Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVJ0PNW)

• DOT Name: Cytochrome P450 27C1 (CYP27C1)
• Synonyms: EC 1.14.19.53; All-trans retinol 3,4-desaturase
• Gene Name: CYP27C1
• UniProt ID: C27C1_HUMAN
• EC Number: 1.14.19.53
• Pfam ID: PF00067
• Sequence:
  MQTSAMALLARILRAGLRPAPERGGLLGGGAPRRPQPAGARLPAGARAEDKGAGRPGSPP
  GGGRAEGPRSLAAMPGPRTLANLAEFFCRDGFSRIHEIQQKHTREYGKIFKSHFGPQFVV
  SIADRDMVAQVLRAEGAAPQRANMESWREYRDLRGRATGLISAEGEQWLKMRSVLRQRIL
  KPKDVAIYSGEVNQVIADLIKRIYLLRSQAEDGETVTNVNDLFFKYSMEGVATILYESRL
  GCLENSIPQLTVEYIEALELMFSMFKTSMYAGAIPRWLRPFIPKPWREFCRSWDGLFKFS
  QIHVDNKLRDIQYQMDRGRRVSGGLLTYLFLSQALTLQEIYANVTEMLLAGVDTTSFTLS
  WTVYLLARHPEVQQTVYREIVKNLGERHVPTAADVPKVPLVRALLKETLRLFPVLPGNGR
  VTQEDLVIGGYLIPKGTQLALCHYATSYQDENFPRAKEFRPERWLRKGDLDRVDNFGSIP
  FGHGVRSCIGRRIAELEIHLVVIQLLQHFEIKTSSQTNAVHAKTHGLLTPGGPIHVRFVN
  RK
• Function: [Isoform 2]: A cytochrome P450 monooxygenase that catalyzes the 3,4 desaturation of all-trans-retinol (also called vitamin A1) to all-trans-3,4-didehydroretinol (also called vitamin A2) in the skin. Desaturates with lower efficiency all-trans retinal and all-trans retinoic acid. Forms minor amounts of 3-hydroxy and 4-hydroxy all-trans-retinol derivatives. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin).
• Tissue Specificity: Widely expressed, with highest levels in the liver, kidney and pancreas.; [Isoform 2]: Expressed in the skin (at protein level).
• KEGG Pathway: Retinol metabolism (hsa00830)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cytochrome P450 27C1 (CYP27C1).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cytochrome P450 27C1 (CYP27C1).	[6]

5 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 Cytochrome P450 27C1 (CYP27C1).	[2]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cytochrome P450 27C1 (CYP27C1).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cytochrome P450 27C1 (CYP27C1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cytochrome P450 27C1 (CYP27C1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cytochrome P450 27C1 (CYP27C1).	[5]

References

• [1] 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.
• [2] 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.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.
• [5] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.