Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0D7IYD)

• DOT Name: Transmembrane and coiled-coil domains protein 2 (TMCC2)
• Synonyms: Cerebral protein 11
• Gene Name: TMCC2
• UniProt ID: TMCC2_HUMAN
• Pfam ID: PF10267
• Sequence:
  MKRCRSDELQQQQGEEDGAGLEDAASHLPGADLRPGETTGANSAGGPTSDAGAAAAPNPG
  PRSKPPDLKKIQQLSEGSMFGHGLKHLFHSRRRSREREHQTSQDSQQHQQQQGMSDHDSP
  DEKERSPEMHRVSYAMSLHDLPARPTAFNRVLQQIRSRPSIKRGASLHSSSGGGSSGSSS
  RRTKSSSLEPQRGSPHLLRKAPQDSSLAAILHQHQCRPRSSSTTDTALLLADGSNVYLLA
  EEAEGIGDKVDKGDLVALSLPAGHGDTDGPISLDVPDGAPDPQRTKAAIDHLHQKILKIT
  EQIKIEQEARDDNVAEYLKLANNADKQQVSRIKQVFEKKNQKSAQTIAQLHKKLEHYRRR
  LKEIEQNGPSRQPKDVLRDMQQGLKDVGANVRAGISGFGGGVVEGVKGSLSGLSQATHTA
  VVSKPREFASLIRNKFGSADNIAHLKDPLEDGPPEEAARALSGSATLVSSPKYGSDDECS
  SASASSAGAGSNSGAGPGGALGSPKSNALYGAPGNLDALLEELREIKEGQSHLEDSMEDL
  KTQLQRDYTYMTQCLQEERYRYERLEEQLNDLTELHQNEMTNLKQELASMEEKVAYQSYE
  RARDIQEAVESCLTRVTKLELQQQQQQVVQLEGVENANARALLGKFINVILALMAVLLVF
  VSTIANFITPLMKTRLRITSTTLLVLVLFLLWKHWDSLTYLLEHVLLPS
• Function: May be involved in the regulation of the proteolytic processing of the amyloid precursor protein (APP) possibly also implicating APOE.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[6]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[5]
Oxamflatin	DM1TG3C	Terminated	Oxamflatin increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[13]
Apicidin	DM83WVF	Investigative	Apicidin increases the expression of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[5]

2 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 Transmembrane and coiled-coil domains protein 2 (TMCC2).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transmembrane and coiled-coil domains protein 2 (TMCC2).	[11]

References

• [1] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [6] Caffeine overcomes genistein-induced G2/M cell cycle arrest in breast cancer cells. Nutr Cancer. 2008;60(3):382-8.
• [7] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.