ID IRF7_HUMAN Reviewed; 503 AA. AC Q92985; B9EGL3; O00331; O00332; O00333; O75924; Q9UE79; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 02-OCT-2024, entry version 217. DE RecName: Full=Interferon regulatory factor 7; DE Short=IRF-7; GN Name=IRF7; 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] (ISOFORM A), AND VARIANT GLU-179. RC TISSUE=Spleen; RA Grossman A., Nicholl J., Antonio L., Luethy R., Suggs S., Sutherland G.R., RA Mak T.W.; RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C). RX PubMed=9315633; DOI=10.1128/mcb.17.10.5748; RA Zhang L., Pagano J.S.; RT "IRF-7, a new interferon regulatory factor associated with Epstein-Barr RT virus latency."; RL Mol. Cell. Biol. 17:5748-5757(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D), AND VARIANTS GLU-179 AND ARG-412. RX PubMed=9786932; DOI=10.1074/jbc.273.44.29210; RA Au W.-C., Moore P.A., LaFleur D.W., Tombal B., Pitha P.M.; RT "Characterization of the interferon regulatory factor-7 and its potential RT role in the transcription activation of interferon A genes."; RL J. Biol. Chem. 273:29210-29217(1998). RN [4] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D). 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 FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=11073981; DOI=10.1128/mcb.20.23.8803-8814.2000; RA Marie I.J., Smith E., Prakash A., Levy D.E.; RT "Phosphorylation-induced dimerization of interferon regulatory factor 7 RT unmasks DNA binding and a bipartite transactivation domain."; RL Mol. Cell. Biol. 20:8803-8814(2000). RN [7] RP INHIBITION OF PHOSPHORYLATION BY VACCINIA VIRUS PROTEIN E3. RX PubMed=11124948; DOI=10.1074/jbc.m008717200; RA Smith E.J., Marie I.J., Prakash A., Garcia-Sastre A., Levy D.E.; RT "IRF3 and IRF7 phosphorylation in virus-infected cells does not require RT double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is RT blocked by Vaccinia virus E3L protein."; RL J. Biol. Chem. 276:8951-8957(2001). RN [8] RP INTERACTION WITH HHV-8 PROTEIN VIRF1. RX PubMed=11314014; DOI=10.1038/sj.onc.1204163; RA Lin R., Genin P., Mamane Y., Sgarbanti M., Battistini A., RA Harrington W.J. Jr., Barber G.N., Hiscott J.; RT "HHV-8 encoded vIRF-1 represses the interferon antiviral response by RT blocking IRF-3 recruitment of the CBP/p300 coactivators."; RL Oncogene 20:800-811(2001). RN [9] RP FUNCTION, ACETYLATION AT LYS-92, MUTAGENESIS OF GLY-90; LYS-92 AND THR-93, RP AND PHOSPHORYLATION. RX PubMed=12374802; DOI=10.1074/jbc.m207484200; RA Caillaud A., Prakash A., Smith E., Masumi A., Hovanessian A.G., Levy D.E., RA Marie I.; RT "Acetylation of interferon regulatory factor-7 by p300/CREB-binding protein RT (CBP)-associated factor (PCAF) impairs its DNA binding."; RL J. Biol. Chem. 277:49417-49421(2002). RN [10] RP REVIEW ON FUNCTION. RX PubMed=11846980; DOI=10.1089/107999002753452700; RA Zhang L., Pagano J.S.; RT "Structure and function of IRF-7."; RL J. Interferon Cytokine Res. 22:95-101(2002). RN [11] RP INTERACTION WITH HHV-8 PROTEIN ORF45 (MICROBIAL INFECTION). RX PubMed=11943871; DOI=10.1073/pnas.082420599; RA Zhu F.X., King S.M., Smith E.J., Levy D.E., Yuan Y.; RT "A Kaposi's sarcoma-associated herpesviral protein inhibits virus-mediated RT induction of type I interferon by blocking IRF-7 phosphorylation and RT nuclear accumulation."; RL Proc. Natl. Acad. Sci. U.S.A. 99:5573-5578(2002). RN [12] RP INTERACTION WITH TICAM2. RX PubMed=14517278; DOI=10.1084/jem.20031023; RA Fitzgerald K.A., Rowe D.C., Barnes B.J., Caffrey D.R., Visintin A., RA Latz E., Monks B., Pitha P.M., Golenbock D.T.; RT "LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters RT TRAM and TRIF."; RL J. Exp. Med. 198:1043-1055(2003). RN [13] RP ERRATUM OF PUBMED:14517278. RA Fitzgerald K.A., Rowe D.C., Barnes B.J., Caffrey D.R., Visintin A., RA Latz E., Monks B., Pitha P.M., Golenbock D.T.; RL J. Exp. Med. 198:1451-1451(2003). RN [14] RP INTERACTION WITH TICAM1. RX PubMed=14739303; DOI=10.1074/jbc.m311629200; RA Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B.; RT "Mechanisms of the TRIF-induced interferon-stimulated response element and RT NF-kappaB activation and apoptosis pathways."; RL J. Biol. Chem. 279:15652-15661(2004). RN [15] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [16] RP PHOSPHORYLATION AT SER-477 AND SER-479 BY TBK1 AND IKKE, AND MUTAGENESIS OF RP 477-SER--SER-479. RX PubMed=15367631; DOI=10.1128/jvi.78.19.10636-10649.2004; RA tenOever B.R., Sharma S., Zou W., Sun Q., Grandvaux N., Julkunen I., RA Hemmi H., Yamamoto M., Akira S., Yeh W.C., Lin R., Hiscott J.; RT "Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus RT infection and the role of viral ribonucleoprotein in the development of RT interferon antiviral immunity."; RL J. Virol. 78:10636-10649(2004). RN [17] RP SUBCELLULAR LOCATION, AND INTERACTION WITH MYD88. RX PubMed=15492225; DOI=10.1073/pnas.0406933101; RA Honda K., Yanai H., Mizutani T., Negishi H., Shimada N., Suzuki N., RA Ohba Y., Takaoka A., Yeh W.C., Taniguchi T.; RT "Role of a transductional-transcriptional processor complex involving MyD88 RT and IRF-7 in Toll-like receptor signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15416-15421(2004). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MYD88 AND TRAF6. RX PubMed=15361868; DOI=10.1038/ni1118; RA Kawai T., Sato S., Ishii K.J., Coban C., Hemmi H., Yamamoto M., Terai K., RA Matsuda M., Inoue J., Uematsu S., Takeuchi O., Akira S.; RT "Interferon-alpha induction through Toll-like receptors involves a direct RT interaction of IRF7 with MyD88 and TRAF6."; RL Nat. Immunol. 5:1061-1068(2004). RN [19] RP PHOSPHORYLATION BY IRAK1. RX PubMed=15767370; DOI=10.1084/jem.20042372; RA Uematsu S., Sato S., Yamamoto M., Hirotani T., Kato H., Takeshita F., RA Matsuda M., Coban C., Ishii K.J., Kawai T., Takeuchi O., Akira S.; RT "Interleukin-1 receptor-associated kinase-1 plays an essential role for RT Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} RT induction."; RL J. Exp. Med. 201:915-923(2005). RN [20] RP REVIEW ON FUNCTION. RX PubMed=16846591; DOI=10.1016/j.bcp.2006.06.002; RA Solis M., Goubau D., Romieu-Mourez R., Genin P., Civas A., Hiscott J.; RT "Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and RT control of anti-tumor activity in primary macrophages."; RL Biochem. Pharmacol. 72:1469-1476(2006). RN [21] RP REVIEW ON FUNCTION. RX PubMed=16979567; DOI=10.1016/j.immuni.2006.08.009; RA Honda K., Takaoka A., Taniguchi T.; RT "Type I interferon gene induction by the interferon regulatory factor RT family of transcription factors."; RL Immunity 25:349-360(2006). RN [22] RP ERRATUM OF PUBMED:16979567. RA Honda K., Takaoka A., Taniguchi T.; RL Immunity 25:849-849(2006). RN [23] RP FUNCTION. RX PubMed=17404045; DOI=10.1196/annals.1397.036; RA Sgarbanti M., Marsili G., Remoli A.L., Orsatti R., Battistini A.; RT "IRF-7: new role in the regulation of genes involved in adaptive RT immunity."; RL Ann. N. Y. Acad. Sci. 1095:325-333(2007). RN [24] RP INTERACTION WITH ROTAVIRUS A NSP1 (MICROBIAL INFECTION). RX PubMed=17301153; DOI=10.1128/jvi.02498-06; RA Barro M., Patton J.T.; RT "Rotavirus NSP1 inhibits expression of type I interferon by antagonizing RT the function of interferon regulatory factors IRF3, IRF5, and IRF7."; RL J. Virol. 81:4473-4481(2007). RN [25] RP INTERACTION WITH EPSTEIN-BARR VIRUS/EBV LMP1 (MICROBIAL INFECTION). RX PubMed=19017798; DOI=10.1073/pnas.0809933105; RA Song Y.J., Izumi K.M., Shinners N.P., Gewurz B.E., Kieff E.; RT "IRF7 activation by Epstein-Barr virus latent membrane protein 1 requires RT localization at activation sites and TRAF6, but not TRAF2 or TRAF3."; RL Proc. Natl. Acad. Sci. U.S.A. 105:18448-18453(2008). RN [26] RP INTERACTION WITH EPSTEIN-BARR VIRUS/EBV LF2 (MICROBIAL INFECTION). RX PubMed=18987133; DOI=10.1128/jvi.00602-08; RA Wu L., Fossum E., Joo C.H., Inn K.S., Shin Y.C., Johannsen E., RA Hutt-Fletcher L.M., Hass J., Jung J.U.; RT "Epstein-Barr virus LF2: an antagonist to type I interferon."; RL J. Virol. 83:1140-1146(2009). RN [27] RP INTERACTION WITH EBOLAVIRUS VP35 (MICROBIAL INFECTION). RX PubMed=19557165; DOI=10.1371/journal.ppat.1000493; RA Chang T.H., Kubota T., Matsuoka M., Jones S., Bradfute S.B., Bray M., RA Ozato K.; RT "Ebola Zaire virus blocks type I interferon production by exploiting the RT host SUMO modification machinery."; RL PLoS Pathog. 5:e1000493-e1000493(2009). RN [28] RP REVIEW ON FUNCTION. RX PubMed=20049431; DOI=10.1007/s00262-009-0804-6; RA Savitsky D., Tamura T., Yanai H., Taniguchi T.; RT "Regulation of immunity and oncogenesis by the IRF transcription factor RT family."; RL Cancer Immunol. Immunother. 59:489-510(2010). RN [29] RP UBIQUITINATION. RX PubMed=21167755; DOI=10.1016/j.immuni.2010.11.027; RA Yu Y., Hayward G.S.; RT "The ubiquitin E3 ligase RAUL negatively regulates type i interferon RT through ubiquitination of the transcription factors IRF7 and IRF3."; RL Immunity 33:863-877(2010). RN [30] RP REVIEW ON FUNCTION. RX PubMed=21490621; DOI=10.1038/gene.2011.21; RA Ning S., Pagano J.S., Barber G.N.; RT "IRF7: activation, regulation, modification and function."; RL Genes Immun. 12:399-414(2011). RN [31] RP SUMOYLATION AT LYS-444 AND LYS-446 BY TRIM28. RX PubMed=21940674; DOI=10.4049/jimmunol.1101704; RA Liang Q., Deng H., Li X., Wu X., Tang Q., Chang T.H., Peng H., RA Rauscher F.J. III, Ozato K., Zhu F.; RT "Tripartite motif-containing protein 28 is a small ubiquitin-related RT modifier E3 ligase and negative regulator of IFN regulatory factor 7."; RL J. Immunol. 187:4754-4763(2011). RN [32] RP INTERACTION WITH TRIM35, AND UBIQUITINATION. RX PubMed=25907537; DOI=10.1016/j.febslet.2015.04.019; RA Wang Y., Yan S., Yang B., Wang Y., Zhou H., Lian Q., Sun B.; RT "TRIM35 negatively regulates TLR7- and TLR9-mediated type I interferon RT production by targeting IRF7."; RL FEBS Lett. 589:1322-1330(2015). RN [33] RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION), AND MUTAGENESIS OF GLN-167 AND RP GLN-189. RX PubMed=26608321; DOI=10.1128/jvi.02395-15; RA Xiang Z., Liu L., Lei X., Zhou Z., He B., Wang J.; RT "3C Protease of Enterovirus D68 Inhibits Cellular Defense Mediated by RT Interferon Regulatory Factor 7."; RL J. Virol. 90:1613-1621(2016). RN [34] RP INTERACTION WITH HUMAN T-CELL LEUKEMIA VIRUS 1/HTLV-1 PROTEIN HBZ RP (MICROBIAL INFECTION). RX PubMed=28768861; DOI=10.1128/jvi.00853-17; RA Narulla M.S., Alasiri A., Charmier L., Noonan S., Conroy D., Hall W.W., RA Sheehy N.; RT "Positive and Negative Regulation of Type I Interferons by the Human T Cell RT Leukemia Virus Antisense Protein HBZ."; RL J. Virol. 91:0-0(2017). RN [35] RP FUNCTION, INTERACTION WITH HUMAN METAPNEUMOVIRUS M2-2 (MICROBIAL RP INFECTION), AND PHOSPHORYLATION AT SER-477. RX PubMed=28768858; DOI=10.1128/jvi.00579-17; RA Kitagawa Y., Sakai M., Funayama M., Itoh M., Gotoh B.; RT "Human Metapneumovirus M2-2 Protein Acts as a Negative Regulator of Alpha RT Interferon Production by Plasmacytoid Dendritic Cells."; RL J. Virol. 91:0-0(2017). RN [36] RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION), AND MUTAGENESIS OF GLN-151; RP GLN-167; GLN-185; GLN-188; GLN-189 AND GLN-215. RX PubMed=23175366; DOI=10.1128/jvi.01855-12; RA Lei X., Xiao X., Xue Q., Jin Q., He B., Wang J.; RT "Cleavage of interferon regulatory factor 7 by enterovirus 71 3C suppresses RT cellular responses."; RL J. Virol. 87:1690-1698(2013). RN [37] RP FUNCTION, AND INTERACTION WITH HERPES VIRUS 8/HHV-8 PROTEIN VIRF-4 RP (MICROBIAL INFECTION). RX PubMed=28342865; DOI=10.1016/j.bbrc.2017.03.101; RA Hwang S.W., Kim D., Jung J.U., Lee H.R.; RT "KSHV-encoded viral interferon regulatory factor 4 (vIRF4) interacts with RT IRF7 and inhibits interferon alpha production."; RL Biochem. Biophys. Res. Commun. 486:700-705(2017). RN [38] RP INTERACTION WITH SENECA VALLEY VIRUS PROTEASE 3C (MICROBIAL INFECTION). RX PubMed=29427864; DOI=10.1016/j.virol.2018.01.028; RA Xue Q., Liu H., Zhu Z., Yang F., Ma L., Cai X., Xue Q., Zheng H.; RT "Seneca Valley Virus 3Cpro abrogates the IRF3- and IRF7-mediated innate RT immune response by degrading IRF3 and IRF7."; RL Virology 518:1-7(2018). RN [39] RP INTERACTION WITH SFTSV VIRUS NSS (MICROBIAL INFECTION). RX PubMed=30598516; DOI=10.4049/jimmunol.1800576; RA Hong Y., Bai M., Qi X., Li C., Liang M., Li D., Cardona C.J., Xing Z.; RT "Suppression of the IFN-alpha and -beta Induction through Sequestering IRF7 RT into Viral Inclusion Bodies by Nonstructural Protein NSs in Severe Fever RT with Thrombocytopenia Syndrome Bunyavirus Infection."; RL J. Immunol. 202:841-856(2019). RN [40] RP UBIQUITINATION BY NEURL3 AT LYS-375, AND MUTAGENESIS OF LYS-375. RX PubMed=35792897; DOI=10.1096/fj.202200316r; RA Qi F., Zhang X., Wang L., Ren C., Zhao X., Luo J., Lu D.; RT "E3 ubiquitin ligase NEURL3 promotes innate antiviral response through RT catalyzing K63-linked ubiquitination of IRF7."; RL FASEB J. 36:e22409-e22409(2022). RN [41] {ECO:0007744|PDB:2O61} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 8-125 IN COMPLEX WITH IRF3 AND RP DNA, SUBUNIT, AND FUNCTION. RX PubMed=17574024; DOI=10.1016/j.cell.2007.05.019; RA Panne D., Maniatis T., Harrison S.C.; RT "An atomic model of the interferon-beta enhanceosome."; RL Cell 129:1111-1123(2007). RN [42] RP INVOLVEMENT IN IMD39, VARIANT IMD39 VAL-410, AND CHARACTERIZATION OF RP VARIANT IMD39 VAL-410. RX PubMed=25814066; DOI=10.1126/science.aaa1578; RA Ciancanelli M.J., Huang S.X., Luthra P., Garner H., Itan Y., Volpi S., RA Lafaille F.G., Trouillet C., Schmolke M., Albrecht R.A., Israelsson E., RA Lim H.K., Casadio M., Hermesh T., Lorenzo L., Leung L.W., Pedergnana V., RA Boisson B., Okada S., Picard C., Ringuier B., Troussier F., Chaussabel D., RA Abel L., Pellier I., Notarangelo L.D., Garcia-Sastre A., Basler C.F., RA Geissmann F., Zhang S.Y., Snoeck H.W., Casanova J.L.; RT "Infectious disease. Life-threatening influenza and impaired interferon RT amplification in human IRF7 deficiency."; RL Science 348:448-453(2015). RN [43] RP VARIANTS HIS-37; SER-95; ASN-117; ARG-133; 185-GLN--ALA-503 DEL; LEU-214; RP ALA-254; GLN-369; VAL-371; VAL-410; THR-419 AND 421-GLN--ALA-503 DEL, RP CHARACTERIZATION OF VARIANTS HIS-37; SER-95; ASN-117; ARG-133; RP 185-GLN--ALA-503 DEL; LEU-214; ALA-254; GLN-369; VAL-371; VAL-410; THR-419 RP AND 421-GLN--ALA-503 DEL, AND FUNCTION. RX PubMed=32972995; DOI=10.1126/science.abd4570; RG COVID-STORM Clinicians; RG COVID Clinicians; RG Imagine COVID Group; RG French COVID Cohort Study Group; RG CoV-Contact Cohort; RG Amsterdam UMC Covid-19 Biobank; RG COVID Human Genetic Effort; RG NIAID-USUHS/TAGC COVID Immunity Group; RA Zhang Q., Bastard P., Liu Z., Le Pen J., Moncada-Velez M., Chen J., RA Ogishi M., Sabli I.K.D., Hodeib S., Korol C., Rosain J., Bilguvar K., RA Ye J., Bolze A., Bigio B., Yang R., Arias A.A., Zhou Q., Zhang Y., RA Onodi F., Korniotis S., Karpf L., Philippot Q., Chbihi M., Bonnet-Madin L., RA Dorgham K., Smith N., Schneider W.M., Razooky B.S., Hoffmann H.H., RA Michailidis E., Moens L., Han J.E., Lorenzo L., Bizien L., Meade P., RA Neehus A.L., Ugurbil A.C., Corneau A., Kerner G., Zhang P., Rapaport F., RA Seeleuthner Y., Manry J., Masson C., Schmitt Y., Schlueter A., Le Voyer T., RA Khan T., Li J., Fellay J., Roussel L., Shahrooei M., Alosaimi M.F., RA Mansouri D., Al-Saud H., Al-Mulla F., Almourfi F., Al-Muhsen S.Z., RA Alsohime F., Al Turki S., Hasanato R., van de Beek D., Biondi A., RA Bettini L.R., D'Angio' M., Bonfanti P., Imberti L., Sottini A., Paghera S., RA Quiros-Roldan E., Rossi C., Oler A.J., Tompkins M.F., Alba C., RA Vandernoot I., Goffard J.C., Smits G., Migeotte I., Haerynck F., RA Soler-Palacin P., Martin-Nalda A., Colobran R., Morange P.E., Keles S., RA Coelkesen F., Ozcelik T., Yasar K.K., Senoglu S., Karabela S.N., RA Rodriguez-Gallego C., Novelli G., Hraiech S., Tandjaoui-Lambiotte Y., RA Duval X., Laouenan C., Snow A.L., Dalgard C.L., Milner J.D., Vinh D.C., RA Mogensen T.H., Marr N., Spaan A.N., Boisson B., Boisson-Dupuis S., RA Bustamante J., Puel A., Ciancanelli M.J., Meyts I., Maniatis T., RA Soumelis V., Amara A., Nussenzweig M., Garcia-Sastre A., Krammer F., RA Pujol A., Duffy D., Lifton R.P., Zhang S.Y., Gorochov G., Beziat V., RA Jouanguy E., Sancho-Shimizu V., Rice C.M., Abel L., Notarangelo L.D., RA Cobat A., Su H.C., Casanova J.L.; RT "Inborn errors of type I IFN immunity in patients with life-threatening RT COVID-19."; RL Science 370:0-0(2020). CC -!- FUNCTION: Key transcriptional regulator of type I interferon (IFN)- CC dependent immune responses and plays a critical role in the innate CC immune response against DNA and RNA viruses (PubMed:28342865, CC PubMed:28768858). Regulates the transcription of type I IFN genes (IFN- CC alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an CC interferon-stimulated response element (ISRE) in their promoters CC (PubMed:17574024, PubMed:32972995). Can efficiently activate both the CC IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their CC induction via both the virus-activated, MyD88-independent pathway and CC the TLR-activated, MyD88-dependent pathway. Induces transcription of CC ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) CC or viral infection in a type I IFN-dependent manner (By similarity). CC Required during both the early and late phases of the IFN gene CC induction but is more critical for the late than for the early phase. CC Exists in an inactive form in the cytoplasm of uninfected cells and CC following viral infection, double-stranded RNA (dsRNA), or toll-like CC receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 CC kinases. This induces a conformational change, leading to its CC dimerization and nuclear localization where along with other CC coactivators it can activate transcription of the type I IFN and ISG CC genes. Can also play a role in regulating adaptive immune responses by CC inducing PSMB9/LMP2 expression, either directly or through induction of CC IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) CC and may play a role in the regulation of EBV latency. Can activate CC distinct gene expression programs in macrophages and regulate the anti- CC tumor properties of primary macrophages (By similarity) CC (PubMed:11073981, PubMed:12374802, PubMed:15361868, PubMed:17404045). CC {ECO:0000250|UniProtKB:P70434, ECO:0000269|PubMed:11073981, CC ECO:0000269|PubMed:12374802, ECO:0000269|PubMed:15361868, CC ECO:0000269|PubMed:17404045, ECO:0000269|PubMed:17574024, CC ECO:0000269|PubMed:28342865, ECO:0000269|PubMed:28768858, CC ECO:0000269|PubMed:32972995}. CC -!- ACTIVITY REGULATION: In the absence of viral infection, maintained as a CC monomer in an autoinhibited state and phosphorylation disrupts this CC autoinhibition leading to the liberation of the DNA-binding and CC dimerization activities and its nuclear localization where it can CC activate type I IFN and ISG genes. CC -!- SUBUNIT: Monomer. Homodimer; phosphorylation-induced. Heterodimer with CC IRF3 (PubMed:17574024). Interacts with TICAM1 and TICAM2. Interacts CC with MYD88 and TRAF6. Interacts with TRIM35 (PubMed:11073981, CC PubMed:11314014, PubMed:14517278, PubMed:14739303, PubMed:15361868, CC PubMed:15492225, PubMed:25907537). Interacts with NMI; the interaction CC is direct and leads to the inhibition of IRF7-mediated type I IFN CC production (By similarity). Interacts with GBP4; preventing interaction CC between TRAF6 and IRF7, resulting in impaired TRAF6-mediated IRF7 CC ubiquitination (By similarity). {ECO:0000250|UniProtKB:P70434, CC ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:11314014, CC ECO:0000269|PubMed:14517278, ECO:0000269|PubMed:14739303, CC ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:15492225, CC ECO:0000269|PubMed:17574024, ECO:0000269|PubMed:25907537}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus LF2 CC and LMP1. {ECO:0000269|PubMed:18987133, ECO:0000269|PubMed:19017798}. CC -!- SUBUNIT: (Microbial infection) Interacts with rotavirus A NSP1; this CC interaction leads to the proteasome-dependent degradation of IRF7. CC {ECO:0000269|PubMed:17301153}. CC -!- SUBUNIT: (Microbial infection) Interacts with human herpes virus 8/HHV- CC 8 proteins ORF45 and vIRF-1. {ECO:0000269|PubMed:11943871}. CC -!- SUBUNIT: (Microbial infection) Interacts with human T-cell leukemia CC virus 1/HTLV-1 protein HBZ. {ECO:0000269|PubMed:28768861}. CC -!- SUBUNIT: (Microbial infection) Interacts with Seneca Valley virus CC protease 3C; this interaction is involved in the suppression of IRF7 CC expression and phosphorylation by the virus. CC {ECO:0000269|PubMed:29427864}. CC -!- SUBUNIT: (Microbial infection) Interacts with ebolavirus VP35; this CC interaction mediates the sumoylation of IRF7 and contributes to the CC viral inhibition of IFN-type I production. CC {ECO:0000269|PubMed:19557165}. CC -!- SUBUNIT: (Microbial infection) Interacts with severe fever with CC thrombocytopenia syndrome virus (SFTSV) NSs; this interaction CC sequesters IRF7 in NSs-induced cytoplasmic inclusion bodies. CC {ECO:0000269|PubMed:30598516}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8/HHV-8 CC protein vIRF-4; this interaction prevents IRF7 dimerization and CC subsequent activation (PubMed:28342865). {ECO:0000269|PubMed:28342865}. CC -!- SUBUNIT: (Microbial infection) Interacts with human metapneumovirus CC protein M2-2; this interaction prevents IRF7 phosphorlyation and CC subsequent TLR7/9-dependent IFN-alpha induction. CC {ECO:0000269|PubMed:28768858}. CC -!- INTERACTION: CC Q92985; O00170: AIP; NbExp=2; IntAct=EBI-968267, EBI-704197; CC Q92985; P10398: ARAF; NbExp=2; IntAct=EBI-968267, EBI-365961; CC Q92985; Q96A33: CCDC47; NbExp=2; IntAct=EBI-968267, EBI-720151; CC Q92985; O15111: CHUK; NbExp=4; IntAct=EBI-968267, EBI-81249; CC Q92985; P51617: IRAK1; NbExp=2; IntAct=EBI-968267, EBI-358664; CC Q92985; O94822: LTN1; NbExp=2; IntAct=EBI-968267, EBI-1044684; CC Q92985; Q9ULE6: PALD1; NbExp=2; IntAct=EBI-968267, EBI-3957166; CC Q92985; Q9UHD2: TBK1; NbExp=2; IntAct=EBI-968267, EBI-356402; CC Q92985; Q86UE8: TLK2; NbExp=2; IntAct=EBI-968267, EBI-1047967; CC Q92985; Q9BVS5: TRMT61B; NbExp=3; IntAct=EBI-968267, EBI-3197877; CC Q92985; P29128: BICP0; Xeno; NbExp=5; IntAct=EBI-968267, EBI-11292028; CC Q92985; F5HDE4: ORF45; Xeno; NbExp=3; IntAct=EBI-968267, EBI-8843990; CC Q92985; Q77M19: P; Xeno; NbExp=3; IntAct=EBI-968267, EBI-6149376; CC Q92985-1; P03230: LMP1; Xeno; NbExp=5; IntAct=EBI-8850881, EBI-6973030; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=The phosphorylated and CC active form accumulates selectively in the nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=A; CC IsoId=Q92985-1; Sequence=Displayed; CC Name=B; Synonyms=Beta; CC IsoId=Q92985-2; Sequence=VSP_002760; CC Name=C; Synonyms=Gamma; CC IsoId=Q92985-3; Sequence=VSP_002758, VSP_002759; CC Name=D; Synonyms=H; CC IsoId=Q92985-4; Sequence=VSP_002757; CC -!- TISSUE SPECIFICITY: Expressed predominantly in spleen, thymus and CC peripheral blood leukocytes. CC -!- INDUCTION: By type I interferon (IFN) and viruses. CC -!- PTM: Acetylation inhibits its DNA-binding ability and activity. CC {ECO:0000269|PubMed:12374802}. CC -!- PTM: In response to a viral infection, phosphorylated on Ser-477 and CC Ser-479 by TBK1 and IKBKE1. Phosphorylation, and subsequent activation CC is inhibited by vaccinia virus protein E3. In TLR7- and TLR9-mediated CC signaling pathway, phosphorylated by IRAK1. CC {ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:12374802, CC ECO:0000269|PubMed:15367631, ECO:0000269|PubMed:15767370}. CC -!- PTM: TRAF6-mediated ubiquitination is required for IRF7 activation (By CC similarity). TRIM35 mediates IRF7 'Lys-48'-linked polyubiquitination CC and subsequent proteasomal degradation (PubMed:25907537). Ubiquitinated CC by UBE3C, leading to its degradation (PubMed:21167755). CC {ECO:0000250|UniProtKB:P70434, ECO:0000269|PubMed:21167755, CC ECO:0000269|PubMed:25907537}. CC -!- PTM: Sumoylated by TRIM28, which inhibits its transactivation activity. CC {ECO:0000269|PubMed:21940674}. CC -!- PTM: (Microbial infection) Cleaved and inactivated by the protease 3C CC of enterovirus 71 allowing the virus to disrupt the host type I CC interferon production. {ECO:0000269|PubMed:23175366}. CC -!- PTM: (Microbial infection) Cleaved and inactivated by the protease 3C CC of human enterovirus 68D (EV68) allowing the virus to disrupt the host CC type I interferon production. {ECO:0000269|PubMed:26608321}. CC -!- PTM: 'Lys-48'-linked polyubiquitination and subsequent proteasomal CC degradation is NMI-dependent in response to Sendai virus infection. CC {ECO:0000250|UniProtKB:P70434}. CC -!- PTM: 'Lys-63'-linked ubiquitination by NEURL3 promotes IRF7 activation. CC {ECO:0000269|PubMed:35792897}. CC -!- DISEASE: Immunodeficiency 39 (IMD39) [MIM:616345]: A primary CC immunodeficiency causing severe, life-threatening acute respiratory CC distress upon infection with H1N1 influenza A. CC {ECO:0000269|PubMed:25814066}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform C]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE- CC ProRule:PRU00840}. 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; U73036; AAB17190.1; -; mRNA. DR EMBL; U53830; AAB80686.1; -; mRNA. DR EMBL; U53831; AAB80688.1; -; mRNA. DR EMBL; U53832; AAB80690.1; -; mRNA. DR EMBL; U53832; AAB80691.1; -; mRNA. DR EMBL; AF076494; AAC70999.1; -; mRNA. DR EMBL; CH471158; EAX02360.1; -; Genomic_DNA. DR EMBL; BC136555; AAI36556.1; -; mRNA. DR CCDS; CCDS7703.1; -. [Q92985-1] DR CCDS; CCDS7704.1; -. [Q92985-2] DR CCDS; CCDS7705.1; -. [Q92985-4] DR RefSeq; NP_001563.2; NM_001572.3. [Q92985-1] DR RefSeq; NP_004020.1; NM_004029.2. [Q92985-2] DR RefSeq; NP_004022.2; NM_004031.2. [Q92985-4] DR RefSeq; XP_005252963.1; XM_005252906.3. DR RefSeq; XP_016873163.1; XM_017017674.1. DR PDB; 2O61; X-ray; 2.80 A; A=8-125. DR PDBsum; 2O61; -. DR AlphaFoldDB; Q92985; -. DR SMR; Q92985; -. DR BioGRID; 109873; 97. DR DIP; DIP-34895N; -. DR IntAct; Q92985; 58. DR MINT; Q92985; -. DR STRING; 9606.ENSP00000380697; -. DR GlyGen; Q92985; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q92985; -. DR PhosphoSitePlus; Q92985; -. DR BioMuta; IRF7; -. DR DMDM; 116242593; -. DR MassIVE; Q92985; -. DR PaxDb; 9606-ENSP00000380697; -. DR PeptideAtlas; Q92985; -. DR ProteomicsDB; 75643; -. [Q92985-1] DR ProteomicsDB; 75644; -. [Q92985-2] DR ProteomicsDB; 75645; -. [Q92985-3] DR ProteomicsDB; 75646; -. [Q92985-4] DR Pumba; Q92985; -. DR Antibodypedia; 4325; 716 antibodies from 40 providers. DR DNASU; 3665; -. DR Ensembl; ENST00000330243.9; ENSP00000329411.5; ENSG00000185507.21. [Q92985-4] DR Ensembl; ENST00000348655.11; ENSP00000331803.9; ENSG00000185507.21. [Q92985-2] DR Ensembl; ENST00000397566.5; ENSP00000380697.1; ENSG00000185507.21. [Q92985-4] DR Ensembl; ENST00000469048.6; ENSP00000434607.1; ENSG00000185507.21. [Q92985-3] DR Ensembl; ENST00000525445.6; ENSP00000434009.2; ENSG00000185507.21. [Q92985-1] DR Ensembl; ENST00000533182.5; ENSP00000433903.1; ENSG00000185507.21. [Q92985-3] DR Ensembl; ENST00000612534.4; ENSP00000479615.1; ENSG00000276561.4. [Q92985-4] DR Ensembl; ENST00000621391.4; ENSP00000480358.1; ENSG00000276561.4. [Q92985-1] DR Ensembl; ENST00000632827.1; ENSP00000488039.1; ENSG00000276561.4. [Q92985-4] DR Ensembl; ENST00000633274.1; ENSP00000488591.1; ENSG00000276561.4. [Q92985-3] DR Ensembl; ENST00000633943.1; ENSP00000488666.1; ENSG00000276561.4. [Q92985-2] DR Ensembl; ENST00000634105.1; ENSP00000488581.1; ENSG00000276561.4. [Q92985-3] DR GeneID; 3665; -. DR KEGG; hsa:3665; -. DR MANE-Select; ENST00000525445.6; ENSP00000434009.2; NM_001572.5; NP_001563.2. DR UCSC; uc001lqg.3; human. [Q92985-1] DR AGR; HGNC:6122; -. DR CTD; 3665; -. DR DisGeNET; 3665; -. DR GeneCards; IRF7; -. DR HGNC; HGNC:6122; IRF7. DR HPA; ENSG00000185507; Tissue enhanced (liver, lymphoid tissue). DR MalaCards; IRF7; -. DR MIM; 605047; gene. DR MIM; 616345; phenotype. DR neXtProt; NX_Q92985; -. DR OpenTargets; ENSG00000185507; -. DR Orphanet; 574918; Predisposition to severe viral infection due to IRF7 deficiency. DR PharmGKB; PA29921; -. DR VEuPathDB; HostDB:ENSG00000185507; -. DR eggNOG; ENOG502R2I9; Eukaryota. DR GeneTree; ENSGT00940000160931; -. DR HOGENOM; CLU_031544_2_0_1; -. DR InParanoid; Q92985; -. DR OMA; HEIAQME; -. DR OrthoDB; 3740806at2759; -. DR PhylomeDB; Q92985; -. DR TreeFam; TF328512; -. DR PathwayCommons; Q92985; -. DR Reactome; R-HSA-3134963; DEx/H-box helicases activate type I IFN and inflammatory cytokines production. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-9013973; TICAM1-dependent activation of IRF3/IRF7. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway. DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation. DR Reactome; R-HSA-936964; Activation of IRF3, IRF7 mediated by TBK1, IKKEpsilon (IKBKE). DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-975110; TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling. DR SignaLink; Q92985; -. DR SIGNOR; Q92985; -. DR BioGRID-ORCS; 3665; 17 hits in 1182 CRISPR screens. DR ChiTaRS; IRF7; human. DR GeneWiki; IRF7; -. DR GenomeRNAi; 3665; -. DR Pharos; Q92985; Tbio. DR PRO; PR:Q92985; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q92985; protein. DR Bgee; ENSG00000185507; Expressed in granulocyte and 94 other cell types or tissues. DR ExpressionAtlas; Q92985; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:UniProt. DR GO; GO:0005737; C:cytoplasm; IDA:AgBase. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:CACAO. DR GO; GO:0003677; F:DNA binding; IMP:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IDA:UniProt. DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; TAS:UniProtKB. DR GO; GO:0019043; P:establishment of viral latency; TAS:UniProtKB. DR GO; GO:0002376; P:immune system process; IBA:GO_Central. DR GO; GO:0016064; P:immunoglobulin mediated immune response; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; TAS:UniProtKB. DR GO; GO:0039530; P:MDA-5 signaling pathway; TAS:UniProtKB. DR GO; GO:2000110; P:negative regulation of macrophage apoptotic process; TAS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:ProtInc. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:BHF-UCL. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:CACAO. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0032481; P:positive regulation of type I interferon production; IDA:UniProt. DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0002819; P:regulation of adaptive immune response; IDA:UniProtKB. DR GO; GO:0050776; P:regulation of immune response; TAS:UniProtKB. DR GO; GO:0045655; P:regulation of monocyte differentiation; TAS:UniProtKB. DR GO; GO:0034124; P:regulation of MyD88-dependent toll-like receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0034127; P:regulation of MyD88-independent toll-like receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0032479; P:regulation of type I interferon production; TAS:UniProtKB. DR GO; GO:0009615; P:response to virus; TAS:UniProtKB. DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IEA:Ensembl. DR CDD; cd00103; IRF; 1. DR Gene3D; 2.60.200.10; -; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR IDEAL; IID00491; -. DR InterPro; IPR019817; Interferon_reg_fac_CS. DR InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom. DR InterPro; IPR019471; Interferon_reg_factor-3. DR InterPro; IPR017855; SMAD-like_dom_sf. DR InterPro; IPR008984; SMAD_FHA_dom_sf. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR11949; INTERFERON REGULATORY FACTOR; 1. DR PANTHER; PTHR11949:SF2; INTERFERON REGULATORY FACTOR 7; 1. DR Pfam; PF00605; IRF; 1. DR Pfam; PF10401; IRF-3; 1. DR PRINTS; PR00267; INTFRNREGFCT. DR SMART; SM00348; IRF; 1. DR SMART; SM01243; IRF-3; 1. DR SUPFAM; SSF49879; SMAD/FHA domain; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS00601; IRF_1; 1. DR PROSITE; PS51507; IRF_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Antiviral defense; Cytoplasm; Disease variant; DNA-binding; KW Host-virus interaction; Immunity; Innate immunity; Isopeptide bond; KW Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; KW Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1..503 FT /note="Interferon regulatory factor 7" FT /id="PRO_0000154562" FT DNA_BIND 11..126 FT /note="IRF tryptophan pentad repeat" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840" FT REGION 69..88 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 133..156 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 242..277 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 284..456 FT /note="Necessary for the interaction with NMI" FT /evidence="ECO:0000250|UniProtKB:P70434" FT SITE 167..168 FT /note="(Microbial infection) Cleavage; by viral EV68 FT protease 3C" FT /evidence="ECO:0000269|PubMed:26608321" FT SITE 189..190 FT /note="(Microbial infection) Cleavage; by viral EV 71 FT protease 3C and EV68 protease 3C" FT /evidence="ECO:0000269|PubMed:23175366, FT ECO:0000269|PubMed:26608321" FT MOD_RES 92 FT /note="N6-acetyllysine; by KAT2A and KAT2B" FT /evidence="ECO:0000269|PubMed:12374802" FT MOD_RES 471 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70434" FT MOD_RES 472 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70434" FT MOD_RES 475 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70434" FT MOD_RES 477 FT /note="Phosphoserine; by TBK1 and IKKE" FT /evidence="ECO:0000269|PubMed:15367631, FT ECO:0000269|PubMed:28768858" FT MOD_RES 479 FT /note="Phosphoserine; by TBK1 and IKKE" FT /evidence="ECO:0000269|PubMed:15367631" FT MOD_RES 483 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70434" FT MOD_RES 484 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70434" FT MOD_RES 487 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70434" FT CROSSLNK 375 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT CROSSLNK 444 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT CROSSLNK 446 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT VAR_SEQ 1..6 FT /note="MALAPE -> MPVPERPAAGPDSPRPGTR (in isoform D)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9786932" FT /id="VSP_002757" FT VAR_SEQ 152..164 FT /note="GGPPGPFLAHTHA -> AQGSLLGSCTGGQ (in isoform C)" FT /evidence="ECO:0000303|PubMed:9315633" FT /id="VSP_002758" FT VAR_SEQ 165..503 FT /note="Missing (in isoform C)" FT /evidence="ECO:0000303|PubMed:9315633" FT /id="VSP_002759" FT VAR_SEQ 228..256 FT /note="Missing (in isoform B)" FT /evidence="ECO:0000303|PubMed:9315633" FT /id="VSP_002760" FT VARIANT 37 FT /note="R -> H (no effect on IFNB induction upon Sendai FT virus infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084074" FT VARIANT 95 FT /note="F -> S (abolished IFNB induction upon Sendai virus FT infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084075" FT VARIANT 117 FT /note="D -> N (abolished IFNB induction upon Sendai virus FT infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084076" FT VARIANT 133 FT /note="G -> R (no effect on IFNB induction upon Sendai FT virus infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084077" FT VARIANT 179 FT /note="K -> E (in dbSNP:rs1061502)" FT /evidence="ECO:0000269|PubMed:9786932, ECO:0000269|Ref.1" FT /id="VAR_027957" FT VARIANT 185..503 FT /note="Missing (abolishes IFNB induction upon Sendai virus FT infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084078" FT VARIANT 204 FT /note="D -> N (in dbSNP:rs41313489)" FT /id="VAR_061273" FT VARIANT 214 FT /note="G -> L (no effect on IFNB induction upon Sendai FT virus infection; requires 2 nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084079" FT VARIANT 254 FT /note="T -> A (no effect IFNB induction upon Sendai virus FT infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084080" FT VARIANT 369 FT /note="R -> Q (no effect on IFNB induction upon Sendai FT virus infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084081" FT VARIANT 371 FT /note="M -> V (decreased IFNB induction upon Sendai virus FT infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084082" FT VARIANT 410 FT /note="F -> V (in IMD39; loss of function mutation; shows FT abnormal localization to the cytoplasm rather than the FT nucleus; abolished IFNB induction upon Sendai virus FT infection; dbSNP:rs786205223)" FT /evidence="ECO:0000269|PubMed:25814066, FT ECO:0000269|PubMed:32972995" FT /id="VAR_073779" FT VARIANT 412 FT /note="Q -> R (in dbSNP:rs1131665)" FT /evidence="ECO:0000269|PubMed:9786932" FT /id="VAR_034017" FT VARIANT 419 FT /note="A -> T (no effect on IFNB induction upon Sendai FT virus infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084083" FT VARIANT 421..503 FT /note="Missing (abolished IFNB induction upon Sendai virus FT infection)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084084" FT MUTAGEN 90 FT /note="G->T: Loss of acetylation, increased DNA-binding and FT activity; when associated with R-93." FT /evidence="ECO:0000269|PubMed:12374802" FT MUTAGEN 92 FT /note="K->R: Loss of acetylation, DNA-binding and FT activity." FT /evidence="ECO:0000269|PubMed:12374802" FT MUTAGEN 93 FT /note="T->R: Loss of acetylation, increased DNA-binding and FT activity; when associated with T-90." FT /evidence="ECO:0000269|PubMed:12374802" FT MUTAGEN 151 FT /note="Q->A: No effect on cleavage by enterovirus 71." FT /evidence="ECO:0000269|PubMed:23175366" FT MUTAGEN 167 FT /note="Q->A: Complete loss of inactivation of IFN-I FT production; when associated with R-189." FT /evidence="ECO:0000269|PubMed:26608321" FT MUTAGEN 167 FT /note="Q->A: No effect on cleavage by enterovirus 71." FT /evidence="ECO:0000269|PubMed:23175366" FT MUTAGEN 185 FT /note="Q->A: No effect on cleavage by enterovirus 71." FT /evidence="ECO:0000269|PubMed:23175366" FT MUTAGEN 188 FT /note="Q->A: No effect on cleavage by enterovirus 71." FT /evidence="ECO:0000269|PubMed:23175366" FT MUTAGEN 189 FT /note="Q->A: Complete loss of cleavage by enterovirus 71." FT /evidence="ECO:0000269|PubMed:23175366" FT MUTAGEN 189 FT /note="Q->R: Complete loss of inactivation of IFN-I FT production; when associated with A-167." FT /evidence="ECO:0000269|PubMed:26608321" FT MUTAGEN 215 FT /note="Q->A: No effect on cleavage by enterovirus 71." FT /evidence="ECO:0000269|PubMed:23175366" FT MUTAGEN 375 FT /note="K->R: Loss of NEURL3-mediated ubiquitination." FT /evidence="ECO:0000269|PubMed:35792897" FT MUTAGEN 477..479 FT /note="SLS->ALA: Complete loss of TBK1 and IKKE FT phosphorylation." FT /evidence="ECO:0000269|PubMed:15367631" FT HELIX 14..24 FT /evidence="ECO:0007829|PDB:2O61" FT STRAND 31..36 FT /evidence="ECO:0007829|PDB:2O61" FT STRAND 39..43 FT /evidence="ECO:0007829|PDB:2O61" FT HELIX 55..57 FT /evidence="ECO:0007829|PDB:2O61" FT HELIX 58..66 FT /evidence="ECO:0007829|PDB:2O61" FT HELIX 84..102 FT /evidence="ECO:0007829|PDB:2O61" FT STRAND 105..112 FT /evidence="ECO:0007829|PDB:2O61" FT STRAND 119..125 FT /evidence="ECO:0007829|PDB:2O61" SQ SEQUENCE 503 AA; 54278 MW; 9863C147514652DE CRC64; MALAPERAAP RVLFGEWLLG EISSGCYEGL QWLDEARTCF RVPWKHFARK DLSEADARIF KAWAVARGRW PPSSRGGGPP PEAETAERAG WKTNFRCALR STRRFVMLRD NSGDPADPHK VYALSRELCW REGPGTDQTE AEAPAAVPPP QGGPPGPFLA HTHAGLQAPG PLPAPAGDKG DLLLQAVQQS CLADHLLTAS WGADPVPTKA PGEGQEGLPL TGACAGGPGL PAGELYGWAV ETTPSPGPQP AALTTGEAAA PESPHQAEPY LSPSPSACTA VQEPSPGALD VTIMYKGRTV LQKVVGHPSC TFLYGPPDPA VRATDPQQVA FPSPAELPDQ KQLRYTEELL RHVAPGLHLE LRGPQLWARR MGKCKVYWEV GGPPGSASPS TPACLLPRNC DTPIFDFRVF FQELVEFRAR QRRGSPRYTI YLGFGQDLSA GRPKEKSLVL VKLEPWLCRV HLEGTQREGV SSLDSSSLSL CLSSANSLYD DIECFLMELE QPA //