Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLVPY2E)

• DOT Name: Transmembrane emp24 domain-containing protein 4 (TMED4)
• Synonyms: Endoplasmic reticulum stress-response protein 25; ERS25; GMP25iso; Putative NF-kappa-B-activating protein 156; p24 family protein alpha-3; p24alpha3
• Gene Name: TMED4
• Related Disease: Adenocarcinoma
• UniProt ID: TMED4_HUMAN
• Pfam ID: PF01105
• Sequence:
  MAGVGAGPLRAMGRQALLLLALCATGAQGLYFHIGETEKRCFIEEIPDETMVIGNYRTQM
  WDKQKEVFLPSTPGLGMHVEVKDPDGKVVLSRQYGSEGRFTFTSHTPGDHQICLHSNSTR
  MALFAGGKLRVHLDIQVGEHANNYPEIAAKDKLTELQLRARQLLDQVEQIQKEQDYQRYR
  EERFRLTSESTNQRVLWWSIAQTVILILTGIWQMRHLKSFFEAKKLV
• Function: Involved in vesicular protein trafficking, mainly in the early secretory pathway. targeting. Involved in the maintenance of the Golgi apparatus. Appears to play a role in the biosynthesis of secreted cargo including processing. Involved in endoplasmic reticulum stress response. May play a role in the regulation of heat-shock response and apoptosis.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[1]

13 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 Transmembrane emp24 domain-containing protein 4 (TMED4).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transmembrane emp24 domain-containing protein 4 (TMED4).	[14]

References

• [1] OCIA domain containing 2 is highly expressed in adenocarcinoma mixed subtype with bronchioloalveolar carcinoma component and is associated with better prognosis.Cancer Sci. 2007 Jan;98(1):50-7. doi: 10.1111/j.1349-7006.2006.00346.x.
• [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] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [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] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [12] 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.
• [13] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.