IRF3

Interferon regulatory factor 3
	; PDB rendering based on 1j2f.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1J2F, 1QWT, 1T2K, 1ZOQ, 2O61, 2O6G, 2PI0, 3A77
Identifiers
Symbols	IRF3;
External IDs	OMIM: 603734 MGI: 1859179 HomoloGene: 1208 GeneCards: IRF3 Gene
Gene Ontology
Molecular function	• regulatory region DNA binding; • DNA binding; • sequence-specific DNA binding transcription factor activity; • transcription cofactor activity; • protein binding; • identical protein binding; • protein homodimerization activity; • transcription regulatory region DNA binding;
Cellular component	• nucleus; • nucleoplasm; • cytoplasm; • cytosol; • plasma membrane; • endosome membrane;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • MyD88-independent toll-like receptor signaling pathway; • transcription from RNA polymerase II promoter; • Toll signaling pathway; • response to virus; • response to bacterium; • cytokine-mediated signaling pathway; • lipopolysaccharide-mediated signaling pathway; • negative regulation of type I interferon production; • response to lipopolysaccharide; • toll-like receptor 3 signaling pathway; • toll-like receptor 4 signaling pathway; • TRIF-dependent toll-like receptor signaling pathway; • positive regulation of I-kappaB kinase/NF-kappaB cascade; • response to exogenous dsRNA; • interspecies interaction between organisms; • innate immune response; • type I interferon biosynthetic process; • negative regulation of interferon-beta biosynthetic process; • negative regulation of defense response to virus by host; • positive regulation of cytokine secretion; • interferon-gamma-mediated signaling pathway; • type I interferon-mediated signaling pathway; • cellular response to dsRNA;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.^[1]

[edit] Function

IRF3 is a member of the interferon regulatory transcription factor (IRF) family.^[1] IRF3 was originally discovered as a homolog of IRF1 and IRF2. RF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a DNA-binding domain, a C-terminal IRF association domain and several regulatory phosphorylation sites. ^[2] IRF3 is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP.^[3] This complex translocates to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes.^[4]

IRF3 plays an important role in the innate immune system's response to viral infection. ^[5] Aggregated MAVS have been found to activate IRF3 dimerization. ^[6]

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations

[edit] Interactions

IRF3 has been shown to interact with IRF7.^[7]

[edit] References

^ ^a ^b Hiscott J, Pitha P, Genin P, Nguyen H, Heylbroeck C, Mamane Y, Algarte M, Lin R (1999). "Triggering the interferon response: the role of IRF-3 transcription factor". J. Interferon Cytokine Res. 19 (1): 1–13. doi:10.1089/107999099314360. PMID 10048763.
^ Lin, R.; Heylbroeck, C.; Genin, P.; Pitha, PM.; Hiscott, J. (Feb 1999). "Essential Role of Interferon Regulatory Factor 3 in Direct Activation of RANTES Chemokine Transcription". Mol Cell Biol 19 (2): 959–66. PMC 116027. PMID 9891032. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=116027.
^ Yoneyama M, Suhara W, Fujita T (2002). "Control of IRF-3 activation by phosphorylation". J. Interferon Cytokine Res. 22 (1): 73–6. doi:10.1089/107999002753452674. PMID 11846977.
^ "Entrez Gene: IRF3 interferon regulatory factor 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3661.
^ Collins, SE.; Noyce, RS.; Mossman, KL. (Feb 2004). "Innate Cellular Response to Virus Particle Entry Requires IRF3 but Not Virus Replication". J Virol 78 (4): 1706–17. doi:10.1128/JVI.78.4.1706-1717.2004. PMC 369475. PMID 14747536. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=369475.
^ Hou, F; Sun, L, Zheng, H, Skaug, B, Jiang, QX, Chen, ZJ (2011 Aug 5). "MAVS Forms Functional Prion-Like Aggregates To Activate and Propagate Antiviral Innate Immune Response". Cell 146 (3): 448–61. doi:10.1016/j.cell.2011.06.041. PMC 3179916. PMID 21782231. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3179916.
^ Au, W C; Yeow W S, Pitha P M (Feb. 2001). "Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3". Virology (United States) 280 (2): 273–82. doi:10.1006/viro.2000.0782. ISSN 0042-6822. PMID 11162841.

[edit] Further reading

Pitha PM, Au WC, Lowther W, et al. (1999). "Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth". Biochimie 80 (8–9): 651–8. doi:10.1016/S0300-9084(99)80018-2. PMID 9865487.
Yoneyama M, Suhara W, Fujita T (2002). "Control of IRF-3 activation by phosphorylation". J. Interferon Cytokine Res. 22 (1): 73–6. doi:10.1089/107999002753452674. PMID 11846977.
Au WC, Moore PA, Lowther W, et al. (1996). "Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes". Proc. Natl. Acad. Sci. U.S.A. 92 (25): 11657–61. doi:10.1073/pnas.92.25.11657. PMC 40461. PMID 8524823. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=40461.
Yoneyama M, Suhara W, Fukuhara Y, et al. (1998). "Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300". EMBO J. 17 (4): 1087–95. doi:10.1093/emboj/17.4.1087. PMC 1170457. PMID 9463386. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170457.
Weaver BK, Kumar KP, Reich NC (1998). "Interferon Regulatory Factor 3 and CREB-Binding Protein/p300 Are Subunits of Double-Stranded RNA-Activated Transcription Factor DRAF1". Mol. Cell. Biol. 18 (3): 1359–68. PMC 108849. PMID 9488451. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=108849.
Lin R, Heylbroeck C, Pitha PM, Hiscott J (1998). "Virus-Dependent Phosphorylation of the IRF-3 Transcription Factor Regulates Nuclear Translocation, Transactivation Potential, and Proteasome-Mediated Degradation". Mol. Cell. Biol. 18 (5): 2986–96. PMC 110678. PMID 9566918. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=110678.
Ronco LV, Karpova AY, Vidal M, Howley PM (1998). "Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity". Genes Dev. 12 (13): 2061–72. doi:10.1101/gad.12.13.2061. PMC 316980. PMID 9649509. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316980.
Bellingham J, Gregory-Evans K, Gregory-Evans CY (1999). "Mapping of human interferon regulatory factor 3 (IRF3) to chromosome 19q13.3-13.4 by an intragenic polymorphic marker". Ann. Hum. Genet. 62 (Pt 3): 231–4. doi:10.1046/j.1469-1809.1998.6230231.x. PMID 9803267.
Lowther WJ, Moore PA, Carter KC, Pitha PM (1999). "Cloning and functional analysis of the human IRF-3 promoter". DNA Cell Biol. 18 (9): 685–92. doi:10.1089/104454999314962. PMID 10492399.
Kim T, Kim TY, Song YH, et al. (1999). "Activation of interferon regulatory factor 3 in response to DNA-damaging agents". J. Biol. Chem. 274 (43): 30686–9. doi:10.1074/jbc.274.43.30686. PMID 10521456.
Kumar KP, McBride KM, Weaver BK, et al. (2000). "Regulated Nuclear-Cytoplasmic Localization of Interferon Regulatory Factor 3, a Subunit of Double-Stranded RNA-Activated Factor 1". Mol. Cell. Biol. 20 (11): 4159–68. doi:10.1128/MCB.20.11.4159-4168.2000. PMC 85785. PMID 10805757. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85785.
Suhara W, Yoneyama M, Iwamura T, et al. (2000). "Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300". J. Biochem. 128 (2): 301–7. PMID 10920266.
Servant MJ, ten Oever B, LePage C, et al. (2001). "Identification of distinct signaling pathways leading to the phosphorylation of interferon regulatory factor 3". J. Biol. Chem. 276 (1): 355–63. doi:10.1074/jbc.M007790200. PMID 11035028.
Smith EJ, Marié I, Prakash A, et al. (2001). "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. 276 (12): 8951–7. doi:10.1074/jbc.M008717200. PMID 11124948.
Au WC, Yeow WS, Pitha PM (2001). "Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3". Virology 280 (2): 273–82. doi:10.1006/viro.2000.0782. PMID 11162841.
Barnes BJ, Moore PA, Pitha PM (2001). "Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes". J. Biol. Chem. 276 (26): 23382–90. doi:10.1074/jbc.M101216200. PMID 11303025.
Mach CM, Hargrove BW, Kunkel GR (2002). "The Small RNA gene activator protein, SphI postoctamer homology-binding factor/selenocysteine tRNA gene transcription activating factor, stimulates transcription of the human interferon regulatory factor-3 gene". J. Biol. Chem. 277 (7): 4853–8. doi:10.1074/jbc.M108308200. PMID 11724783.
Morin P, Bragança J, Bandu MT, et al. (2002). "Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription". J. Mol. Biol. 316 (5): 1009–22. doi:10.1006/jmbi.2001.5401. PMID 11884139.
Dang O, Navarro L, Anderson K, David, M (2004). "Cutting edge: anthrax lethal toxin inhibits activation of IFN-regulatory factor 3 by lipopolysaccharide". J. Immunology 172 (2): 747–51. PMID 14707042.

[edit] External links

This biochemistry article is a stub. You can help Wikipedia by expanding it.

[pmid10048763-0] Hiscott J, Pitha P, Genin P, Nguyen H, Heylbroeck C, Mamane Y, Algarte M, Lin R (1999). "Triggering the interferon response: the role of IRF-3 transcription factor". J. Interferon Cytokine Res. 19 (1): 1–13. doi:10.1089/107999099314360. PMID 10048763.

[Lin-1999-1] Lin, R.; Heylbroeck, C.; Genin, P.; Pitha, PM.; Hiscott, J. (Feb 1999). "Essential Role of Interferon Regulatory Factor 3 in Direct Activation of RANTES Chemokine Transcription". Mol Cell Biol 19 (2): 959–66. PMC 116027. PMID 9891032. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=116027.

[pmid11846977-2] Yoneyama M, Suhara W, Fujita T (2002). "Control of IRF-3 activation by phosphorylation". J. Interferon Cytokine Res. 22 (1): 73–6. doi:10.1089/107999002753452674. PMID 11846977.

[3] "Entrez Gene: IRF3 interferon regulatory factor 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3661.

[Collins-2004-4] Collins, SE.; Noyce, RS.; Mossman, KL. (Feb 2004). "Innate Cellular Response to Virus Particle Entry Requires IRF3 but Not Virus Replication". J Virol 78 (4): 1706–17. doi:10.1128/JVI.78.4.1706-1717.2004. PMC 369475. PMID 14747536. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=369475.

[5] Hou, F; Sun, L, Zheng, H, Skaug, B, Jiang, QX, Chen, ZJ (2011 Aug 5). "MAVS Forms Functional Prion-Like Aggregates To Activate and Propagate Antiviral Innate Immune Response". Cell 146 (3): 448–61. doi:10.1016/j.cell.2011.06.041. PMC 3179916. PMID 21782231. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3179916.

[pmid11162841-6] Au, W C; Yeow W S, Pitha P M (Feb. 2001). "Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3". Virology (United States) 280 (2): 273–82. doi:10.1006/viro.2000.0782. ISSN 0042-6822. PMID 11162841.

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IRF3

Contents

[edit] Function

[edit] Interactions

[edit] References

[edit] Further reading

[edit] External links

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