Details of Drug Off-Target (DOT)

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

• DOT Name: RWD domain-containing protein 1 (RWDD1)
• Synonyms: DRG family-regulatory protein 2
• Gene Name: RWDD1
• UniProt ID: RWDD1_HUMAN
• PDB ID: 2EBM
• Pfam ID: PF16543 ; PF05773
• Sequence:
  MTDYGEEQRNELEALESIYPDSFTVLSENPPSFTITVTSEAGENDETVQTTLKFTYSEKY
  PDEAPLYEIFSQENLEDNDVSDILKLLALQAEENLGMVMIFTLVTAVQEKLNEIVDQIKT
  RREEEKKQKEKEAEEAEKQLFHGTPVTIENFLNWKAKFDAELLEIKKKRMKEEEQAGKNK
  LSGKQLFETDHNLDTSDIQFLEDAGNNVEVDESLFQEMDDLELEDDEDDPDYNPADPESD
  SAD
• Function: Protects DRG2 from proteolytic degradation.
• Reactome Pathway: Protein hydroxylation (R-HSA-9629569)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of RWD domain-containing protein 1 (RWDD1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RWD domain-containing protein 1 (RWDD1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RWD domain-containing protein 1 (RWDD1).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of RWD domain-containing protein 1 (RWDD1).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of RWD domain-containing protein 1 (RWDD1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RWD domain-containing protein 1 (RWDD1).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of RWD domain-containing protein 1 (RWDD1).	[8]
AM251	DMTAWHL	Investigative	AM251 increases the expression of RWD domain-containing protein 1 (RWDD1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of RWD domain-containing protein 1 (RWDD1).	[4]

References

• [1] 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.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [7] 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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.