Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM647IV)

• DOT Name: Trans-Golgi network integral membrane protein 2 (TGOLN2)
• Synonyms: Trans-Golgi network glycoprotein 46; TGN38 homolog; hTGN46; Trans-Golgi network glycoprotein 48; hTGN48; Trans-Golgi network glycoprotein 51; hTGN51; Trans-Golgi network protein 2
• Gene Name: TGOLN2
• UniProt ID: TGON2_HUMAN
• PDB ID: 6YAF
• Pfam ID: PF17818
• Sequence:
  MRFVVALVLLNVAAAGAVPLLATESVKQEEAGVRPSAGNVSTHPSLSQRPGGSTKSHPEP
  QTPKDSPSKSSAEAQTPEDTPNKSGAEAKTQKDSSNKSGAEAKTQKGSTSKSGSEAQTTK
  DSTSKSHPELQTPKDSTGKSGAEAQTPEDSPNRSGAEAKTQKDSPSKSGSEAQTTKDVPN
  KSGADGQTPKDGSSKSGAEDQTPKDVPNKSGAEKQTPKDGSNKSGAEEQGPIDGPSKSGA
  EEQTSKDSPNKVVPEQPSRKDHSKPISNPSDNKELPKADTNQLADKGKLSPHAFKTESGE
  ETDLISPPQEEVKSSEPTEDVEPKEAEDDDTGPEEGSPPKEEKEKMSGSASSENREGTLS
  DSTGSEKDDLYPNGSGNGSAESSHFFAYLVTAAILVAVLYIAHHNKRKIIAFVLEGKRSK
  VTRRPKASDYQRLDQKS
• Function: May be involved in regulating membrane traffic to and from trans-Golgi network.
• Tissue Specificity: Isoform TGN46 is widely expressed. Isoform TGN51 is more abundant in fetal lung and kidney. Isoform TGN48 is barely expressed in embryonic kidney and promyelocytic cells.
• Reactome Pathway:
  Golgi Associated Vesicle Biogenesis (R-HSA-432722)
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

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 Trans-Golgi network integral membrane protein 2 (TGOLN2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[7]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[8]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[9]
Methimazole	DM25FL8	Approved	Methimazole increases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[9]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[10]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[12]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[6]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine affects the localization of Trans-Golgi network integral membrane protein 2 (TGOLN2).	[11]

References

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• [3] 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.
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• [6] 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.
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• [8] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [9] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [10] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [11] Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy. 2018;14(8):1435-1455. doi: 10.1080/15548627.2018.1474314. Epub 2018 Jul 20.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [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] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [15] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.