Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT70V8MZ)

• DOT Name: Taste receptor type 2 member 43 (TAS2R43)
• Synonyms: T2R43; Taste receptor type 2 member 52; T2R52
• Gene Name: TAS2R43
• Related Disease: Pseudotumor cerebri
• UniProt ID: T2R43_HUMAN
• Pfam ID: PF05296
• Sequence:
  MITFLPIIFSSLVVVTFVIGNFANGFIALVNSIEWFKRQKISFADQILTALAVSRVGLLW
  VLLLNWYSTVLNPAFNSVEVRTTAYNIWAVINHFSNWLATTLSIFYLLKIANFSNFIFLH
  LKRRVKSVILVMLLGPLLFLACHLFVINMNEIVRTKEFEGNMTWKIKLKSAMYFSNMTVT
  MVANLVPFTLTLLSFMLLICSLCKHLKKMQLHGKGSQDPSTKVHIKALQTVISFLLLCAI
  YFLSIMISVWSFGSLENKPVFMFCKAIRFSYPSIHPFILIWGNKKLKQTFLSVFWQMRYW
  VKGEKTSSP
• Function: Gustducin-coupled receptor immplicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5. Activated by the sulfonyl amide sweeteners saccharin and acesulfame K. In airway epithelial cells, binding of bitter compounds increases the intracellular calcium ion concentration and stimulates ciliary beat frequency. May act as chemosensory receptors in airway epithelial cells to detect and eliminate potential noxious agents from the airways.
• Tissue Specificity: Expressed in subsets of taste receptor cells of the tongue and exclusively in gustducin-positive cells. Expressed in airway epithelia.
• KEGG Pathway: Taste transduction (hsa04742)
• Reactome Pathway:
  Class C/3 (Metabotropic glutamate/pheromone receptors) (R-HSA-420499)
  Sensory perception of sweet, bitter, and umami (glutamate) taste (R-HSA-9717207)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pseudotumor cerebri	DISLLY7S	Definitive	Genetic Variation	[1]

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 Taste receptor type 2 member 43 (TAS2R43).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Taste receptor type 2 member 43 (TAS2R43).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Taste receptor type 2 member 43 (TAS2R43).	[4]
Probenecid	DMMFWOJ	Approved	Probenecid decreases the activity of Taste receptor type 2 member 43 (TAS2R43).	[5]

References

• [1] Genetic Survey of Adult-Onset Idiopathic Intracranial Hypertension.J Neuroophthalmol. 2019 Mar;39(1):50-55. doi: 10.1097/WNO.0000000000000648.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [5] Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One. 2011;6(5):e20123.