Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHPN53C)

• DOT Name: F-box only protein 42 (FBXO42)
• Synonyms: Just one F-box and Kelch domain-containing protein
• Gene Name: FBXO42
• Related Disease: Parkinson disease
• UniProt ID: FBX42_HUMAN
• Pfam ID: PF12937 ; PF13415 ; PF13854
• Sequence:
  MASSSDSEDDSFMAVDQEETVLEGTMDQDEEPHPVLEAEETRHNRSMSELPEEVLEYILS
  FLSPYQEHKTAALVCKQWYRLIKGVAHQCYHGFMKAVQEGNIQWESRTYPYPGTPITQRF
  SHSACYYDANQSMYVFGGCTQSSCNAAFNDLWRLDLNSKEWIRPLASGSYPSPKAGATLV
  VYKDLLVLFGGWTRPSPYPLHQPERFFDEIHTYSPSKNWWNCIVTTHGPPPMAGHSSCVI
  DDKMIVFGGSLGSRQMSNDVWVLDLEQWAWSKPNISGPSPHPRGGQSQIVIDDATILILG
  GCGGPNALFKDAWLLHMHSGPWAWQPLKVENEEHGAPELWCHPACRVGQCVVVFSQAPSG
  RAPLSPSLNSRPSPISATPPALVPETREYRSQSPVRSMDEAPCVNGRWGTLRPRAQRQTP
  SGSREGSLSPARGDGSPILNGGSLSPGTAAVGGSSLDSPVQAISPSTPSAPEGYDLKIGL
  SLAPRRGSLPDQKDLRLGSIDLNWDLKPASSSNPMDGMDNRTVGGSMRHPPEQTNGVHTP
  PHVASALAGAVSPGALRRSLEAIKAMSSKGPSASAALSPPLGSSPGSPGSQSLSSGETVP
  IPRPGPAQGDGHSLPPIARRLGHHPPQSLNVGKPLYQSMNCKPMQMYVLDIKDTKEKGRV
  KWKVFNSSSVVGPPETSLHTVVQGRGELIIFGGLMDKKQNVKYYPKTNALYFVRAKR
• Function: Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Specifically recognizes p53/TP53, promoting its ubiquitination and degradation.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[1]

11 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 F-box only protein 42 (FBXO42).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of F-box only protein 42 (FBXO42).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of F-box only protein 42 (FBXO42).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of F-box only protein 42 (FBXO42).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of F-box only protein 42 (FBXO42).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of F-box only protein 42 (FBXO42).	[7]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of F-box only protein 42 (FBXO42).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of F-box only protein 42 (FBXO42).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of F-box only protein 42 (FBXO42).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of F-box only protein 42 (FBXO42).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of F-box only protein 42 (FBXO42).	[13]

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 F-box only protein 42 (FBXO42).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of F-box only protein 42 (FBXO42).	[14]

References

• [1] Genetic analysis of the FBXO42 gene in Chinese Han patients with Parkinson's disease.BMC Neurol. 2013 Sep 25;13:125. doi: 10.1186/1471-2377-13-125.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] 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.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [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] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.