Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMGVT01)

• DOT Name: Choline-phosphate cytidylyltransferase B (PCYT1B)
• Synonyms: EC 2.7.7.15; CCT-beta; CTP:phosphocholine cytidylyltransferase B; CCT B; CT B; Phosphorylcholine transferase B
• Gene Name: PCYT1B
• UniProt ID: PCY1B_HUMAN
• EC Number: 2.7.7.15
• Pfam ID: PF01467
• Sequence:
  MPVVTTDAESETGIPKSLSNEPPSETMEEIEHTCPQPRLTLTAPAPFADETNCQCQAPHE
  KLTIAQARLGTPADRPVRVYADGIFDLFHSGHARALMQAKTLFPNSYLLVGVCSDDLTHK
  FKGFTVMNEAERYEALRHCRYVDEVIRDAPWTLTPEFLEKHKIDFVAHDDIPYSSAGSDD
  VYKHIKEAGMFVPTQRTEGISTSDIITRIVRDYDVYARRNLQRGYTAKELNVSFINEKRY
  RFQNQVDKMKEKVKNVEERSKEFVNRVEEKSHDLIQKWEEKSREFIGNFLELFGPDGAWK
  QMFQERSSRMLQALSPKQSPVSSPTRSRSPSRSPSPTFSWLPLKTSPPSSPKAASASISS
  MSEGDEDEK
• Function: [Isoform 1]: Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis; [Isoform 2]: Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.
• Tissue Specificity: .Highly expressed in testis, placenta, brain, ovary, liver and fetal lung.; [Isoform 2]: Expressed in brain, liver and fetal lung.
• KEGG Pathway:
  Phospho.te and phosphi.te metabolism (hsa00440)
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway: Synthesis of PC (R-HSA-1483191)

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 Choline-phosphate cytidylyltransferase B (PCYT1B).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[4]
Marinol	DM70IK5	Approved	Marinol increases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[6]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[7]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Choline-phosphate cytidylyltransferase B (PCYT1B).	[11]

2 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 Choline-phosphate cytidylyltransferase B (PCYT1B).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Choline-phosphate cytidylyltransferase B (PCYT1B).	[10]

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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] 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.