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Functional and genomic comparative study of the bitter taste receptor family TAS2R: Insight into the role of human TAS2R5

Journal

FASEB JOURNAL
Volume 36, Issue 3, Pages -

Publisher

WILEY
DOI: 10.1096/fj.202101128RR

Keywords

agonist assays; bitter taste receptor

Funding

  1. Ministerio de Ciencia e Innovacion (MICINN) [AGL2017-83477-R]

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Bitter taste receptor hTAS2R5 has a unique functional specificity in humans and its closest functional homolog in mouse is mTas2r144, which is phylogenetically distant from hTAS2R5. There is no consensus about the role of hTAS2R5. Comparison with other species' bitter taste receptors reveals that hTAS2R5 has no ortholog in pig, mouse, or rat genomes.
Bitterness is perceived in humans by 25 subtypes of bitter taste receptors (hTAS2R) that range from broadly tuned to more narrowly tuned receptors. hTAS2R5 is one of the most narrowly tuned bitter taste receptors in humans. In this study, we review the literature on this receptor and show there is no consensus about its role. We then compare the possible role of hTAS2R5 with that of the proteins of the TAS2R family in rat, mouse, and pig. A phylogenetic tree of all mammalian TAS2R domain-containing proteins showed that human hTAS2R5 has no ortholog in pig, mouse, or rat genomes. By comparing the agonists that are common to hTAS2R5 and other members of the family, we observed that hTAS2R39 is the receptor that shares most agonists with hTAS2R5. In mouse, some of these agonists activate mTas2r105 and mTas2r144, which are distant paralogs of hTAS2R5. mTas2r144 seems to be the receptor that is most similar to hTAS2R5 because they are both activated by the same agonists and have affinities in the same range of values. Then, we can conclude that hTAS2R5 has a unique functional specificity in humans as it is activated by selective agonists and that its closest functional homolog in mouse is the phylogenetically distant mTas2r144.

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