Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ4C6FH)

• DOT Name: mRNA turnover protein 4 homolog (MRTO4)
• Synonyms: Ribosome assembly factor MRTO4
• Gene Name: MRTO4
• UniProt ID: MRT4_HUMAN
• PDB ID: 8FKR; 8FKS; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY; 8FKZ; 8FL0; 8FL2; 8FL3; 8FL4; 8FL6; 8FL7; 8FL9; 8FLA; 8FLB; 8FLC; 8FLD; 8FLE; 8FLF; 8IDT; 8IDY; 8IE3; 8INE; 8INF; 8INK; 8IPD; 8IPX; 8IPY; 8IR1; 8IR3
• Pfam ID: PF00466 ; PF17777
• Sequence:
  MPKSKRDKKVSLTKTAKKGLELKQNLIEELRKCVDTYKYLFIFSVANMRNSKLKDIRNAW
  KHSRMFFGKNKVMMVALGRSPSDEYKDNLHQVSKRLRGEVGLLFTNRTKEEVNEWFTKYT
  EMDYARAGNKAAFTVSLDPGPLEQFPHSMEPQLRQLGLPTALKRGVVTLLSDYEVCKEGD
  VLTPEQARVLKLFGYEMAEFKVTIKYMWDSQSGRFQQMGDDLPESASESTEESDSEDDD
• Function: Component of the ribosome assembly machinery. Nuclear paralog of the ribosomal protein P0, it binds pre-60S subunits at an early stage of assembly in the nucleolus, and is replaced by P0 in cytoplasmic pre-60S subunits and mature 80S ribosomes.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of mRNA turnover protein 4 homolog (MRTO4).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of mRNA turnover protein 4 homolog (MRTO4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of mRNA turnover protein 4 homolog (MRTO4).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of mRNA turnover protein 4 homolog (MRTO4).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of mRNA turnover protein 4 homolog (MRTO4).	[5]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of mRNA turnover protein 4 homolog (MRTO4).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of mRNA turnover protein 4 homolog (MRTO4).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of mRNA turnover protein 4 homolog (MRTO4).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of mRNA turnover protein 4 homolog (MRTO4).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of mRNA turnover protein 4 homolog (MRTO4).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of mRNA turnover protein 4 homolog (MRTO4).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of mRNA turnover protein 4 homolog (MRTO4).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of mRNA turnover protein 4 homolog (MRTO4).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of mRNA turnover protein 4 homolog (MRTO4).	[12]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [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] 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.
• [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] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 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] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.