Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPO62JI)

• DOT Name: Histone H2A type 3 (H2AC25)
• Synonyms: H2A-clustered histone 25
• Gene Name: H2AC25
• UniProt ID: H2A3_HUMAN
• Pfam ID: PF00125 ; PF16211
• Sequence:
  MSGRGKQGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGNYSERVGAGAPVYLAAVLEYLT
  AEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGRVTIAQGGVLPNIQAVLLPKK
  TESHHKAKGK
• 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 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 Histone H2A type 3 (H2AC25).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Histone H2A type 3 (H2AC25).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H2A type 3 (H2AC25).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Histone H2A type 3 (H2AC25).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Histone H2A type 3 (H2AC25).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone H2A type 3 (H2AC25).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Histone H2A type 3 (H2AC25).	[7]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Histone H2A type 3 (H2AC25).	[8]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone H2A type 3 (H2AC25).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Histone H2A type 3 (H2AC25).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Histone H2A type 3 (H2AC25).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Histone H2A type 3 (H2AC25).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Histone H2A type 3 (H2AC25).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Histone H2A type 3 (H2AC25).	[14]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of Histone H2A type 3 (H2AC25).	[15]

References

• [1] 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.
• [2] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [7] 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.
• [8] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [9] 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.
• [10] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [11] 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.
• [12] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.