IFN21_HUMAN
ID IFN21_HUMAN Reviewed; 189 AA.
AC P01568; Q14608; Q5VWD1; Q7M4Q4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Interferon alpha-21;
DE Short=IFN-alpha-21;
DE AltName: Full=Interferon alpha-F;
DE Short=LeIF F;
DE Flags: Precursor;
GN Name=IFNA21;
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], AND VARIANT MET-119.
RX PubMed=6163083; DOI=10.1038/290020a0;
RA Goeddel D.V., Leung D.W., Dull T.J., Gross M., Lawn R.M., McCandliss R.,
RA Seeburg P.H., Ullrich A., Yelverton E., Gray P.W.;
RT "The structure of eight distinct cloned human leukocyte interferon cDNAs.";
RL Nature 290:20-26(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Gren E.Y., Berzin V.M., Tsimanis A.Y., Apsalon U.R., Vishnevskii Y.I.,
RA Yansone I.V., Dishler A.V., Pudova N.V., Smorodintsev A.A., Iovlev V.I.,
RA Stepanov A.N., Feldmane G.Y., Meldrais Y.A., Lozha V.P., Kavsan V.M.,
RA Efimov V.A., Sverdlov E.D.;
RT "A new type of leukocytic interferon.";
RL Dokl. Biochem. 269:91-95(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6548765; DOI=10.1089/jir.1984.4.609;
RA Gren E., Berzin V.M., Jansone I., Tsimanis A., Vishnevsky Y., Apsalons U.;
RT "Novel human leukocyte interferon subtype and structural comparison of
RT alpha interferon genes.";
RL J. Interferon Res. 4:609-617(1984).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 24-189.
RC TISSUE=Lymphoblast;
RX PubMed=3803589; DOI=10.1016/0014-5793(87)81278-4;
RA Ohara O., Teraoka H.;
RT "Anomalous behavior of human leukocyte interferon subtypes on
RT polyacrylamide gel electrophoresis in the presence of dodecyl sulfate.";
RL FEBS Lett. 211:78-82(1987).
RN [8]
RP PROTEIN SEQUENCE OF 24-62, AND FUNCTION.
RX PubMed=1634550; DOI=10.1016/s0021-9258(18)42167-9;
RA Zoon K.C., Miller D., Bekisz J., zur Nedden D., Enterline J.C.,
RA Nguyen N.Y., Hu R.-Q.;
RT "Purification and characterization of multiple components of human
RT lymphoblastoid interferon-alpha.";
RL J. Biol. Chem. 267:15210-15216(1992).
RN [9]
RP PROTEIN SEQUENCE OF 24-58.
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 [10]
RP ABSENCE OF POLYMORPHISM.
RX PubMed=8910771; DOI=10.1089/jir.1996.16.853;
RA Hussain M., Gill D.S., Liao M.-J.;
RT "Identification of interferon-alpha 7, -alpha 14, and -alpha 21 variants in
RT the genome of a large human population.";
RL J. Interferon Cytokine Res. 16:853-859(1996).
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. {ECO:0000269|PubMed:1634550}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the alpha/beta interferon family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36041.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; V00540; CAA23801.1; -; mRNA.
DR EMBL; M12350; AAA52718.1; -; mRNA.
DR EMBL; X00145; CAA24980.1; -; mRNA.
DR EMBL; M28586; AAA36041.1; ALT_INIT; mRNA.
DR EMBL; AL390882; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58623.1; -; Genomic_DNA.
DR EMBL; BC069329; AAH69329.1; -; mRNA.
DR EMBL; BC069372; AAH69372.1; -; mRNA.
DR EMBL; BC069408; AAH69408.1; -; mRNA.
DR EMBL; BC096699; AAH96699.1; -; mRNA.
DR EMBL; BC101638; AAI01639.1; -; mRNA.
DR EMBL; BC101640; AAI01641.1; -; mRNA.
DR CCDS; CCDS6497.1; -.
DR PIR; A01832; IVHUF.
DR PIR; D42753; D42753.
DR PIR; E25843; E25843.
DR PIR; I56313; I56313.
DR PIR; I84464; I84464.
DR RefSeq; NP_002166.2; NM_002175.2.
DR AlphaFoldDB; P01568; -.
DR SMR; P01568; -.
DR BioGRID; 109674; 32.
DR ComplexPortal; CPX-6006; Interferon alpha receptor-ligand complex, IFNA21 variant.
DR IntAct; P01568; 25.
DR STRING; 9606.ENSP00000369574; -.
DR ChEMBL; CHEMBL3856161; -.
DR iPTMnet; P01568; -.
DR PhosphoSitePlus; P01568; -.
DR BioMuta; IFNA21; -.
DR DMDM; 20178289; -.
DR MassIVE; P01568; -.
DR PaxDb; P01568; -.
DR PeptideAtlas; P01568; -.
DR PRIDE; P01568; -.
DR ABCD; P01568; 2 sequenced antibodies.
DR Antibodypedia; 24851; 121 antibodies from 16 providers.
DR DNASU; 3452; -.
DR Ensembl; ENST00000380225.1; ENSP00000369574.1; ENSG00000137080.4.
DR GeneID; 3452; -.
DR KEGG; hsa:3452; -.
DR MANE-Select; ENST00000380225.1; ENSP00000369574.1; NM_002175.2; NP_002166.2.
DR UCSC; uc003zom.2; human.
DR CTD; 3452; -.
DR GeneCards; IFNA21; -.
DR HGNC; HGNC:5424; IFNA21.
DR HPA; ENSG00000137080; Not detected.
DR MIM; 147584; gene.
DR neXtProt; NX_P01568; -.
DR OpenTargets; ENSG00000137080; -.
DR PharmGKB; PA29663; -.
DR VEuPathDB; HostDB:ENSG00000137080; -.
DR eggNOG; ENOG502SQAC; Eukaryota.
DR GeneTree; ENSGT01000000214430; -.
DR HOGENOM; CLU_109427_0_0_1; -.
DR InParanoid; P01568; -.
DR OMA; CAWERIQ; -.
DR OrthoDB; 1358010at2759; -.
DR PhylomeDB; P01568; -.
DR TreeFam; TF336177; -.
DR PathwayCommons; P01568; -.
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; P01568; -.
DR BioGRID-ORCS; 3452; 69 hits in 989 CRISPR screens.
DR GeneWiki; IFNA21; -.
DR GenomeRNAi; 3452; -.
DR Pharos; P01568; Tbio.
DR PRO; PR:P01568; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P01568; protein.
DR Bgee; ENSG00000137080; Expressed in cerebellar hemisphere and 17 other tissues.
DR Genevisible; P01568; 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:0005126; F:cytokine receptor binding; TAS:ProtInc.
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: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:1634550,
FT ECO:0000269|PubMed:9425112"
FT CHAIN 24..189
FT /note="Interferon alpha-21"
FT /id="PRO_0000016370"
FT DISULFID 24..122
FT /evidence="ECO:0000250"
FT DISULFID 52..162
FT /evidence="ECO:0000250"
FT VARIANT 119
FT /note="L -> M (in dbSNP:rs1053885)"
FT /evidence="ECO:0000269|PubMed:6163083"
FT /id="VAR_055325"
FT VARIANT 179
FT /note="K -> E (in dbSNP:rs3750478)"
FT /id="VAR_049638"
FT CONFLICT 60
FT /note="G -> E (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 189 AA; 21741 MW; F0B6C9C392905802 CRC64;
MALSFSLLMA VLVLSYKSIC SLGCDLPQTH SLGNRRALIL LAQMGRISPF SCLKDRHDFG
FPQEEFDGNQ FQKAQAISVL HEMIQQTFNL FSTKDSSATW EQSLLEKFST ELNQQLNDLE
ACVIQEVGVE ETPLMNVDSI LAVKKYFQRI TLYLTEKKYS PCAWEVVRAE IMRSFSLSKI
FQERLRRKE