IFNA4_HUMAN
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 03-AUG-2022, entry version 193.
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 -!- 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 alpha/beta interferon family. {ECO:0000305}.
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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_021068.2.
DR AlphaFoldDB; P05014; -.
DR SMR; P05014; -.
DR BioGRID; 109664; 43.
DR ComplexPortal; CPX-5998; Interferon alpha receptor-ligand complex, IFNA4 variant.
DR IntAct; P05014; 11.
DR STRING; 9606.ENSP00000412897; -.
DR ChEMBL; CHEMBL3856161; -.
DR iPTMnet; P05014; -.
DR PhosphoSitePlus; P05014; -.
DR BioMuta; IFNA4; -.
DR DMDM; 84029375; -.
DR jPOST; P05014; -.
DR MassIVE; P05014; -.
DR PaxDb; P05014; -.
DR PeptideAtlas; P05014; -.
DR PRIDE; P05014; -.
DR ABCD; P05014; 2 sequenced antibodies.
DR Antibodypedia; 24852; 188 antibodies from 22 providers.
DR DNASU; 3441; -.
DR Ensembl; ENST00000421715.2; ENSP00000412897.1; ENSG00000236637.4.
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 CTD; 3441; -.
DR DisGeNET; 3441; -.
DR GeneCards; IFNA4; -.
DR HGNC; HGNC:5425; IFNA4.
DR HPA; ENSG00000236637; Not detected.
DR MIM; 147564; gene.
DR neXtProt; NX_P05014; -.
DR OpenTargets; ENSG00000236637; -.
DR PharmGKB; PA29664; -.
DR VEuPathDB; HostDB:ENSG00000236637; -.
DR eggNOG; ENOG502SQAC; Eukaryota.
DR GeneTree; ENSGT01000000214430; -.
DR HOGENOM; CLU_109427_0_0_1; -.
DR InParanoid; P05014; -.
DR OMA; MARSCAF; -.
DR OrthoDB; 1358010at2759; -.
DR PhylomeDB; P05014; -.
DR TreeFam; TF336177; -.
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 SignaLink; P05014; -.
DR BioGRID-ORCS; 3441; 56 hits in 980 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 tissues.
DR Genevisible; P05014; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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:0030183; P:B cell differentiation; IBA:GO_Central.
DR GO; GO:0042100; P:B cell proliferation; IBA:GO_Central.
DR GO; GO:0098586; P:cellular response to virus; IC:ComplexPortal.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
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:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; 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 signaling pathway; IC:ComplexPortal.
DR CDD; cd00095; IFab; 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; PTHR11691; 1.
DR Pfam; PF00143; Interferon; 1.
DR PRINTS; PR00266; INTERFERONAB.
DR SMART; SM00076; IFabd; 1.
DR SUPFAM; SSF47266; SSF47266; 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 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:0000250"
FT DISULFID 52..162
FT /evidence="ECO:0000250"
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
