R10 R13 R14 R50 R49 R48 R44 R46 R43 R47r42 R45

Fig. 1 Chromosomal locations and orientations of the human TAS2R genes. Locations of TAS2R genes are roughly drawn to scale. Genes in plus orientation are shown above the lines, genes in minus orientation below the lines. Circles represent centromeric regions. Numbers identify chromosomes. The order of theT4S2R genes within the loci is displayed the T2R nomenclature of Adler et al. (2000), when referring to the rodent genes, and to the TAS2R nomenclature of Bufe et al. (2002), when referring to the human genes. The TAS2R nomenclature will also be used when generally referring to members of this gene family. For a compilation of the different nomenclatures, the readers' attention is drawn to the review of Andres-Barquin and Conte (2004).

Based on latest counts the gene repertoire in humans comprises 25 full-length genes and 11 pseudogenes (Go et al. 2005). With the exception of TAS2R1 on chromosomes 5, 9 and 15 TAS2R genes are present in extended clusters on chromosomes 7 and 12, respectively (Fig. 1; Adler et al. 2000; Matsunami et al. 2000). The mouse genome contains slightly more T2R genes, namely 35 genes and six pseudogenes (Go et al. 2005) located on chromosomes 2, 6, and 15 (Adler et al. 2000; Matsunami et al. 2000; Conte et al. 2003). All but two genes, which are found on chromosomes 2 and 15 respectively, are located in two clusters on chromosome 6 (Andres-Barquin and Conte 2004). TAS2R genes that lack introns in their coding regions specify proteins composed of approximately 290-330 amino acids. TAS2Rs are structurally diverse; the paralogs display approximately 17-90% sequence identity at the amino acid level, suggesting that different family members may recognize chemicals with widely different structures (Matsunami et al. 2000). However, they share the heptahelical structure and other sequence motifs with one another, classifying them as members of the same GPCR receptor subfamily. Figure 2 shows that, in general, the cytoplasmic part of the putative transmembrane (TM) segments and the intracellular loops are comparably well conserved, consistent with the idea that intracellular coupling to signal transduction proteins is of limited variability. The 20 amino acids present in all or almost all of the TAS2Rs are, depending on their position in the intracellular domains or lower part of the TM segments, likely to be involved in G protein coupling, receptor activation, and folding of the three-dimensional structure of the receptor. The extracellular loops and upper parts of the TM segments are less conserved. This is not surprising, since these parts of the TAS2Rs are likely to form heterogeneous binding motifs for the numerous and structurally diverse bitter compounds. In these regions there are only two highly conserved residues in extracellular loop (EL)-2 forming an N-linked glycosylation site. Thus, unlike most other GPCRs,

Fig. 2 Schematic representation of hTAS2Rs. Amino acid residues are indicated by colored circles. Sequence identity of hTAS2Rs has been analyzed using the pileup program (Genetics Computer group) and is depicted by the color code. Letters within the circles indicate the most frequent amino acids (in one letter code) present in the respective positions of the 25 hTAS2Rs. Transmembrane domains were predicted using the TMHMM program http://www.cbs.dtu.dk/services/TMHMM-2.07). Dotted circles, corresponding residues are not present in all hTAS2Rs. Magenta squares, regions that contain additional amino acids in a few hTAS2Rs

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Fig. 2 Schematic representation of hTAS2Rs. Amino acid residues are indicated by colored circles. Sequence identity of hTAS2Rs has been analyzed using the pileup program (Genetics Computer group) and is depicted by the color code. Letters within the circles indicate the most frequent amino acids (in one letter code) present in the respective positions of the 25 hTAS2Rs. Transmembrane domains were predicted using the TMHMM program http://www.cbs.dtu.dk/services/TMHMM-2.07). Dotted circles, corresponding residues are not present in all hTAS2Rs. Magenta squares, regions that contain additional amino acids in a few hTAS2Rs

TAS2Rs do not possess N-linked glycosylation sites in their amino-terminal parts. As in other TM or secretory proteins N-linked glycosylation may be involved in protein function, biosynthesis, and/or protein quality control. The carboxyl-terminal part of TAS2Rs is also highly variable, reflecting possible differences between TAS2Rs in receptor regulation and trafficking.

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