B, IL28C, ZCYTO22
Organism
Homo sapiens (Human)
Status
Reviewed - 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.

GO - Biological processi

  1. JAK-STAT cascade Source: InterPro
  2. defense response to virus Source: UniProtKB
  3. negative regulation of viral genome replication Source: UniProtKB
  4. positive regulation of immune response Source: InterPro
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: Chromosome 19

Organism-specific databases

HGNCiHGNC:18365. IFNL3.

Subcellular locationi

Secreted 1 Publication

GO - Cellular componenti

  1. extracellular space Source: UniProtKB-KW
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 polyethylene glycol/interferon-ribavirin in hepatitis C.
PharmGKBiPA134952671.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121 Reviewed prediction
Add
BLAST
Chaini22 – 196175Interferon lambda-3
PRO_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.
GenevestigatoriQ8IZI9.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000347165.

Structurei

Secondary structure

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

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiQ8IZI9.

Family & Domainsi

Sequence similaritiesi

Belongs to the lambda interferon family.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG40189.
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

MTGDCMPVLV LMAAVLTVTG AVPVARLRGA LPDARGCHIA QFKSLSPQEL    50
QAFKRAKDAL EESLLLKDCK CRSRLFPRTW DLRQLQVRER PVALEAELAL 100
TLKVLEATAD TDPALGDVLD QPLHTLHHIL SQLRACIQPQ PTAGPRTRGR 150
LHHWLHRLQE APKKESPGCL EASVTFNLFR LLTRDLNCVA SGDLCV 196
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.

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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti108 – 1081T → S in AAN86127. 1 Publication
Sequence conflicti120 – 1201D → G in AAQ01561. 1 Publication
Sequence conflicti155 – 1551L → P in AAQ01561. 1 Publication
Sequence conflicti156 – 1561H → Y in AAN86127. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_005258765.2.
UniGeneiHs.406744.

Genome annotation databases

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

Polymorphism databases

DMDMi300669648.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS12530.1.
RefSeqi NP_742151.2. NM_172139.2.
XP_005258822.1. XM_005258765.2.
UniGenei Hs.406744.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3HHC X-ray 2.80 A/B/C/D 1-196 [» ]
ProteinModelPortali Q8IZI9.
SMRi Q8IZI9. Positions 37-196.
ModBasei Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000347165.

Polymorphism databases

DMDMi 300669648.

Proteomic databases

PaxDbi Q8IZI9.
PRIDEi Q8IZI9.

Protocols and materials databases

DNASUi 282617.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000413851 ; ENSP00000409000 ; ENSG00000197110 .
GeneIDi 282617.
KEGGi hsa:282617.
UCSCi uc010xut.2. human.

Organism-specific databases

CTDi 282617.
GeneCardsi GC19M039735.
HGNCi HGNC:18365. IFNL3.
MIMi 607402. gene.
neXtProti NX_Q8IZI9.
Orphaneti 284102. Response to polyethylene glycol/interferon-ribavirin in hepatitis C.
PharmGKBi PA134952671.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG40189.
HOGENOMi HOG000232074.
HOVERGENi HBG052108.
InParanoidi Q8IZI9.
KOi K05447.
OMAi RTWDLQQ.
OrthoDBi EOG7F24V6.
PhylomeDBi Q8IZI9.
TreeFami TF336172.

Enzyme and pathway databases

SignaLinki Q8IZI9.

Miscellaneous databases

EvolutionaryTracei Q8IZI9.
GeneWikii Interleukin_28B.
GenomeRNAii 282617.
NextBioi 93470.
PROi Q8IZI9.
SOURCEi Search...

Gene expression databases

CleanExi HS_IL28B.
Genevestigatori Q8IZI9.

Family and domain databases

InterProi IPR029177. INF_lambda.
[Graphical view ]
Pfami PF15177. IL28A. 1 hit.
[Graphical view ]
ProtoNeti Search...

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. 0:0-0(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: September 3, 2014
This is version 85 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

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