Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAM5C0G)

• DOT Name: Regulator of hemoglobinization and erythroid cell expansion protein (RHEX)
• Synonyms: Regulator of human erythroid cell expansion protein
• Gene Name: RHEX
• UniProt ID: RHEX_HUMAN
• Pfam ID: PF15763
• Sequence:
  MLTEVMEVWHGLVIAVVSLFLQACFLTAINYLLSRHMAHKSEQILKAASLQVPRPSPGHH
  HPPAVKEMKETQTERDIPMSDSLYRHDSDTPSDSLDSSCSSPPACQATEDVDYTQVVFSD
  PGELKNDSPLDYENIKEITDYVNVNPERHKPSFWYFVNPALSEPAEYDQVAM
• Function: Acts as a signaling transduction factor of the EPO-EPOR signaling pathway promoting erythroid cell differentiation.
• Tissue Specificity: Expressed in the proerythroblasts (at protein level) . Expressed strongly in the kidney . Expressed weakly in the pancreas, liver and lung . Expressed strongly in erythroid progenitor cells (EPCs) . Expressed weakly in T-cells and neutrophils .

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Regulator of hemoglobinization and erythroid cell expansion protein (RHEX).	[1]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Regulator of hemoglobinization and erythroid cell expansion protein (RHEX).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Regulator of hemoglobinization and erythroid cell expansion protein (RHEX).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Regulator of hemoglobinization and erythroid cell expansion protein (RHEX).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Regulator of hemoglobinization and erythroid cell expansion protein (RHEX).	[5]

References

• [1] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [2] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [5] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.