General Information of Drug Off-Target (DOT) (ID: OTS96V19)

DOT Name Guanine nucleotide-binding protein G(t) subunit alpha-3 (GNAT3)
Synonyms Gustducin alpha-3 chain
Gene Name GNAT3
Related Disease
Laryngeal disorder ( )
Male infertility ( )
Neoplasm ( )
Obesity ( )
Dental caries ( )
UniProt ID
GNAT3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00503
Sequence
MGSGISSESKESAKRSKELEKKLQEDAERDARTVKLLLLGAGESGKSTIVKQMKIIHKNG
YSEQECMEFKAVIYSNTLQSILAIVKAMTTLGIDYVNPRSAEDQRQLYAMANTLEDGGMT
PQLAEVIKRLWRDPGIQACFERASEYQLNDSAAYYLNDLDRITASGYVPNEQDVLHSRVK
TTGIIETQFSFKDLHFRMFDVGGQRSERKKWIHCFEGVTCIIFCAALSAYDMVLVEDEEV
NRMHESLHLFNSICNHKYFSTTSIVLFLNKKDIFQEKVTKVHLSICFPEYTGPNTFEDAG
NYIKNQFLDLNLKKEDKEIYSHMTCATDTQNVKFVFDAVTDIIIKENLKDCGLF
Function
Guanine nucleotide-binding protein (G protein) alpha subunit playing a prominent role in bitter and sweet taste transduction as well as in umami (monosodium glutamate, monopotassium glutamate, and inosine monophosphate) taste transduction. Transduction by this alpha subunit involves coupling of specific cell-surface receptors with a cGMP-phosphodiesterase; Activation of phosphodiesterase lowers intracellular levels of cAMP and cGMP which may open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, ultimately leading to release of neurotransmitter. Indeed, denatonium and strychnine induce transient reduction in cAMP and cGMP in taste tissue, whereas this decrease is inhibited by GNAT3 antibody. Gustducin heterotrimer transduces response to bitter and sweet compounds via regulation of phosphodiesterase for alpha subunit, as well as via activation of phospholipase C for beta and gamma subunits, with ultimate increase inositol trisphosphate and increase of intracellular Calcium. GNAT3 can functionally couple to taste receptors to transmit intracellular signal: receptor heterodimer TAS1R2/TAS1R3 senses sweetness and TAS1R1/TAS1R3 transduces umami taste, whereas the T2R family GPCRs act as bitter sensors. Functions also as lumenal sugar sensors in the gut to control the expression of the Na+-glucose transporter SGLT1 in response to dietaty sugar, as well as the secretion of Glucagon-like peptide-1, GLP-1 and glucose-dependent insulinotropic polypeptide, GIP. Thus, may modulate the gut capacity to absorb sugars, with implications in malabsorption syndromes and diet-related disorders including diabetes and obesity.
Tissue Specificity
Expressed in taste buds (sensory organs of clustered epithelial cells) of the circumvallate and foliate papillae of the tongue at protein level. Expressed in enteroendocrine L cells of the gut. Detected also in spermatozoa.
KEGG Pathway
Taste transduction (hsa04742 )
Carbohydrate digestion and absorption (hsa04973 )
Reactome Pathway
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (R-HSA-381771 )
ADP signalling through P2Y purinoceptor 12 (R-HSA-392170 )
G alpha (s) signalling events (R-HSA-418555 )
G alpha (i) signalling events (R-HSA-418594 )
G alpha (z) signalling events (R-HSA-418597 )
Extra-nuclear estrogen signaling (R-HSA-9009391 )
GPER1 signaling (R-HSA-9634597 )
ADORA2B mediated anti-inflammatory cytokines production (R-HSA-9660821 )
Sensory perception of sweet, bitter, and umami (glutamate) taste (R-HSA-9717207 )
Adenylate cyclase inhibitory pathway (R-HSA-170670 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Laryngeal disorder DISDKUQO Strong Biomarker [1]
Male infertility DISY3YZZ Strong Biomarker [2]
Neoplasm DISZKGEW Strong Biomarker [3]
Obesity DIS47Y1K Strong Genetic Variation [4]
Dental caries DISRBCMD Limited Genetic Variation [5]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Guanine nucleotide-binding protein G(t) subunit alpha-3 (GNAT3). [6]
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References

1 Morphology of GNAT3-immunoreactive chemosensory cells in the rat larynx.J Anat. 2019 Feb;234(2):149-164. doi: 10.1111/joa.12914. Epub 2018 Nov 23.
2 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.
3 Bile acids affect the growth of human cholangiocarcinoma via NF-kB pathway.Cancer Invest. 2013 Feb;31(2):111-20. doi: 10.3109/07357907.2012.762781.
4 Gustation genetics: sweet gustducin!.Chem Senses. 2010 Sep;35(7):549-50. doi: 10.1093/chemse/bjq059. Epub 2010 Jul 21.
5 Taste genes associated with dental caries.J Dent Res. 2010 Nov;89(11):1198-202. doi: 10.1177/0022034510381502. Epub 2010 Sep 21.
6 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.