Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9Q1V8N)

• DOT Name: Interferon regulatory factor 2-binding protein 1 (IRF2BP1)
• Synonyms: IRF-2-binding protein 1; IRF-2BP1; Probable E3 ubiquitin-protein ligase IRF2BP1; EC 2.3.2.27; Probable RING-type E3 ubiquitin transferase IRF2BP1
• Gene Name: IRF2BP1
• UniProt ID: I2BP1_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF11261
• Sequence:
  MASVQASRRQWCYLCDLPKMPWAMVWDFSEAVCRGCVNFEGADRIELLIDAARQLKRSHV
  LPEGRSPGPPALKHPATKDLAAAAAQGPQLPPPQAQPQPSGTGGGVSGQDRYDRATSSGR
  LPLPSPALEYTLGSRLANGLGREEAVAEGARRALLGSMPGLMPPGLLAAAVSGLGSRGLT
  LAPGLSPARPLFGSDFEKEKQQRNADCLAELNEAMRGRAEEWHGRPKAVREQLLALSACA
  PFNVRFKKDHGLVGRVFAFDATARPPGYEFELKLFTEYPCGSGNVYAGVLAVARQMFHDA
  LREPGKALASSGFKYLEYERRHGSGEWRQLGELLTDGVRSFREPAPAEALPQQYPEPAPA
  ALCGPPPRAPSRNLAPTPRRRKASPEPEGEAAGKMTTEEQQQRHWVAPGGPYSAETPGVP
  SPIAALKNVAEALGHSPKDPGGGGGPVRAGGASPAASSTAQPPTQHRLVARNGEAEVSPT
  AGAEAVSGGGSGTGATPGAPLCCTLCRERLEDTHFVQCPSVPGHKFCFPCSREFIKAQGP
  AGEVYCPSGDKCPLVGSSVPWAFMQGEIATILAGDIKVKKERDP
• Function: Acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities. May act as an E3 ligase towards JDP2, enhancing its polyubiquitination. Represses ATF2-dependent transcriptional activation.

Molecular Interaction Atlas (MIA) of This DOT

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[10]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[12]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Interferon regulatory factor 2-binding protein 1 (IRF2BP1).	[11]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.