Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGV8KK4)

• DOT Name: Transmembrane protein 205 (TMEM205)
• Gene Name: TMEM205
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
• UniProt ID: TM205_HUMAN
• Pfam ID: PF13664
• Sequence:
  MEEGGNLGGLIKMVHLLVLSGAWGMQMWVTFVSGFLLFRSLPRHTFGLVQSKLFPFYFHI
  SMGCAFINLCILASQHAWAQLTFWEASQLYLLFLSLTLATVNARWLEPRTTAAMWALQTV
  EKERGLGGEVPGSHQGPDPYRQLREKDPKYSALRQNFFRYHGLSSLCNLGCVLSNGLCLA
  GLALEIRSL
• Function: In cancer cells, plays a role in resistance to the chemotherapeutic agent cisplatin.
• Tissue Specificity: Widely expressed with highest levels in pancreas, followed by adrenal gland, thyroid, liver, mammary gland, prostate, kidney, and retina; lowest levels in skeletal muscle. Overexpressed in cisplatin-resistant cancer cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Limited	Biomarker	[2]
Lung carcinoma	DISTR26C	Limited	Biomarker	[2]

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 205 (TMEM205).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 205 (TMEM205).	[1]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transmembrane protein 205 (TMEM205).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transmembrane protein 205 (TMEM205).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transmembrane protein 205 (TMEM205).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane protein 205 (TMEM205).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane protein 205 (TMEM205).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein 205 (TMEM205).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 205 (TMEM205).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane protein 205 (TMEM205).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Transmembrane protein 205 (TMEM205).	[12]

References

• [1] Elevated expression of TMEM205, a hypothetical membrane protein, is associated with cisplatin resistance. J Cell Physiol. 2010 Nov;225(3):822-8. doi: 10.1002/jcp.22287.
• [2] The association of transporter genes polymorphisms and lung cancer chemotherapy response.PLoS One. 2014 Mar 18;9(3):e91967. doi: 10.1371/journal.pone.0091967. eCollection 2014.
• [3] 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.
• [4] Elevated expression of TMEM205, a hypothetical membrane protein, is associated with cisplatin resistance. J Cell Physiol. 2010 Nov;225(3):822-8. doi: 10.1002/jcp.22287.
• [5] 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.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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] 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.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.