Alternative titles; symbols
HGNC Approved Gene Symbol: GRM8
Cytogenetic location: 7q31.33 Genomic coordinates (GRCh38): 7:126,438,598-127,252,941 (from NCBI)
The neurotransmitter L-glutamate interacts with both ionotropic and metabotropic receptors. The metabotropic glutamate receptors (mGluRs), which are G protein-coupled receptors, have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group II and group III mGluRs are linked to the inhibition of the cyclic AMP cascade, but differ in their agonist selectivities. GRM8 is a group III mGlur (summary by Wu et al., 1998).
Wu et al. (1998) isolated cDNAs encoding 3 human group III mGluRs, mGluR4 (604100), mGluR7 (604101) and mGluR8, and compared the pharmacologic properties of these receptors. They reported that the predicted 908-amino acid human mGluR8 protein shares 67 to 70% sequence similarity with mGluR4 and mGluR7 and 99% amino acid identity with mouse mGluR8.
Bjarnadottir et al. (2005) stated that the deduced 915-amino acid GRM8 protein contains the 7 transmembrane domains characteristic of G protein-coupled receptors. The N terminus of GRM8 is predicted to function in ligand binding. Bjarnadottir et al. (2005) also identified mouse Grm8, which encodes a deduced 920-amino acid protein.
Scherer et al. (1997) found that while the coding region of the GRM8 gene spans only 2.3 kb, the entire gene encompasses approximately 1 Mb of DNA at the boundary of bands 7q31.3 and 7q32.1. Scherer et al. (1997) cited examples of other genes that encompass extensive structures of DNA, including DMD (300377), with 2,400 kb at chromosome Xp21.2. Large genes tend to be located in Giesma dark bands on chromosomes, and 7q31.3 is Giesma dark, whereas 7q32.1 is Giesma light. Average-sized genes contain 8 exons and are 4 to 10 times larger than the mRNA. The enormous DMD gene, however, contains a minimum of 79 exons and encodes a 14-kb mRNA in muscle, indicating that the gene is 171 times larger than the mRNA. While GRM8 is about one-half the genomic size of DMD, its coding region is only 2.8 kb (or 357 times smaller than the full gene), making GRM8 the larger of the 2 genes when comparing coding to genomic lengths. The DMD gene requires 16 hours to be transcribed, and comparison of accumulation profiles for spliced and total transcript indicate that transcripts are spliced at the 5-prime end before transcription is complete, providing strong evidence for cotranscriptional splicing. Scherer et al. (1997) commented that similar studies for GRM8 should provide insight into the regulation of the gene during retinal and brain development.
Bjarnadottir et al. (2005) determined that the GRM8 gene contains 10 exons.
By analysis of a series of somatic cell hybrids with various rearrangements of chromosome 7 by fluorescence in situ hybridization, Scherer et al. (1996) mapped the GRM8 gene to chromosome 7q31.3-q32.1. Smith-Lemli-Opitz syndrome (SLO; 270400) maps to 7q32.1, and a form of retinitis pigmentosa (RP10; 180105) maps to 7q31-q35. Scherer et al. (1996) found that GRM8 maps to a YAC that encompasses a 7q32.1 translocation breakpoint in a patient with SLO and that the same YAC contains a microsatellite marker that demonstrated the strongest linkage to RP10.
Bjarnadottir et al. (2005) mapped the mouse Grm8 gene to chromosome 6.
Bjarnadottir, T. K., Fredriksson, R., Schioth, H. B. The gene repertoire and the common evolutionary history of glutamate, pheromone (V2R), taste(1) and other related G protein-coupled receptors. Gene 362: 70-84, 2005. [PubMed: 16229975] [Full Text: https://doi.org/10.1016/j.gene.2005.07.029]
Scherer, S. W., Duvoisin, R. M., Kuhn, R., Heng, H. H. Q., Belloni, E., Tsui, L.-C. Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q. Genomics 31: 230-233, 1996. [PubMed: 8824806] [Full Text: https://doi.org/10.1006/geno.1996.0036]
Scherer, S. W., Soder, S., Duvoisin, R. M., Huizenga, J. J., Tsui, L.-C. The human metabotropic glutamate receptor 8 (GRM8) gene: a disproportionately large gene located at 7q31.3-q32.1. Genomics 44: 232-236, 1997. [PubMed: 9299241] [Full Text: https://doi.org/10.1006/geno.1997.4842]
Wu, S., Wright, R. A., Rockey, P. K., Burgett, S. G., Arnold, J. S., Rosteck, P. R., Jr., Johnson, B. G., Schoepp, D. D., Belagaje, R. M. Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells. Molec. Brain Res. 53: 88-97, 1998. [PubMed: 9473604] [Full Text: https://doi.org/10.1016/s0169-328x(97)00277-5]