ID IFNA2_HUMAN Reviewed; 188 AA. AC P01563; H2DF54; H2DF55; P01564; Q14606; Q6DJX8; Q96KI6; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 16-MAR-2016, entry version 163. DE RecName: Full=Interferon alpha-2; DE Short=IFN-alpha-2; DE AltName: Full=Interferon alpha-A; DE Short=LeIF A; DE Flags: Precursor; GN Name=IFNA2; Synonyms=IFNA2A, IFNA2B, IFNA2C; 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 [GENOMIC DNA / MRNA]. RX PubMed=6159538; DOI=10.1038/287411a0; RA Goeddel D.V., Yelverton E., Ullrich A., Heyneker H.L., Miozzari G., RA Holmes W., Seeburg P.H., Dull T.J., May L., Stebbing N., Crea R., RA Maeda S., McCandliss R., Sloma A., Tabor J.M., Gross M., RA Familletti P.C., Pestka S.; RT "Human leukocyte interferon produced by E. coli is biologically RT active."; RL Nature 287:411-416(1980). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=6163083; DOI=10.1038/290020a0; RA Goeddel D.V., Leung D.W., Dull T.J., Gross M., Lawn R.M., RA McCandliss R., Seeburg P.H., Ullrich A., Yelverton E., Gray P.W.; RT "The structure of eight distinct cloned human leukocyte interferon RT cDNAs."; RL Nature 290:20-26(1981). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=6170983; DOI=10.1073/pnas.78.9.5435; RA Lawn R.M., Gross M., Houck C.M., Franke A.E., Gray P.V., Goeddel D.V.; RT "DNA sequence of a major human leukocyte interferon gene."; RL Proc. Natl. Acad. Sci. U.S.A. 78:5435-5439(1981). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Bone marrow tumor; RX PubMed=3906813; RA Oliver G., Balbas P., Valle F., Soberon X., Bolivar F.; RT "Cloning of human leukocyte interferon cDNA and a strategy for its RT production in E. coli."; RL Rev. Latinoam. Microbiol. 27:141-150(1985). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta; RX PubMed=9694076; RA Austruy E., Bagnis C., Carbuccia N., Maroc C., Birg F., Dubreuil P., RA Mannoni P., Chabannon C.; RT "A defective retroviral vector encoding human interferon alpha 2 can RT transduce human leukemic cell lines."; RL Cancer Gene Ther. 5:247-256(1998). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-46. RX PubMed=23875128; DOI=10.1186/2193-1801-2-264; RA Gull I., Samra Z.Q., Aslam M.S., Athar M.A.; RT "Heterologous expression, immunochemical and computational analysis of RT recombinant human interferon alpha 2b."; RL Springerplus 2:264-264(2013). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Hanif K., Noor S., Naveed Y., Bashir B., Hussain T., Kanwal N.; RL Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [10] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 7-188. RX PubMed=6158094; DOI=10.1126/science.6158094; RA Streuli M., Nagata S., Weissmann C.; RT "At least three human type alpha interferons: structure of alpha 2."; RL Science 209:1343-1347(1980). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 24-188. RX PubMed=6310510; DOI=10.1093/nar/11.16.5661; RA Weber H., Weissmann C.; RT "Formation of genes coding for hybrid proteins by recombination RT between related, cloned genes in E. coli."; RL Nucleic Acids Res. 11:5661-5669(1983). RN [13] RP PROTEIN SEQUENCE OF 24-112 AND 136-188. RX PubMed=6159537; DOI=10.1038/287408a0; RA Allen G., Fantes K.H.; RT "A family of structural genes for human lymphoblastoid (leukocyte- RT type) interferon."; RL Nature 287:408-411(1980). RN [14] RP PROTEIN SEQUENCE OF 24-58. RX PubMed=9425112; RA Nyman T.A., Toeloe H., Parkkinen J., Kalkkinen N.; RT "Identification of nine interferon-alpha subtypes produced by Sendai RT virus-induced human peripheral blood leucocytes."; RL Biochem. J. 329:295-302(1998). RN [15] RP DISULFIDE BONDS. RX PubMed=6162107; DOI=10.1038/289606a0; RA Wetzel R.; RT "Assignment of the disulphide bonds of leukocyte interferon."; RL Nature 289:606-607(1981). RN [16] RP GLYCOSYLATION AT THR-129, AND ALLELES ALPHA-2B AND ALPHA-2C. RX PubMed=2049076; RA Adolf G.R., Kalsner I., Ahorn H., Maurer-Fogy I., Cantell K.; RT "Natural human interferon-alpha 2 is O-glycosylated."; RL Biochem. J. 276:511-518(1991). RN [17] RP POLYMORPHISM. RX PubMed=7627809; DOI=10.1089/jir.1995.15.341; RA Lee N., Ni D., Brissette R., Chou M., Hussain M., Gill D.S., RA Liao M.-J., Testa D.; RT "Interferon-alpha 2 variants in the human genome."; RL J. Interferon Cytokine Res. 15:341-349(1995). RN [18] RP 3D-STRUCTURE MODELING. RX PubMed=8234245; DOI=10.1002/prot.340170109; RA Murgolo N.J., Windsor W.T., Hruza A., Reichert P., Tsarbopoulos A., RA Baldwin S., Huang E., Pramanik B., Ealick S., Trotta P.P.; RT "A homology model of human interferon alpha-2."; RL Proteins 17:62-74(1993). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS). RX PubMed=8994971; DOI=10.1016/S0969-2126(96)00152-9; RA Radhakrishnan R., Walter L.J., Hruza A., Reichert P., Trotta P.P., RA Nagabhushan T.L., Walter M.R.; RT "Zinc mediated dimer of human interferon-alpha 2b revealed by X-ray RT crystallography."; RL Structure 4:1453-1463(1996). RN [20] RP STRUCTURE BY NMR. RX PubMed=9417943; DOI=10.1006/jmbi.1997.1396; RA Klaus W., Gsell B., Labhardt A.M., Wipf B., Senn H.; RT "The three-dimensional high resolution structure of human interferon RT alpha-2a determined by heteronuclear NMR spectroscopy in solution."; RL J. Mol. Biol. 274:661-675(1997). RN [21] RP STRUCTURE BY NMR OF 24-188 IN COMPLEX WITH IFNAR2, SUBUNIT, AND RP DISULFIDE BONDS. RX PubMed=17001036; DOI=10.1110/ps.062283006; RA Quadt-Akabayov S.R., Chill J.H., Levy R., Kessler N., Anglister J.; RT "Determination of the human type I interferon receptor binding site on RT human interferon-alpha2 by cross saturation and an NMR-based model of RT the complex."; RL Protein Sci. 15:2656-2668(2006). RN [22] RP STRUCTURE BY NMR OF 24-188 IN COMPLEX WITH IFNAR2, SUBUNIT, AND RP DISULFIDE BONDS. RX PubMed=20496919; DOI=10.1021/bi100041f; RA Nudelman I., Akabayov S.R., Schnur E., Biron Z., Levy R., Xu Y., RA Yang D., Anglister J.; RT "Intermolecular interactions in a 44 kDa interferon-receptor complex RT detected by asymmetric reverse-protonation and two-dimensional RT NOESY."; RL Biochemistry 49:5117-5133(2010). RN [23] RP VARIANT [LARGE SCALE ANALYSIS] LEU-177. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Produced by macrophages, IFN-alpha have antiviral CC activities. CC -!- SUBUNIT: Interacts with IFNAR2. {ECO:0000269|PubMed:17001036, CC ECO:0000269|PubMed:20496919}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- POLYMORPHISM: Three forms exist; alpha-2a (shown here), alpha-2b CC and alpha-2c (PubMed:7627809). {ECO:0000269|PubMed:7627809}. CC -!- PHARMACEUTICAL: Available under the names Roferon-A (Roche) or CC Intron-A (Schering-Plough). Used as an anticancer drug for its CC antiproliferative activity. CC -!- SIMILARITY: Belongs to the alpha/beta interferon family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J00207; AAB59402.1; -; Genomic_DNA. DR EMBL; V00544; CAA23805.1; -; mRNA. DR EMBL; V00548; CAA23809.1; -; mRNA. DR EMBL; V00549; CAA23810.1; -; mRNA. DR EMBL; Y11834; CAA72532.1; -; Genomic_DNA. DR EMBL; JN591568; AEX60802.1; -; mRNA. DR EMBL; JN591569; AEX60803.1; -; mRNA. DR EMBL; JN591570; AEX60804.1; -; mRNA. DR EMBL; JN848522; AET86951.1; -; mRNA. DR EMBL; CR541921; CAG46719.1; -; mRNA. DR EMBL; CH471071; EAW58611.1; -; Genomic_DNA. DR EMBL; BC074936; AAH74936.1; -; mRNA. DR EMBL; BC074937; AAH74937.1; -; mRNA. DR EMBL; BC104163; AAI04164.1; -; mRNA. DR EMBL; BC104164; AAI04165.1; -; mRNA. DR EMBL; M54886; AAA59181.1; -; mRNA. DR EMBL; M29883; AAA52715.1; -; Genomic_DNA. DR CCDS; CCDS6506.1; -. DR PIR; A93234; IVHUA2. DR PIR; I78570; I78570. DR RefSeq; NP_000596.2; NM_000605.3. DR UniGene; Hs.211575; -. DR PDB; 1ITF; NMR; -; A=24-188. DR PDB; 1RH2; X-ray; 2.90 A; A/B/C/D/E/F=24-188. DR PDB; 2HIE; Model; -; A=24-188. DR PDB; 2HYM; NMR; -; B=24-188. DR PDB; 2KZ1; NMR; -; A=24-188. DR PDB; 2LAG; NMR; -; A=24-188. DR PDB; 2LMS; NMR; -; A=24-188. DR PDB; 3S9D; X-ray; 2.00 A; A/C=24-188. DR PDB; 3SE3; X-ray; 4.00 A; B=24-188. DR PDB; 4YPG; X-ray; 3.00 A; C/D=24-182. DR PDB; 4Z5R; X-ray; 3.00 A; D/E/F/G/H/I/N/X=24-188. DR PDBsum; 1ITF; -. DR PDBsum; 1RH2; -. DR PDBsum; 2HIE; -. DR PDBsum; 2HYM; -. DR PDBsum; 2KZ1; -. DR PDBsum; 2LAG; -. DR PDBsum; 2LMS; -. DR PDBsum; 3S9D; -. DR PDBsum; 3SE3; -. DR PDBsum; 4YPG; -. DR PDBsum; 4Z5R; -. DR ProteinModelPortal; P01563; -. DR SMR; P01563; 24-182. DR BioGrid; 109663; 8. DR DIP; DIP-3784N; -. DR DIP; DIP-481N; -. DR IntAct; P01563; 1. DR STRING; 9606.ENSP00000369554; -. DR Allergome; 9876; Hom s IFN alpha. DR PhosphoSite; P01563; -. DR UniCarbKB; P01563; -. DR BioMuta; IFNA2; -. DR DMDM; 124449; -. DR PaxDb; P01563; -. DR PRIDE; P01563; -. DR DNASU; 3440; -. DR Ensembl; ENST00000380206; ENSP00000369554; ENSG00000188379. DR GeneID; 3440; -. DR KEGG; hsa:3440; -. DR UCSC; uc003zpb.4; human. DR CTD; 3440; -. DR GeneCards; IFNA2; -. DR H-InvDB; HIX0034810; -. DR HGNC; HGNC:5423; IFNA2. DR HPA; HPA047557; -. DR MIM; 147562; gene. DR neXtProt; NX_P01563; -. DR PharmGKB; PA29662; -. DR eggNOG; ENOG410J735; Eukaryota. DR eggNOG; ENOG410ZH91; LUCA. DR HOGENOM; HOG000230500; -. DR HOVERGEN; HBG052086; -. DR InParanoid; P01563; -. DR KO; K05414; -. DR OrthoDB; EOG7M98HV; -. DR PhylomeDB; P01563; -. DR TreeFam; TF336177; -. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR Reactome; R-HSA-912694; Regulation of IFNA signaling. DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR EvolutionaryTrace; P01563; -. DR GeneWiki; IFNA2; -. DR GenomeRNAi; 3440; -. DR NextBio; 13556; -. DR PRO; PR:P01563; -. DR Proteomes; UP000005640; Chromosome 9. DR CleanEx; HS_IFNA2; -. DR Genevisible; P01563; 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; TAS:ProtInc. DR GO; GO:0002250; P:adaptive immune response; IBA:GO_Central. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. 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:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0051607; P:defense response to virus; IDA:BHF-UCL. DR GO; GO:0006959; P:humoral immune response; IBA:GO_Central. DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0002323; P:natural killer cell activation involved in immune response; IBA:GO_Central. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB. DR GO; GO:2000666; P:negative regulation of interleukin-13 secretion; IDA:UniProtKB. DR GO; GO:2000663; P:negative regulation of interleukin-5 secretion; IDA:UniProtKB. DR GO; GO:0045581; P:negative regulation of T cell differentiation; IDA:UniProtKB. DR GO; GO:2000552; P:negative regulation of T-helper 2 cell cytokine production; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IDA:BHF-UCL. DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; IBA:GO_Central. DR GO; GO:0042327; P:positive regulation of phosphorylation; IMP:AgBase. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:AgBase. DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IDA:BHF-UCL. DR GO; GO:0060338; P:regulation of type I interferon-mediated signaling pathway; TAS:Reactome. 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; TAS:Reactome. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR012351; 4_helix_cytokine_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 3D-structure; Antiviral defense; Complete proteome; Cytokine; KW Direct protein sequencing; Disulfide bond; Glycoprotein; KW Pharmaceutical; Polymorphism; Reference proteome; Secreted; Signal. FT SIGNAL 1 23 {ECO:0000269|PubMed:6159537, FT ECO:0000269|PubMed:9425112}. FT CHAIN 24 188 Interferon alpha-2. FT /FTId=PRO_0000016360. FT CARBOHYD 129 129 O-linked (GalNAc...). FT {ECO:0000269|PubMed:2049076}. FT /FTId=CAR_000049. FT DISULFID 24 121 {ECO:0000269|PubMed:6162107}. FT DISULFID 52 161 {ECO:0000269|PubMed:6162107}. FT VARIANT 6 6 A -> D (in dbSNP:rs35971916). FT /FTId=VAR_055972. FT VARIANT 46 46 K -> R (in alpha-2B and alpha-2C; FT dbSNP:rs1061959). FT {ECO:0000269|PubMed:23875128}. FT /FTId=VAR_004012. FT VARIANT 57 57 H -> R (in alpha-2C). FT /FTId=VAR_013001. FT VARIANT 177 177 S -> L (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036329. FT CONFLICT 85 85 Q -> L (in Ref. 6; AEX60803). FT {ECO:0000305}. FT CONFLICT 93 93 K -> M (in Ref. 6; AEX60802). FT {ECO:0000305}. FT HELIX 27 30 {ECO:0000244|PDB:4YPG}. FT HELIX 32 44 {ECO:0000244|PDB:3S9D}. FT HELIX 50 55 {ECO:0000244|PDB:3S9D}. FT HELIX 63 65 {ECO:0000244|PDB:3S9D}. FT STRAND 66 70 {ECO:0000244|PDB:4Z5R}. FT TURN 72 74 {ECO:0000244|PDB:4YPG}. FT HELIX 76 89 {ECO:0000244|PDB:3S9D}. FT HELIX 93 98 {ECO:0000244|PDB:3S9D}. FT HELIX 101 120 {ECO:0000244|PDB:3S9D}. FT STRAND 126 129 {ECO:0000244|PDB:2HYM}. FT TURN 132 135 {ECO:0000244|PDB:4YPG}. FT HELIX 138 155 {ECO:0000244|PDB:3S9D}. FT TURN 156 158 {ECO:0000244|PDB:3S9D}. FT HELIX 160 177 {ECO:0000244|PDB:3S9D}. FT STRAND 180 182 {ECO:0000244|PDB:4Z5R}. SQ SEQUENCE 188 AA; 21550 MW; 101DD21D394CBF97 CRC64; MALTFALLVA LLVLSCKSSC SVGCDLPQTH SLGSRRTLML LAQMRKISLF SCLKDRHDFG FPQEEFGNQF QKAETIPVLH EMIQQIFNLF STKDSSAAWD ETLLDKFYTE LYQQLNDLEA CVIQGVGVTE TPLMKEDSIL AVRKYFQRIT LYLKEKKYSP CAWEVVRAEI MRSFSLSTNL QESLRSKE //