Q8IZI9 (IFNL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	IFNL3
Synonyms:	IL28B, IL28C, ZCYTO22

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	196 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cytokine with immunomodulatory activity. Up-regulates MHC class I antigen expression. Displays potent antiviral activity. Also displays antitumor activity. Ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1. The ligand/receptor complex seems to signal through the Jak-STAT pathway. 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. Ref.1 Ref.2
Subcellular location	Secreted Ref.2.
Induction	By viral infections or double-stranded RNA. Ref.1 Ref.2
Sequence similarities	Belongs to the lambda interferon family.
Sequence caution	The sequence AAN28264.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Antiviral defense
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 196

175

Interferon lambda-3

PRO_0000015510

Amino acid modifications

Disulfide bond

37 ↔ 136

Ref.6

Disulfide bond

71 ↔ 169

Ref.6

Disulfide bond

188 ↔ 195

Ref.6

Natural variations

Natural variant

28

1

R → H.
Corresponds to variant rs629976 [ dbSNP | Ensembl ].

VAR_063419

Natural variant

70

1

K → R. Ref.3
Corresponds to variant rs8103142 [ dbSNP | Ensembl ].

VAR_063420

Experimental info

Mutagenesis

57

1

K → A: 51 fold decrease in antiviral activity. Ref.6

Mutagenesis

58

1

D → A: 43 fold decrease in antiviral activity. Ref.6

Mutagenesis

118

1

V → A: 68 fold decrease in antiviral activity. Ref.6

Mutagenesis

121

1

Q → A: 46 fold decrease in antiviral activity. Ref.6

Mutagenesis

176

1

F → A: 40 fold decrease in antiviral activity. Ref.6

Mutagenesis

179

1

F → A: 650 fold decrease in antiviral activity. Ref.6

Sequence conflict

108

1

T → S in AAN86127. Ref.2

Sequence conflict

120

1

D → G in AAQ01561. Ref.3

Sequence conflict

155

1

L → P in AAQ01561. Ref.3

Sequence conflict

156

1

H → Y in AAN86127. Ref.2

Secondary structure

1

.

.

.

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.

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196

Helix Strand Turn

Details...

Helix

40 – 42

3

Helix

47 – 65

19

Beta strand

71 – 73

3

Helix

82 – 84

3

Helix

87 – 89

3

Helix

90 – 111

22

Helix

113 – 134

22

Helix

150 – 159

10

Helix

161 – 163

3

Helix

167 – 176

10

Helix

178 – 182

5

Helix

184 – 190

7

Helix

191 – 194

4

Sequences

	Sequence		Length	Mass (Da)
	Q8IZI9 [UniParc]. Last modified July 13, 2010. Version 2. Checksum: F2322E10C887184B	FASTA	196	21,706
	10 20 30 40 50 60 MTGDCMPVLV LMAAVLTVTG AVPVARLRGA LPDARGCHIA QFKSLSPQEL QAFKRAKDAL 70 80 90 100 110 120 EESLLLKDCK CRSRLFPRTW DLRQLQVRER PVALEAELAL TLKVLEATAD TDPALGDVLD 130 140 150 160 170 180 QPLHTLHHIL SQLRACIQPQ PTAGPRTRGR LHHWLHRLQE APKKESPGCL EASVTFNLFR 190 LLTRDLNCVA SGDLCV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"IL-28, IL-29 and their class II cytokine receptor IL-28R." Sheppard P., Kindsvogel W., Xu W., Henderson K., Schlutsmeyer S., Whitmore T.E., Kuestner R., Garrigues U., Birks C., Roraback J., Ostrander C., Dong D., Shin J., Presnell S., Fox B., Haldeman B., Cooper E., Taft D. , Gilbert T., Grant F.J., Tackett M., Krivan W., McKnight G., Clegg C., Foster D., Klucher K.M. Nat. Immunol. 4:63-68(2003) [PubMed] [Europe PMC] [Abstract] 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 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00969047.

RefSeq

NP_742151.2. NM_172139.2.

UniGene

Hs.406744.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3HHC	X-ray	2.80	A/B/C/D	1-196	[»]

ProteinModelPortal

Q8IZI9.

SMR

Q8IZI9. Positions 37-196.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000347165.

Polymorphism databases

DMDM

300669648.

Proteomic databases

PaxDb

Q8IZI9.

PRIDE

Q8IZI9.

Protocols and materials databases

DNASU

282617.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000413851; ENSP00000409000; ENSG00000197110.

GeneID

282617.

KEGG

hsa:282617.

UCSC

uc010xut.2. human.

Organism-specific databases

CTD

282617.

GeneCards

GC19M039734.

HGNC

HGNC:18365. IFNL3.

MIM

607402. gene.

neXtProt

NX_Q8IZI9.

Orphanet

284102. Response to polyethylene glycol/interferon-ribavirin in hepatitis C virus.

PharmGKB

PA134952671.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40189.

HOGENOM

HOG000232074.

HOVERGEN

HBG052108.

InParanoid

Q8IZI9.

KO

K05447.

OMA

CLEASAI.

OrthoDB

EOG4X6C9D.

PhylomeDB

Q8IZI9.

Gene expression databases

CleanEx

HS_IL28B.

Genevestigator

Q8IZI9.

GermOnline

ENSG00000197110. Homo sapiens.

Family and domain databases

ProtoNet

Search...

Other

EvolutionaryTrace

Q8IZI9.

GenomeRNAi

282617.

NextBio

93470.

SOURCE

Search...

Entry information

Entry name

IFNL3_HUMAN

Accession

Primary (citable) accession number: Q8IZI9
Secondary accession number(s): A2BDE1 , Q6VN56, Q7Z4J3, Q8IWL6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	July 13, 2010
Last modified:	May 1, 2013
This is version 74 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.