Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8SIIAP)

DOT Name Interferon regulatory factor 5 (IRF5)
Synonyms IRF-5
Gene Name IRF5
Related Disease
Glioblastoma multiforme ( )
Multiple sclerosis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Autoimmune disease, susceptibility to, 6 ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colitis ( )
Colorectal carcinoma ( )
Diffuse systemic sclerosis ( )
Epstein barr virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Hypothyroidism ( )
Juvenile idiopathic arthritis ( )
Kaposi sarcoma ( )
Lung cancer ( )
Lung carcinoma ( )
Melanoma ( )
Myocardial infarction ( )
Myositis disease ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
Primary biliary cholangitis ( )
Pulmonary fibrosis ( )
Sjogren syndrome ( )
STAT3-related early-onset multisystem autoimmune disease ( )
Stroke ( )
Systemic sclerosis ( )
Type-1 diabetes ( )
Ulcerative colitis ( )
Adult lymphoma ( )
Crohn disease ( )
Ductal breast carcinoma in situ ( )
Lymphoma ( )
Pediatric lymphoma ( )
Advanced cancer ( )
Arthritis ( )
Asthma ( )
Immune system disorder ( )
Inflammatory bowel disease ( )
Obesity ( )
UniProt ID
IRF5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3DSH
Pfam ID
PF00605 ; PF10401
Sequence
MNQSIPVAPTPPRRVRLKPWLVAQVNSCQYPGLQWVNGEKKLFCIPWRHATRHGPSQDGD
NTIFKAWAKETGKYTEGVDEADPAKWKANLRCALNKSRDFRLIYDGPRDMPPQPYKIYEV
CSNGPAPTDSQPPEDYSFGAGEEEEEEEELQRMLPSLSLTEDVKWPPTLQPPTLRPPTLQ
PPTLQPPVVLGPPAPDPSPLAPPPGNPAGFRELLSEVLEPGPLPASLPPAGEQLLPDLLI
SPHMLPLTDLEIKFQYRGRPPRALTISNPHGCRLFYSQLEATQEQVELFGPISLEQVRFP
SPEDIPSDKQRFYTNQLLDVLDRGLILQLQGQDLYAIRLCQCKVFWSGPCASAHDSCPNP
IQREVKTKLFSLEHFLNELILFQKGQTNTPPPFEIFFCFGEEWPDRKPREKKLITVQVVP
VAARLLLEMFSGELSWSADSIRLQISNPDLKDRMVEQFKELHHIWQSQQRLQPVAQAPPG
AGLGVGQGPWPMHPAGMQ
Function
Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway. Key transcription factor regulating the IFN response during SARS-CoV-2 infection.
KEGG Pathway
Toll-like receptor sig.ling pathway (hsa04620 )
Reactome Pathway
Interferon alpha/beta signaling (R-HSA-909733 )
Interferon gamma signaling (R-HSA-877300 )

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Glioblastoma multiforme DISK8246 Definitive Altered Expression [1]
Multiple sclerosis DISB2WZI Definitive Biomarker [2]
Arteriosclerosis DISK5QGC Strong Biomarker [3]
Atherosclerosis DISMN9J3 Strong Biomarker [3]
Autoimmune disease, susceptibility to, 6 DISHNUXI Strong Genetic Variation [4]
Breast cancer DIS7DPX1 Strong Altered Expression [5]
Breast carcinoma DIS2UE88 Strong Altered Expression [5]
Breast neoplasm DISNGJLM Strong Biomarker [5]
Colitis DISAF7DD Strong Biomarker [6]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [7]
Diffuse systemic sclerosis DISYF5LP Strong SusceptibilityMutation [8]
Epstein barr virus infection DISOO0WT Strong Biomarker [9]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [10]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [11]
Hypothyroidism DISR0H6D Strong Genetic Variation [4]
Juvenile idiopathic arthritis DISQZGBV Strong Genetic Variation [12]
Kaposi sarcoma DISC1H1Z Strong Biomarker [13]
Lung cancer DISCM4YA Strong Biomarker [14]
Lung carcinoma DISTR26C Strong Biomarker [14]
Melanoma DIS1RRCY Strong Genetic Variation [15]
Myocardial infarction DIS655KI Strong Genetic Variation [16]
Myositis disease DISCIXF0 Strong Genetic Variation [17]
Neoplasm DISZKGEW Strong Biomarker [1]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [18]
Osteoarthritis DIS05URM Strong Altered Expression [19]
Primary biliary cholangitis DIS43E0O Strong Genetic Variation [20]
Pulmonary fibrosis DISQKVLA Strong Genetic Variation [21]
Sjogren syndrome DISUBX7H Strong Genetic Variation [22]
STAT3-related early-onset multisystem autoimmune disease DISAXTN7 Strong Genetic Variation [4]
Stroke DISX6UHX Strong Altered Expression [23]
Systemic sclerosis DISF44L6 Strong Altered Expression [24]
Type-1 diabetes DIS7HLUB Strong Genetic Variation [25]
Ulcerative colitis DIS8K27O Strong Genetic Variation [6]
Adult lymphoma DISK8IZR moderate Biomarker [26]
Crohn disease DIS2C5Q8 moderate Genetic Variation [27]
Ductal breast carcinoma in situ DISLCJY7 moderate Biomarker [28]
Lymphoma DISN6V4S moderate Biomarker [26]
Pediatric lymphoma DIS51BK2 moderate Biomarker [26]
Advanced cancer DISAT1Z9 Limited Biomarker [18]
Arthritis DIST1YEL Limited Biomarker [29]
Asthma DISW9QNS Limited Biomarker [30]
Immune system disorder DISAEGPH Limited Biomarker [31]
Inflammatory bowel disease DISGN23E Limited Biomarker [32]
Obesity DIS47Y1K Limited Altered Expression [33]
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⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Interferon regulatory factor 5 (IRF5). [34]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Interferon regulatory factor 5 (IRF5). [35]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Interferon regulatory factor 5 (IRF5). [36]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Interferon regulatory factor 5 (IRF5). [37]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Interferon regulatory factor 5 (IRF5). [38]
Menadione DMSJDTY Approved Menadione affects the expression of Interferon regulatory factor 5 (IRF5). [37]
Amphotericin B DMTAJQE Approved Amphotericin B increases the expression of Interferon regulatory factor 5 (IRF5). [39]
Sorafenib DMS8IFC Approved Sorafenib increases the expression of Interferon regulatory factor 5 (IRF5). [40]
Diphenylpyraline DMW4X37 Approved Diphenylpyraline increases the expression of Interferon regulatory factor 5 (IRF5). [41]
Curcumin DMQPH29 Phase 3 Curcumin increases the expression of Interferon regulatory factor 5 (IRF5). [40]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Interferon regulatory factor 5 (IRF5). [42]
Hydroxydimethylarsine Oxide DMPS2B1 Investigative Hydroxydimethylarsine Oxide decreases the expression of Interferon regulatory factor 5 (IRF5). [43]
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⏷ Show the Full List of 11 Drug(s)

References

1 Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers.Nat Commun. 2019 Sep 3;10(1):3974. doi: 10.1038/s41467-019-11911-5.
2 RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling.Sci Rep. 2017 Jun 2;7(1):2683. doi: 10.1038/s41598-017-02857-z.
3 Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis.Circulation. 2017 Sep 19;136(12):1140-1154. doi: 10.1161/CIRCULATIONAHA.117.027844. Epub 2017 Jul 11.
4 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
5 IRF5 is a novel regulator of CXCL13 expression in breast cancer that regulates CXCR5(+) B- and T-cell trafficking to tumor-conditioned media.Immunol Cell Biol. 2015 May-Jun;93(5):486-99. doi: 10.1038/icb.2014.110. Epub 2014 Dec 23.
6 Reducing IRF5 expression attenuates colitis in mice, but impairs the clearance of intestinal pathogens.Mucosal Immunol. 2019 Jul;12(4):874-887. doi: 10.1038/s41385-019-0165-1. Epub 2019 May 3.
7 Single nucleotide polymorphisms within interferon signaling pathway genes are associated with colorectal cancer susceptibility and survival.PLoS One. 2014 Oct 28;9(10):e111061. doi: 10.1371/journal.pone.0111061. eCollection 2014.
8 The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis.PLoS One. 2013;8(1):e54419. doi: 10.1371/journal.pone.0054419. Epub 2013 Jan 23.
9 Hypermethylation of the interferon regulatory factor 5 promoter in Epstein-Barr virus-associated gastric carcinoma.J Microbiol. 2015 Jan;53(1):70-6. doi: 10.1007/s12275-014-4654-3. Epub 2015 Jan 4.
10 Depletion of MicroRNA-373 Represses the Replication of Hepatitis C Virus via Activation of Type 1 Interferon Response by Targeting IRF5.Yonsei Med J. 2018 Dec;59(10):1181-1189. doi: 10.3349/ymj.2018.59.10.1181.
11 The Reciprocal Interaction Between LncRNA CCAT1 and miR-375-3p Contribute to the Downregulation of IRF5 Gene Expression by Solasonine in HepG2 Human Hepatocellular Carcinoma Cells.Front Oncol. 2019 Oct 18;9:1081. doi: 10.3389/fonc.2019.01081. eCollection 2019.
12 Association of interferon regulatory factor 5 (IRF5) gene polymorphisms with juvenile idiopathic arthritis.Clin Rheumatol. 2018 Oct;37(10):2661-2665. doi: 10.1007/s10067-018-4010-9. Epub 2018 Feb 8.
13 Modulation of interferon regulatory factor 5 activities by the Kaposi sarcoma-associated herpesvirus-encoded viral interferon regulatory factor 3 contributes to immune evasion and lytic induction.J Interferon Cytokine Res. 2011 Apr;31(4):373-82. doi: 10.1089/jir.2010.0084. Epub 2010 Dec 6.
14 Transcription factor E2F1 positively regulates interferon regulatory factor 5 expression in non-small cell lung cancer.Onco Targets Ther. 2019 Aug 23;12:6907-6915. doi: 10.2147/OTT.S215701. eCollection 2019.
15 IRF5 gene polymorphisms in melanoma.J Transl Med. 2012 Aug 21;10:170. doi: 10.1186/1479-5876-10-170.
16 Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
17 Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.Ann Rheum Dis. 2019 Mar;78(3):311-319. doi: 10.1136/annrheumdis-2018-214127. Epub 2018 Dec 20.
18 A promising role of interferon regulatory factor 5 as an early warning biomarker for the development of human non-small cell lung cancer.Lung Cancer. 2019 Sep;135:47-55. doi: 10.1016/j.lungcan.2019.07.008. Epub 2019 Jul 9.
19 The Role of Interferon Regulatory Factor 5 in Macrophage Inflammation During Osteoarthritis.Inflammation. 2019 Oct;42(5):1821-1829. doi: 10.1007/s10753-019-01044-8.
20 Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.Nat Genet. 2012 Oct;44(10):1137-41. doi: 10.1038/ng.2395. Epub 2012 Sep 9.
21 The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5, STAT4, IRAK1, and CTGF polymorphisms.Rheumatol Int. 2017 Aug;37(8):1303-1310. doi: 10.1007/s00296-017-3722-5. Epub 2017 Apr 22.
22 Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjgren's Syndrome According to Ancestry.Arthritis Rheumatol. 2017 Jun;69(6):1294-1305. doi: 10.1002/art.40040. Epub 2017 May 9.
23 Interferon regulatory factor 4/5 signaling impacts on microglial activation after ischemic stroke in mice.Eur J Neurosci. 2018 Jan;47(2):140-149. doi: 10.1111/ejn.13778.
24 An Allele-Specific Functional SNP Associated with Two Systemic Autoimmune Diseases Modulates IRF5 Expression by Long-Range Chromatin Loop Formation.J Invest Dermatol. 2020 Feb;140(2):348-360.e11. doi: 10.1016/j.jid.2019.06.147. Epub 2019 Aug 15.
25 Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants.PLoS Genet. 2012;8(6):e1002707. doi: 10.1371/journal.pgen.1002707. Epub 2012 Jun 7.
26 Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma.Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4513-22. doi: 10.1073/pnas.1406985111. Epub 2014 Oct 6.
27 Association between genetic polymorphisms in interferon regulatory factor 5 (IRF5) gene and Malaysian patients with Crohn's disease.J Dig Dis. 2015 Apr;16(4):205-16. doi: 10.1111/1751-2980.12229.
28 A conserved region within interferon regulatory factor 5 controls breast cancer cell migration through a cytoplasmic and transcription-independent mechanism.Mol Cancer. 2015 Feb 4;14(1):32. doi: 10.1186/s12943-015-0305-5.
29 MiR-let-7a regulates anti-citrullinated protein antibody-induced macrophage activation and correlates with the development of experimental rheumatoid arthritis.Int Immunopharmacol. 2017 Oct;51:40-46. doi: 10.1016/j.intimp.2017.08.001. Epub 2017 Aug 10.
30 A critical role for IRF5 in regulating allergic airway inflammation.Mucosal Immunol. 2017 May;10(3):716-726. doi: 10.1038/mi.2016.92. Epub 2016 Oct 19.
31 IRF5-mediated immune responses and its implications in immunological disorders.Int Rev Immunol. 2018;37(5):229-248. doi: 10.1080/08830185.2018.1469629. Epub 2018 Jul 9.
32 Advances and challenges in targeting IRF5, a key regulator of inflammation.FEBS J. 2019 May;286(9):1624-1637. doi: 10.1111/febs.14654. Epub 2018 Sep 21.
33 Increased Adipose Tissue Expression of Interferon Regulatory Factor (IRF)-5 in Obesity: Association with Metabolic Inflammation.Cells. 2019 Nov 11;8(11):1418. doi: 10.3390/cells8111418.
34 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
35 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
36 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
37 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
38 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
39 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
40 Novel carbocyclic curcumin analog CUR3d modulates genes involved in multiple apoptosis pathways in human hepatocellular carcinoma cells. Chem Biol Interact. 2015 Dec 5;242:107-22.
41 Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
42 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
43 Identification of interspecies concordance of mechanisms of arsenic-induced bladder cancer. Toxicol In Vitro. 2007 Dec;21(8):1513-29. doi: 10.1016/j.tiv.2007.06.021. Epub 2007 Jul 21.