Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEKO8CT)

• DOT Name: Ornithine aminotransferase, mitochondrial (OAT)
• Synonyms: EC 2.6.1.13; Ornithine delta-aminotransferase; Ornithine--oxo-acid aminotransferase
• Gene Name: OAT
• Related Disease: Ornithine aminotransferase deficiency
• UniProt ID: OAT_HUMAN
• PDB ID: 1GBN; 1OAT; 2BYJ; 2BYL; 2CAN; 2OAT; 5VWO; 6HX7; 6OIA; 6V8C; 6V8D; 7JX9; 7LK0; 7LK1; 7LNM; 7LOM; 7LON; 7T9Z; 7TA0; 7TA1; 7TED; 7TEV; 7TFP; 8EZ1
• EC Number: 2.6.1.13
• Pfam ID: PF00202
• Sequence:
  MFSKLAHLQRFAVLSRGVHSSVASATSVATKKTVQGPPTSDDIFEREYKYGAHNYHPLPV
  ALERGKGIYLWDVEGRKYFDFLSSYSAVNQGHCHPKIVNALKSQVDKLTLTSRAFYNNVL
  GEYEEYITKLFNYHKVLPMNTGVEAGETACKLARKWGYTVKGIQKYKAKIVFAAGNFWGR
  TLSAISSSTDPTSYDGFGPFMPGFDIIPYNDLPALERALQDPNVAAFMVEPIQGEAGVVV
  PDPGYLMGVRELCTRHQVLFIADEIQTGLARTGRWLAVDYENVRPDIVLLGKALSGGLYP
  VSAVLCDDDIMLTIKPGEHGSTYGGNPLGCRVAIAALEVLEEENLAENADKLGIILRNEL
  MKLPSDVVTAVRGKGLLNAIVIKETKDWDAWKVCLRLRDNGLLAKPTHGDIIRFAPPLVI
  KEDELRESIEIINKTILSF
• Function: Catalyzes the reversible interconversion of L-ornithine and 2-oxoglutarate to L-glutamate semialdehyde and L-glutamate.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Glutamate and glutamine metabolism (R-HSA-8964539)
• BioCyc Pathway: MetaCyc:HS00832-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ornithine aminotransferase deficiency	DISHMWCY	Definitive	Autosomal recessive	[1]

21 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 Ornithine aminotransferase, mitochondrial (OAT).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ornithine aminotransferase, mitochondrial (OAT).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ornithine aminotransferase, mitochondrial (OAT).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[11]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[5]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[19]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Ornithine aminotransferase, mitochondrial (OAT).	[20]

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 decreases the methylation of Ornithine aminotransferase, mitochondrial (OAT).	[14]

References

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• [12] Mitochondrial dysfunction induced by leflunomide and its active metabolite. Toxicology. 2018 Mar 1;396-397:33-45.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] 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.
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• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
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• [20] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.