IRF5

Interferon regulatory factor 5 is a protein that in humans is encoded by the IRF5 gene.^[5] The IRF family is a group of transcription factors that are involved in signaling for virus responses in mammals along with regulation of certain cellular functions.^[6]

IRF5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3DSH
Identifiers
Aliases	IRF5, SLEB10, interferon regulatory factor 5
External IDs	OMIM: 607218; MGI: 1350924; HomoloGene: 8088; GeneCards: IRF5; OMA:IRF5 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q32.1 Start 128,937,457 bp[1] End 128,950,038 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 A3.3|6 12.36 cM Start 29,526,624 bp[2] End 29,541,870 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte granulocyte spleen blood bone marrow cells lymph node upper lobe of left lung testicle right uterine tube right coronary artery Top expressed in mesenteric lymph nodes stroma of bone marrow granulocyte spleen lip right kidney female urethra proximal tubule esophagus blastocyst More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding DNA-binding transcription factor activity protein 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 cytosol nucleus Biological process regulation of transcription, DNA-templated positive regulation of interleukin-12 production interferon-gamma-mediated signaling pathway immune system process regulation of transcription by RNA polymerase II positive regulation of interferon-alpha production response to muramyl dipeptide transcription, DNA-templated defense response to virus type I interferon signaling pathway response to peptidoglycan positive regulation of apoptotic process innate immune response positive regulation of transcription by RNA polymerase II positive regulation of interferon-beta production cytokine-mediated signaling pathway transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3663 27056 Ensembl ENSG00000128604 ENSMUSG00000029771 UniProt Q13568 P56477 RefSeq (mRNA) NM_001098627 NM_001098629 NM_001098630 NM_001242452 NM_032643 NM_001347928 NM_001364314 NM_001252382 NM_012057 NM_001311083 RefSeq (protein) NP_001092097 NP_001092099 NP_001092100 NP_001229381 NP_116032 NP_001334857 NP_001351243 NP_001092099.1 NP_001239311 NP_001298012 NP_036187 Location (UCSC) Chr 7: 128.94 – 128.95 Mb Chr 6: 29.53 – 29.54 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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] The regulatory and repression regions of the IRF family are mainly located in the C-terminal of the IRF.^[7]

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,^[8] drawing a similar analogy to the IRF3 activation pathway through the adaptor proteins MAVS, STING and TRIF.^[9]

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."^[10]

Signaling

The IRF family regulates the gene expression for the interferon (IFN) response to viral infections.^[6] IRF5 is a direct transducer to interferon signaling and is activated via phosphorylation.^[11] The IRF family can also initiate the JAK/STAT signaling pathway by binding to transmembrane receptors that activate JAK.^[12] IRFs, IFNs, and the JAK/STAT signaling pathway work together to fight viral infections in mammals through specific signals.^[13]

See also

• Interferon regulatory factors

References

1. GRCh38: Ensembl release 89: ENSG00000128604 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029771 – 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. "Entrez Gene: IRF5 interferon regulatory factor 5".
6. Negishi H, Taniguchi T, Yanai H (November 2018). "The Interferon (IFN) Class of Cytokines and the IFN Regulatory Factor (IRF) Transcription Factor Family". Cold Spring Harbor Perspectives in Biology. 10 (11): a028423. doi:10.1101/cshperspect.a028423. PMC 6211389. PMID 28963109.
7. Chistiakov DA, Myasoedova VA, Revin VV, Orekhov AN, Bobryshev YV (January 2018). "The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2". Immunobiology. 223 (1): 101–111. doi:10.1016/j.imbio.2017.10.005. PMID 29032836.
8. Heinz LX, Lee J, Kapoor U, Kartnig F, Sedlyarov V, Papakostas K, et al. (May 2020). "TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9". Nature. 581 (7808): 316–322. Bibcode:2020Natur.581..316H. doi:10.1038/s41586-020-2282-0. PMC 7610944. PMID 32433612. S2CID 218625265.
9. Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, et al. (March 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.
10. Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, et al. (March 2011). "IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses". Nature Immunology. 12 (3): 231–238. doi:10.1038/ni.1990. PMID 21240265. S2CID 13730047.
11. Barnes B, Lubyova B, Pitha PM (January 2002). "On the role of IRF in host defense". Journal of Interferon & Cytokine Research. 22 (1): 59–71. doi:10.1089/107999002753452665. PMID 11846976.
12. Bousoik E, Montazeri Aliabadi H (2018). ""Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway". Frontiers in Oncology. 8: 287. doi:10.3389/fonc.2018.00287. PMC 6079274. PMID 30109213.
13. Chiang HS, Liu HM (2019). "The Molecular Basis of Viral Inhibition of IRF- and STAT-Dependent Immune Responses". Frontiers in Immunology. 9: 3086. doi:10.3389/fimmu.2018.03086. PMC 6332930. PMID 30671058.

Further reading

• Pitha PM, Au WC, Lowther W, Juang YT, Schafer SL, Burysek L, et al. (1999). "Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth". Biochimie. 80 (8–9): 651–658. doi:10.1016/S0300-9084(99)80018-2. PMID 9865487.
• Barnes B, Lubyova B, Pitha PM (January 2002). "On the role of IRF in host defense". Journal of Interferon & Cytokine Research. 22 (1): 59–71. doi:10.1089/107999002753452665. PMID 11846976.
• Barnes BJ, Moore PA, Pitha PM (June 2001). "Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes". The Journal of Biological Chemistry. 276 (26): 23382–23390. doi:10.1074/jbc.M101216200. PMID 11303025.
• Nehyba J, Hrdlicková R, Burnside J, Bose HR (June 2002). "A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein". Molecular and Cellular Biology. 22 (11): 3942–3957. doi:10.1128/MCB.22.11.3942-3957.2002. PMC 133824. PMID 11997525.
• Barnes BJ, Kellum MJ, Field AE, Pitha PM (August 2002). "Multiple regulatory domains of IRF-5 control activation, cellular localization, and induction of chemokines that mediate recruitment of T lymphocytes". Molecular and Cellular Biology. 22 (16): 5721–5740. doi:10.1128/MCB.22.16.5721-5740.2002. PMC 133975. PMID 12138184.
• Barnes BJ, Field AE, Pitha-Rowe PM (May 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". The Journal of Biological Chemistry. 278 (19): 16630–16641. doi:10.1074/jbc.M212609200. PMID 12600985.
• Barnes BJ, Kellum MJ, Pinder KE, Frisancho JA, Pitha PM (October 2003). "Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death". Cancer Research. 63 (19): 6424–6431. PMID 14559832.
• Barnes BJ, Richards J, Mancl M, Hanash S, Beretta L, Pitha PM (October 2004). "Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection". The Journal of Biological Chemistry. 279 (43): 45194–45207. doi:10.1074/jbc.M400726200. PMID 15308637.
• Lin R, Yang L, Arguello M, Penafuerte C, Hiscott J (January 2005). "A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization". The Journal of Biological Chemistry. 280 (4): 3088–3095. doi:10.1074/jbc.M408452200. PMID 15556946.
• Sigurdsson S, Nordmark G, Göring HH, Lindroos K, Wiman AC, Sturfelt G, et al. (March 2005). "Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus". American Journal of Human Genetics. 76 (3): 528–537. doi:10.1086/428480. PMC 1196404. PMID 15657875.
• Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, et al. (March 2005). "Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors". Nature. 434 (7030): 243–249. Bibcode:2005Natur.434..243T. doi:10.1038/nature03308. PMID 15665823. S2CID 667829.
• Schoenemeyer A, Barnes BJ, Mancl ME, Latz E, Goutagny N, Pitha PM, et al. (April 2005). "The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling". The Journal of Biological Chemistry. 280 (17): 17005–17012. doi:10.1074/jbc.M412584200. PMID 15695821.
• Mancl ME, Hu G, Sangster-Guity N, Olshalsky SL, Hoops K, Fitzgerald-Bocarsly P, et al. (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". The Journal of Biological Chemistry. 280 (22): 21078–21090. doi:10.1074/jbc.M500543200. PMID 15805103.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, et al. (May 2006). "A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus". Nature Genetics. 38 (5): 550–555. doi:10.1038/ng1782. PMID 16642019. S2CID 21426281.

External links

• IRF5+protein,+human at the U.S. 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.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.