Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6MS96W)

• DOT Name: TM2 domain-containing protein 3 (TM2D3)
• Synonyms: Beta-amyloid-binding protein-like protein 2; BBP-like protein 2
• Gene Name: TM2D3
• Related Disease:
  Neoplasm
  Alzheimer disease
  Osteoarthritis
• UniProt ID: TM2D3_HUMAN
• Pfam ID: PF05154
• Sequence:
  MAGGVLPLRGLRALCRVLLFLSQFCILSGGEQSQALAQSIKDPGPTRTFTVVPRAAESTE
  IPPYVMKCPSNGLCSRLPADCIDCTTNFSCTYGKPVTFDCAVKPSVTCVDQDFKSQKNFI
  INMTCRFCWQLPETDYECTNSTSCMTVSCPRQRYPANCTVRDHVHCLGNRTFPKMLYCNW
  TGGYKWSTALALSITLGGFGADRFYLGQWREGLGKLFSFGGLGIWTLIDVLLIGVGYVGP
  ADGSLYI
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Genetic Variation	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[3]

11 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 TM2 domain-containing protein 3 (TM2D3).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TM2 domain-containing protein 3 (TM2D3).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of TM2 domain-containing protein 3 (TM2D3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TM2 domain-containing protein 3 (TM2D3).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of TM2 domain-containing protein 3 (TM2D3).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of TM2 domain-containing protein 3 (TM2D3).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of TM2 domain-containing protein 3 (TM2D3).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of TM2 domain-containing protein 3 (TM2D3).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of TM2 domain-containing protein 3 (TM2D3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of TM2 domain-containing protein 3 (TM2D3).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of TM2 domain-containing protein 3 (TM2D3).	[15]

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 TM2 domain-containing protein 3 (TM2D3).	[12]

References

• [1] TM2D3 rs675436 or FGFR2 rs755793 polymorphisms and susceptibility to Epstein-Barr virus-associated tumors in Chinese Han population.J Med Virol. 2018 Jun;90(6):1128-1133. doi: 10.1002/jmv.25057. Epub 2018 Feb 27.
• [2] Identification of phagocytosis regulators using magnetic genome-wide CRISPR screens.Nat Genet. 2018 Dec;50(12):1716-1727. doi: 10.1038/s41588-018-0254-1. Epub 2018 Nov 5.
• [3] Cis- and trans-acting gene regulation is associated with osteoarthritis.Am J Hum Genet. 2006 May;78(5):793-803. doi: 10.1086/503849. Epub 2006 Mar 22.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] 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.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.