Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTODTW0I)

• DOT Name: Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3)
• Synonyms: hnRNP H3; Heterogeneous nuclear ribonucleoprotein 2H9; hnRNP 2H9
• Gene Name: HNRNPH3
• Related Disease:
  Hepatocellular carcinoma
  Hypotrichosis simplex
  Keloid
• UniProt ID: HNRH3_HUMAN
• Pfam ID: PF00076
• Sequence:
  MDWVMKHNGPNDASDGTVRLRGLPFGCSKEEIVQFFQGLEIVPNGITLTMDYQGRSTGEA
  FVQFASKEIAENALGKHKERIGHRYIEIFRSSRSEIKGFYDPPRRLLGQRPGPYDRPIGG
  RGGYYGAGRGSMYDRMRRGGDGYDGGYGGFDDYGGYNNYGYGNDGFDDRMRDGRGMGGHG
  YGGAGDASSGFHGGHFVHMRGLPFRATENDIANFFSPLNPIRVHIDIGADGRATGEADVE
  FVTHEDAVAAMSKDKNNMQHRYIELFLNSTPGGGSGMGGSGMGGYGRDGMDNQGGYGSVG
  RMGMGNNYSGGYGTPDGLGGYGRGGGGSGGYYGQGGMSGGGWRGMY
• Function: Involved in the splicing process and participates in early heat shock-induced splicing arrest. Due to their great structural variations the different isoforms may possess different functions in the splicing reaction.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Hypotrichosis simplex	DIS8WHDJ	moderate	Altered Expression	[2]
Keloid	DISV09JY	moderate	Biomarker	[2]

18 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 H3 (HNRNPH3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[12]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[19]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[20]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[21]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[22]

2 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 H3 (HNRNPH3).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein H3 (HNRNPH3).	[16]

References

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• [2] Tacrolimus fails to regulate collagen expression in dermal fibroblasts.J Surg Res. 2013 Sep;184(1):678-90. doi: 10.1016/j.jss.2013.04.006. Epub 2013 Apr 25.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):197-210. doi: 10.1016/j.taap.2006.12.030. Epub 2007 Jan 9.
• [11] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [18] 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.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [21] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.
• [22] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.