ID   IFNA4_HUMAN             Reviewed;         189 AA.
AC   P05014; P13358; Q14CS4; Q5VV15;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2005, sequence version 2.
DT   02-SEP-2026, entry version 211.
DE   RecName: Full=Interferon alpha-4;
DE            Short=IFN-alpha-4;
DE   AltName: Full=Interferon alpha-4B;
DE   AltName: Full=Interferon alpha-76;
DE   AltName: Full=Interferon alpha-M1;
DE   Flags: Precursor;
GN   Name=IFNA4;
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].
RX   PubMed=6089830;
RA   Linnane A.W., Beilharz M.W., McMullen G.L., Macreadie I.G., Murphy M.,
RA   Nisbet I.T., Novitski C.E., Woodrow G.C.;
RT   "Nucleotide sequence and expression in E. coli of a human interferon-alpha
RT   gene selected from a genomic library using synthetic oligonucleotides.";
RL   Biochem. Int. 8:725-732(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALPHA-4B THR-74 AND
RP   VAL-137.
RX   PubMed=4057246; DOI=10.1016/0022-2836(85)90401-2;
RA   Henco K., Brosius J., Fujisawa A., Fujisawa J., Haynes J.R., Hochstadt J.,
RA   Kovacic T., Pasek M., Schamboeck A., Schmid J., Todokoro K., Waelchli M.,
RA   Nagata S., Weissmann C.;
RT   "Structural relationship of human interferon alpha genes and pseudogenes.";
RL   J. Mol. Biol. 185:227-260(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT THR-74.
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-74.
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   PROTEIN SEQUENCE OF 24-56.
RX   PubMed=9425112; DOI=10.1042/bj3290295;
RA   Nyman T.A., Toeloe H., Parkkinen J., Kalkkinen N.;
RT   "Identification of nine interferon-alpha subtypes produced by Sendai virus-
RT   induced human peripheral blood leucocytes.";
RL   Biochem. J. 329:295-302(1998).
RN   [7]
RP   POLYMORPHISM.
RX   PubMed=9335434; DOI=10.1089/jir.1997.17.559;
RA   Hussain M., Gill D.S., Liao M.-J.;
RT   "Both variant forms of interferon-alpha4 gene (IFNA4a and IFNA4b) are
RT   present in the human population.";
RL   J. Interferon Cytokine Res. 17:559-566(1997).
CC   -!- FUNCTION: Produced by macrophages, IFN-alpha have antiviral activities.
CC       Interferon stimulates the production of two enzymes: a protein kinase
CC       and an oligoadenylate synthetase.
CC   -!- INTERACTION:
CC       P05014; P04075-2: ALDOA; NbExp=3; IntAct=EBI-10194381, EBI-10194102;
CC       P05014; P19429: TNNI3; NbExp=2; IntAct=EBI-10194381, EBI-704146;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- POLYMORPHISM: Two forms exist; alpha-4a (shown here) and alpha-4b
CC       (PubMed:9335434). They seem to be equally abundant (PubMed:9335434).
CC       {ECO:0000269|PubMed:9335434}.
CC   -!- SIMILARITY: Belongs to the type-I (or alpha/beta) interferon family.
CC       {ECO:0000255|PROSITE-ProRule:PRU01420}.
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DR   EMBL; M27318; AAA52726.1; -; mRNA.
DR   EMBL; X02955; CAA26701.1; -; Genomic_DNA.
DR   EMBL; AL512606; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471071; EAW58621.1; -; Genomic_DNA.
DR   EMBL; BC074965; AAH74965.1; -; mRNA.
DR   EMBL; BC074966; AAH74966.1; -; mRNA.
DR   EMBL; BC113640; AAI13641.1; -; mRNA.
DR   EMBL; BC113642; AAI13643.1; -; mRNA.
DR   CCDS; CCDS6498.1; -.
DR   PIR; E23753; IVHU4B.
DR   PIR; I52347; I52347.
DR   RefSeq; NP_066546.1; NM_021068.4.
DR   AlphaFoldDB; P05014; -.
DR   SMR; P05014; -.
DR   BioGRID; 109664; 43.
DR   ComplexPortal; CPX-5998; Interferon alpha receptor-ligand complex, IFNA4 variant.
DR   FunCoup; P05014; 966.
DR   IntAct; P05014; 40.
DR   NDEx; IQUERY-CP-IFNA4; 17 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000412897; -.
DR   ChEMBL; CHEMBL3856161; -.
DR   iPTMnet; P05014; -.
DR   PhosphoSitePlus; P05014; -.
DR   BioMuta; IFNA4; -.
DR   DMDM; 84029375; -.
DR   MassIVE; P05014; -.
DR   PaxDb; 9606-ENSP00000412897; -.
DR   PeptideAtlas; P05014; -.
DR   ABCD; P05014; 2 sequenced antibodies.
DR   Antibodypedia; 24852; 182 antibodies from 22 providers.
DR   DNASU; 3441; -.
DR   Ensembl; ENST00000421715.3; ENSP00000412897.1; ENSG00000236637.5.
DR   GeneID; 3441; -.
DR   KEGG; hsa:3441; -.
DR   MANE-Select; ENST00000421715.3; ENSP00000412897.1; NM_021068.4; NP_066546.1.
DR   UCSC; uc003zon.3; human.
DR   AGR; HGNC:5425; -.
DR   ClinPGx; PA29664; -.
DR   CTD; 3441; -.
DR   DisGeNET; 3441; -.
DR   GeneCards; IFNA4; -.
DR   HGNC; HGNC:5425; IFNA4.
DR   HPA; ENSG00000236637; Not detected.
DR   MIM; 147564; gene.
DR   OpenTargets; ENSG00000236637; -.
DR   VEuPathDB; HostDB:ENSG00000236637; -.
DR   eggNOG; ENOG502SQAC; Eukaryota.
DR   GeneTree; ENSGT01000000214430; -.
DR   HOGENOM; CLU_109427_0_0_1; -.
DR   InParanoid; P05014; -.
DR   OMA; CFLFITQ; -.
DR   OrthoDB; 9526363at2759; -.
DR   PAN-GO; P05014; 10 GO annotations based on evolutionary models.
DR   PhylomeDB; P05014; -.
DR   PathwayCommons; P05014; -.
DR   Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR   Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling.
DR   Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation.
DR   Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR   Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR   Reactome; R-HSA-9833109; Evasion by RSV of host interferon responses.
DR   SignaLink; P05014; -.
DR   Agora; ENSG00000236637; -.
DR   BioGRID-ORCS; 3441; 57 hits in 1029 CRISPR screens.
DR   GeneWiki; IFNA4; -.
DR   GenomeRNAi; 3441; -.
DR   Pharos; P05014; Tbio.
DR   PRO; PR:P05014; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; P05014; protein.
DR   Bgee; ENSG00000236637; Expressed in aorta and 2 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0005132; F:type I interferon receptor binding; IBA:GO_Central.
DR   GO; GO:0002250; P:adaptive immune response; IBA:GO_Central.
DR   GO; GO:0002312; P:B cell activation involved in immune response; IBA:GO_Central.
DR   GO; GO:0098586; P:cellular response to virus; NAS:ComplexPortal.
DR   GO; GO:0006959; P:humoral immune response; IBA:GO_Central.
DR   GO; GO:0002323; P:natural killer cell activation involved in immune response; IBA:GO_Central.
DR   GO; GO:0043330; P:response to exogenous dsRNA; IBA:GO_Central.
DR   GO; GO:0009615; P:response to virus; TAS:ProtInc.
DR   GO; GO:0002286; P:T cell activation involved in immune response; IBA:GO_Central.
DR   GO; GO:0060337; P:type I interferon-mediated signaling pathway; IBA:GO_Central.
DR   CDD; cd00095; IFab; 1.
DR   FunFam; 1.20.1250.10:FF:000001; Interferon alpha; 1.
DR   Gene3D; 1.20.1250.10; -; 1.
DR   InterPro; IPR009079; 4_helix_cytokine-like_core.
DR   InterPro; IPR000471; Interferon_alpha/beta/delta.
DR   PANTHER; PTHR11691:SF66; INTERFERON ALPHA-10-RELATED; 1.
DR   PANTHER; PTHR11691; TYPE I INTERFERON; 1.
DR   Pfam; PF00143; Interferon; 1.
DR   PRINTS; PR00266; INTERFERONAB.
DR   SMART; SM00076; IFabd; 1.
DR   SUPFAM; SSF47266; 4-helical cytokines; 1.
DR   PROSITE; PS52075; IFN_I; 1.
DR   PROSITE; PS00252; INTERFERON_A_B_D; 1.
PE   1: Evidence at protein level;
KW   Antiviral defense; Cytokine; Direct protein sequencing; Disulfide bond;
KW   Proteomics identification; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000269|PubMed:9425112"
FT   CHAIN           24..189
FT                   /note="Interferon alpha-4"
FT                   /id="PRO_0000016361"
FT   DISULFID        24..122
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01420"
FT   DISULFID        52..162
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01420"
FT   VARIANT         49
FT                   /note="H -> P (in dbSNP:rs201964250)"
FT                   /id="VAR_034010"
FT   VARIANT         74
FT                   /note="A -> T (in alpha-4B; dbSNP:rs1062571)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:4057246, ECO:0000269|Ref.4"
FT                   /id="VAR_013002"
FT   VARIANT         137
FT                   /note="E -> V (in alpha-4B; dbSNP:rs3750480)"
FT                   /evidence="ECO:0000269|PubMed:4057246"
FT                   /id="VAR_013003"
SQ   SEQUENCE   189 AA;  21808 MW;  828DF9C33ABC337F CRC64;
     MALSFSLLMA VLVLSYKSIC SLGCDLPQTH SLGNRRALIL LAQMGRISHF SCLKDRHDFG
     FPEEEFDGHQ FQKAQAISVL HEMIQQTFNL FSTEDSSAAW EQSLLEKFST ELYQQLNDLE
     ACVIQEVGVE ETPLMNEDSI LAVRKYFQRI TLYLTEKKYS PCAWEVVRAE IMRSLSFSTN
     LQKRLRRKD
//