TAS2R45 Membrane Protein Introduction

Introduction of TAS2R45

TAS2R45, also known as GPR59, is a member of the G-protein coupled receptor T2R family (TAS2Rs). The perception of bitter taste is mediated by the family. Encoded by the gene TAS2R45, the receptor contains 299 amino acids, and the molecular weight is predicted to be 34 kDa. From the predicted results performed using TOPCONS, we can see TAS2R45 has 7 transmembrane regions and 1 glycosylation site (161) and some other most conserved sites. It is documented that TAS2Rs are mainly expressed in bitter taste cells of our tongue and palate epithelia, and function with G-protein to transduce intracellular signals.

Basic Information of TAS2R45
Protein Name	Taste receptor type 2 member 45
Gene Name	TAS2R45
Aliases	G-protein coupled receptor 59, GPR59
Organism	Homo sapiens (Human)
UniProt ID	P59539
Transmembrane Times	7
Length (aa)	299
Sequence	MITFLPIIFSILVVVTFVIGNFANGFIALVNSTEWVKRQKISFADQIVTALAVSRVGLLW VLLLNWYSTVLNPAFCSVELRTTAYNIWAVTGHFSNWPATSLSIFYLLKIANFSNLIFLR LKRRVKSVILVVLLGPLLFLACHLFVVNMNQIVWTKEYEGNMTWKIKLRRAMYLSDTTVT MLANLVPFTVTLISFLLLVCSLCKHLKKMQLHGKGSQDPSTKVHIKVLQTVISFFLLRAI YFVSVIISVWSFKNLENKPVFMFCQAIGFSCSSAHPFILIWGNKKLKQTYLSVLWQMRY

Function of TAS2R45 Membrane Protein

As a member of TAS2R family, TAS2R45 can recognize bitter compounds various in chemical structure. So, it plays a key role in the perception of bitterness and is gustducin-linked. It also plays a role in sensing the chemical composition of the gastrointestinal content. It is reported that the activated TAS2R45 receptor may cause α-gustducin stimulated, mediate PLC-beta-2 activation, and result in the gating of TRPM5. Gene Ontology (GO) annotations related to TAS2R45 gene include bitter taste receptor activity. First identified in taste buds and subsequently discovered in extra-oral systems, TAS2Rs can bind different bitter compounds to generate different bitter tastes. TAS2Rs, as opposed to TAS1R proteins, have short extracellular domains and are located in circumvallate papillae, palate, foliate papillae, and epiglottis taste buds, with reduced expression in fungiform papillae. In the last decades, TAS2Rs have shown to be sensing potentially harmful bitter substances in the oral cavity to act with various physiological effects.

Fig.1 Networks from TAS2R genes. (Valente, 2018)

Application of TAS2R45 Membrane Protein in Literature

Meyerhof W., et al. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses. 2010, 35(2): 157-70. PubMed ID: 20022913

This article reveals TAS2R45 membrane protein is an orphan G protein-coupled receptors (GPCRs) and doesn't respond to 46 synthetic bitter compounds.
Roudnitzky N., et al. Copy Number Variation in TAS2R Bitter Taste Receptor Genes: Structure, Origin, and Population Genetics. Chem Senses. 2016, 41(8): 649-59. PubMed ID: 27340135

This article demonstrates that patterns of diversity at TAS2R45 are primarily due to genetic drift by structural mapping, copy-number estimates, population genetic analysis.
Thalmann S., et al. Major haplotypes of the human bitter taste receptor TAS2R41 encode functional receptors for chloramphenicol. Biochem Biophys Res Commun. 2013, 435(2): 267-73. PubMed ID: 23632330

This article finds a cognate agonist of TAS2R41 the same as TAS2R45 known as orphan receptor before. The newfound agonist of TAS2R41 is considered to be a “specialist” receptor highly selective for this antibiotic, which is the reason that the author forms a hypothesis TAS2R43 may be highly selective for bitter substances absent in out compound library.
Valente C., et al. Genes from the TAS1R and TAS2R Families of Taste Receptors: Looking for Signatures of Their Adaptive Role in Human Evolution. Genome Biol Evol. 2018, 10(4): 1139–1152. PubMed ID: 29635333

This article surveys the available sequence variation data of TAS1R and TAS2R families from the 1000 Genomes Project Phase 3 and reveals that genes from these two families have experienced contrasting evolutionary histories.

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Reference

Valente C, et al. (2018). Genes from the TAS1R and TAS2R Families of Taste Receptors: Looking for Signatures of Their Adaptive Role in Human Evolution. Genome Biol Evol. 10(4), 1139–1152.

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