Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAMSBK5)

• DOT Name: RING finger protein 150 (RNF150)
• Gene Name: RNF150
• Related Disease:
  Depression
  Chronic obstructive pulmonary disease
• UniProt ID: RN150_HUMAN
• Pfam ID: PF02225 ; PF13639
• Sequence:
  MAMSLIQACCSLALSTWLLSFCFVHLLCLDFTVAEKEEWYTAFVNITYAEPAPDPGAGAA
  GGGGAELHTEKTECGRYGEHSPKQDARGEVVMASSAHDRLACDPNTKFAAPTRGKNWIAL
  IPKGNCTYRDKIRNAFLQNASAVVIFNVGSNTNETITMPHAGVEDIVAIMIPEPKGKEIV
  SLLERNITVTMYITIGTRNLQKYVSRTSVVFVSISFIVLMIISLAWLVFYYIQRFRYANA
  RDRNQRRLGDAAKKAISKLQIRTIKKGDKETESDFDNCAVCIEGYKPNDVVRILPCRHLF
  HKSCVDPWLLDHRTCPMCKMNILKALGIPPNADCMDDLPTDFEGSLGGPPTNQITGASDT
  TVNESSVTLDPAVRTVGALQVVQDTDPIPQEGDVIFTTNSEQEPAVSSDSDISLIMAMEV
  GLSDVELSTDQDCEEVKS

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Depression	DIS3XJ69	Strong	Genetic Variation	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[2]

14 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 RING finger protein 150 (RNF150).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RING finger protein 150 (RNF150).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RING finger protein 150 (RNF150).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RING finger protein 150 (RNF150).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of RING finger protein 150 (RNF150).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RING finger protein 150 (RNF150).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of RING finger protein 150 (RNF150).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of RING finger protein 150 (RNF150).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RING finger protein 150 (RNF150).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of RING finger protein 150 (RNF150).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of RING finger protein 150 (RNF150).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of RING finger protein 150 (RNF150).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of RING finger protein 150 (RNF150).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of RING finger protein 150 (RNF150).	[17]

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 increases the methylation of RING finger protein 150 (RNF150).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of RING finger protein 150 (RNF150).	[15]

References

• [1] Network Analysis of Depression-Related Transcriptomic Profiles.Neuromolecular Med. 2019 Jun;21(2):143-149. doi: 10.1007/s12017-019-08527-9. Epub 2019 Mar 1.
• [2] EGLN2 and RNF150 genetic variants are associated with chronic obstructive pulmonary disease risk in the Chinese population.Int J Chron Obstruct Pulmon Dis. 2015 Jan 13;10:145-51. doi: 10.2147/COPD.S73031. eCollection 2015.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] 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.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] 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.
• [16] 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.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.