Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO2ZATJ)

• DOT Name: All-trans-retinol dehydrogenase ADH7 (ADH7)
• Synonyms: EC 1.1.1.105; Alcohol dehydrogenase class 4 mu/sigma chain; EC 1.1.1.1; Alcohol dehydrogenase class IV mu/sigma chain; Gastric alcohol dehydrogenase; Omega-hydroxydecanoate dehydrogenase ADH7; EC 1.1.1.66; Retinol dehydrogenase
• Gene Name: ADH7
• UniProt ID: ADH7_HUMAN
• PDB ID: 1AGN; 1D1S; 1D1T
• EC Number: 1.1.1.1; 1.1.1.105; 1.1.1.66
• Pfam ID: PF08240 ; PF00107
• Sequence:
  MFAEIQIQDKDRMGTAGKVIKCKAAVLWEQKQPFSIEEIEVAPPKTKEVRIKILATGICR
  TDDHVIKGTMVSKFPVIVGHEATGIVESIGEGVTTVKPGDKVIPLFLPQCRECNACRNPD
  GNLCIRSDITGRGVLADGTTRFTCKGKPVHHFMNTSTFTEYTVVDESSVAKIDDAAPPEK
  VCLIGCGFSTGYGAAVKTGKVKPGSTCVVFGLGGVGLSVIMGCKSAGASRIIGIDLNKDK
  FEKAMAVGATECISPKDSTKPISEVLSEMTGNNVGYTFEVIGHLETMIDALASCHMNYGT
  SVVVGVPPSAKMLTYDPMLLFTGRTWKGCVFGGLKSRDDVPKLVTEFLAKKFDLDQLITH
  VLPFKKISEGFELLNSGQSIRTVLTF
• Function: Catalyzes the NAD-dependent oxidation of all-trans-retinol, alcohol, and omega-hydroxy fatty acids and their derivatives. Oxidizes preferentially all trans-retinol, all-trans-4-hydroxyretinol, 9-cis-retinol, 2-hexenol, and long chain omega-hydroxy fatty acids such as juniperic acid. In vitro can also catalyzes the NADH-dependent reduction of all-trans-retinal and aldehydes and their derivatives. Reduces preferentially all trans-retinal, all-trans-4-oxoretinal and hexanal. Catalyzes in the oxidative direction with higher efficiency. Therefore may participate in retinoid metabolism, fatty acid omega-oxidation, and elimination of cytotoxic aldehydes produced by lipid peroxidation.
• Tissue Specificity: Preferentially expressed in stomach.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Fatty acid degradation (hsa00071)
  Tyrosine metabolism (hsa00350)
  Pyruvate metabolism (hsa00620)
  Retinol metabolism (hsa00830)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Metabolic pathways (hsa01100)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway: Ethanol oxidation (R-HSA-71384)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Polyethylene glycol	DM4I1JP	Approved	All-trans-retinol dehydrogenase ADH7 (ADH7) increases the oxidation of Polyethylene glycol.	[5]
2-Propanol, Isopropanol	DML5O0H	Investigative	All-trans-retinol dehydrogenase ADH7 (ADH7) increases the oxidation of 2-Propanol, Isopropanol.	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of All-trans-retinol dehydrogenase ADH7 (ADH7).	[1]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of All-trans-retinol dehydrogenase ADH7 (ADH7).	[2]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of All-trans-retinol dehydrogenase ADH7 (ADH7).	[3]

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 All-trans-retinol dehydrogenase ADH7 (ADH7).	[4]

References

• [1] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [2] Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321. doi: 10.1016/j.redox.2019.101321. Epub 2019 Sep 5.
• [3] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [4] 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.
• [5] Oxidation of methanol, ethylene glycol, and isopropanol with human alcohol dehydrogenases and the inhibition by ethanol and 4-methylpyrazole. Chem Biol Interact. 2011 May 30;191(1-3):26-31. doi: 10.1016/j.cbi.2010.12.005. Epub 2010 Dec 15.