Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB51WEY)

• DOT Name: TM2 domain-containing protein 2 (TM2D2)
• Synonyms: Beta-amyloid-binding protein-like protein 1; BBP-like protein 1
• Gene Name: TM2D2
• Related Disease: Nasopharyngeal carcinoma
• UniProt ID: TM2D2_HUMAN
• Pfam ID: PF05154
• Sequence:
  MVLGGCPVSYLLLCGQAALLLGNLLLLHCVSRSHSQNATAEPELTSAGAAQPEGPGGAAS
  WEYGDPHSPVILCSYLPDEFIECEDPVDHVGNATASQELGYGCLKFGGQAYSDVEHTSVQ
  CHALDGIECASPRTFLRENKPCIKYTGHYFITTLLYSFFLGCFGVDRFCLGHTGTAVGKL
  LTLGGLGIWWFVDLILLITGGLMPSDGSNWCTVY
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Genetic Variation	[1]

10 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 TM2 domain-containing protein 2 (TM2D2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of TM2 domain-containing protein 2 (TM2D2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of TM2 domain-containing protein 2 (TM2D2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of TM2 domain-containing protein 2 (TM2D2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of TM2 domain-containing protein 2 (TM2D2).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of TM2 domain-containing protein 2 (TM2D2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of TM2 domain-containing protein 2 (TM2D2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of TM2 domain-containing protein 2 (TM2D2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of TM2 domain-containing protein 2 (TM2D2).	[11]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of TM2 domain-containing protein 2 (TM2D2).	[12]

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 TM2 domain-containing protein 2 (TM2D2).	[9]

References

• [1] Correlation of p21 gene codon 31 polymorphism and TNF-alpha gene polymorphism with nasopharyngeal carcinoma.J Clin Lab Anal. 2002;16(3):146-50. doi: 10.1002/jcla.10032.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.