Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXZYMB9)

• DOT Name: Ret finger protein-like 2 (RFPL2)
• Synonyms: RING finger protein 79
• Gene Name: RFPL2
• UniProt ID: RFPL2_HUMAN
• Pfam ID: PF13765 ; PF11002 ; PF00622 ; PF15227
• Sequence:
  MEVAELGFPETAVSQSRICLCAVLCGHWDFADMMVIRSLSLIRLEGVEGRDPVGGGNLTN
  KRPSCAPSPQDLSAQWKQLEDRGASSRRVDMAALFQEASSCPVCSDYLEKPMSLECGCAV
  CLKCINSLQKEPHGEDLLCCCSSMVSRKNKIRRNRQLERLASHIKELEPKLKKILQMNPR
  MRKFQVDMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGR
  HCWEVDVGTSTEWDLGVCRESVHRKGRIQLTTELGFWTVSLRDGGRLSATTVPLTFLFVD
  RKLQRVGIFLDMGMQNVSFFDAESGSHVYTFRSVSAEEPLRPFLAPSVPPNGDQGVLSIC
  PLMNSGTTDAPVRPGEAK
• Tissue Specificity: Seems to be expressed in prostate and less abundantly in adult brain, fetal liver, and fetal kidney.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Ret finger protein-like 2 (RFPL2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Ret finger protein-like 2 (RFPL2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ret finger protein-like 2 (RFPL2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ret finger protein-like 2 (RFPL2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ret finger protein-like 2 (RFPL2).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ret finger protein-like 2 (RFPL2).	[5]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Ret finger protein-like 2 (RFPL2).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ret finger protein-like 2 (RFPL2).	[8]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [7] 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.
• [8] 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.