Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI49DD6)

• DOT Name: Tripartite motif-containing protein 54 (TRIM54)
• Synonyms: Muscle-specific RING finger protein; MuRF; Muscle-specific RING finger protein 3; MuRF-3; MuRF3; RING finger protein 30
• Gene Name: TRIM54
• Related Disease:
  Congenital myopathy 7A, myosin storage, autosomal dominant
  Gout
  Myopathy
  Non-small-cell lung cancer
• UniProt ID: TRI54_HUMAN
• PDB ID: 3Q1D
• Pfam ID: PF00643 ; PF13445
• Sequence:
  MNFTVGFKPLLGDAHSMDNLEKQLICPICLEMFSKPVVILPCQHNLCRKCANDVFQASNP
  LWQSRGSTTVSSGGRFRCPSCRHEVVLDRHGVYGLQRNLLVENIIDIYKQESSRPLHSKA
  EQHLMCEEHEEEKINIYCLSCEVPTCSLCKVFGAHKDCEVAPLPTIYKRQKSELSDGIAM
  LVAGNDRVQAVITQMEEVCQTIEDNSRRQKQLLNQRFESLCAVLEERKGELLQALAREQE
  EKLQRVRGLIRQYGDHLEASSKLVESAIQSMEEPQMALYLQQAKELINKVGAMSKVELAG
  RPEPGYESMEQFTVRVEHVAEMLRTIDFQPGASGEEEEVAPDGEEGSAGPEEERPDGP
• Function: May bind and stabilize microtubules during myotubes formation.
• Tissue Specificity: Specifically expressed in heart and skeletal muscle.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital myopathy 7A, myosin storage, autosomal dominant	DISUV37B	Strong	Genetic Variation	[1]
Gout	DISHC0U7	Strong	Genetic Variation	[2]
Myopathy	DISOWG27	Strong	Genetic Variation	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]

4 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 Tripartite motif-containing protein 54 (TRIM54).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Tripartite motif-containing protein 54 (TRIM54).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Tripartite motif-containing protein 54 (TRIM54).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tripartite motif-containing protein 54 (TRIM54).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tripartite motif-containing protein 54 (TRIM54).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tripartite motif-containing protein 54 (TRIM54).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tripartite motif-containing protein 54 (TRIM54).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Tripartite motif-containing protein 54 (TRIM54).	[11]

References

• [1] New cardiac and skeletal protein aggregate myopathy associated with combined MuRF1 and MuRF3 mutations.Hum Mol Genet. 2015 Jul 1;24(13):3638-50. doi: 10.1093/hmg/ddv108. Epub 2015 Mar 23.
• [2] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [3] TRIM59 Promotes the Proliferation and Migration of Non-Small Cell Lung Cancer Cells by Upregulating Cell Cycle Related Proteins.PLoS One. 2015 Nov 24;10(11):e0142596. doi: 10.1371/journal.pone.0142596. eCollection 2015.
• [4] 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.
• [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] 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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [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] 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.