Wikipedia

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
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesIRF5, SLEB10, interferon regulatory factor 5
External IDsOMIM: 607218; MGI: 1350924; HomoloGene: 8088; GeneCards: IRF5; OMA:IRF5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

3663

27056

Ensembl

ENSG00000128604

ENSMUSG00000029771

UniProt

Q13568

P56477

RefSeq (mRNA)

NM_001252382
NM_012057
NM_001311083

RefSeq (protein)

NP_001239311
NP_001298012
NP_036187

Location (UCSC)Chr 7: 128.94 – 128.95 MbChr 6: 29.53 – 29.54 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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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

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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

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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

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000128604 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "Entrez Gene: IRF5 interferon regulatory factor 5".
  6. ^ a b 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

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

 

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