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Interferon regulatory factor 1
Protein IRF1 PDB 1if1.png
PDB rendering based on 1if1.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols IRF1 ; IRF-1; MAR
External IDs OMIM147575 MGI96590 HomoloGene1658 GeneCards: IRF1 Gene
RNA expression pattern
PBB GE IRF1 202531 at tn.png
More reference expression data
Species Human Mouse
Entrez 3659 16362
Ensembl ENSG00000125347 ENSMUSG00000018899
UniProt P10914 P15314
RefSeq (mRNA) NM_002198 NM_001159393
RefSeq (protein) NP_002189 NP_001152865
Location (UCSC) Chr 5:
131.82 – 131.83 Mb
Chr 11:
53.77 – 53.78 Mb
PubMed search [1] [2]

Interferon regulatory factor 1 is a protein that in humans is encoded by the IRF1 gene.[1][2]


Interferon regulatory factor 1 was the first member of the interferon regulatory transcription factor (IRF) family identified. Initially described as a transcription factor able to activate expression of the cytokine Interferon beta,[3] IRF-1 was subsequently shown to function as a transcriptional activator or repressor of a variety of target genes. IRF-1 regulates expression of target genes by binding to an interferon stimulated response element (ISRE) in their promoters. The IRF-1 protein binds to the ISRE via an N-terminal helix-turn-helix DNA binding domain,[4] which is highly conserved among all IRF proteins.

Beyond its function as a transcription factor, IRF-1 has also been shown to trans-activate the tumour suppressor protein p53 through the recruitment of its co-factor p300.[5]

IRF-1 has been shown to play roles in the immune response, regulating apoptosis, DNA damage and tumor suppression.[6]


It has been shown that the extreme C-terminus of IRF-1 regulates its ability to activate transcription, nanobodies targeting this domain (MF1) are able to increase IRF-1 activity.[7]

Model organisms[edit]

Model organisms have been used in the study of IRF1 function. A conditional knockout mouse line, called Irf1tm1a(EUCOMM)Wtsi[11][12] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty five tests were carried out and two phenotypes were reported. Homozygous mutant animals had abnormal peripheral blood lymphocytes, specifically decreased CD8-positive T cell and NK cell numbers and an increase in CD4-positive T cells. The mice also had an abnormal integument phenotype determined by a study of tail epidermis.[9]


IRF1 has been shown to interact with:

See also[edit]


  1. ^ Maruyama M, Fujita T, Taniguchi T (Jun 1989). "Sequence of a cDNA coding for human IRF-1". Nucleic Acids Res 17 (8): 3292. doi:10.1093/nar/17.8.3292. PMC 317732. PMID 2726461. 
  2. ^ Itoh S, Harada H, Nakamura Y, White R, Taniguchi T (Nov 1991). "Assignment of the human interferon regulatory factor-1 (IRF1) gene to chromosome 5q23-q31". Genomics 10 (4): 1097–9. doi:10.1016/0888-7543(91)90208-V. PMID 1680796. 
  3. ^ Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y et al. (September 1988). "Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements". Cell 54 (6): 903–13. doi:10.1016/S0092-8674(88)91307-4. PMID 3409321. 
  4. ^ Escalante C, Yie J, Thanos D, Aggarwal A (January 1998). "Structure of IRF-1 with bound DNA reveals determinants of interferon regulation". Nature 391 (6662): 103–6. doi:10.1038/34224. PMID 9422515. 
  5. ^ Dornan D, Eckert M, Wallace M, Shimizu H, Ramsay E, Hupp T et al. (November 2004). "Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53". Mol. Cell. Biol. 24 (22): 10083–98. doi:10.1128/MCB.24.22.10083-10098.2004. PMC 525491. PMID 15509808. 
  6. ^ "Entrez Gene: IRF1 interferon regulatory factor 1". 
  7. ^ Möller A, Pion E, Narayan V, Ball K (December 2010). "Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain". J. Biol. Chem. 285 (49): 38348–61. doi:10.1074/jbc.M110.149476. PMC 2992268. PMID 20817723. 
  8. ^ "Citrobacter infection data for Irf1". Wellcome Trust Sanger Institute. 
  9. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. 
  10. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  11. ^ "International Knockout Mouse Consortium". 
  12. ^ "Mouse Genome Informatics". 
  13. ^ Skarnes W, Rosen B, West A, Koutsourakis M, Bushell W, Iyer V et al. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750. 
  14. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  15. ^ Collins F, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  16. ^ van der Weyden L, White J, Adams D, Logan D (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  17. ^ Narayan V, Pion E, Landré V, Müller P, Ball K (October 2010). "Docking dependent ubiquitination of the interferon regulatory factor-1 tumour suppressor protein by the ubiquitin ligase CHIP". J Biol Chem. 286 (1): 607–19. doi:10.1074/jbc.M110.153122. PMC 3013021. PMID 20947504. 
  18. ^ Kular R, Yehiely F, Kotlo K, Cilensek Z, Bedi R, Deiss L (October 2009). "GAGE, an antiapoptotic protein binds and modulates the expression of nucleophosmin/B23 and interferon regulatory factor 1". J. Interferon Cytokine Res. 29 (10): 645–55. doi:10.1089/jir.2008.0099. PMID 19642896. 
  19. ^ Narayan V, Eckert M, Zylicz A, Zylicz M, Ball K (September 2009). "Cooperative regulation of the interferon regulatory factor-1 tumor suppressor protein by core components of the molecular chaperone machinery". J Biol Chem. 284 (38): 25889–99. doi:10.1074/jbc.M109.019505. PMC 2757990. PMID 19502235. 
  20. ^ Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R et al. (October 1998). "Functional domains of interferon regulatory factor I (IRF-1)". Biochem. J. 335 (1): 147–57. PMC 1219763. PMID 9742224. 
  21. ^ Sharf R, Azriel A, Lejbkowicz F, Winograd S, Ehrlich R, Levi B (June 1995). "Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors". J. Biol. Chem. 270 (22): 13063–9. doi:10.1074/jbc.270.22.13063. PMID 7768900. 
  22. ^ Umegaki N, Tamai K, Nakano H, Moritsugu R, Yamazaki T, Hanada K et al. (June 2007). "Differential regulation of karyopherin alpha 2 expression by TGF-beta1 and IFN-gamma in normal human epidermal keratinocytes: evident contribution of KPNA2 for nuclear translocation of IRF-1". J. Invest. Dermatol. 127 (6): 1456–64. doi:10.1038/sj.jid.5700716. PMID 17255955. 
  23. ^ Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M et al. (October 2006). "Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program". Proc. Natl. Acad. Sci. U.S.A. 103 (41): 15136–41. doi:10.1073/pnas.0607181103. PMC 1586247. PMID 17018642. 
  24. ^ Masumi A, Wang I, Lefebvre B, Yang X, Nakatani Y, Ozato K (March 1999). "The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness". Mol. Cell. Biol. 19 (3): 1810–20. PMC 83974. PMID 10022868. 
  25. ^ Chatterjee-Kishore M, van Den Akker F, Stark G (July 2000). "Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1". J. Biol. Chem. 275 (27): 20406–11. doi:10.1074/jbc.M001861200. PMID 10764778. 
  26. ^ Sgarbanti M, Borsetti A, Moscufo N, Bellocchi M, Ridolfi B, Nappi F et al. (May 2002). "Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors". J. Exp. Med. 195 (10): 1359–70. doi:10.1084/jem.20010753. PMC 2193759. PMID 12021315. 
  27. ^ Lee J, Chun T, Park S, Rho S (September 2008). "Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs". Biochim. Biophys. Acta 1783 (9): 1654–62. doi:10.1016/j.bbamcr.2008.04.006. PMID 18472010. 

Further reading[edit]

External links[edit]

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