Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT67LPGF)

• DOT Name: Thioredoxin-related transmembrane protein 4 (TMX4)
• Synonyms: Thioredoxin domain-containing protein 13
• Gene Name: TMX4
• UniProt ID: TMX4_HUMAN
• Pfam ID: PF00085
• Sequence:
  MAGGRCGPQLTALLAAWIAAVAATAGPEEAALPPEQSRVQPMTASNWTLVMEGEWMLKFY
  APWCPSCQQTDSEWEAFAKNGEILQISVGKVDVIQEPGLSGRFFVTTLPAFFHAKDGIFR
  RYRGPGIFEDLQNYILEKKWQSVEPLTGWKSPASLTMSGMAGLFSISGKIWHLHNYFTVT
  LGIPAWCSYVFFVIATLVFGLFMGLVLVVISECFYVPLPRHLSERSEQNRRSEEAHRAEQ
  LQDAEEEKDDSNEEENKDSLVDDEEEKEDLGDEDEAEEEEEEDNLAAGVDEERSEANDQG
  PPGEDGVTREEVEPEEAEEGISEQPCPADTEVVEDSLRQRKSQHADKGL

Molecular Interaction Atlas (MIA) of This DOT

8 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 Thioredoxin-related transmembrane protein 4 (TMX4).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Thioredoxin-related transmembrane protein 4 (TMX4).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Thioredoxin-related transmembrane protein 4 (TMX4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Thioredoxin-related transmembrane protein 4 (TMX4).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Thioredoxin-related transmembrane protein 4 (TMX4).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Thioredoxin-related transmembrane protein 4 (TMX4).	[6]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Thioredoxin-related transmembrane protein 4 (TMX4).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Thioredoxin-related transmembrane protein 4 (TMX4).	[9]

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 Thioredoxin-related transmembrane protein 4 (TMX4).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [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] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Soy isoflavones alter expression of genes associated with cancer progression, including interleukin-8, in androgen-independent PC-3 human prostate cancer cells. J Nutr. 2006 Jan;136(1):75-82.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.