Details of Drug Off-Target (DOT)

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

• DOT Name: Putative hydroxypyruvate isomerase (HYI)
• Synonyms: EC 5.3.1.22; Endothelial cell apoptosis protein E-CE1
• Gene Name: HYI
• Related Disease: Alzheimer disease
• UniProt ID: HYI_HUMAN
• EC Number: 5.3.1.22
• Pfam ID: PF01261
• Sequence:
  MAPLRFSANLSWLFPELSGLPARVRAAGSSGFEAVEVAWPYAETPEALARAAREAGLRLV
  LINTPPGDQEKGEMGLGAVPGRQAAFREGLEQAVRYAKALGCPRIHLMAGRVPQGADRIA
  VKAEMEAVFLENLRHAAGVLAQEDLVGLLEPINTRITDPQYFLDTPQQAAAILQKVGRPN
  LQLQMDIFHWQIMDGNLTGNIREFLPIVGHVQVAQVPGRGEPSSPGELNFPYLFQLLEDE
  GYKGFVGCEYQPRGDTVEGLSWLRSYWDRRGHPEAGQ
• Function: Catalyzes the reversible isomerization between hydroxypyruvate and 2-hydroxy-3-oxopropanoate (also termed tartronate semialdehyde).
• KEGG Pathway:
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Putative hydroxypyruvate isomerase (HYI).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Putative hydroxypyruvate isomerase (HYI).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Putative hydroxypyruvate isomerase (HYI).	[7]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Putative hydroxypyruvate isomerase (HYI).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Putative hydroxypyruvate isomerase (HYI).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Putative hydroxypyruvate isomerase (HYI).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Putative hydroxypyruvate isomerase (HYI).	[6]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Putative hydroxypyruvate isomerase (HYI).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Putative hydroxypyruvate isomerase (HYI).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Putative hydroxypyruvate isomerase (HYI).	[10]

References

• [1] Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [6] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.