IFNL3

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

cytokine activity Source: UniProtKB-KW
signaling receptor binding Source: GO_Central

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cytokine-mediated signaling pathway Source: Reactome
defense response to virus Source: UniProtKB
innate immune response Source: GO_Central
JAK-STAT cascade Source: InterPro
negative regulation of viral genome replication Source: UniProtKB
positive regulation of immune response Source: InterPro
regulation of T cell activation Source: GO_Central

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Cytokine
Biological process	Antiviral defense

Enzyme and pathway databases

Reactomeⁱ	R-HSA-8854691 Interleukin-20 family signaling
SignaLinkⁱ	Q8IZI9
SIGNORⁱ	Q8IZI9

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 19

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000197110.8
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:18365 IFNL3
MIMⁱ	607402 gene
neXtProtⁱ	NX_Q8IZI9

Keywords - Cellular componentⁱ

Secreted

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	57	K → A: 51 fold decrease in antiviral activity. 1 Publication	1
Mutagenesisⁱ	58	D → A: 43 fold decrease in antiviral activity. 1 Publication	1
Mutagenesisⁱ	118	V → A: 68 fold decrease in antiviral activity. 1 Publication	1
Mutagenesisⁱ	121	Q → A: 46 fold decrease in antiviral activity. 1 Publication	1
Mutagenesisⁱ	176	F → A: 40 fold decrease in antiviral activity. 1 Publication	1
Mutagenesisⁱ	179	F → A: 650 fold decrease in antiviral activity. 1 Publication	1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	282617
MalaCards human disease database More...MalaCardsⁱ	IFNL3
Open Targets More...OpenTargetsⁱ	ENSG00000197110
Orphanetⁱ	284102 Response to antiviral treatment in hepatitis C
PharmGKBⁱ	PA134952671

Polymorphism and mutation databases

BioMutaⁱ	IFNL3
DMDMⁱ	300669648

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 21	Sequence analysisAdd BLAST		21
ChainⁱPRO_0000015510	22 – 196	Interferon lambda-3Add BLAST		175

Amino acid modifications

Feature key	Position(s)	DescriptionActions
Disulfide bondⁱ	37 ↔ 136	1 Publication
Disulfide bondⁱ	71 ↔ 169	1 Publication
Disulfide bondⁱ	188 ↔ 195	1 Publication

Keywords - PTMⁱ

Disulfide bond

Proteomic databases

PaxDbⁱ	Q8IZI9
PeptideAtlas More...PeptideAtlasⁱ	Q8IZI9
PRIDEⁱ	Q8IZI9
ProteomicsDBⁱ	71353

PTM databases

iPTMnetⁱ	Q8IZI9
PhosphoSitePlusⁱ	Q8IZI9

Expressionⁱ

Inductionⁱ

By viral infections or double-stranded RNA.2 Publications

Gene expression databases

Bgeeⁱ	ENSG00000197110
CleanExⁱ	HS_IL28B
ExpressionAtlasⁱ	Q8IZI9 baseline and differential
Genevisibleⁱ	Q8IZI9 HS

Interactionⁱ

GO - Molecular functionⁱ

cytokine activity Source: UniProtKB-KW
signaling receptor binding Source: GO_Central

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	129395, 2 interactors
IntActⁱ	Q8IZI9, 1 interactor
Molecular INTeraction database More...MINTⁱ	Q8IZI9
STRINGⁱ	9606.ENSP00000409000

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Show more details

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	40 – 42	Combined sources	3
Helixⁱ	47 – 65	Combined sources	19
Beta strandⁱ	71 – 73	Combined sources	3
Helixⁱ	82 – 84	Combined sources	3
Helixⁱ	87 – 89	Combined sources	3
Helixⁱ	90 – 111	Combined sources	22
Helixⁱ	113 – 134	Combined sources	22
Helixⁱ	150 – 159	Combined sources	10
Helixⁱ	161 – 163	Combined sources	3
Helixⁱ	167 – 176	Combined sources	10
Helixⁱ	178 – 182	Combined sources	5
Helixⁱ	184 – 190	Combined sources	7
Helixⁱ	191 – 194	Combined sources	4

3D structure databases

ProteinModelPortalⁱ	Q8IZI9
SMRⁱ	Q8IZI9
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ

Q8IZI9

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the lambda interferon family.Curated

Keywords - Domainⁱ

Signal

Phylogenomic databases

eggNOGⁱ	ENOG410J0IH Eukaryota ENOG410ZDRD LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000014310
HOGENOMⁱ	HOG000232074
HOVERGENⁱ	HBG052108
InParanoidⁱ	Q8IZI9
KEGG Orthology (KO) More...KOⁱ	K22669
PhylomeDBⁱ	Q8IZI9
TreeFamⁱ	TF336172

Family and domain databases

Gene3Dⁱ	1.20.1250.60, 1 hit
InterProⁱ	View protein in InterPro IPR038326 IFN-lambda_sf IPR029177 INF_lambda
PANTHERⁱ	PTHR31943 PTHR31943, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF15177 IL28A, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

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

Q8IZI9-1 [UniParc]FASTA Add 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 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	108	T → S in AAN86127 (PubMed:12483210).Curated	1
Sequence conflictⁱ	120	D → G in AAQ01561 (PubMed:16539846).Curated	1
Sequence conflictⁱ	155	L → P in AAQ01561 (PubMed:16539846).Curated	1
Sequence conflictⁱ	156	H → Y in AAN86127 (PubMed:12483210).Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_063419	28	R → H. Corresponds to variant dbSNP:rs629976Ensembl.		1
Natural variantⁱVAR_063420	70	K → R1 PublicationCorresponds to variant dbSNP:rs8103142EnsemblClinVar.		1

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS12530.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001333866.1, NM_001346937.1 NP_742151.2, NM_172139.3
UniGeneⁱ	Hs.406744

Genome annotation databases

Ensemblⁱ	ENST00000413851; ENSP00000409000; ENSG00000197110
GeneIDⁱ	282617
KEGGⁱ	hsa:282617
UCSC genome browser More...UCSCⁱ	uc010xut.3 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length
Q8IZI9	Interferon lambda-3		HUMAN		200
Uncharacterized protein		CHLSB		205
Uncharacterized protein		MACMU		200
Uncharacterized protein		COLAP		200
Uncharacterized protein		PONAB		200
+23

Protein	Similar proteins		Species	Score	Length
Q8IZI9	Interferon lambda-1	)	HUMAN		200
Uncharacterized protein		MACFA		208
UPI000B7B2320		PAPAN		202
Interferon lambda 1		MACMU		202
UPI00083C7EB3		RHIBE		202
+61

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS12530.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001333866.1, NM_001346937.1 NP_742151.2, NM_172139.3
UniGeneⁱ	Hs.406744

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	3HHC	X-ray	2.80	A/B/C/D	1-196	[»]
	5T5W	X-ray	2.85	C	34-195	[»]
ProteinModelPortalⁱ	Q8IZI9
SMRⁱ	Q8IZI9
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	129395, 2 interactors
IntActⁱ	Q8IZI9, 1 interactor
Molecular INTeraction database More...MINTⁱ	Q8IZI9
STRINGⁱ	9606.ENSP00000409000

PTM databases

iPTMnetⁱ	Q8IZI9
PhosphoSitePlusⁱ	Q8IZI9

Polymorphism and mutation databases

BioMutaⁱ	IFNL3
DMDMⁱ	300669648

Proteomic databases

PaxDbⁱ	Q8IZI9
PeptideAtlas More...PeptideAtlasⁱ	Q8IZI9
PRIDEⁱ	Q8IZI9
ProteomicsDBⁱ	71353

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	282617
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000413851; ENSP00000409000; ENSG00000197110
GeneIDⁱ	282617
KEGGⁱ	hsa:282617
UCSC genome browser More...UCSCⁱ	uc010xut.3 human

Organism-specific databases

CTDⁱ	282617
DisGeNET More...DisGeNETⁱ	282617
EuPathDBⁱ	HostDB:ENSG00000197110.8
GeneCardsⁱ	IFNL3
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:18365 IFNL3
MalaCards human disease database More...MalaCardsⁱ	IFNL3
MIMⁱ	607402 gene
neXtProtⁱ	NX_Q8IZI9
Open Targets More...OpenTargetsⁱ	ENSG00000197110
Orphanetⁱ	284102 Response to antiviral treatment in hepatitis C
PharmGKBⁱ	PA134952671
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410J0IH Eukaryota ENOG410ZDRD LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000014310
HOGENOMⁱ	HOG000232074
HOVERGENⁱ	HBG052108
InParanoidⁱ	Q8IZI9
KEGG Orthology (KO) More...KOⁱ	K22669
PhylomeDBⁱ	Q8IZI9
TreeFamⁱ	TF336172

Enzyme and pathway databases

Reactomeⁱ	R-HSA-8854691 Interleukin-20 family signaling
SignaLinkⁱ	Q8IZI9
SIGNORⁱ	Q8IZI9

Miscellaneous databases

EvolutionaryTraceⁱ	Q8IZI9
GeneWikiⁱ	Interleukin_28B
GenomeRNAiⁱ	282617
Protein Ontology More...PROⁱ	PR:Q8IZI9
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000197110
CleanExⁱ	HS_IL28B
ExpressionAtlasⁱ	Q8IZI9 baseline and differential
Genevisibleⁱ	Q8IZI9 HS

Family and domain databases

Gene3Dⁱ	1.20.1250.60, 1 hit
InterProⁱ	View protein in InterPro IPR038326 IFN-lambda_sf IPR029177 INF_lambda
PANTHERⁱ	PTHR31943 PTHR31943, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF15177 IL28A, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	IFNL3_HUMAN
Accessionⁱ	Q8IZI9Primary (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:	July 18, 2018
	This is version 116 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

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

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UniProtKB - Q8IZI9 (IFNL3_HUMAN)

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Interferon lambda-3

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted

Extracellular region or secreted

Other locations

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Experimental Info

Natural variant

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequence cautionⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ