Alternative titles; symbols
HGNC Approved Gene Symbol: GRIK4
Cytogenetic location: 11q23.3 Genomic coordinates (GRCh38): 11:120,511,748-120,988,906 (from NCBI)
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Its physiologic action is exerted through the activation of ligand-gated ion channels and G protein-coupled membrane receptors. Glutamate-gated ionic channels are broadly classified into N-methyl-D-aspartate (NMDA) and non-NMDA types. Three related non-NMDA receptor subunit gene families have been defined: the AMPA-preferring family, e.g., GLUR1 (138248), and the 2 kainate-preferring families. GRIK1 (138245), GRIK2 (138244), and GRIK3 (138243) constitute one of the GRIK gene families, and KA1 (GRIK4) and KA2 (GRIK5; 600283) constitute the second GRIK gene family. GRIK4 and GRIK5 form functional heteromeric kainate-preferring ionic channels with the subunits encoded by the GRIK1, GRIK2, and GRIK3 genes, but not with those falling in the AMP-preferring family (Szpirer et al., 1994).
GRIK4 and GRIK5 display 68% identity in their amino acid sequence (Szpirer et al., 1994).
By Southern analysis of rat/mouse and human/mouse somatic cell hybrid panels and by fluorescence in situ hybridization, Szpirer et al. (1994) determined that the GRIK4 and GRIK5 genes are located on human 11q22.3 and human 19q13.2, respectively; on mouse chromosome 9 and mouse chromosome 7, respectively; and on rat chromosome 8 and rat chromosome 1, respectively. (The localization of the mouse Grik4 and Grik5 genes was established by interspecific backcross mapping.)
Human evolution is characterized by a dramatic increase in brain size and complexity. To probe its genetic basis, Dorus et al. (2004) examined the evolution of genes involved in diverse aspects of nervous system biology. These genes, including GRIK4, displayed significantly higher rates of protein evolution in primates than in rodents. This trend was most pronounced for the subset of genes implicated in nervous system development. Moreover, within primates, the acceleration of protein evolution was most prominent in the lineage leading from ancestral primates to humans. Dorus et al. (2004) concluded that the phenotypic evolution of the human nervous system has a salient molecular correlate, i.e., accelerated evolution of the underlying genes, particularly those linked to nervous system development.
Dorus, S., Vallender, E. J., Evans, P. D., Anderson, J. R., Gilbert, S. L., Mahowald, M., Wyckoff, G. J., Malcom, C. M., Lahn, B. T. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell 119: 1027-1040, 2004. [PubMed: 15620360] [Full Text: https://doi.org/10.1016/j.cell.2004.11.040]
Szpirer, C., Molne, M., Antonacci, R., Jenkins, N. A., Finelli, P., Szpirer, J., Riviere, M., Rocchi, M., Gilbert, D. J., Copeland, N. G., Gallo, V. The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat. Proc. Nat. Acad. Sci. 91: 11849-11853, 1994. [PubMed: 7527545] [Full Text: https://doi.org/10.1073/pnas.91.25.11849]