Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE0Q78Q)

• DOT Name: R3H domain-containing protein 4 (R3HDM4)
• Gene Name: R3HDM4
• UniProt ID: R3HD4_HUMAN
• Pfam ID: PF01424 ; PF13902
• Sequence:
  MVALENPECGPEAAEGTPGGRRLLPLPSCLPALASSQVKRLSASRRKQHFINQAVRNSDL
  VPKAKGRKSLQRLENTQYLLTLLETDGGLPGLEDGDLAPPASPGIFAEACNNATYVEVWN
  DFMNRSGEEQERVLRYLEDEGRSKARRRGPGRGEDRRREDPAYTPRECFQRISRRLRAVL
  KRSRIPMETLETWEERLLRFFSVSPQAVYTAMLDNSFERLLLHAVCQYMDLISASADLEG
  KRQMKVSNRHLDFLPPGLLLSAYLEQHS

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 R3H domain-containing protein 4 (R3HDM4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of R3H domain-containing protein 4 (R3HDM4).	[7]

5 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 R3H domain-containing protein 4 (R3HDM4).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of R3H domain-containing protein 4 (R3HDM4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of R3H domain-containing protein 4 (R3HDM4).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of R3H domain-containing protein 4 (R3HDM4).	[5]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of R3H domain-containing protein 4 (R3HDM4).	[6]

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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [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] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.