Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOVM44D)

DOT Name Taste receptor type 1 member 3 (TAS1R3)
Synonyms Sweet taste receptor T1R3
Gene Name TAS1R3
Related Disease
Adult respiratory distress syndrome ( )
Brain disease ( )
Diabetic retinopathy ( )
Glucose metabolism disease ( )
Male infertility ( )
Neoplasm ( )
Dental caries ( )
Non-insulin dependent diabetes ( )
UniProt ID
TS1R3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00003 ; PF01094 ; PF07562
Sequence
MLGPAVLGLSLWALLHPGTGAPLCLSQQLRMKGDYVLGGLFPLGEAEEAGLRSRTRPSSP
VCTRFSSNGLLWALAMKMAVEEINNKSDLLPGLRLGYDLFDTCSEPVVAMKPSLMFLAKA
GSRDIAAYCNYTQYQPRVLAVIGPHSSELAMVTGKFFSFFLMPQVSYGASMELLSARETF
PSFFRTVPSDRVQLTAAAELLQEFGWNWVAALGSDDEYGRQGLSIFSALAAARGICIAHE
GLVPLPRADDSRLGKVQDVLHQVNQSSVQVVLLFASVHAAHALFNYSISSRLSPKVWVAS
EAWLTSDLVMGLPGMAQMGTVLGFLQRGAQLHEFPQYVKTHLALATDPAFCSALGEREQG
LEEDVVGQRCPQCDCITLQNVSAGLNHHQTFSVYAAVYSVAQALHNTLQCNASGCPAQDP
VKPWQLLENMYNLTFHVGGLPLRFDSSGNVDMEYDLKLWVWQGSVPRLHDVGRFNGSLRT
ERLKIRWHTSDNQKPVSRCSRQCQEGQVRRVKGFHSCCYDCVDCEAGSYRQNPDDIACTF
CGQDEWSPERSTRCFRRRSRFLAWGEPAVLLLLLLLSLALGLVLAALGLFVHHRDSPLVQ
ASGGPLACFGLVCLGLVCLSVLLFPGQPSPARCLAQQPLSHLPLTGCLSTLFLQAAEIFV
ESELPLSWADRLSGCLRGPWAWLVVLLAMLVEVALCTWYLVAFPPEVVTDWHMLPTEALV
HCRTRSWVSFGLAHATNATLAFLCFLGTFLVRSQPGCYNRARGLTFAMLAYFITWVSFVP
LLANVQVVLRPAVQMGALLLCVLGILAAFHLPRCYLLMRQPGLNTPEFFLGGGPGDAQGQ
NDGNTGNQGKHE
Function
Putative taste receptor. TAS1R1/TAS1R3 responds to the umami taste stimulus (the taste of monosodium glutamate). TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners. TAS1R3 is essential for the recognition and response to the disaccharide trehalose. Sequence differences within and between species can significantly influence the selectivity and specificity of taste responses.
KEGG Pathway
Taste transduction (hsa04742 )
Carbohydrate digestion and absorption (hsa04973 )
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

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult respiratory distress syndrome DISIJV47 Strong Altered Expression [1]
Brain disease DIS6ZC3X Strong Biomarker [2]
Diabetic retinopathy DISHGUJM Strong Biomarker [3]
Glucose metabolism disease DIS5IK09 Strong Biomarker [2]
Male infertility DISY3YZZ Strong Biomarker [4]
Neoplasm DISZKGEW Strong Biomarker [5]
Dental caries DISRBCMD Limited Genetic Variation [6]
Non-insulin dependent diabetes DISK1O5Z Limited Altered Expression [7]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Taste receptor type 1 member 3 (TAS1R3). [8]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Taste receptor type 1 member 3 (TAS1R3). [10]
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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 affects the methylation of Taste receptor type 1 member 3 (TAS1R3). [9]
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References

1 Activation of the sweet taste receptor, T1R3, by the artificial sweetener sucralose regulates the pulmonary endothelium.Am J Physiol Lung Cell Mol Physiol. 2018 Jan 1;314(1):L165-L176. doi: 10.1152/ajplung.00490.2016. Epub 2017 Sep 28.
2 Emerging Concepts in Brain Glucose Metabolic Functions: From Glucose Sensing to How the Sweet Taste of Glucose Regulates Its Own Metabolism in Astrocytes and Neurons.Neuromolecular Med. 2018 Sep;20(3):281-300. doi: 10.1007/s12017-018-8503-0. Epub 2018 Jul 18.
3 Activation of the sweet taste receptor T1R3 by sucralose attenuates VEGF-induced vasculogenesis in a cell model of the retinal microvascular endothelium.Graefes Arch Clin Exp Ophthalmol. 2019 Jan;257(1):71-81. doi: 10.1007/s00417-018-4157-8. Epub 2018 Oct 23.
4 Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility.Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12319-24. doi: 10.1073/pnas.1302827110. Epub 2013 Jul 1.
5 Noncaloric Sweeteners Induce Peripheral Serotonin Secretion via the T1R3-Dependent Pathway in Human Gastric Parietal Tumor Cells (HGT-1).J Agric Food Chem. 2018 Jul 11;66(27):7044-7053. doi: 10.1021/acs.jafc.8b02071. Epub 2018 Jun 25.
6 Association of sweet taste receptor gene polymorphisms with dental caries experience in school children.Caries Res. 2015;49(3):275-81. doi: 10.1159/000381426. Epub 2015 Apr 24.
7 Expression of taste molecules in the upper gastrointestinal tract in humans with and without type 2 diabetes.Gut. 2009 Mar;58(3):337-46. doi: 10.1136/gut.2008.148932. Epub 2008 Nov 27.
8 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
9 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.
10 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.