Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT83U7VZ)

• DOT Name: LON peptidase N-terminal domain and RING finger protein 3 (LONRF3)
• Synonyms: RING finger protein 127
• Gene Name: LONRF3
• UniProt ID: LONF3_HUMAN
• Pfam ID: PF02190 ; PF00097 ; PF13923
• Sequence:
  MESVRIEQMLSLPAEVSSDNLESAERGASAAQVDMGPHPKVAAEGPAPLPTREPEQEQSP
  GTSTPESKVLLTQADALASRGRIREALEVYRQLSERQQLVAEQLEQLVRCLAEKVPQGEA
  LAPAPPDEGSTASGTVAAEETGAAAAAAATEVWDGFKCRKCHGFLSDPVSLSCGHTFCKL
  CLERGRAADRRCALCGVKLSALMVATGRARGARRAGQQPPPPLRVNVVLSGLLGKLFPGP
  ARASQLRHEGNRLYRERQVEAALLKYNEAVKLAPNDHLLYSNRSQIYFTLESHENALHDA
  EIACKLRPMGFKAHFRKAQALATLGKVEEALREFLYCVSLDGKNKRARCEAQRDNLELPH
  CSSQEEAAARGDGSSLMDPAKVKGDGQQHHMKDQEEEEEKWDATSPKAASSKTGKCQEKK
  RKHCQIESQEETGMPNKASKQDPPTDQGDKPALSLPLASFDASDLECALCMRLFYEPVTT
  PCGHTFCLKCLERCLDHNAKCPLCKDGLSQCLASRKYSKNVIMEELIAKFLPEELKERRK
  LYEEEMEELSNLNKNVPIFVCTMAYPTVPCPLHIFEPCYRLMIRRCIETGTRQFGMCLGD
  PVKGFAEYGCILEIRNVQFFADGRSVVDSIGKRRFRVLHQSQRDGYNTADIEYIEDQKVQ
  GEDCAELMGLHNCVYQQASLWFHSLKLSLKNRILNHFGPMPEKDADPQMNPNGPAWCWWM
  LAVLPLESRAQLPFLAMRSLKDRLNGIRRVLAFISRNQN

Molecular Interaction Atlas (MIA) of This DOT

2 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 LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[1]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of LON peptidase N-terminal domain and RING finger protein 3 (LONRF3).	[11]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [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] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.