Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7BJD1M)

• DOT Name: Epidermal retinol dehydrogenase 2 (SDR16C5)
• Synonyms: EPHD-2; RDH-E2; EC 1.1.1.105; Retinal short-chain dehydrogenase reductase 2; retSDR2; Short-chain dehydrogenase/reductase family 16C member 5
• Gene Name: SDR16C5
• UniProt ID: RDHE2_HUMAN
• EC Number: 1.1.1.105
• Pfam ID: PF00106
• Sequence:
  MSFNLQSSKKLFIFLGKSLFSLLEAMIFALLPKPRKNVAGEIVLITGAGSGLGRLLALQF
  ARLGSVLVLWDINKEGNEETCKMAREAGATRVHAYTCDCSQKEGVYRVADQVKKEVGDVS
  ILINNAGIVTGKKFLDCPDELMEKSFDVNFKAHLWTYKAFLPAMIANDHGHLVCISSSAG
  LSGVNGLADYCASKFAAFGFAESVFVETFVQKQKGIKTTIVCPFFIKTGMFEGCTTGCPS
  LLPILEPKYAVEKIVEAILQEKMYLYMPKLLYFMMFLKSFLPLKTGLLIADYLGILHAMD
  GFVDQKKKL
• Function: Oxidoreductase with strong preference for NAD. Active in both the oxidative and reductive directions. Oxidizes all-trans-retinol in all-trans-retinaldehyde. No activity was detected with 11-cis-retinol or 11-cis-retinaldehyde as substrates with either NAD(+)/NADH or NADP(+)/NADPH.
• Tissue Specificity: Detected in adult lung. Detected at low levels in adult brain, heart, testis, placenta, cervix, pancreas, uterus, stomach, rectum, small intestine, colon, esophagus, thymus, skin, and skin keratinocyte. Expression is higher in psoriasis lesions relative to unaffected skin from psoriasis patients. Detected in fetal kidney, skin and lung.
• KEGG Pathway:
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: RA biosynthesis pathway (R-HSA-5365859)
• BioCyc Pathway: MetaCyc:ENSG00000170786-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vitamin A	DMJ2AH4	Approved	Epidermal retinol dehydrogenase 2 (SDR16C5) increases the metabolism of Vitamin A.	[3]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
All-trans-retinal	DM6CEVB	Investigative	Epidermal retinol dehydrogenase 2 (SDR16C5) increases the chemical synthesis of All-trans-retinal.	[3]

10 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 Epidermal retinol dehydrogenase 2 (SDR16C5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Epidermal retinol dehydrogenase 2 (SDR16C5).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Epidermal retinol dehydrogenase 2 (SDR16C5).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Epidermal retinol dehydrogenase 2 (SDR16C5).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Epidermal retinol dehydrogenase 2 (SDR16C5).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Epidermal retinol dehydrogenase 2 (SDR16C5).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Epidermal retinol dehydrogenase 2 (SDR16C5).	[1]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Epidermal retinol dehydrogenase 2 (SDR16C5).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Epidermal retinol dehydrogenase 2 (SDR16C5).	[9]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	Investigative	Nicotinamide-Adenine-Dinucleotide affects the activity of Epidermal retinol dehydrogenase 2 (SDR16C5).	[10]

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 Epidermal retinol dehydrogenase 2 (SDR16C5).	[7]

References

• [1] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Characterization of human short chain dehydrogenase/reductase SDR16C family members related to retinol dehydrogenase 10. Chem Biol Interact. 2017 Oct 1;276:88-94. doi: 10.1016/j.cbi.2016.10.019. Epub 2016 Oct 25.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [10] Biochemical characterization of human epidermal retinol dehydrogenase 2. Chem Biol Interact. 2009 Mar 16;178(1-3):182-7. doi: 10.1016/j.cbi.2008.09.019. Epub 2008 Sep 24.
• [11] Characterization of human short chain dehydrogenase/reductase SDR16C family members related to retinol dehydrogenase 10. Chem Biol Interact. 2017 Oct 1;276:88-94. doi: 10.1016/j.cbi.2016.10.019. Epub 2016 Oct 25.