Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWA9CYC)

• DOT Name: Taste receptor type 2 member 14 (TAS2R14)
• Synonyms: T2R14; Taste receptor family B member 1; TRB1
• Gene Name: TAS2R14
• Related Disease:
  Pseudotumor cerebri
  Epithelial recurrent erosion dystrophy
  Esophageal squamous cell carcinoma
  Obesity
  Neoplasm
  Asthma
  Colorectal carcinoma
• UniProt ID: T2R14_HUMAN
• Pfam ID: PF05296
• Sequence:
  MGGVIKSIFTFVLIVEFIIGNLGNSFIALVNCIDWVKGRKISSVDRILTALAISRISLVW
  LIFGSWCVSVFFPALFATEKMFRMLTNIWTVINHFSVWLATGLGTFYFLKIANFSNSIFL
  YLKWRVKKVVLVLLLVTSVFLFLNIALINIHINASINGYRRNKTCSSDSSNFTRFSSLIV
  LTSTVFIFIPFTLSLAMFLLLIFSMWKHRKKMQHTVKISGDASTKAHRGVKSVITFFLLY
  AIFSLSFFISVWTSERLEENLIILSQVMGMAYPSCHSCVLILGNKKLRQASLSVLLWLRY
  MFKDGEPSGHKEFRESS
• 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 palate epithelium and exclusively in gustducin-positive cells. Expressed in testis .
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pseudotumor cerebri	DISLLY7S	Definitive	Genetic Variation	[1]
Epithelial recurrent erosion dystrophy	DIS2XPWB	Strong	Genetic Variation	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[3]
Obesity	DIS47Y1K	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[5]
Asthma	DISW9QNS	Limited	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Taste receptor type 2 member 14 (TAS2R14).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Taste receptor type 2 member 14 (TAS2R14).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Taste receptor type 2 member 14 (TAS2R14).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Taste receptor type 2 member 14 (TAS2R14).	[12]

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 decreases the methylation of Taste receptor type 2 member 14 (TAS2R14).	[11]

References

• [1] Genetic Survey of Adult-Onset Idiopathic Intracranial Hypertension.J Neuroophthalmol. 2019 Mar;39(1):50-55. doi: 10.1097/WNO.0000000000000648.
• [2] A COL17A1 Splice-Altering Mutation Is Prevalent in Inherited Recurrent Corneal Erosions. Ophthalmology. 2016 Apr;123(4):709-22. doi: 10.1016/j.ophtha.2015.12.008. Epub 2016 Jan 16.
• [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] Control of adipose tissue inflammation through TRB1.Diabetes. 2010 Aug;59(8):1991-2000. doi: 10.2337/db09-1537. Epub 2010 Jun 3.
• [5] Tribbles-1 and -2 are tumour suppressors, down-regulated in human acute myeloid leukaemia.Immunol Lett. 2010 May 4;130(1-2):115-24. doi: 10.1016/j.imlet.2009.12.007. Epub 2009 Dec 11.
• [6] Discovery of TAS2R14 Agonists from Platycodon grandiflorum Using Virtual Screening and Affinity Screening Based on a Novel TAS2R14-Functionalized HEMT Sensor Combined with UPLC-MS Analysis.J Agric Food Chem. 2018 Nov 7;66(44):11663-11671. doi: 10.1021/acs.jafc.8b04455. Epub 2018 Oct 19.
• [7] A gene-wide investigation on polymorphisms in the taste receptor 2R14 (TAS2R14) and susceptibility to colorectal cancer.BMC Med Genet. 2010 Jun 9;11:88. doi: 10.1186/1471-2350-11-88.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] 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.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] 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.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.