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   16-JAN-2019, entry version 26.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Chen S., Brand N., Tarway M., Liu L., Sheikh F., Astemborski J.,
RA   Bonkovsky H.L., Edlin B.R., Howell C.D., Morgan T.R., Thomas D.L.,
RA   Rehermann B., Donnelly R.P., O'Brien T.R.;
RT   "A variant upstream of IFNL3 (IL28B) creating a new interferon gene
RT   IFNL4 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.,
RA   Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA   Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA   Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA   Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA   Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA   Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA   Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA   Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA   Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA   Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA   Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA   Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA   Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA   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
CC       activating the JAK-STAT pathway and up-regulating specifically
CC       some interferon-stimulated genes. {ECO:0000269|PubMed:23291588}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23291588}.
CC       Secreted {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         Note=Active form which is able to induce an antiviral response
CC         and prevent hepatitis C virus (HCV) replication in cell
CC         cultures.;
CC       Name=2; Synonyms=p170;
CC         IsoId=K9M1U5-2; Sequence=VSP_046394;
CC         Note=Inactive form.;
CC       Name=3; Synonyms=p131;
CC         IsoId=K9M1U5-3; Sequence=VSP_046393;
CC         Note=Inactive form unable to elicit an antiviral response.;
CC       Name=4; Synonyms=p107;
CC         IsoId=K9M1U5-4; Sequence=VSP_046392;
CC         Note=Inactive form unable to elicit an antiviral response.;
CC   -!- INDUCTION: Up-regulated by polyinosinic:polycytidylic acid
CC       (polyI:C) which mimics the double-stranded hepatitis C virus.
CC       {ECO:0000269|PubMed:23291588}.
CC   -!- POLYMORPHISM: Genetic variation in IFNL4 is associated with
CC       susceptibility to hepatitis C virus (HCV) infection [MIM:609532].
CC       A one-base insertion, introducing a frameshift at position 22,
CC       results in inactivation of the gene in a majority of the
CC       population. That polymorphism is a good marker for predicting
CC       spontaneous HCV clearance and the response to treatment of chronic
CC       hepatitis C. Noteworthily, 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
CC       populations and is associated with impaired spontaneous clearance
CC       of HCV.
CC   -!- SIMILARITY: Belongs to the lambda interferon family.
CC       {ECO:0000305}.
CC   -!- CAUTION: The reference genome assembly, GRCh37, describes the non-
CC       functional copy of that gene, frameshifted at position 22, that is
CC       more 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   UniGene; Hs.745579; -.
DR   ProteinModelPortal; K9M1U5; -.
DR   BioMuta; IFNL4; -.
DR   jPOST; K9M1U5; -.
DR   PRIDE; K9M1U5; -.
DR   GeneID; 101180976; -.
DR   KEGG; hsa:101180976; -.
DR   CTD; 101180976; -.
DR   DisGeNET; 101180976; -.
DR   GeneCards; IFNL4; -.
DR   HGNC; HGNC:44480; IFNL4.
DR   MalaCards; IFNL4; -.
DR   MIM; 615090; gene.
DR   neXtProt; NX_K9M1U5; -.
DR   Orphanet; 284102; Response to antiviral treatment in hepatitis C.
DR   InParanoid; K9M1U5; -.
DR   PRO; PR:K9M1U5; -.
DR   Proteomes; UP000005640; Unplaced.
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: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: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; Complete proteome; Cytokine;
KW   Cytoplasm; Reference proteome; Secreted; Signal.
FT   SIGNAL        1     21       {ECO:0000255}.
FT   CHAIN        22    179       Interferon lambda-4.
FT                                /FTId=PRO_0000422094.
FT   VAR_SEQ      51    122       Missing (in isoform 4).
FT                                {ECO:0000303|PubMed:23291588}.
FT                                /FTId=VSP_046392.
FT   VAR_SEQ      75    122       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:23291588}.
FT                                /FTId=VSP_046393.
FT   VAR_SEQ     123    179       LELARPGSSRKVPGAQKRRHKPRRADSPRCRKASVVFNLLR
FT                                LLTWELRLAAHSGPCL -> VSDGRAPPPLSPASFSASSGP
FT                                RRAPALCQSVLLSGKTHPDRSRVLWVS (in isoform
FT                                2). {ECO:0000303|PubMed:23291588}.
FT                                /FTId=VSP_046394.
FT   CONFLICT    161    161       L -> P (in Ref. 1; AFQ38550).
FT                                {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
//