Details of Drug Off-Target (DOT)

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

• DOT Name: Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB)
• Synonyms: hnRNP A/B; APOBEC1-binding protein 1; ABBP-1
• Gene Name: HNRNPAB
• Related Disease:
  Non-small-cell lung cancer
  Mixed connective tissue disease
  Prostate cancer
  Prostate carcinoma
• UniProt ID: ROAA_HUMAN
• PDB ID: 3S7R
• Pfam ID: PF08143 ; PF00076
• Sequence:
  MSEAGEEQPMETTGATENGHEAVPEASRGRGWTGAAAGAGGATAAPPSGNQNGAEGDQIN
  ASKNEEDAGKMFVGGLSWDTSKKDLKDYFTKFGEVVDCTIKMDPNTGRSRGFGFILFKDA
  ASVEKVLDQKEHRLDGRVIDPKKAMAMKKDPVKKIFVGGLNPESPTEEKIREYFGEFGEI
  EAIELPMDPKLNKRRGFVFITFKEEEPVKKVLEKKFHTVSGSKCEIKVAQPKEVYQQQQY
  GSGGRGNRNRGNRGSGGGGGGGGQSQSWNQGYGNYWNQGYGYQQGYGPGYGGYDYSPYGY
  YGYGPGYDYSQGSTNYGKSQRRGGHQNNYKPY
• Function: Binds single-stranded RNA. Has a high affinity for G-rich and U-rich regions of hnRNA. Also binds to APOB mRNA transcripts around the RNA editing site.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[1]
Mixed connective tissue disease	DISXX0H8	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[12]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[14]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[20]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[21]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[16]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB).	[18]

References

• [1] Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues.BMC Cancer. 2010 Aug 17;10:434. doi: 10.1186/1471-2407-10-434.
• [2] Identification of autoantibodies to the I protein of the heterogeneous nuclear ribonucleoprotein complex in patients with systemic sclerosis.Arthritis Rheum. 1996 Oct;39(10):1669-76. doi: 10.1002/art.1780391009.
• [3] Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19.Cell. 2018 Jul 26;174(3):564-575.e18. doi: 10.1016/j.cell.2018.06.014. Epub 2018 Jul 19.
• [4] 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.
• [5] Proteomics investigations of drug-induced hepatotoxicity in HepG2 cells. Toxicol Sci. 2011 Mar;120(1):109-22.
• [6] Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: proteomic characterization. Exp Cell Res. 2007 Jan 15;313(2):357-68. doi: 10.1016/j.yexcr.2006.10.016. Epub 2006 Oct 25.
• [7] 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.
• [8] Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1. Mol Endocrinol. 2004 Feb;18(2):402-11. doi: 10.1210/me.2003-0202. Epub 2003 Nov 6.
• [9] 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.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] 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.
• [12] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [13] Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.
• [14] Identification of potential biomarkers for predicting acute dermal irritation by proteomic analysis. J Appl Toxicol. 2011 Nov;31(8):762-72.
• [15] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [20] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [21] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [22] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.