Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2H0MCE)

• DOT Name: tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13)
• Synonyms: EC 2.1.1.225; Coiled-coil domain-containing protein 76
• Gene Name: TRMT13
• UniProt ID: TRM13_HUMAN
• EC Number: 2.1.1.225
• Pfam ID: PF05206 ; PF11722 ; PF05253
• Sequence:
  MATSATSPHAPGFPAEGRCGYYVEKKKRFCRMVVAAGKRFCGEHAGAAEEEDARKRILCP
  LDPKHTVYEDQLAKHLKKCNSREKPKPDFYIQDINAGLRDETEIPEQLVPISSLSEEQLE
  KLIKKLRKASEGLNSTLKDHIMSHPALHDALNDPKNGDSATKHLKQQASILGNIENLKLL
  GPRRCFVEFGAGKGKLSHWVDIALKDAEKVHFILVEKVTTRFKVDGKHRKKNSVFERLQI
  DIQHLCLNKIPVLREEKLPVVGIGKHLCGMATDLALRCLVETYAASFEERNEEPLAKRIK
  NDKTEKEIYTLAKEGNEKNVPEKWNPVAGIVIALCCHHRCDWRHYVGKEYFRALGLGAVE
  FHYFQRMSSWATCGMRKTSLETSNSTTKRQDNQNDDSEEHDDGGYRITDDGADCLPGLLS
  VEEKKKIGHLCKLLIDQGRIQYLQQKGFSPALQYYTDPLVSLENVLLTALPNHSSSPETT
  A
• Function: tRNA methylase which 2'-O-methylates cytidine(4) in tRNA(Pro) and tRNA(Gly)(GCC), and adenosine(4) in tRNA(His).
• Reactome Pathway: tRNA modification in the nucleus and cytosol (R-HSA-6782315)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[1]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[8]

12 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 tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[7]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[9]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[10]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[12]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13).	[13]

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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [8] 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.
• [9] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [10] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.