Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYF1USY)

• DOT Name: U3 small nucleolar ribonucleoprotein protein IMP4 (IMP4)
• Synonyms: U3 snoRNP protein IMP4; Brix domain-containing protein 4
• Gene Name: IMP4
• Related Disease: Bacteremia
• UniProt ID: IMP4_HUMAN
• PDB ID: 7MQ8; 7MQ9; 7MQA
• Pfam ID: PF04427
• Sequence:
  MLRREARLRREYLYRKAREEAQRSAQERKERLRRALEENRLIPTELRREALALQGSLEFD
  DAGGEGVTSHVDDEYRWAGVEDPKVMITTSRDPSSRLKMFAKELKLVFPGAQRMNRGRHE
  VGALVRACKANGVTDLLVVHEHRGTPVGLIVSHLPFGPTAYFTLCNVVMRHDIPDLGTMS
  EAKPHLITHGFSSRLGKRVSDILRYLFPVPKDDSHRVITFANQDDYISFRHHVYKKTDHR
  NVELTEVGPRFELKLYMIRLGTLEQEATADVEWRWHPYTNTARKRVFLSTE
• Function: Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)
• Reactome Pathway:
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacteremia	DIS6N9RZ	Definitive	Biomarker	[1]

8 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 U3 small nucleolar ribonucleoprotein protein IMP4 (IMP4).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of U3 small nucleolar ribonucleoprotein protein IMP4 (IMP4).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP4 (IMP4).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of U3 small nucleolar ribonucleoprotein protein IMP4 (IMP4).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of U3 small nucleolar ribonucleoprotein protein IMP4 (IMP4).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of U3 small nucleolar ribonucleoprotein protein IMP4 (IMP4).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP4 (IMP4).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of U3 small nucleolar ribonucleoprotein protein IMP4 (IMP4).	[9]

References

• [1] First reported nosocomial outbreak of Serratia marcescens harboring bla (IMP-4) and bla (VIM-2) in a neonatal intensive care unit in Cairo, Egypt.Infect Drug Resist. 2018 Nov 8;11:2211-2217. doi: 10.2147/IDR.S174869. eCollection 2018.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] 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.
• [7] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.