Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRAIGA4)

• DOT Name: TLC domain-containing protein 5 (TLCD5)
• Synonyms: Transmembrane protein 136
• Gene Name: TLCD5
• UniProt ID: TLCD5_HUMAN
• Sequence:
  MALALCLQVLCSLCGWLSLYISFCHLNKHRSYEWSCRLVTFTHGVLSIGLSAYIGFIDGP
  WPFTHPGSPNTPLQVHVLCLTLGYFIFDLGWCVYFQSEGALMLAHHTLSILGIIMALVLG
  ESGTEVNAVLFGSELTNPLLQMRWFLRETGHYHSFTGDVVDFLFVALFTGVRIGVGACLL
  FCEMVSPTPKWFVKAGGVAMYAVSWCFMFSIWRFAWRKSIKKYHAWRSRRSEERQLKHNG
  HLKIH

Molecular Interaction Atlas (MIA) of This DOT

10 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 TLC domain-containing protein 5 (TLCD5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TLC domain-containing protein 5 (TLCD5).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of TLC domain-containing protein 5 (TLCD5).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of TLC domain-containing protein 5 (TLCD5).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of TLC domain-containing protein 5 (TLCD5).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of TLC domain-containing protein 5 (TLCD5).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of TLC domain-containing protein 5 (TLCD5).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of TLC domain-containing protein 5 (TLCD5).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of TLC domain-containing protein 5 (TLCD5).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of TLC domain-containing protein 5 (TLCD5).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of TLC domain-containing protein 5 (TLCD5).	[7]

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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.