Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZZ4SFP)

• DOT Name: AT-rich interactive domain-containing protein 3A (ARID3A)
• Synonyms: ARID domain-containing protein 3A; B-cell regulator of IgH transcription; Bright; Dead ringer-like protein 1; E2F-binding protein 1
• Gene Name: ARID3A
• Related Disease:
  Acute monocytic leukemia
  Adult lymphoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  High blood pressure
  Hypoglycemia
  Leukemia
  Lupus
  Lymphoma
  Non-insulin dependent diabetes
  Pediatric lymphoma
  Peutz-Jeghers syndrome
  Primary biliary cholangitis
  Promyelocytic leukaemia
  Pulmonary fibrosis
  Rectal carcinoma
  Systemic lupus erythematosus
  Acute myelogenous leukaemia
• UniProt ID: ARI3A_HUMAN
• PDB ID: 2KK0; 4LJX
• Pfam ID: PF01388
• Sequence:
  MKLQAVMETLLQRQQRARQELEARQQLPPDPPAAPPGRARAAPDEDREPESARMQRAQMA
  ALAAMRAAAAGLGHPASPGGSEDGPPGSEEEDAAREGTPGSPGRGREGPGEEHFEDMASD
  EDMKPKWEEEEMEEDLGEDEEEEEEDYEDEEEEEDEEGLGPPGPASLGTTALFPRKAQPP
  QAFRGDGVPRVLGGQERPGPGPAHPGGAAHVAPQLQPPDHGDWTYEEQFKQLYELDGDPK
  RKEFLDDLFSFMQKRGTPVNRIPIMAKQVLDLFMLYVLVTEKGGLVEVINKKLWREITKG
  LNLPTSITSAAFTLRTQYMKYLYPYECEKRGLSNPNELQAAIDSNRREGRRQSFGGSLFA
  YSPGGAHGMLSSPKLPVSSLGLAASTNGSSITPAPKIKKEEDSAIPITVPGRLPVSLAGH
  PVVAAQAAAVQAAAAQAAVAAQAAALEQLREKLESAEPPEKKMALVADEQQRLMQRALQQ
  NFLAMAAQLPMSIRINSQASESRQDSAVNLTGTNGSNSISMSVEINGIMYTGVLFAQPPA
  PTPTSAPNKGGGGGGGSSSNAGGRGGNTGTSGGQAGPAGLSTPSTSTSNNSLP
• Function: Transcription factor which may be involved in the control of cell cycle progression by the RB1/E2F1 pathway and in B-cell differentiation.
• Tissue Specificity: Widely expressed, with highest expression in skeletal muscle, thalamus, and colon.
• Reactome Pathway: TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest (R-HSA-6804116)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[5]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[6]
Hypoglycemia	DISRCKR7	Strong	Genetic Variation	[7]
Leukemia	DISNAKFL	Strong	Altered Expression	[8]
Lupus	DISOKJWA	Strong	Altered Expression	[9]
Lymphoma	DISN6V4S	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[7]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Peutz-Jeghers syndrome	DISF27ZJ	Strong	Genetic Variation	[10]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[11]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[8]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[12]
Rectal carcinoma	DIS8FRR7	Strong	Altered Expression	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[13]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[1]

5 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 AT-rich interactive domain-containing protein 3A (ARID3A).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of AT-rich interactive domain-containing protein 3A (ARID3A).	[20]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of AT-rich interactive domain-containing protein 3A (ARID3A).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of AT-rich interactive domain-containing protein 3A (ARID3A).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of AT-rich interactive domain-containing protein 3A (ARID3A).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of AT-rich interactive domain-containing protein 3A (ARID3A).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of AT-rich interactive domain-containing protein 3A (ARID3A).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of AT-rich interactive domain-containing protein 3A (ARID3A).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of AT-rich interactive domain-containing protein 3A (ARID3A).	[18]
Menadione	DMSJDTY	Approved	Menadione affects the expression of AT-rich interactive domain-containing protein 3A (ARID3A).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of AT-rich interactive domain-containing protein 3A (ARID3A).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of AT-rich interactive domain-containing protein 3A (ARID3A).	[25]

References

• [1] Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials.Future Oncol. 2019 Nov;15(31):3531-3545. doi: 10.2217/fon-2019-0373. Epub 2019 Sep 13.
• [2] Crucial Role of Increased Arid3a at the Pre-B and Immature B Cell Stages for B1a Cell Generation.Front Immunol. 2019 Mar 15;10:457. doi: 10.3389/fimmu.2019.00457. eCollection 2019.
• [3] ARID3A Positivity Correlated With Favorable Prognosis in Patients With Residual Rectal Cancer After Neoadjuvant Chemoradiotherapy.Anticancer Res. 2019 Jun;39(6):2845-2853. doi: 10.21873/anticanres.13413.
• [4] High expression of AT-rich interactive domain 3A (ARID3A) is associated with good prognosis in colorectal carcinoma.Ann Surg Oncol. 2014 Dec;21 Suppl 4:S481-9. doi: 10.1245/s10434-013-3435-2. Epub 2013 Dec 24.
• [5] Effects of carvedilol vs bisoprolol on inflammation and oxidative stress in patients with chronic heart failure.J Cardiol. 2020 Feb;75(2):140-147. doi: 10.1016/j.jjcc.2019.07.011. Epub 2019 Aug 21.
• [6] Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations.Hum Mol Genet. 2009 Jun 15;18(12):2288-96. doi: 10.1093/hmg/ddp135. Epub 2009 Mar 20.
• [7] Similar glycaemic control and less hypoglycaemia during active titration after insulin initiation with glargine 300 units/mL and degludec 100 units/mL: A subanalysis of the BRIGHT study.Diabetes Obes Metab. 2020 Mar;22(3):346-354. doi: 10.1111/dom.13901. Epub 2019 Dec 20.
• [8] E2FBP1/hDril1 modulates cell growth through downregulation of promyelocytic leukemia bodies.Cell Death Differ. 2004 Jul;11(7):747-59. doi: 10.1038/sj.cdd.4401412.
• [9] Differential expression of the transcription factor ARID3a in lupus patient hematopoietic progenitor cells.J Immunol. 2015 Feb 1;194(3):940-9. doi: 10.4049/jimmunol.1401941. Epub 2014 Dec 22.
• [10] The human dead ringer/bright homolog, DRIL1: cDNA cloning, gene structure, and mapping to D19S886, a marker on 19p13.3 that is strictly linked to the Peutz-Jeghers syndrome.Genomics. 1998 Jul 15;51(2):288-92. doi: 10.1006/geno.1998.5259.
• [11] A genome-wide association study identifies six novel risk loci for primary biliary cholangitis.Nat Commun. 2017 Apr 20;8:14828. doi: 10.1038/ncomms14828.
• [12] Cross talk between Id1 and its interactive protein Dril1 mediate fibroblast responses to transforming growth factor-beta in pulmonary fibrosis.Am J Pathol. 2008 Aug;173(2):337-46. doi: 10.2353/ajpath.2008.070915. Epub 2008 Jun 26.
• [13] ARID3a gene profiles are strongly associated with human interferon alpha production.J Autoimmun. 2019 Jan;96:158-167. doi: 10.1016/j.jaut.2018.09.013. Epub 2018 Oct 5.
• [14] 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.
• [15] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [16] 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.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [25] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.