IRF3

IRF3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3QU6, 1J2F, 1QWT, 1T2K, 1ZOQ, 2O61, 2O6G, 2PI0, 3A77, 5JEO, 5JEK, 5JER, 5JEM, 5JEL, 5JEJ
Identifiers
Aliases	IRF3 , entrez:3661, IIAE7, interferon regulatory factor 3
External IDs	OMIM: 603734; MGI: 1859179; HomoloGene: 1208; GeneCards: IRF3; OMA:IRF3 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19q13.33 Start 49,659,569 bp [1] End 49,665,875 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 B3 Start 44,647,072 bp [2] End 44,652,272 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte right uterine tube mucosa of transverse colon spleen right lobe of thyroid gland canal of the cervix left lobe of thyroid gland anterior pituitary lymph node ectocervix Top expressed in neural layer of retina spermatocyte lip granulocyte tibiofemoral joint thymus yolk sac right kidney crypt of lieberkuhn of small intestine vestibular membrane of cochlear duct More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein homodimerization activity DNA-binding transcription factor activity transcription coregulator activity DNA-binding transcription repressor activity, RNA polymerase II-specific protein binding protein domain specific binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific sequence-specific DNA binding identical protein binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cytoplasm nucleoplasm nucleus cytosol Biological process apoptotic process positive regulation of type I interferon-mediated signaling pathway macrophage apoptotic process regulation of transcription, DNA-templated response to bacterium response to exogenous dsRNA positive regulation of interferon-alpha production MDA-5 signaling pathway interferon-gamma-mediated signaling pathway immune system process negative regulation of transcription by RNA polymerase II transcription by RNA polymerase II cellular response to dsRNA transcription, DNA-templated cellular response to DNA damage stimulus TRIF-dependent toll-like receptor signaling pathway response to lipopolysaccharide defense response to virus type I interferon signaling pathway positive regulation of I-kappaB kinase/NF-kappaB signaling negative regulation of type I interferon production programmed necrotic cell death viral process cellular response to lipopolysaccharide positive regulation of type I interferon production lipopolysaccharide-mediated signaling pathway positive regulation of interferon-beta production innate immune response regulation of type I interferon production positive regulation of transcription by RNA polymerase II negative regulation of defense response to virus by host regulation of gene expression regulation of inflammatory response cellular response to exogenous dsRNA positive regulation of transcription, DNA-templated Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3661 54131 Ensembl ENSG00000126456 ENSMUSG00000003184 UniProt Q14653 P70671 RefSeq (mRNA) NM_001197122 NM_001197123 NM_001197124 NM_001197125 NM_001197126 NM_001197127 NM_001197128 NM_001571 NM_016849 RefSeq (protein) NP_001184051 NP_001184052 NP_001184053 NP_001184054 NP_001184055 NP_001184056 NP_001184057 NP_001562 NP_001184053.1 NP_001184056.1 NP_001184057.1 NP_058545 Location (UCSC) Chr 19: 49.66 – 49.67 Mb Chr 7: 44.65 – 44.65 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor. ^[5]

Function

IRF3 is a member of the interferon regulatory transcription factor (IRF) family. ^[5] IRF3 was originally discovered as a homolog of IRF1 and IRF2. IRF3 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. ^[6] IRF3 is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. ^[7] The complex translocates into the nucleus for the transcriptional activation of interferons alpha and beta, and further interferon-induced genes. ^[8]

IRF3 plays an important role in the innate immune system's response to viral infection. ^[9] Aggregated MAVS have been found to activate IRF3 dimerization. ^[10] A 2015 study shows phosphorylation of innate immune adaptor proteins MAVS, STING and TRIF at a conserved pLxIS motif recruits and specifies IRF3 phosphorylation and activation by the Serine/threonine-protein kinase TBK1, thereby activating the production of type-I interferons. ^[11] Another study has shown that IRF3-/- knockouts protect from myocardial infarction. ^[12] The same study identified IRF3 and the type I IFN response as a potential therapeutic target for post-myocardial infarction cardioprotection. ^[12]

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

Interactions

IRF3 has been shown to interact with IRF7. ^[13]

References

1. GRCh38: Ensembl release 89: ENSG00000126456 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000003184 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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. doi:10.1128/MCB.19.2.959. PMC   116027 . PMID   9891032.
7. 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.
8. "Entrez Gene: IRF3 interferon regulatory factor 3".
9. 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.
10. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ (Aug 5, 2011). "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.
11. Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, Du F, Ren J, Wu Y, Grishin N, and Chen ZJ (Mar 13, 2015). "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation". Science. 347 (6227): aaa2630. doi: 10.1126/science.aaa2630 . PMID   25636800.
12. King KR, Aguirre AD, Ye YX, Sun Y, Roh JD, Ng Jr RP, Kohler RH, Arlauckas SP, Iwamoto Y, Savol A, Sadreyev RI, Kelly M, Fitzgibbons TP, Fitzgerald KA, Mitchison T, Libby P, Nahrendorf M, Weissleder R (Nov 6, 2017). "IRF3 and type I interferons fuel a fatal response to myocardial infarction". Nature Medicine. 23 (12): 1481–1487. doi:10.1038/nm.4428. PMC   6477926 . PMID   29106401.
13. Au WC, Yeow WS, Pitha PM (Feb 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.

Further reading

• Pitha PM, Au WC, Lowther W, Juang YT, Schafer SL, Burysek L, Hiscott J, Moore PA (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, Juang YT, Pitha PM (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.
• Yoneyama M, Suhara W, Fukuhara Y, Fukuda M, Nishida E, Fujita T (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.
• 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. doi:10.1128/MCB.18.3.1359. PMC   108849 . PMID   9488451.
• 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. doi:10.1128/MCB.18.5.2986. PMC   110678 . PMID   9566918.
• 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.
• 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". Annals of Human Genetics. 62 (Pt 3): 231–4. doi: 10.1046/j.1469-1809.1998.6230231.x . PMID   9803267. S2CID   46070705.
• 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, Min IM, Yim J, Kim TK (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, Dingwall C, Reich NC (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.
• Suhara W, Yoneyama M, Iwamura T, Yoshimura S, Tamura K, Namiki H, Aimoto S, Fujita T (2000). "Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300". J. Biochem. 128 (2): 301–7. doi:10.1093/oxfordjournals.jbchem.a022753. PMID   10920266.
• Servant MJ, ten Oever B, LePage C, Conti L, Gessani S, Julkunen I, Lin R, Hiscott J (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, García-Sastre A, Levy DE (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, Lin R, Hiscott J, Doly J, Civas A (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". Journal of Immunology. 172 (2): 747–51. doi: 10.4049/jimmunol.172.2.747 . PMID   14707042.

External links

• Interferon+Regulatory+Factor-3 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook IRF3