IRF5
Interferon regulatory factor 5 is a protein that in humans is encoded by the IRF5 gene.[5]
Function
IRF5 is a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative splice variants encoding different isoforms exist.[5]
A 2020 study showed that an adaptor protein named TASL play an important regulatory role in IRF5 activation by being phosphorylated at the pLxIS motif,[6] drawing a similar analogy to the IRF3 activation pathway through the adaptor proteins MAVS, STING and TRIF.[7]
Clinical significance
IRF5 acts as a molecular switch that controls whether macrophages will promote or inhibit inflammation. Blocking the production of IRF5 in macrophages may help treat a wide range of autoimmune diseases, and that boosting IRF5 levels might help treat people whose immune systems are weak, compromised, or damaged. IRF5 seems to work "either by interacting with DNA directly, or by interacting with other proteins that themselves control which genes are switched on."[8]
See also
References
- GRCh38: Ensembl release 89: ENSG00000128604 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000029771 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: IRF5 interferon regulatory factor 5".
- Heinz, Leonhard X.; Lee, JangEun; Kapoor, Utkarsh; Kartnig, Felix; Sedlyarov, Vitaly; Papakostas, Konstantinos; César-Razquin, Adrian; Essletzbichler, Patrick; Goldmann, Ulrich; Stefanovic, Adrijana; Bigenzahn, Johannes W.; Scorzoni, Stefania; Pizzagalli, Mattia D.; Bensimon, Ariel; Müller, André C.; King, F. James; Li, Jun; Girardi, Enrico; Mbow, M. Lamine; Whitehurst, Charles E.; Rebsamen, Manuele; Superti-Furga, Giulio (13 May 2020). "TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7–9". Nature. 581: 1–7. doi:10.1038/s41586-020-2282-0.
- 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.
- Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, Hussell T, Feldmann M, Udalova IA (January 2011). "IRF5 promotes inflammatory macrophage polarization and T(H)1-T(H)17 responses". Nat Immunol. 12 (3): 231–238. doi:10.1038/ni.1990. PMID 21240265. Lay summary – MedScape.
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.
- Barnes B, Lubyova B, Pitha PM (2002). "On the role of IRF in host defense". J. Interferon Cytokine Res. 22 (1): 59–71. doi:10.1089/107999002753452665. PMID 11846976.
- 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.
- Nehyba J, Hrdlicková R, Burnside J, Bose HR (2002). "A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein". Mol. Cell. Biol. 22 (11): 3942–57. doi:10.1128/MCB.22.11.3942-3957.2002. PMC 133824. PMID 11997525.
- Barnes BJ, Kellum MJ, Field AE, Pitha PM (2002). "Multiple regulatory domains of IRF-5 control activation, cellular localization, and induction of chemokines that mediate recruitment of T lymphocytes". Mol. Cell. Biol. 22 (16): 5721–40. doi:10.1128/MCB.22.16.5721-5740.2002. PMC 133975. PMID 12138184.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Barnes BJ, Field AE, Pitha-Rowe PM (2003). "Virus-induced heterodimer formation between IRF-5 and IRF-7 modulates assembly of the IFNA enhanceosome in vivo and transcriptional activity of IFNA genes". J. Biol. Chem. 278 (19): 16630–41. doi:10.1074/jbc.M212609200. PMID 12600985.
- Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology". Science. 300 (5620): 767–72. Bibcode:2003Sci...300..767S. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
- Barnes BJ, Kellum MJ, Pinder KE, et al. (2003). "Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death". Cancer Res. 63 (19): 6424–31. PMID 14559832.
- Barnes BJ, Richards J, Mancl M, et al. (2004). "Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection". J. Biol. Chem. 279 (43): 45194–207. doi:10.1074/jbc.M400726200. PMID 15308637.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Lin R, Yang L, Arguello M, et al. (2005). "A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization". J. Biol. Chem. 280 (4): 3088–95. doi:10.1074/jbc.M408452200. PMID 15556946.
- Sigurdsson S, Nordmark G, Göring HH, et al. (2005). "Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus". Am. J. Hum. Genet. 76 (3): 528–37. doi:10.1086/428480. PMC 1196404. PMID 15657875.
- Takaoka A, Yanai H, Kondo S, et al. (2005). "Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors". Nature. 434 (7030): 243–9. Bibcode:2005Natur.434..243T. doi:10.1038/nature03308. PMID 15665823.
- Schoenemeyer A, Barnes BJ, Mancl ME, et al. (2005). "The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling". J. Biol. Chem. 280 (17): 17005–12. doi:10.1074/jbc.M412584200. PMID 15695821.
- Mancl ME, Hu G, Sangster-Guity N, Olshalsky SL, Hoops K, Fitzgerald-Bocarsly P, Pitha PM, Pinder K, Barnes BJ (June 2005). "Two discrete promoters regulate the alternatively spliced human interferon regulatory factor-5 isoforms. Multiple isoforms with distinct cell type-specific expression, localization, regulation, and function". J. Biol. Chem. 280 (22): 21078–90. doi:10.1074/jbc.M500543200. PMID 15805103.
- Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.
- Graham RR, Kozyrev SV, Baechler EC, et al. (2006). "A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus". Nat. Genet. 38 (5): 550–5. doi:10.1038/ng1782. PMID 16642019.
External links
- IRF5+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: Q13568 (Interferon regulatory factor 5) at the PDBe-KB.
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