Details of Drug Off-Target (DOT)

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

• DOT Name: Acylpyruvase FAHD1, mitochondrial (FAHD1)
• Synonyms: EC 3.7.1.5; Fumarylacetoacetate hydrolase domain-containing protein 1; FAH domain-containing protein 1; Oxaloacetate decarboxylase; OAA decarboxylase; EC 4.1.1.112; YisK-like protein
• Gene Name: FAHD1
• UniProt ID: FAHD1_HUMAN
• PDB ID: 1SAW; 6FOG; 6FOH
• EC Number: 3.7.1.5; 4.1.1.112
• Pfam ID: PF01557
• Sequence:
  MAASRPLSRFWEWGKNIVCVGRNYADHVREMRSAVLSEPVLFLKPSTAYAPEGSPILMPA
  YTRNLHHELELGVVMGKRCRAVPEAAAMDYVGGYALCLDMTARDVQDECKKKGLPWTLAK
  SFTASCPVSAFVPKEKIPDPHKLKLWLKVNGELRQEGETSSMIFSIPYIISYVSKIITLE
  EGDIILTGTPKGVGPVKENDEIEAGIHGLVSMTFKVEKPEY
• Function: Probable mitochondrial acylpyruvase which is able to hydrolyze acetylpyruvate and fumarylpyruvate in vitro. Also has oxaloacetate decarboxylase activity.
• Tissue Specificity: Ubiquitous (at protein level).
• KEGG Pathway:
  Tyrosine metabolism (hsa00350)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Citric acid cycle (TCA cycle) (R-HSA-71403)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[10]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[11]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acylpyruvase FAHD1, mitochondrial (FAHD1).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [11] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [12] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.