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GRIN2B  -  glutamate receptor, ionotropic, N-methyl D...

Homo sapiens

Synonyms: EIEE27, GluN2B, Glutamate receptor ionotropic, NMDA 2B, MRD6, N-methyl D-aspartate receptor subtype 2B, ...
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Disease relevance of GRIN2B


Psychiatry related information on GRIN2B


High impact information on GRIN2B

  • At immature synapses, a high probability of glutamate release (Pr) was correlated with the expression of postsynaptic NMDA (N-methyl-D-aspartate) receptors containing the NR2B subunit [11].
  • CaMKII-NR2B interaction may be prototypical for direct activation of a kinase by its targeting protein [12].
  • Here we show that regulated CaMKII interaction with two sites on the NMDA receptor subunit NR2B provides a mechanism for the glutamate-induced translocation of the kinase to the synapse in hippocampal neurons [12].
  • Here we show that overexpression of NMDA receptor 2B (NR2B) in the forebrains of transgenic mice leads to enhanced activation of NMDA receptors, facilitating synaptic potentiation in response to stimulation at 10-100 Hz [13].
  • PXR binds as a heterodimer with the 9-cis retinoic acid receptor (NR2B) to DNA response elements in the regulatory regions of cytochrome P450 3A monooxygenase genes and a number of other genes involved in the metabolism and elimination of xenobiotics from the body [14].

Chemical compound and disease context of GRIN2B


Biological context of GRIN2B

  • Although we did not detect NMDAR2B protein variants, our findings support the possibility that the GRIN2B gene or a locus in linkage disequilibrium with it may confer susceptibility to schizophrenia [19].
  • In the present work we report the localization of the gene encoding the human NMDAR2B receptor subunit (called GRIN2B for glutamate receptor, ionotropic, N-methyl-D-aspartate 2B) to chromosome 12p12 by in situ hybridization and somatic cell hybrids [20].
  • In the studied cohort of 167 HD patients, the repeat range from 41 to 45 CAG units accounted for 30.8% of the variance in AO; 12.3% additional variance could be attributed to GRIN2B genotype variation and 4.5% to GRIN2A genotype variation [21].
  • No significant frequency differences were found in the analysis of the alleles but some were found in the haplotypes of the GRIN2B gene [22].
  • These findings suggest that the combined effects of the polymorphisms in the GRIN1 and GRIN2B genes might be involved in the etiology of schizophrenia.European Journal of Human Genetics (2005) 13, 807-814. doi:10.1038/sj.ejhg.5201418 Published online 20 April 2005 [22].

Anatomical context of GRIN2B

  • GRIN2B gene is expressed at high levels in the fronto-parieto-temporal cortex and hippocampus pyramidal cells and, at a lower extent, in the basal ganglia (amygdala and striatum) [23].
  • The non-ubiquitous anatomical distribution of the GRIN2B mRNA in the central nervous system suggests that the gene could be involved in specific functions pertaining to the expressing cell groups [23].
  • This subunit is found enriched in the basal ganglia, and PD-monotherapy potential has been determined for GRIN2B antagonists [1].
  • High affinity sites for CGP 61594 were exclusively displayed by NR1/2B receptors, as shown by their co-distribution with the NR2B subunit, by subunit-selective immunoprecipitation and by functional analysis of NR1/2B receptors expressed in Xenopus oocytes (inhibitory potency, IC50 = 45 +/- 11 nM) [24].
  • NR1/NR2B and GLT1mRNA expression was not homogeneously lower in the neostriatum; zones with stronger hybridization signals corresponded to the matrix compartment and consisted of a larger number of cells with high mRNA levels [25].

Associations of GRIN2B with chemical compounds

  • We postulated that N-methyl- d-aspartate (NMDA) receptors were involved in OCD, and specifically that polymorphisms in the 3' untranslated region of GRIN2B (glutamate receptor, ionotropic, N-methyl- d-aspartate 2B) were associated with OCD in affected families [7].
  • mRNA distribution in adult human brain of GRIN2B, a N-methyl-D-aspartate (NMDA) receptor subunit [23].
  • Analysis of correlation between serum D-serine levels and functional promoter polymorphisms of GRIN2A and GRIN2B genes [26].
  • For this study of a sample population consisting of 101 PD patients and 108 controls, we tested the hypothesis that an ACC --> ACT transversion (2664(th) nucleotide of the coding sequence) affecting codon 888 (tyrosine) of GRIN2B confers susceptibility to PD, or relates to the age of onset [1].
  • We also show a similar interaction between the ifenprodil binding site and the glutamate binding site of NR1/NR2B receptors [27].

Physical interactions of GRIN2B

  • Switching synaptic NR2B-containing NMDA-Rs that bind CaMKII with high affinity with those containing NR2A, a subunit with low affinity for CaMKII, dramatically reduces LTP [28].
  • The NMDA receptor also serves as a CaMKII docking site in dendritic spines with high affinity binding sites located on its NR1 and NR2B subunits [29].
  • Gp120-induced phosphorylation of NR2B resulted in a sustained elevation of intracellular Ca(2+) in neurons and in a significant increase of NR2B binding to PSD95 [30].

Regulatory relationships of GRIN2B

  • Here, we demonstrate that CaMKIIalpha enhances the extent and/or rate of desensitization of NMDA-induced macroscopic currents in HEK293 cells co-expressing NR2B with either the NR1(011) or NR1(101) splice variants, without significantly changing other current parameters [31].
  • Single-cell reverse transcriptase polymerase chain reaction showed that all non-CD neurons expressed NR2B subunit mRNA [32].
  • Pressure ejection of HIV-1-infected and CD40 ligand-stimulated human monocyte-derived macrophage (MDM) fluids produced inward currents in oocytes expressing NR1a/NR2B (30.2+/-5.1 nA, n=42, mean+/-SE), but not in uninjected cells [33].
  • NMDA-induced GluR2 endocytosis was completely inhibited by pharmacological block of NR2B-containing NMDARs [34].

Other interactions of GRIN2B

  • Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell [35].
  • For example, in rat cultured mesencephalic neurons, NR2C expression was developmentally increased, whereas expression of NR2A and NR2B was decreased [36].
  • Subjects with the DRD2 A1/A1 genotype had a significantly higher mean performance IQ than A2/A2 carriers, while no significant differences in IQ scores were determined for the three GRIN2B genotype groups [37].
  • We observed increased protein expression of the NR2B NMDA receptor subunit and its associated intracellular protein, PSD95, in the dorsomedial thalamus of patients with schizophrenia, but the other molecules were unchanged, and we found no changes in the ventral thalamus [38].
  • Thus, human embryonic kidney 293 cells were transfected with the NR1-1a and NR2A NMDA receptor subunits in combination with both FLAG- and c-Myc epitope-tagged NR2B subunits [39].

Analytical, diagnostic and therapeutic context of GRIN2B


  1. Association analysis for genetic variants of the NMDA receptor 2b subunit (GRIN2B) and Parkinson's disease. Tsai, S.J., Liu, H.C., Liu, T.Y., Cheng, C.Y., Hong, C.J. Journal of neural transmission (Vienna, Austria : 1996) (2002) [Pubmed]
  2. Pharmacological and immunological characterization of N-methyl-D-aspartate receptors in human NT2-N neurons. Munir, M., Lu, L., Wang, Y.H., Luo, J., Wolfe, B.B., McGonigle, P. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  3. The NR2B-selective NMDA receptor antagonist CP-101,606 exacerbates L-DOPA-induced dyskinesia and provides mild potentiation of anti-parkinsonian effects of L-DOPA in the MPTP-lesioned marmoset model of Parkinson's disease. Nash, J.E., Ravenscroft, P., McGuire, S., Crossman, A.R., Menniti, F.S., Brotchie, J.M. Exp. Neurol. (2004) [Pubmed]
  4. Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death. Gao, J., Duan, B., Wang, D.G., Deng, X.H., Zhang, G.Y., Xu, L., Xu, T.L. Neuron (2005) [Pubmed]
  5. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Dalmau, J., Tüzün, E., Wu, H.Y., Masjuan, J., Rossi, J.E., Voloschin, A., Baehring, J.M., Shimazaki, H., Koide, R., King, D., Mason, W., Sansing, L.H., Dichter, M.A., Rosenfeld, M.R., Lynch, D.R. Ann. Neurol. (2007) [Pubmed]
  6. N-methyl-D-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: Polymorphisms and mRNA levels. Martucci, L., Wong, A.H., De Luca, V., Likhodi, O., Wong, G.W., King, N., Kennedy, J.L. Schizophr. Res. (2006) [Pubmed]
  7. Association of a glutamate (NMDA) subunit receptor gene (GRIN2B) with obsessive-compulsive disorder: a preliminary study. Arnold, P.D., Rosenberg, D.R., Mundo, E., Tharmalingam, S., Kennedy, J.L., Richter, M.A. Psychopharmacology (Berl.) (2004) [Pubmed]
  8. Association analysis for NMDA receptor subunit 2B (GRIN2B) genetic variants and psychopathology and clozapine response in schizophrenia. Hong, C.J., Yu, Y.W., Lin, C.H., Cheng, C.Y., Tsai, S.J. Psychiatr. Genet. (2001) [Pubmed]
  9. N-methyl-D-aspartate receptor subunit NR2A and NR2B messenger RNA levels are altered in the hippocampus and entorhinal cortex in Alzheimer's disease. Bi, H., Sze, C.I. J. Neurol. Sci. (2002) [Pubmed]
  10. The NMDA receptor NR2B subunit: a valid therapeutic target for multiple CNS pathologies. Chazot, P.L. Current medicinal chemistry. (2004) [Pubmed]
  11. Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse. Chavis, P., Westbrook, G. Nature (2001) [Pubmed]
  12. Interaction with the NMDA receptor locks CaMKII in an active conformation. Bayer, K.U., De Koninck, P., Leonard, A.S., Hell, J.W., Schulman, H. Nature (2001) [Pubmed]
  13. Genetic enhancement of learning and memory in mice. Tang, Y.P., Shimizu, E., Dube, G.R., Rampon, C., Kerchner, G.A., Zhuo, M., Liu, G., Tsien, J.Z. Nature (1999) [Pubmed]
  14. The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Kliewer, S.A., Goodwin, B., Willson, T.M. Endocr. Rev. (2002) [Pubmed]
  15. Expression of polyglutamine-expanded huntingtin induces tyrosine phosphorylation of N-methyl-D-aspartate receptors. Song, C., Zhang, Y., Parsons, C.G., Liu, Y.F. J. Biol. Chem. (2003) [Pubmed]
  16. CP-101606 Pfizer Inc. Chazot, P.L. Current opinion in investigational drugs (London, England : 2000) (2000) [Pubmed]
  17. Antiparkinsonian actions of ifenprodil in the MPTP-lesioned marmoset model of Parkinson's disease. Nash, J.E., Fox, S.H., Henry, B., Hill, M.P., Peggs, D., McGuire, S., Maneuf, Y., Hille, C., Brotchie, J.M., Crossman, A.R. Exp. Neurol. (2000) [Pubmed]
  18. The NMDA receptor NR2B subtype selective antagonist Ro 25-6981 aggravates paroxysmal dyskinesia in the dt(sz) mutant. Richter, A. Eur. J. Pharmacol. (2003) [Pubmed]
  19. Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia. Ohtsuki, T., Sakurai, K., Dou, H., Toru, M., Yamakawa-Kobayashi, K., Arinami, T. Mol. Psychiatry (2001) [Pubmed]
  20. Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12. Mandich, P., Schito, A.M., Bellone, E., Antonacci, R., Finelli, P., Rocchi, M., Ajmar, F. Genomics (1994) [Pubmed]
  21. NR2A and NR2B receptor gene variations modify age at onset in Huntington disease. Arning, L., Kraus, P.H., Valentin, S., Saft, C., Andrich, J., Epplen, J.T. Neurogenetics (2005) [Pubmed]
  22. An association study of the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B) in schizophrenia with universal DNA microarray. Qin, S., Zhao, X., Pan, Y., Liu, J., Feng, G., Fu, J., Bao, J., Zhang, Z., He, L. Eur. J. Hum. Genet. (2005) [Pubmed]
  23. mRNA distribution in adult human brain of GRIN2B, a N-methyl-D-aspartate (NMDA) receptor subunit. Schito, A.M., Pizzuti, A., Di Maria, E., Schenone, A., Ratti, A., Defferrari, R., Bellone, E., Mancardi, G.L., Ajmar, F., Mandich, P. Neurosci. Lett. (1997) [Pubmed]
  24. Differentiation of glycine antagonist sites of N-methyl-D-aspartate receptor subtypes. Preferential interaction of CGP 61594 with NR1/2B receptors. Honer, M., Benke, D., Laube, B., Kuhse, J., Heckendorn, R., Allgeier, H., Angst, C., Monyer, H., Seeburg, P.H., Betz, H., Mohler, H. J. Biol. Chem. (1998) [Pubmed]
  25. Changes of NMDA receptor subunit (NR1, NR2B) and glutamate transporter (GLT1) mRNA expression in Huntington's disease--an in situ hybridization study. Arzberger, T., Krampfl, K., Leimgruber, S., Weindl, A. J. Neuropathol. Exp. Neurol. (1997) [Pubmed]
  26. Analysis of correlation between serum D-serine levels and functional promoter polymorphisms of GRIN2A and GRIN2B genes. Iwayama, Y., Hashimoto, K., Nakajima, M., Toyota, T., Yamada, K., Shimizu, E., Itokawa, M., Hoshika, A., Iyo, M., Yoshikawa, T. Neurosci. Lett. (2006) [Pubmed]
  27. Allosteric interaction between the amino terminal domain and the ligand binding domain of NR2A. Zheng, F., Erreger, K., Low, C.M., Banke, T., Lee, C.J., Conn, P.J., Traynelis, S.F. Nat. Neurosci. (2001) [Pubmed]
  28. NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Barria, A., Malinow, R. Neuron (2005) [Pubmed]
  29. Regulation of calcium/calmodulin-dependent protein kinase II docking to N-methyl-D-aspartate receptors by calcium/calmodulin and alpha-actinin. Leonard, A.S., Bayer, K.U., Merrill, M.A., Lim, I.A., Shea, M.A., Schulman, H., Hell, J.W. J. Biol. Chem. (2002) [Pubmed]
  30. Interleukin-1beta Released by gp120 Drives Neural Death through Tyrosine Phosphorylation and Trafficking of NMDA Receptors. Viviani, B., Gardoni, F., Bartesaghi, S., Corsini, E., Facchi, A., Galli, C.L., Di Luca, M., Marinovich, M. J. Biol. Chem. (2006) [Pubmed]
  31. CaMKIIalpha enhances the desensitization of NR2B-containing NMDA receptors by an autophosphorylation-dependent mechanism. Sessoms-Sikes, S., Honse, Y., Lovinger, D.M., Colbran, R.J. Mol. Cell. Neurosci. (2005) [Pubmed]
  32. NMDA receptor alterations in neurons from pediatric cortical dysplasia tissue. André, V.M., Flores-Hernández, J., Cepeda, C., Starling, A.J., Nguyen, S., Lobo, M.K., Vinters, H.V., Levine, M.S., Mathern, G.W. Cereb. Cortex (2004) [Pubmed]
  33. Activation of NR1a/NR2B receptors by monocyte-derived macrophage secretory products: implications for human immunodeficiency virus type one-associated dementia. Xiong, H., McCabe, L., Skifter, D., Monaghan, D.T., Gendelman, H.E. Neurosci. Lett. (2003) [Pubmed]
  34. Subunit dependencies of N-methyl-D-aspartate (NMDA) receptor-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization. Tigaret, C.M., Thalhammer, A., Rast, G.F., Specht, C.G., Auberson, Y.P., Stewart, M.G., Schoepfer, R. Mol. Pharmacol. (2006) [Pubmed]
  35. Hippocampal N-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients. Mathern, G.W., Pretorius, J.K., Mendoza, D., Leite, J.P., Chimelli, L., Born, D.E., Fried, I., Assirati, J.A., Ojemann, G.A., Adelson, P.D., Cahan, L.D., Kornblum, H.I. Ann. Neurol. (1999) [Pubmed]
  36. Ethanol sensitivity of NMDA receptors. Allgaier, C. Neurochem. Int. (2002) [Pubmed]
  37. Dopamine D2 receptor and N-methyl-D-aspartate receptor 2B subunit genetic variants and intelligence. Tsai, S.J., Yu, Y.W., Lin, C.H., Chen, T.J., Chen, S.P., Hong, C.J. Neuropsychobiology (2002) [Pubmed]
  38. Up-regulation of NMDA receptor subunit and post-synaptic density protein expression in the thalamus of elderly patients with schizophrenia. Clinton, S.M., Haroutunian, V., Meador-Woodruff, J.H. J. Neurochem. (2006) [Pubmed]
  39. Biochemical evidence for the co-association of three N-methyl-D-aspartate (NMDA) R2 subunits in recombinant NMDA receptors. Hawkins, L.M., Chazot, P.L., Stephenson, F.A. J. Biol. Chem. (1999) [Pubmed]
  40. Variations in the NMDA receptor subunit 2B gene (GRIN2B) and schizophrenia: a case-control study. Di Maria, E., Gulli, R., Begni, S., De Luca, A., Bignotti, S., Pasini, A., Bellone, E., Pizzuti, A., Dallapiccola, B., Novelli, G., Ajmar, F., Gennarelli, M., Mandich, P. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2004) [Pubmed]
  41. Differential expression of N-methyl-D-aspartate receptor NR2 isoforms in Alzheimer's disease. Hynd, M.R., Scott, H.L., Dodd, P.R. J. Neurochem. (2004) [Pubmed]
  42. Expression of functional NR1/NR2B-type NMDA receptors in neuronally differentiated SK-N-SH human cell line. Pizzi, M., Boroni, F., Bianchetti, A., Moraitis, C., Sarnico, I., Benarese, M., Goffi, F., Valerio, A., Spano, P. Eur. J. Neurosci. (2002) [Pubmed]
  43. Protons trap NR1/NR2B NMDA receptors in a nonconducting state. Banke, T.G., Dravid, S.M., Traynelis, S.F. J. Neurosci. (2005) [Pubmed]
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