Details of Drug Off-Target (DOT)

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

• DOT Name: Taste receptor type 2 member 50 (TAS2R50)
• Synonyms: T2R50; Taste receptor type 2 member 51; T2R51
• Gene Name: TAS2R50
• Related Disease:
  Cardiac disease
  Cardiovascular disease
  Esophageal squamous cell carcinoma
  Stroke
  Colorectal adenoma
  Myocardial infarction
• UniProt ID: T2R50_HUMAN
• Pfam ID: PF05296
• Sequence:
  MITFLYIFFSILIMVLFVLGNFANGFIALVNFIDWVKRKKISSADQILTALAVSRIGLLW
  ALLLNWYLTVLNPAFYSVELRITSYNAWVVTNHFSMWLAANLSIFYLLKIANFSNLLFLH
  LKRRVRSVILVILLGTLIFLVCHLLVANMDESMWAEEYEGNMTGKMKLRNTVHLSYLTVT
  TLWSFIPFTLSLISFLMLICSLCKHLKKMQLHGEGSQDLSTKVHIKALQTLISFLLLCAI
  FFLFLIVSVWSPRRLRNDPVVMVSKAVGNIYLAFDSFILIWRTKKLKHTFLLILCQIRC
• 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.
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[3]
Stroke	DISX6UHX	Strong	Biomarker	[1]
Colorectal adenoma	DISTSVHM	Limited	Genetic Variation	[4]
Myocardial infarction	DIS655KI	Limited	Biomarker	[1]

1 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 50 (TAS2R50).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Taste receptor type 2 member 50 (TAS2R50).	[6]

References

• [1] KIF6, LPA, TAS2R50, and VAMP8 genetic variation, low density lipoprotein cholesterol lowering response to pravastatin, and heart disease risk reduction in the elderly.Atherosclerosis. 2012 Feb;220(2):456-62. doi: 10.1016/j.atherosclerosis.2011.11.037. Epub 2011 Dec 7.
• [2] Association of gene variants with incident myocardial infarction in the Cardiovascular Health Study.Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):173-9. doi: 10.1161/ATVBAHA.107.153981. Epub 2007 Nov 1.
• [3] Pathway, in silico and tissue-specific expression quantitative analyses of oesophageal squamous cell carcinoma genome-wide association studies data.Int J Epidemiol. 2016 Feb;45(1):206-20. doi: 10.1093/ije/dyv294. Epub 2015 Dec 3.
• [4] Variations in bitter-taste receptor genes, dietary intake, and colorectal adenoma risk.Nutr Cancer. 2013;65(7):982-90. doi: 10.1080/01635581.2013.807934. Epub 2013 Oct 1.
• [5] 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.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.