General Information of Drug Off-Target (DOT) (ID: OTMH0YLN)

DOT Name Choline-phosphate cytidylyltransferase A (PCYT1A)
Synonyms EC 2.7.7.15; CCT-alpha; CTP:phosphocholine cytidylyltransferase A; CCT A; CT A; Phosphorylcholine transferase A
Gene Name PCYT1A
Related Disease
Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome ( )
Leber congenital amaurosis ( )
UniProt ID
PCY1A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.7.15
Pfam ID
PF01467
Sequence
MDAQCSAKVNARKRRKEAPGPNGATEEDGVPSKVQRCAVGLRQPAPFSDEIEVDFSKPYV
RVTMEEASRGTPCERPVRVYADGIFDLFHSGHARALMQAKNLFPNTYLIVGVCSDELTHN
FKGFTVMNENERYDAVQHCRYVDEVVRNAPWTLTPEFLAEHRIDFVAHDDIPYSSAGSDD
VYKHIKEAGMFAPTQRTEGISTSDIITRIVRDYDVYARRNLQRGYTAKELNVSFINEKKY
HLQERVDKVKKKVKDVEEKSKEFVQKVEEKSIDLIQKWEEKSREFIGSFLEMFGPEGALK
HMLKEGKGRMLQAISPKQSPSSSPTRERSPSPSFRWPFSGKTSPPCSPANLSRHKAAAYD
ISEDEED
Function Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.
Tissue Specificity Brain, placenta, liver, fetal and adult 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 )
BioCyc Pathway
MetaCyc:HS08577-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome DISXRSJE Definitive Autosomal recessive [1]
Leber congenital amaurosis DISMGH8F Supportive Autosomal dominant [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 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 A (PCYT1A). [3]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Choline-phosphate cytidylyltransferase A (PCYT1A). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Choline-phosphate cytidylyltransferase A (PCYT1A). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Choline-phosphate cytidylyltransferase A (PCYT1A). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Choline-phosphate cytidylyltransferase A (PCYT1A). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Choline-phosphate cytidylyltransferase A (PCYT1A). [8]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Choline-phosphate cytidylyltransferase A (PCYT1A). [10]
DTI-015 DMXZRW0 Approved DTI-015 decreases the expression of Choline-phosphate cytidylyltransferase A (PCYT1A). [11]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of Choline-phosphate cytidylyltransferase A (PCYT1A). [15]
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⏷ Show the Full List of 9 Drug(s)
5 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Quercetin DM3NC4M Approved Quercetin increases the phosphorylation of Choline-phosphate cytidylyltransferase A (PCYT1A). [9]
G1 DMTV42K Phase 1/2 G1 decreases the phosphorylation of Choline-phosphate cytidylyltransferase A (PCYT1A). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Choline-phosphate cytidylyltransferase A (PCYT1A). [13]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Choline-phosphate cytidylyltransferase A (PCYT1A). [14]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Choline-phosphate cytidylyltransferase A (PCYT1A). [9]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Mutations in the PCYT1A gene are responsible for isolated forms of retinal dystrophy. Eur J Hum Genet. 2017 May;25(5):651-655. doi: 10.1038/ejhg.2017.23. Epub 2017 Mar 8.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 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.
5 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.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
8 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
9 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.
10 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
11 Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
12 The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
13 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.
14 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
15 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.