Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTI9M2D)

• DOT Name: rRNA-processing protein FCF1 homolog (FCF1)
• Gene Name: FCF1
• Related Disease: Osteomyelitis
• UniProt ID: FCF1_HUMAN
• PDB ID: 7MQ8; 7MQ9; 7MQA
• Pfam ID: PF04900
• Sequence:
  MGKQKKTRKYATMKRMLSLRDQRLKEKDRLKPKKKEKKDPSALKEREVPQHPSCLFFQYN
  TQLGPPYHILVDTNFINFSIKAKLDLVQSMMDCLYAKCIPCITDCVMAEIEKLGQKYRVA
  LRIAKDPRFERLPCTHKGTYADDCLVQRVTQHKCYIVATVDRDLKRRIRKIPGVPIMYIS
  NHRYNIERMPDDYGAPRF
• Function: 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
Osteomyelitis	DIS0VUZL	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of rRNA-processing protein FCF1 homolog (FCF1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of rRNA-processing protein FCF1 homolog (FCF1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of rRNA-processing protein FCF1 homolog (FCF1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of rRNA-processing protein FCF1 homolog (FCF1).	[6]
Irinotecan	DMP6SC2	Approved	Irinotecan affects the expression of rRNA-processing protein FCF1 homolog (FCF1).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of rRNA-processing protein FCF1 homolog (FCF1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of rRNA-processing protein FCF1 homolog (FCF1).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of rRNA-processing protein FCF1 homolog (FCF1).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of rRNA-processing protein FCF1 homolog (FCF1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of rRNA-processing protein FCF1 homolog (FCF1).	[5]

References

• [1] Arthroscopic versus open ankle arthrodesis.Foot Ankle Surg. 2018 Apr;24(2):137-142. doi: 10.1016/j.fas.2017.01.004. Epub 2017 Feb 3.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [5] 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.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.