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GRIK5  -  glutamate receptor, ionotropic, kainate 5

Homo sapiens

Synonyms: EAA2, Excitatory amino acid receptor 2, GRIK2, GluK5, Glutamate receptor KA-2, ...
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Disease relevance of GRIK5

  • In the present study, HEK cells expressing the GluR6 +/- KA2 receptor subunit(s) were studied for their susceptibility to toxicity through the kainate receptor by kainate ligands [1].

Psychiatry related information on GRIK5


High impact information on GRIK5

  • GRIK4 is the fifth gene shared by human Chr 11 and rat Chr 8, whereas GRIK5 is 1 out of the 12 genes that are located on both human Chr 19 and rat Chr 1 [4].
  • A key ligand-binding residue in the KA2 subunit, threonine 675, was mutated to either alanine or glutamate, which eliminated affinity for the receptor ligands kainate and glutamate [5].
  • Surface expression of homomeric KA2 receptors lacking a retention/retrieval determinant (KA2-R/A) was also reduced upon mutation of Thr-675 and elimination of the ligand binding site [5].
  • Characterization of the rat GRIK5 kainate receptor subunit gene promoter and its intragenic regions involved in neural cell specificity [6].
  • When placed downstream of the GRIK5 promoter, a 77-bp sequence from the deleted fragment completely silenced reporter expression in NIH3T3 fibroblasts while attenuating activity in CG-4 cells [6].

Biological context of GRIK5


Anatomical context of GRIK5


Associations of GRIK5 with chemical compounds

  • Evaluation of a positional candidate gene, the glutamate receptor subunit GRIK5, revealed no mutations [15].
  • Immunoblot analysis and electrophysiological recordings failed to demonstrate expression of hGluR1-hGluR4, EAA1/EAA2 proteins and the formation of functional AMPA/kainate receptor channels [16].
  • The mRNAs encoding kainic acid (KA) preferring glutamate receptor subunits (GluR5-7, KA1 and KA2) are differentially expressed in rat brain [10].
  • Most notably, mutation of Met725 to serine in KA2 increased the affinity of DH by 350-fold; in contrast, mutation of one or more of the residues in GluR5 did not markedly alter DH binding [17].
  • Homomeric and heteromeric GluR5 KA receptors were all inhibited to a similar extent by ethanol; however, there was slightly more inhibition of GluR5-R + KA2 receptors [18].

Other interactions of GRIK5

  • In contrast, co-expression with GluR6 disrupts ER-retention of KA2 and allows plasma membrane expression [11].
  • GluR5/KA-2 receptors had a higher EC50 value than homomeric GluR5 and exhibited a much faster recovery from desensitization [19].
  • To elucidate why DH, an agonist, and MSVIII-19, a competitive antagonist, bind selectively to glutamate receptor (GluR) 5 but not to the KA2 KAR subunit, we used molecular dynamics simulations to generate binding models that were tested experimentally in radioligand binding and electrophysiological assays [17].
  • The distribution of ionotropic AMPA receptor subunits GluR1-4, kainate receptor subunits GluR5-7 and KA2, delta receptors 1-2, as well as the metabotropic receptor mGluR6 were studied in the frog retina [20].

Analytical, diagnostic and therapeutic context of GRIK5

  • Immunoprecipitation studies showed that antibodies to GluR6 and KA2 selectively immunoprecipitated [3H]kainate binding activity, but not 3H-labeled alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) binding activity, from Triton X-100-solubilized rat brain membranes [21].
  • We performed a case-control study in 156 patients and 141 controls and the transmission disequilibrium test in 124 parent-offspring trios to search for association between OCD and two kainate receptors, GRIK2 and GRIK3 [2].


  1. Cytotoxic effects of kainate ligands on HEK cell lines expressing recombinant kainate receptors. Carver, J.M., Mansson, P.E., Cortes-Burgos, L., Shu, J., Zhou, L.M., Howe, J.R., Giordano, T. Brain Res. (1996) [Pubmed]
  2. Frequency and transmission of glutamate receptors GRIK2 and GRIK3 polymorphisms in patients with obsessive compulsive disorder. Delorme, R., Krebs, M.O., Chabane, N., Roy, I., Millet, B., Mouren-Simeoni, M.C., Maier, W., Bourgeron, T., Leboyer, M. Neuroreport (2004) [Pubmed]
  3. Replication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindreds. Andresen, J.M., Gay??n, J., Cherny, S.S., Brocklebank, D., Alkorta-Aranburu, G., Addis, E.A., Cardon, L.R., Housman, D.E., Wexler, N.S. J. Med. Genet. (2007) [Pubmed]
  4. The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat. Szpirer, C., Molné, M., Antonacci, R., Jenkins, N.A., Finelli, P., Szpirer, J., Riviere, M., Rocchi, M., Gilbert, D.J., Copeland, N.G. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  5. Ligand binding is a critical requirement for plasma membrane expression of heteromeric kainate receptors. Valluru, L., Xu, J., Zhu, Y., Yan, S., Contractor, A., Swanson, G.T. J. Biol. Chem. (2005) [Pubmed]
  6. Characterization of the rat GRIK5 kainate receptor subunit gene promoter and its intragenic regions involved in neural cell specificity. Chew, L.J., Yuan, X., Scherer, S.E., Qie, L., Huang, F., Hayes, W.P., Gallo, V. J. Biol. Chem. (2001) [Pubmed]
  7. Association study of polymorphisms in the GluR7, KA1 and KA2 kainate receptor genes (GRIK3, GRIK4, GRIK5) with schizophrenia. Shibata, H., Aramaki, T., Sakai, M., Ninomiya, H., Tashiro, N., Iwata, N., Ozaki, N., Fukumaki, Y. Psychiatry research. (2006) [Pubmed]
  8. Genomic organization of the human GRIK2 gene and evidence for multiple splicing variants. Barbon, A., Vallini, I., Barlati, S. Gene (2001) [Pubmed]
  9. Family-based association study between autism and glutamate receptor 6 gene in Chinese Han trios. Shuang, M., Liu, J., Jia, M.X., Yang, J.Z., Wu, S.P., Gong, X.H., Ling, Y.S., Ruan, Y., Yang, X.L., Zhang, D. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2004) [Pubmed]
  10. Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia. Porter, R.H., Eastwood, S.L., Harrison, P.J. Brain Res. (1997) [Pubmed]
  11. Trafficking and surface expression of the glutamate receptor subunit, KA2. Hayes, D.M., Braud, S., Hurtado, D.E., McCallum, J., Standley, S., Isaac, J.T., Roche, K.W. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  12. Localization of glutamate receptors to distal dendrites depends on subunit composition and the kinesin motor protein KIF17. Kayadjanian, N., Lee, H.S., Piña-Crespo, J., Heinemann, S.F. Mol. Cell. Neurosci. (2007) [Pubmed]
  13. Assembly and cell surface expression of KA-2 subunit-containing kainate receptors. Gallyas, F., Ball, S.M., Molnar, E. J. Neurochem. (2003) [Pubmed]
  14. Distribution of kainate receptor subunits at hippocampal mossy fiber synapses. Darstein, M., Petralia, R.S., Swanson, G.T., Wenthold, R.J., Heinemann, S.F. J. Neurosci. (2003) [Pubmed]
  15. Refined linkage to the RDP/DYT12 locus on 19q13.2 and evaluation of GRIK5 as a candidate gene. Kamm, C., Leung, J., Joseph, S., Dobyns, W.B., Brashear, A., Breakefield, X.O., Ozelius, L.J. Mov. Disord. (2004) [Pubmed]
  16. Expression of human glutamate receptors (GluR) in neuroblastoma cell lines. Korczak, B., McWhinnie, E.A., Fletcher, E.J., Kamboj, R.K. Neuroreport (1995) [Pubmed]
  17. Determination of binding site residues responsible for the subunit selectivity of novel marine-derived compounds on kainate receptors. Sanders, J.M., Pentikäinen, O.T., Settimo, L., Pentikäinen, U., Shoji, M., Sasaki, M., Sakai, R., Johnson, M.S., Swanson, G.T. Mol. Pharmacol. (2006) [Pubmed]
  18. Acute effects of ethanol on kainate receptors with different subunit compositions. Valenzuela, C.F., Cardoso, R.A. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  19. Kainate receptors exhibit differential sensitivities to (S)-5-iodowillardiine. Swanson, G.T., Green, T., Heinemann, S.F. Mol. Pharmacol. (1998) [Pubmed]
  20. Non-NMDA receptors in frog retina: An immunocytochemical study. Vitanova, L. Acta Histochem. (2007) [Pubmed]
  21. Biochemical and assembly properties of GluR6 and KA2, two members of the kainate receptor family, determined with subunit-specific antibodies. Wenthold, R.J., Trumpy, V.A., Zhu, W.S., Petralia, R.S. J. Biol. Chem. (1994) [Pubmed]
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