NameInterferon regulatory factor 1
Synonyms
  • IRF-1
Gene NameIRF1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0019758|Interferon regulatory factor 1
MPITRMRMRPWLEMQINSNQIPGLIWINKEEMIFQIPWKHAAKHGWDINKDACLFRSWAI
HTGRYKAGEKEPDPKTWKANFRCAMNSLPDIEEVKDQSRNKGSSAVRVYRMLPPLTKNQR
KERKSKSSRDAKSKAKRKSCGDSSPDTFSDGLSSSTLPDDHSSYTVPGYMQDLEVEQALT
PALSPCAVSSTLPDWHIPVEVVPDSTSDLYNFQVSPMPSTSEATTDEDEEGKLPEDIMKL
LEQSEWQPTNVDGKGYLLNEPGVQPTSVYGDFSCKEEPEIDSPGGDIGLSLQRVFTDLKN
MDATWLDSLLTPVRLPSIQAIPCAP
Number of residues325
Molecular Weight36501.86
Theoretical pINot Available
GO Classification
Functions
  • DNA binding
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
Processes
  • interferon-gamma-mediated signaling pathway
  • cellular response to interferon-beta
  • regulation of cell cycle
  • cell cycle arrest
  • transcription from RNA polymerase II promoter
  • defense response to virus
  • positive regulation of interleukin-12 biosynthetic process
  • positive regulation of type I interferon production
  • cellular response to mechanical stimulus
  • regulation of innate immune response
  • positive regulation of transcription, DNA-templated
  • positive regulation of interferon-beta production
  • apoptotic process
  • regulation of adaptive immune response
  • negative regulation of cell proliferation
  • negative regulation of regulatory T cell differentiation
  • positive regulation of transcription from RNA polymerase II promoter
  • CD8-positive, alpha-beta T cell differentiation
  • cytokine-mediated signaling pathway
  • regulation of CD8-positive, alpha-beta T cell proliferation
  • regulation of MyD88-dependent toll-like receptor signaling pathway
  • type I interferon signaling pathway
  • negative regulation of transcription, DNA-templated
  • blood coagulation
Components
  • nucleus
  • cytosol
  • nucleoplasm
  • nuclear chromatin
  • cytoplasm
General FunctionTranscriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific FunctionTranscriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. These include the regulation of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, DDX58/RIG-I, TNFSF10/TRAIL, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA. Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP10914
UniProtKB Entry NameIRF1_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0019759|Interferon regulatory factor 1 (IRF1)
ATGCCCATCACTCGGATGCGCATGAGACCCTGGCTAGAGATGCAGATTAATTCCAACCAA
ATCCCGGGGCTCATCTGGATTAATAAAGAGGAGATGATCTTCCAGATCCCATGGAAGCAT
GCTGCCAAGCATGGCTGGGACATCAACAAGGATGCCTGTTTGTTCCGGAGCTGGGCCATT
CACACAGGCCGATACAAAGCAGGGGAAAAGGAGCCAGATCCCAAGACGTGGAAGGCCAAC
TTTCGCTGTGCCATGAACTCCCTGCCAGATATCGAGGAGGTGAAAGACCAGAGCAGGAAC
AAGGGCAGCTCAGCTGTGCGAGTGTACCGGATGCTTCCACCTCTCACCAAGAACCAGAGA
AAAGAAAGAAAGTCGAAGTCCAGCCGAGATGCTAAGAGCAAGGCCAAGAGGAAGTCATGT
GGGGATTCCAGCCCTGATACCTTCTCTGATGGACTCAGCAGCTCCACTCTGCCTGATGAC
CACAGCAGCTACACAGTTCCAGGCTACATGCAGGACTTGGAGGTGGAGCAGGCCCTGACT
CCAGCACTGTCGCCATGTGCTGTCAGCAGCACTCTCCCCGACTGGCACATCCCAGTGGAA
GTTGTGCCGGACAGCACCAGTGATCTGTACAACTTCCAGGTGTCACCCATGCCCTCCACC
TCTGAAGCTACAACAGATGAGGATGAGGAAGGGAAATTACCTGAGGACATCATGAAGCTC
TTGGAGCAGTCGGAGTGGCAGCCAACAAACGTGGATGGGAAGGGGTACCTACTCAATGAA
CCTGGAGTCCAGCCCACCTCTGTCTATGGAGACTTTAGCTGTAAGGAGGAGCCAGAAATT
GACAGCCCAGGGGGGGATATTGGGCTGAGTCTACAGCGTGTCTTCACAGATCTGAAGAAC
ATGGATGCCACCTGGCTGGACAGCCTGCTGACCCCAGTCCGGTTGCCCTCCATCCAGGCC
ATTCCCTGTGCACCGTAG
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:6116
Chromosome Location5
LocusNot Available
References
  1. Maruyama M, Fujita T, Taniguchi T: Sequence of a cDNA coding for human IRF-1. Nucleic Acids Res. 1989 Apr 25;17(8):3292. 2726461
  2. Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T: Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903-13. 3409321
  3. Cha Y, Sims SH, Romine MF, Kaufmann M, Deisseroth AB: Human interferon regulatory factor 1: intron-exon organization. DNA Cell Biol. 1992 Oct;11(8):605-11. 1382447
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  5. Willman CL, Sever CE, Pallavicini MG, Harada H, Tanaka N, Slovak ML, Yamamoto H, Harada K, Meeker TC, List AF, et al.: Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia. Science. 1993 Feb 12;259(5097):968-71. 8438156
  6. Lin R, Hiscott J: A role for casein kinase II phosphorylation in the regulation of IRF-1 transcriptional activity. Mol Cell Biochem. 1999 Jan;191(1-2):169-80. 10094406
  7. Taniguchi T, Ogasawara K, Takaoka A, Tanaka N: IRF family of transcription factors as regulators of host defense. Annu Rev Immunol. 2001;19:623-55. 11244049
  8. Kroger A, Koster M, Schroeder K, Hauser H, Mueller PP: Activities of IRF-1. J Interferon Cytokine Res. 2002 Jan;22(1):5-14. 11846971
  9. Romeo G, Fiorucci G, Chiantore MV, Percario ZA, Vannucchi S, Affabris E: IRF-1 as a negative regulator of cell proliferation. J Interferon Cytokine Res. 2002 Jan;22(1):39-47. 11846974
  10. Oshima S, Nakamura T, Namiki S, Okada E, Tsuchiya K, Okamoto R, Yamazaki M, Yokota T, Aida M, Yamaguchi Y, Kanai T, Handa H, Watanabe M: Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells. Mol Cell Biol. 2004 Jul;24(14):6298-310. 15226432
  11. Dornan D, Eckert M, Wallace M, Shimizu H, Ramsay E, Hupp TR, Ball KL: Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53. Mol Cell Biol. 2004 Nov;24(22):10083-98. 15509808
  12. Honda K, Taniguchi T: IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol. 2006 Sep;6(9):644-58. 16932750
  13. Su ZZ, Sarkar D, Emdad L, Barral PM, Fisher PB: Central role of interferon regulatory factor-1 (IRF-1) in controlling retinoic acid inducible gene-I (RIG-I) expression. J Cell Physiol. 2007 Nov;213(2):502-10. 17516545
  14. Maratheftis CI, Giannouli S, Spachidou MP, Panayotou G, Voulgarelis M: RNA interference of interferon regulatory factor-1 gene expression in THP-1 cell line leads to Toll-like receptor-4 overexpression/activation as well as up-modulation of annexin-II. Neoplasia. 2007 Dec;9(12):1012-20. 18084608
  15. Park J, Kim K, Lee EJ, Seo YJ, Lim SN, Park K, Rho SB, Lee SH, Lee JH: Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17028-33. Epub 2007 Oct 17. 17942705
  16. Bowie ML, Ibarra C, Seewalt VL: IRF-1 promotes apoptosis in p53-damaged basal-type human mammary epithelial cells: a model for early basal-type mammary carcinogenesis. Adv Exp Med Biol. 2008;617:367-74. doi: 10.1007/978-0-387-69080-3_35. 18497060
  17. Fragale A, Gabriele L, Stellacci E, Borghi P, Perrotti E, Ilari R, Lanciotti A, Remoli AL, Venditti M, Belardelli F, Battistini A: IFN regulatory factor-1 negatively regulates CD4+ CD25+ regulatory T cell differentiation by repressing Foxp3 expression. J Immunol. 2008 Aug 1;181(3):1673-82. 18641303
  18. Huang Y, Walstrom A, Zhang L, Zhao Y, Cui M, Ye L, Zheng JC: Type I interferons and interferon regulatory factors regulate TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected macrophages. PLoS One. 2009;4(4):e5397. doi: 10.1371/journal.pone.0005397. Epub 2009 Apr 30. 19404407
  19. Savitsky D, Tamura T, Yanai H, Taniguchi T: Regulation of immunity and oncogenesis by the IRF transcription factor family. Cancer Immunol Immunother. 2010 Apr;59(4):489-510. doi: 10.1007/s00262-009-0804-6. Epub 2010 Jan 5. 20049431
  20. Gao J, Senthil M, Ren B, Yan J, Xing Q, Yu J, Zhang L, Yim JH: IRF-1 transcriptionally upregulates PUMA, which mediates the mitochondrial apoptotic pathway in IRF-1-induced apoptosis in cancer cells. Cell Death Differ. 2010 Apr;17(4):699-709. doi: 10.1038/cdd.2009.156. Epub 2009 Oct 23. 19851330
  21. Muto V, Stellacci E, Lamberti AG, Perrotti E, Carrabba A, Matera G, Sgarbanti M, Battistini A, Liberto MC, Foca A: Human papillomavirus type 16 E5 protein induces expression of beta interferon through interferon regulatory factor 1 in human keratinocytes. J Virol. 2011 May;85(10):5070-80. doi: 10.1128/JVI.02114-10. Epub 2011 Mar 9. 21389130
  22. Armstrong MJ, Stang MT, Liu Y, Gao J, Ren B, Zuckerbraun BS, Mahidhara RS, Xing Q, Pizzoferrato E, Yim JH: Interferon Regulatory Factor 1 (IRF-1) induces p21(WAF1/CIP1) dependent cell cycle arrest and p21(WAF1/CIP1) independent modulation of survivin in cancer cells. Cancer Lett. 2012 Jun 1;319(1):56-65. doi: 10.1016/j.canlet.2011.12.027. Epub 2011 Dec 23. 22200613
  23. Qi H, Zhu H, Lou M, Fan Y, Liu H, Shen J, Li Z, Lv X, Shan J, Zhu L, Chin YE, Shao J: Interferon regulatory factor 1 transactivates expression of human DNA polymerase eta in response to carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. J Biol Chem. 2012 Apr 13;287(16):12622-33. doi: 10.1074/jbc.M111.313429. Epub 2012 Feb 24. 22367195
  24. Nozawa H, Oda E, Ueda S, Tamura G, Maesawa C, Muto T, Taniguchi T, Tanaka N: Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer. Int J Cancer. 1998 Aug 12;77(4):522-7. 9679752
  25. Eason DD, Shepherd AT, Blanck G: Interferon regulatory factor 1 tryptophan 11 to arginine point mutation abolishes DNA binding. Biochim Biophys Acta. 1999 Jul 7;1446(1-2):140-4. 10395927