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Identification
HMDB Protein ID HMDBP13795
Secondary Accession Numbers None
Name Interferon regulatory factor 7
Synonyms
  1. IRF-7
Gene Name IRF7
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:17574024, PubMed:32972995). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner (By similarity). Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages (By similarity) (PubMed:11073981, PubMed:12374802, PubMed:15361868, PubMed:17404045).
Pathways
  • Cytosolic DNA-sensing pathway
  • Epstein-Barr virus infection
  • Hepatitis B
  • Hepatitis C
  • Herpes simplex virus 1 infection
  • Influenza A
  • Kaposi sarcoma-associated herpesvirus infection
  • Lipid and atherosclerosis
  • Measles
  • NOD-like receptor signaling pathway
  • RIG-I-like receptor signaling pathway
  • Toll-like receptor signaling pathway
  • Viral carcinogenesis
Reactions Not Available
GO Classification
Biological Process
regulation of type I interferon production
response to DNA damage stimulus
interferon-gamma-mediated signaling pathway
response to virus
type I interferon-mediated signaling pathway
positive regulation of interferon-beta production
regulation of transcription from RNA polymerase II promoter
positive regulation of interferon-alpha production
defense response to virus
innate immune response
positive regulation of transcription, DNA-dependent
negative regulation of transcription from RNA polymerase II promoter
positive regulation of transcription from RNA polymerase II promoter
regulation of adaptive immune response
immunoglobulin mediated immune response
immune system process
TRIF-dependent toll-like receptor signaling pathway
establishment of viral latency
MDA-5 signaling pathway
negative regulation of macrophage apoptotic process
positive regulation of type I interferon-mediated signaling pathway
regulation of immune response
regulation of monocyte differentiation
regulation of MyD88-dependent toll-like receptor signaling pathway
regulation of MyD88-independent toll-like receptor signaling pathway
positive regulation of type I interferon production
Cellular Component
cytosol
cytoplasm
nucleus
nucleoplasm
chromatin
endosome membrane
Molecular Function
DNA-binding transcription factor activity, RNA polymerase II-specific
RNA polymerase II core promoter proximal region sequence-specific DNA binding
sequence-specific double-stranded DNA binding
DNA binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 503
Molecular Weight 54276.99
Theoretical pI 6.261
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q92985
UniProtKB/Swiss-Prot Entry Name IRF7_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [PubMed:14759258 ]
  3. Han KJ, Su X, Xu LG, Bin LH, Zhang J, Shu HB: Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways. J Biol Chem. 2004 Apr 9;279(15):15652-61. Epub 2004 Jan 22. [PubMed:14739303 ]
  4. Zhang L, Pagano JS: IRF-7, a new interferon regulatory factor associated with Epstein-Barr virus latency. Mol Cell Biol. 1997 Oct;17(10):5748-57. doi: 10.1128/MCB.17.10.5748. [PubMed:9315633 ]
  5. Au WC, Moore PA, LaFleur DW, Tombal B, Pitha PM: Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes. J Biol Chem. 1998 Oct 30;273(44):29210-7. doi: 10.1074/jbc.273.44.29210. [PubMed:9786932 ]
  6. Marie I, Smith E, Prakash A, Levy DE: Phosphorylation-induced dimerization of interferon regulatory factor 7 unmasks DNA binding and a bipartite transactivation domain. Mol Cell Biol. 2000 Dec;20(23):8803-14. doi: 10.1128/MCB.20.23.8803-8814.2000. [PubMed:11073981 ]
  7. Smith EJ, Marie I, Prakash A, Garcia-Sastre A, Levy DE: IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein. J Biol Chem. 2001 Mar 23;276(12):8951-7. doi: 10.1074/jbc.M008717200. Epub 2000 Dec 21. [PubMed:11124948 ]
  8. Lin R, Genin P, Mamane Y, Sgarbanti M, Battistini A, Harrington WJ Jr, Barber GN, Hiscott J: HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene. 2001 Feb 15;20(7):800-11. doi: 10.1038/sj.onc.1204163. [PubMed:11314014 ]
  9. Zhang L, Pagano JS: Structure and function of IRF-7. J Interferon Cytokine Res. 2002 Jan;22(1):95-101. doi: 10.1089/107999002753452700. [PubMed:11846980 ]
  10. Zhu FX, King SM, Smith EJ, Levy DE, Yuan Y: A Kaposi's sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7 phosphorylation and nuclear accumulation. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5573-8. doi: 10.1073/pnas.082420599. Epub 2002 Apr 9. [PubMed:11943871 ]
  11. Fitzgerald KA, Rowe DC, Barnes BJ, Caffrey DR, Visintin A, Latz E, Monks B, Pitha PM, Golenbock DT: LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J Exp Med. 2003 Oct 6;198(7):1043-55. doi: 10.1084/jem.20031023. Epub 2003 Sep 29. [PubMed:14517278 ]
  12. tenOever BR, Sharma S, Zou W, Sun Q, Grandvaux N, Julkunen I, Hemmi H, Yamamoto M, Akira S, Yeh WC, Lin R, Hiscott J: Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity. J Virol. 2004 Oct;78(19):10636-49. doi: 10.1128/JVI.78.19.10636-10649.2004. [PubMed:15367631 ]
  13. Honda K, Yanai H, Mizutani T, Negishi H, Shimada N, Suzuki N, Ohba Y, Takaoka A, Yeh WC, Taniguchi T: Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15416-21. doi: 10.1073/pnas.0406933101. Epub 2004 Oct 18. [PubMed:15492225 ]
  14. Kawai T, Sato S, Ishii KJ, Coban C, Hemmi H, Yamamoto M, Terai K, Matsuda M, Inoue J, Uematsu S, Takeuchi O, Akira S: Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol. 2004 Oct;5(10):1061-8. doi: 10.1038/ni1118. Epub 2004 Sep 7. [PubMed:15361868 ]
  15. Uematsu S, Sato S, Yamamoto M, Hirotani T, Kato H, Takeshita F, Matsuda M, Coban C, Ishii KJ, Kawai T, Takeuchi O, Akira S: Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction. J Exp Med. 2005 Mar 21;201(6):915-23. doi: 10.1084/jem.20042372. Epub 2005 Mar 14. [PubMed:15767370 ]
  16. Solis M, Goubau D, Romieu-Mourez R, Genin P, Civas A, Hiscott J: Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and control of anti-tumor activity in primary macrophages. Biochem Pharmacol. 2006 Nov 30;72(11):1469-76. doi: 10.1016/j.bcp.2006.06.002. Epub 2006 Jul 17. [PubMed:16846591 ]
  17. Honda K, Takaoka A, Taniguchi T: Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity. 2006 Sep;25(3):349-60. doi: 10.1016/j.immuni.2006.08.009. [PubMed:16979567 ]
  18. Sgarbanti M, Marsili G, Remoli AL, Orsatti R, Battistini A: IRF-7: new role in the regulation of genes involved in adaptive immunity. Ann N Y Acad Sci. 2007 Jan;1095:325-33. doi: 10.1196/annals.1397.036. [PubMed:17404045 ]
  19. Barro M, Patton JT: Rotavirus NSP1 inhibits expression of type I interferon by antagonizing the function of interferon regulatory factors IRF3, IRF5, and IRF7. J Virol. 2007 May;81(9):4473-81. doi: 10.1128/JVI.02498-06. Epub 2007 Feb 14. [PubMed:17301153 ]
  20. Wu L, Fossum E, Joo CH, Inn KS, Shin YC, Johannsen E, Hutt-Fletcher LM, Hass J, Jung JU: Epstein-Barr virus LF2: an antagonist to type I interferon. J Virol. 2009 Jan;83(2):1140-6. doi: 10.1128/JVI.00602-08. Epub 2008 Nov 5. [PubMed:18987133 ]
  21. Chang TH, Kubota T, Matsuoka M, Jones S, Bradfute SB, Bray M, Ozato K: Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery. PLoS Pathog. 2009 Jun;5(6):e1000493. doi: 10.1371/journal.ppat.1000493. Epub 2009 Jun 26. [PubMed:19557165 ]
  22. Savitsky D, Tamura T, Yanai H, Taniguchi T: Regulation of immunity and oncogenesis by the IRF transcription factor family. Cancer Immunol Immunother. 2010 Apr;59(4):489-510. doi: 10.1007/s00262-009-0804-6. Epub 2010 Jan 5. [PubMed:20049431 ]
  23. Ning S, Pagano JS, Barber GN: IRF7: activation, regulation, modification and function. Genes Immun. 2011 Sep;12(6):399-414. doi: 10.1038/gene.2011.21. Epub 2011 Apr 14. [PubMed:21490621 ]
  24. Liang Q, Deng H, Li X, Wu X, Tang Q, Chang TH, Peng H, Rauscher FJ 3rd, Ozato K, Zhu F: Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3 ligase and negative regulator of IFN regulatory factor 7. J Immunol. 2011 Nov 1;187(9):4754-63. doi: 10.4049/jimmunol.1101704. Epub 2011 Sep 21. [PubMed:21940674 ]
  25. Xiang Z, Liu L, Lei X, Zhou Z, He B, Wang J: 3C Protease of Enterovirus D68 Inhibits Cellular Defense Mediated by Interferon Regulatory Factor 7. J Virol. 2015 Nov 25;90(3):1613-21. doi: 10.1128/JVI.02395-15. Print 2016 Feb 1. [PubMed:26608321 ]
  26. Narulla MS, Alsairi A, Charmier L, Noonan S, Conroy D, Hall WW, Sheehy N: Positive and Negative Regulation of Type I Interferons by the Human T Cell Leukemia Virus Antisense Protein HBZ. J Virol. 2017 Sep 27;91(20). pii: JVI.00853-17. doi: 10.1128/JVI.00853-17. Print 2017 Oct 15. [PubMed:28768861 ]
  27. Lei X, Xiao X, Xue Q, Jin Q, He B, Wang J: Cleavage of interferon regulatory factor 7 by enterovirus 71 3C suppresses cellular responses. J Virol. 2013 Feb;87(3):1690-8. doi: 10.1128/JVI.01855-12. Epub 2012 Nov 21. [PubMed:23175366 ]
  28. Panne D, Maniatis T, Harrison SC: An atomic model of the interferon-beta enhanceosome. Cell. 2007 Jun 15;129(6):1111-23. doi: 10.1016/j.cell.2007.05.019. [PubMed:17574024 ]
  29. Ciancanelli MJ, Huang SX, Luthra P, Garner H, Itan Y, Volpi S, Lafaille FG, Trouillet C, Schmolke M, Albrecht RA, Israelsson E, Lim HK, Casadio M, Hermesh T, Lorenzo L, Leung LW, Pedergnana V, Boisson B, Okada S, Picard C, Ringuier B, Troussier F, Chaussabel D, Abel L, Pellier I, Notarangelo LD, Garcia-Sastre A, Basler CF, Geissmann F, Zhang SY, Snoeck HW, Casanova JL: Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science. 2015 Apr 24;348(6233):448-53. doi: 10.1126/science.aaa1578. Epub 2015 Mar 26. [PubMed:25814066 ]
  30. Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schluter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D'Angio' M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Colkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela SN, Rodriguez-Gallego C, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouenan C, Snow AL, Dalgard CL, Milner JD, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli MJ, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, Garcia-Sastre A, Krammer F, Pujol A, Duffy D, Lifton RP, Zhang SY, Gorochov G, Beziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, Casanova JL: Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020 Oct 23;370(6515). pii: science.abd4570. doi: 10.1126/science.abd4570. Epub 2020 Sep 24. [PubMed:32972995 ]