IFNL4_HUMAN
ID IFNL4_HUMAN Reviewed; 179 AA.
AC K9M1U5; K9M1A5; K9M269; K9M2P7;
DT 01-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Interferon lambda-4;
DE Short=IFN-lambda-4;
DE Flags: Precursor;
GN Name=IFNL4;
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] (ISOFORMS 1; 2; 3 AND 4), FUNCTION,
RP POLYMORPHISM, INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23291588; DOI=10.1038/ng.2521;
RA Prokunina-Olsson L., Muchmore B., Tang W., Pfeiffer R.M., Park H.,
RA Dickensheets H., Hergott D., Porter-Gill P., Mumy A., Kohaar I., Chen S.,
RA Brand N., Tarway M., Liu L., Sheikh F., Astemborski J., Bonkovsky H.L.,
RA Edlin B.R., Howell C.D., Morgan T.R., Thomas D.L., Rehermann B.,
RA Donnelly R.P., O'Brien T.R.;
RT "A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4
RT is associated with impaired clearance of hepatitis C virus.";
RL Nat. Genet. 45:164-171(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
CC -!- FUNCTION: Cytokine that may trigger an antiviral response activating
CC the JAK-STAT pathway and up-regulating specifically some interferon-
CC stimulated genes. {ECO:0000269|PubMed:23291588}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23291588}. Secreted
CC {ECO:0000269|PubMed:23291588}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist. However, they may be
CC produced at very low levels due to a premature stop codon in the
CC mRNA, leading to nonsense-mediated mRNA decay.;
CC Name=1; Synonyms=IFNL4, p179;
CC IsoId=K9M1U5-1; Sequence=Displayed;
CC Name=2; Synonyms=p170;
CC IsoId=K9M1U5-2; Sequence=VSP_046394;
CC Name=3; Synonyms=p131;
CC IsoId=K9M1U5-3; Sequence=VSP_046393;
CC Name=4; Synonyms=p107;
CC IsoId=K9M1U5-4; Sequence=VSP_046392;
CC -!- INDUCTION: Up-regulated by polyinosinic:polycytidylic acid (polyI:C)
CC which mimics the double-stranded hepatitis C virus.
CC {ECO:0000269|PubMed:23291588}.
CC -!- POLYMORPHISM: A one-base insertion, introducing a frameshift at
CC position 22, results in inactivation of the gene in a majority of the
CC population. That polymorphism is a good marker for predicting
CC spontaneous hepatitis C virus (HCV) clearance and the response to
CC treatment of chronic hepatitis C. The allele producing a functional
CC protein able to induce an antiviral response and to prevent HCV
CC replication in cell cultures, is less frequent in human populations and
CC is associated with impaired spontaneous clearance of HCV.
CC {ECO:0000269|PubMed:23291588}.
CC -!- MISCELLANEOUS: [Isoform 1]: Active form which is able to induce an
CC antiviral response and prevent hepatitis C virus (HCV) replication in
CC cell cultures.
CC -!- MISCELLANEOUS: [Isoform 2]: Inactive form. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Inactive form unable to elicit an antiviral
CC response. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Inactive form unable to elicit an antiviral
CC response. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the lambda interferon family. {ECO:0000305}.
CC -!- CAUTION: The reference genome assembly, GRCh37, describes the non-
CC functional copy of that gene, frameshifted at position 22, that is more
CC frequent in human populations. {ECO:0000305}.
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DR EMBL; JN806225; AFQ38550.1; -; mRNA.
DR EMBL; JN806226; AFQ38551.1; -; mRNA.
DR EMBL; JN806233; AFQ38558.1; -; mRNA.
DR EMBL; JN806234; AFQ38559.1; -; mRNA.
DR EMBL; AC011445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001263183.2; NM_001276254.2. [K9M1U5-1]
DR AlphaFoldDB; K9M1U5; -.
DR SMR; K9M1U5; -.
DR ComplexPortal; CPX-6014; Interferon lambda receptor-ligand complex, IFNL4 variant.
DR BioMuta; IFNL4; -.
DR PeptideAtlas; K9M1U5; -.
DR PRIDE; K9M1U5; -.
DR ABCD; K9M1U5; 2 sequenced antibodies.
DR DNASU; 101180976; -.
DR GeneID; 101180976; -.
DR KEGG; hsa:101180976; -.
DR CTD; 101180976; -.
DR DisGeNET; 101180976; -.
DR GeneCards; IFNL4; -.
DR HGNC; HGNC:44480; IFNL4.
DR MIM; 615090; gene.
DR neXtProt; NX_K9M1U5; -.
DR Orphanet; 284102; Prediction of response to antiviral treatment in hepatitis C.
DR InParanoid; K9M1U5; -.
DR BioGRID-ORCS; 101180976; 12 hits in 165 CRISPR screens.
DR Pharos; K9M1U5; Tbio.
DR PRO; PR:K9M1U5; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; K9M1U5; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IMP:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0050778; P:positive regulation of immune response; IEA:InterPro.
DR GO; GO:0038196; P:type III interferon signaling pathway; IC:ComplexPortal.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IDA:UniProtKB.
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 Alternative splicing; Antiviral defense; Cytokine; Cytoplasm;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..179
FT /note="Interferon lambda-4"
FT /id="PRO_0000422094"
FT REGION 130..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 134..149
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 51..122
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:23291588"
FT /id="VSP_046392"
FT VAR_SEQ 75..122
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:23291588"
FT /id="VSP_046393"
FT VAR_SEQ 123..179
FT /note="LELARPGSSRKVPGAQKRRHKPRRADSPRCRKASVVFNLLRLLTWELRLAAH
FT SGPCL -> VSDGRAPPPLSPASFSASSGPRRAPALCQSVLLSGKTHPDRSRVLWVS
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:23291588"
FT /id="VSP_046394"
FT CONFLICT 161
FT /note="L -> P (in Ref. 1; AFQ38550)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 179 AA; 19675 MW; 2010E94B6224D0F7 CRC64;
MRPSVWAAVA AGLWVLCTVI AAAPRRCLLS HYRSLEPRTL AAAKALRDRY EEEALSWGQR
NCSFRPRRDP PRPSSCARLR HVARGIADAQ AVLSGLHRSE LLPGAGPILE LLAAAGRDVA
ACLELARPGS SRKVPGAQKR RHKPRRADSP RCRKASVVFN LLRLLTWELR LAAHSGPCL
