Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLXVB97)

• DOT Name: Histone H2A type 1-H (H2AC12)
• Synonyms: H2A-clustered histone 12; Histone H2A/s
• Gene Name: H2AC12
• Related Disease: Esophageal squamous cell carcinoma
• UniProt ID: H2A1H_HUMAN
• Pfam ID: PF00125 ; PF16211
• Sequence:
  MSGRGKQGGKARAKAKTRSSRAGLQFPVGRVHRLLRKGNYAERVGAGAPVYLAAVLEYLT
  AEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGKVTIAQGGVLPNIQAVLLPKK
  TESHHKAK
• Function: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  Necroptosis (hsa04217)
  Neutrophil extracellular trap formation (hsa04613)
  Alcoholism (hsa05034)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  HATs acetylate histones (R-HSA-3214847)
  RMTs methylate histone arginines (R-HSA-3214858)
  UCH proteinases (R-HSA-5689603)
  Ub-specific processing proteases (R-HSA-5689880)
  Metalloprotease DUBs (R-HSA-5689901)
  HCMV Early Events (R-HSA-9609690)
  HCMV Late Events (R-HSA-9610379)
  HDACs deacetylate histones (R-HSA-3214815)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[1]

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 Histone H2A type 1-H (H2AC12).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone H2A type 1-H (H2AC12).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H2A type 1-H (H2AC12).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone H2A type 1-H (H2AC12).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Histone H2A type 1-H (H2AC12).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Histone H2A type 1-H (H2AC12).	[7]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Histone H2A type 1-H (H2AC12).	[8]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Histone H2A type 1-H (H2AC12).	[9]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Histone H2A type 1-H (H2AC12).	[10]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide increases the expression of Histone H2A type 1-H (H2AC12).	[11]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone H2A type 1-H (H2AC12).	[12]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Histone H2A type 1-H (H2AC12).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Histone H2A type 1-H (H2AC12).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Histone H2A type 1-H (H2AC12).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H2A type 1-H (H2AC12).	[16]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of Histone H2A type 1-H (H2AC12).	[17]

References

• [1] Quantitative Proteomics Identify the Possible Tumor Suppressive Role of Protease-Activated Receptor-4 in Esophageal Squamous Cell Carcinoma Cells.Pathol Oncol Res. 2019 Jul;25(3):937-943. doi: 10.1007/s12253-018-0395-7. Epub 2018 Mar 4.
• [2] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [3] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [8] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [9] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [10] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [11] Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
• [12] Berberine acts as a putative epigenetic modulator by affecting the histone code. Toxicol In Vitro. 2016 Oct;36:10-17. doi: 10.1016/j.tiv.2016.06.004. Epub 2016 Jun 13.
• [13] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [15] 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.
• [16] 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.
• [17] Paraoxon-induced protein expression changes to SH-SY5Y cells. Chem Res Toxicol. 2010 Nov 15;23(11):1656-62. doi: 10.1021/tx100192f. Epub 2010 Oct 8.