Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT82KXU3)

• DOT Name: Ammonium transporter Rh type B (RHBG)
• Synonyms: Rhesus blood group family type B glycoprotein; Rh family type B glycoprotein; Rh type B glycoprotein
• Gene Name: RHBG
• UniProt ID: RHBG_HUMAN
• Pfam ID: PF00909
• Sequence:
  MAGSPSRAAGRRLQLPLLCLFLQGATAVLFAVFVRYNHKTDAALWHRSNHSNADNEFYFR
  YPSFQDVHAMVFVGFGFLMVFLQRYGFSSVGFTFLLAAFALQWSTLVQGFLHSFHGGHIH
  VGVESMINADFCAGAVLISFGAVLGKTGPTQLLLMALLEVVLFGINEFVLLHLLGVRDAG
  GSMTIHTFGAYFGLVLSRVLYRPQLEKSKHRQGSVYHSDLFAMIGTIFLWIFWPSFNAAL
  TALGAGQHRTALNTYYSLAASTLGTFALSALVGEDGRLDMVHIQNAALAGGVVVGTSSEM
  MLTPFGALAAGFLAGTVSTLGYKFFTPILESKFKVQDTCGVHNLHGMPGVLGALLGVLVA
  GLATHEAYGDGLESVFPLIAEGQRSATSQAMHQLFGLFVTLMFASVGGGLGGLLLKLPFL
  DSPPDSQHYEDQVHWQVPGEHEDKAQRPLRVEEADTQA
• Function: Ammonium transporter involved in the maintenance of acid-base homeostasis. Transports ammonium and its related derivative methylammonium across the basolateral plasma membrane of epithelial cells likely contributing to renal transepithelial ammonia transport and ammonia metabolism. May transport either NH4(+) or NH3 ammonia species predominantly mediating an electrogenic NH4(+) transport. May act as a CO2 channel providing for renal acid secretion.
• Tissue Specificity: Specifically expressed in kidney. Also detected in liver and ovary.
• Reactome Pathway: Rhesus glycoproteins mediate ammonium transport. (R-HSA-444411)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ammonium transporter Rh type B (RHBG).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ammonium transporter Rh type B (RHBG).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ammonium transporter Rh type B (RHBG).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ammonium transporter Rh type B (RHBG).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Ammonium transporter Rh type B (RHBG).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ammonium transporter Rh type B (RHBG).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ammonium transporter Rh type B (RHBG).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ammonium transporter Rh type B (RHBG).	[6]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] 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.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] 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.
• [7] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.