Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAI2M1L)

• DOT Name: Taste receptor type 2 member 31 (TAS2R31)
• Synonyms: T2R31; Taste receptor type 2 member 44; T2R44; Taste receptor type 2 member 53; T2R53
• Gene Name: TAS2R31
• Related Disease: Langer mesomelic dysplasia
• UniProt ID: T2R31_HUMAN
• Pfam ID: PF05296
• Sequence:
  MTTFIPIIFSSVVVVLFVIGNFANGFIALVNSIERVKRQKISFADQILTALAVSRVGLLW
  VLLLNWYSTVFNPAFYSVEVRTTAYNVWAVTGHFSNWLATSLSIFYLLKIANFSNLIFLH
  LKRRVKSVILVMLLGPLLFLACQLFVINMKEIVRTKEYEGNLTWKIKLRSAVYLSDATVT
  TLGNLVPFTLTLLCFLLLICSLCKHLKKMQLHGKGSQDPSTKVHIKALQTVIFFLLLCAV
  YFLSIMISVWSFGSLENKPVFMFCKAIRFSYPSIHPFILIWGNKKLKQTFLSVLRQVRYW
  VKGEKPSSP
• Function: Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5. Activated by the sulfonyl amide sweeteners saccharin and acesulfame K.
• Tissue Specificity: Expressed in subsets of taste receptor cells of the tongue and exclusively in gustducin-positive cells.
• 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
Langer mesomelic dysplasia	DISCXVK3	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Taste receptor type 2 member 31 (TAS2R31).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Taste receptor type 2 member 31 (TAS2R31).	[4]

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 31 (TAS2R31).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Taste receptor type 2 member 31 (TAS2R31).	[5]
Saccharin	DMRA736	Investigative	Saccharin increases the activity of Taste receptor type 2 member 31 (TAS2R31).	[6]

References

• [1] Recurrently Mutated Genes Differ between Leptomeningeal and Solid Lung Cancer Brain Metastases.J Thorac Oncol. 2018 Jul;13(7):1022-1027. doi: 10.1016/j.jtho.2018.03.018. Epub 2018 Mar 29.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [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] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [6] Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One. 2011;6(5):e20123.