Details of Drug Off-Target (DOT)

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

• DOT Name: Hydroxyacylglutathione hydrolase-like protein (HAGHL)
• Synonyms: EC 3.1.2.-
• Gene Name: HAGHL
• UniProt ID: HAGHL_HUMAN
• EC Number: 3.1.2.-
• Pfam ID: PF00753
• Sequence:
  MKVKVIPVLEDNYMYLVIEELTREAVAVDVAVPKRLLEIVGREGVSLTAVLTTHHHWDHA
  RGNPELARLRPGLAVLGADERIFSLTRRLAHGEELRFGAIHVRCLLTPGHTAGHMSYFLW
  EDDCPDPPALFSGDALSVAGCGSCLEGSAQQMYQSLAELGTLPPETKVFCGHEHTLSNLE
  FAQKVEPCNDHVRAKLSWAKARPLSRRGKRVGGEGTGFGVGGALRQGLMVTGACGHSRRG
  MRMTCPLCRRLWARSASTTPSCGWREYGCCPGASTVTWTLRKASGDCVLG
• Function: Hydrolase acting on ester bonds.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Hydroxyacylglutathione hydrolase-like protein (HAGHL).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Hydroxyacylglutathione hydrolase-like protein (HAGHL).	[4]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Hydroxyacylglutathione hydrolase-like protein (HAGHL).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Hydroxyacylglutathione hydrolase-like protein (HAGHL).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Hydroxyacylglutathione hydrolase-like protein (HAGHL).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Hydroxyacylglutathione hydrolase-like protein (HAGHL).	[6]

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] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] 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.
• [6] 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.