Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM36JXE)

• DOT Name: Phosphatidylcholine transfer protein (PCTP)
• Synonyms: PC-TP; START domain-containing protein 2; StARD2; StAR-related lipid transfer protein 2
• Gene Name: PCTP
• Related Disease:
  Cholestasis
  Fatty liver disease
  Gestational trophoblastic neoplasia
  Type-1/2 diabetes
• UniProt ID: PPCT_HUMAN
• PDB ID: 1LN1; 1LN2; 1LN3; 7U9D
• Pfam ID: PF01852
• Sequence:
  MELAAGSFSEEQFWEACAELQQPALAGADWQLLVETSGISIYRLLDKKTGLYEYKVFGVL
  EDCSPTLLADIYMDSDYRKQWDQYVKELYEQECNGETVVYWEVKYPFPMSNRDYVYLRQR
  RDLDMEGRKIHVILARSTSMPQLGERSGVIRVKQYKQSLAIESDGKKGSKVFMYYFDNPG
  GQIPSWLINWAAKNGVPNFLKDMARACQNYLKKT
• Function: Catalyzes the transfer of phosphatidylcholine between membranes. Binds a single lipid molecule.
• Tissue Specificity: Highest expression in liver, placenta, testis, kidney and heart. Low levels in brain and lung. No expression detected in thymus.
• Reactome Pathway:
  Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289)
  Synthesis of PC (R-HSA-1483191)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholestasis	DISDJJWE	Strong	Altered Expression	[1]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[2]
Gestational trophoblastic neoplasia	DIS4EJNA	Strong	Altered Expression	[3]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[4]

14 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 Phosphatidylcholine transfer protein (PCTP).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphatidylcholine transfer protein (PCTP).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phosphatidylcholine transfer protein (PCTP).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylcholine transfer protein (PCTP).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphatidylcholine transfer protein (PCTP).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphatidylcholine transfer protein (PCTP).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Phosphatidylcholine transfer protein (PCTP).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Phosphatidylcholine transfer protein (PCTP).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Phosphatidylcholine transfer protein (PCTP).	[12]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Phosphatidylcholine transfer protein (PCTP).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Phosphatidylcholine transfer protein (PCTP).	[14]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of Phosphatidylcholine transfer protein (PCTP).	[15]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Phosphatidylcholine transfer protein (PCTP).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Phosphatidylcholine transfer protein (PCTP).	[19]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Clofibrate	DMPC1J7	Approved	Clofibrate affects the localization of Phosphatidylcholine transfer protein (PCTP).	[16]

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 Phosphatidylcholine transfer protein (PCTP).	[18]

References

• [1] Etiologic significance of defects in cholesterol, phospholipid, and bile acid metabolism in the liver of patients with intrahepatic calculi.Hepatology. 2001 May;33(5):1194-205. doi: 10.1053/jhep.2001.23936.
• [2] Phosphatidylcholine transfer protein/StarD2 promotes microvesicular steatosis and liver injury in murine experimental steatohepatitis.Am J Physiol Gastrointest Liver Physiol. 2017 Jul 1;313(1):G50-G61. doi: 10.1152/ajpgi.00379.2016. Epub 2017 Apr 6.
• [3] GTT1/StarD7, a novel phosphatidylcholine transfer protein-like highly expressed in gestational trophoblastic tumour: cloning and characterization.Placenta. 2004 Jan;25(1):37-44. doi: 10.1016/S0143-4004(03)00214-5.
• [4] Genetic ablation of phosphatidylcholine transfer protein/StarD2 in ob/ob mice improves glucose tolerance without increasing energy expenditure.Metabolism. 2017 Mar;68:145-149. doi: 10.1016/j.metabol.2016.11.012. Epub 2016 Dec 1.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [14] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [15] Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: a microarray study. Biochem Biophys Res Commun. 2008 Aug 8;372(4):785-91.
• [16] Clofibrate-induced relocation of phosphatidylcholine transfer protein to mitochondria in endothelial cells. Exp Cell Res. 2002 Mar 10;274(1):100-11. doi: 10.1006/excr.2001.5460.
• [17] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [18] 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.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.