Details of Drug Off-Target (DOT)

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

• DOT Name: Transmembrane and coiled-coil domain-containing protein 6 (TMCO6)
• Gene Name: TMCO6
• UniProt ID: TMCO6_HUMAN
• Sequence:
  MWSRRQGRLRPTVCGVEELRRRRREREAALRKARREQQLVSKRLLRNDAPEEAGEGCVAA
  ILGETEVQQFLRQAQRGTEEKEREGALVSLRRGLQHPETQQTFIRLEGSMRTLVGLLTSN
  QALLQLEAARCLHELSHSEQSTVAEACLPATSYLLTYLSSHSSDFIELCLYTLGNLIVES
  EAVRRQLLPQGIVPALAACIQSPHVAVLEALGYALSQLLQAEEAPEKIIPSILASTLPQH
  MLQMLQPGPKLNPGVAVEFAWCLHYIICSQVSNPLLIGHGALSTLGLLLLDLAGAVQKTE
  DAGLELLACPVLRCLSNLLTEAAVETVGGQMQLRDERVVAALFILLQFFFQKQPSLLPEG
  LWLLNNLTANSPSFCTSLLSLDLIEPLLQLLPVSNVVSVMVLTVLCNVAEKGPAYCQRLW
  PGPLLPALLHTLAFSDTEVVGQSLELLHLLFLYQPEAVQVFLQQSGLQALERHQEEAQLQ
  DRVYALQQTALQG

Molecular Interaction Atlas (MIA) of This DOT

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[8]
Lindane	DMB8CNL	Approved	Lindane decreases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[9]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[6]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[11]

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 increases the methylation of Transmembrane and coiled-coil domain-containing protein 6 (TMCO6).	[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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Prolyl endopeptidase is involved in cellular signalling in human neuroblastoma SH-SY5Y cells. Neurosignals. 2011;19(2):97-109. doi: 10.1159/000326342. Epub 2011 Apr 10.