Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV7UJ5N)

• DOT Name: RWD domain-containing protein 2A (RWDD2A)
• Gene Name: RWDD2A
• UniProt ID: RWD2A_HUMAN
• PDB ID: 2DAW
• Pfam ID: PF06544 ; PF05773
• Sequence:
  MSASVKESLQLQLLEMEMLFSMFPNQGEVKLEDVNALTNIKRYLEGTREALPPKIEFVIT
  LQIEEPKVKIDLQVTMPHSYPYVALQLFGRSSELDRHQQLLLNKGLTSYIGTFDPGELCV
  CAAIQWLQDNSASYFLNRKLVYEPSTQAKPVKNTFLRMWIYSHHIYQQDLRKKILDVGKR
  LDVTGFCMTGKPGIICVEGFKEHCEEFWHTIRYPNWKHISCKHAESVETEGNGEDLRLFH
  SFEELLLEAHGDYGLRNDYHMNLGQFLEFLKKHKSEHVFQILFGIESKSSDS

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of RWD domain-containing protein 2A (RWDD2A).	[1]

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 RWD domain-containing protein 2A (RWDD2A).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RWD domain-containing protein 2A (RWDD2A).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of RWD domain-containing protein 2A (RWDD2A).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of RWD domain-containing protein 2A (RWDD2A).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of RWD domain-containing protein 2A (RWDD2A).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RWD domain-containing protein 2A (RWDD2A).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of RWD domain-containing protein 2A (RWDD2A).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of RWD domain-containing protein 2A (RWDD2A).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of RWD domain-containing protein 2A (RWDD2A).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of RWD domain-containing protein 2A (RWDD2A).	[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] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.