Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN5DENU)

DOT Name	Histone H2A type 1-A (H2AC1)
Synonyms	H2A-clustered histone 1; Histone H2A/r
Gene Name	H2AC1
Related Disease	Gout ( )
UniProt ID	H2A1A_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5GSU; 5GT0
Pfam ID	PF00125 ; PF16211
Sequence	MSGRGKQGGKARAKSKSRSSRAGLQFPVGRIHRLLRKGNYAERIGAGAPVYLAAVLEYLT AEILELAGNASRDNKKTRIIPRHLQLAIRNDEELNKLLGGVTIAQGGVLPNIQAVLLPKK TESHHHKAQSK
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
Gout	DISHC0U7	Strong	Genetic Variation	[1]
------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Sulforaphane	DMQY3L0	Investigative	Histone H2A type 1-A (H2AC1) affects the binding of Sulforaphane.	[8]
------------------------------------------------------------------------------------

4 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 1-A (H2AC1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Histone H2A type 1-A (H2AC1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Histone H2A type 1-A (H2AC1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Histone H2A type 1-A (H2AC1).	[6]
------------------------------------------------------------------------------------

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H2A type 1-A (H2AC1).	[3]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Histone H2A type 1-A (H2AC1).	[7]
------------------------------------------------------------------------------------

References

1	Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
2	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.
3	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
4	Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults. Environ Health Perspect. 2019 May;127(5):57011. doi: 10.1289/EHP3849. Epub 2019 May 28.
5	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.
6	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.
7	Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
8	Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.