Details of Drug Off-Target (DOT)

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

• DOT Name: Transmembrane protein 203 (TMEM203)
• Gene Name: TMEM203
• UniProt ID: TM203_HUMAN
• Sequence:
  MLFSLRELVQWLGFATFEIFVHLLALLVFSVLLALRVDGLVPGLSWWNVFVPFFAADGLS
  TYFTTIVSVRLFQDGEKRLAVLRLFWVLTVLSLKFVFEMLLCQKLAEQTRELWFGLITSP
  LFILLQLLMIRACRVN
• Function: Involved in the regulation of cellular calcium homeotasis. Required for spermatogenesis. Acts as a regulator of STING-mediated inflammatory signaling in macrophages. Forms a complex with STING, promoting the activity of TBK1 kinase and the transcription factor IRF3, leading to activation of type I interferon expression.
• Tissue Specificity: Increased expression seen in T-lymphocytes from patients with systemic lupus erythematosus (SLE).

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Transmembrane protein 203 (TMEM203).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 203 (TMEM203).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 203 (TMEM203).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 203 (TMEM203).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 203 (TMEM203).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Transmembrane protein 203 (TMEM203).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane protein 203 (TMEM203).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 203 (TMEM203).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 203 (TMEM203).	[9]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.