Details of Drug Off-Target (DOT)

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

• DOT Name: Trinucleotide repeat-containing gene 18 protein (TNRC18)
• Synonyms: Long CAG trinucleotide repeat-containing gene 79 protein
• Gene Name: TNRC18
• UniProt ID: TNC18_HUMAN
• PDB ID: 8DS8
• Pfam ID: PF01426 ; PF21744
• Sequence:
  MDGRDFGPQRSVHGPPPPLLSGLAMDSHRVGAATAGRLPASGLPGPLPPGKYMAGLNLHP
  HPGEAFLGSFVASGMGPSASSHGSPVPLPSDLSFRSPTPSNLPMVQLWAAHAHEGFSHLP
  SGLYPSYLHLNHLEPPSSGSPLLSQLGQPSIFDTQKGQGPGGDGFYLPTAGAPGSLHSHA
  PSARTPGGGHSSGAPAKGSSSRDGPAKERAGRGGEPPPLFGKKDPRARGEEASGPRGVVD
  LTQEARAEGRQDRGPPRLAERLSPFLAESKTKNAALQPSVLTMCNGGAGDVGLPALVAEA
  GRGGAKEAARQDEGARLLRRTETLLPGPRPCPSPLPPPPAPPKGPPAPPAATPAGVYTVF
  REQGREHRVVAPTFVPSVEAFDERPGPIQIASQARDARAREREAGRPGVLQAPPGSPRPL
  DRPEGLREKNSVIRSLKRPPPADAPTVRATRASPDPRAYVPAKELLKPEADPRPCERAPR
  GPAGPAAQQAAKLFGLEPGRPPPTGPEHKWKPFELGNFAATQMAVLAAQHHHSRAEEEAA
  VVAASSSKKAYLDPGAVLPRSAATCGRPVADMHSAAHGSGEASAMQSLIKYSGSFARDAV
  AVRPGGCGKKSPFGGLGTMKPEPAPTSAGASRAQARLPHSGGPAAGGGRQLKRDPERPES
  AKAFGREGSGAQGEAEVRHPPVGIAVAVARQKDSGGSGRLGPGLVDQERSLSLSNVKGHG
  RADEDCVDDRARHREERLLGARLDRDQEKLLRESKELADLARLHPTSCAPNGLNPNLMVT
  GGPALAGSGRWSADPAAHLATHPWLPRSGNASMWLAGHPYGLGPPSLHQGMAPAFPPGLG
  GSLPSAYQFVRDPQSGQLVVIPSDHLPHFAELMERATVPPLWPALYPPGRSPLHHAQQLQ
  LFSQQHFLRQQEFLYLQQQAAQALELQRSAQLVQERLKAQEHRAEMEEKGSKRGLEAAGK
  AGLATAGPGLLPRKPPGLAAGPAGTYGKAVSPPPSPRASPVAALKAKVIQKLEDVSKPPA
  YAYPATPSSHPTSPPPASPPPTPGITRKEEAPENVVEKKDLELEKEAPSPFQALFSDIPP
  RYPFQALPPHYGRPYPFLLQPTAAADADGLAPDVPLPADGPERLALSPEDKPIRLSPSKI
  TEPLREGPEEEPLAEREVKAEVEDMDEGPTELPPLESPLPLPAAEAMATPSPAGGCGGGL
  LEAQALSATGQSCAEPSECPDFVEGPEPRVDSPGRTEPCTAALDLGVQLTPETLVEAKEE
  PVEVPVAVPVVEAVPEEGLAQVAPSESQPTLEMSDCDVPAGEGQCPSLEPQEAVPVLGST
  CFLEEASSDQFLPSLEDPLAGMNALAAAAELPQARPLPSPGAAGAQALEKLEAAESLVLE
  QSFLHGITLLSEIAELELERRSQEMGGAERALVARPSLESLLAAGSHMLREVLDGPVVDP
  LKNLRLPRELKPNKKYSWMRKKEERMYAMKSSLEDMDALELDFRMRLAEVQRQYKEKQRE
  LVKLQRRRDSEDRREEPHRSLARRGPGRPRKRTHAPSALSPPRKRGKSGHSSGKLSSKSL
  LTSDDYELGAGIRKRHKGSEEEHDALIGMGKARGRNQTWDEHEASSDFISQLKIKKKKMA
  SDQEQLASKLDKALSLTKQDKLKSPFKFSDSAGGKSKTSGGCGRYLTPYDSLLGKNRKAL
  AKGLGLSLKSSREGKHKRAAKTRKMEVGFKARGQPKSAHSPFASEVSSYSYNTDSEEDEE
  FLKDEWPAQGPSSSKLTPSLLCSMVAKNSKAAGGPKLTKRGLAAPRTLKPKPATSRKQPF
  CLLLREAEARSSFSDSSEESFDQDESSEEEDEEEELEEEDEASGGGYRLGARERALSPGL
  EESGLGLLARFAASALPSPTVGPSLSVVQLEAKQKARKKEERQSLLGTEFEYTDSESEVK
  VRKRSPAGLLRPKKGLGEPGPSLAAPTPGARGPDPSSPDKAKLAVEKGRKARKLRGPKEP
  GFEAGPEASDDDLWTRRRSERIFLHDASAAAPAPVSTAPATKTSRCAKGGPLSPRKDAGR
  AKDRKDPRKKKKGKEAGPGAGLPPPRAPALPSEARAPHASSLTAAKRSKAKAKGKEVKKE
  NRGKGGAVSKLMESMAAEEDFEPNQDSSFSEDEHLPRGGAVERPLTPAPRSCIIDKDELK
  DGLRVLIPMDDKLLYAGHVQTVHSPDIYRVVVEGERGNRPHIYCLEQLLQEAIIDVRPAS
  TRFLPQGTRIAAYWSQQYRCLYPGTVVRGLLDLEDDGDLITVEFDDGDTGRIPLSHIRLL
  PPDYKIQCAEPSPALLVPSAKRRSRKTSKDTGEGKDGGTAGSEEPGAKARGRGRKPSAKA
  KGDRAATLEEGNPTDEVPSTPLALEPSSTPGSKKSPPEPVDKRAKAPKARPAPPQPSPAP
  PAFTSCPAPEPFAELPAPATSLAPAPLITMPATRPKPKKARAAEESGAKGPRRPGEEAEL
  LVKLDHEGVTSPKSKKAKEALLLREDPGAGGWQEPKSLLSLGSYPPAAGSSEPKAPWPKA
  TDGDLAQEPGPGLTFEDSGNPKSPDKAQAEQDGAEESESSSSSSSGSSSSSSSSSSSGSE
  TEGEEEGDKNGDGGCGTGGRNCSAASSRAASPASSSSSSSSSSSSSSSSSSSSSSSSSSS
  SSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSTTDEDSSCSSDDEAAPAPTAGPSAQAALP
  TKATKQAGKARPSAHSPGKKTPAPQPQAPPPQPTQPLQPKAQAGAKSRPKKREGVHLPTT
  KELAKRQRLPSVENRPKIAAFLPARQLWKWFGKPTQRRGMKGKARKLFYKAIVRGKEMIR
  IGDCAVFLSAGRPNLPYIGRIQSMWESWGNNMVVRVKWFYHPEETSPGKQFHQGQHWDQK
  SSRSLPAALRVSSQRKDFMERALYQSSHVDENDVQTVSHKCLVVGLEQYEQMLKTKKYQD
  SEGLYYLAGTYEPTTGMIFSTDGVPVLC

Molecular Interaction Atlas (MIA) of This DOT

6 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 Trinucleotide repeat-containing gene 18 protein (TNRC18).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[8]

11 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 Trinucleotide repeat-containing gene 18 protein (TNRC18).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Trinucleotide repeat-containing gene 18 protein (TNRC18).	[16]

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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] 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.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] 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.
• [15] 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.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.