The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

GRIN2A  -  glutamate receptor, ionotropic, N-methyl D...

Homo sapiens

Synonyms: EPND, FESD, GluN2A, Glutamate receptor ionotropic, NMDA 2A, LKS, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GRIN2A


Psychiatry related information on GRIN2A


High impact information on GRIN2A

  • In this model, different NMDA receptor scaffolding and signaling complexes effect the trafficking and synaptic localization of NR2A-rich and NR2B-rich receptors, leading to tangential compartmentalization of these receptors and their movement between synaptic and extrasynaptic compartments [9].
  • In cell systems expressing NMDARs with mutant NR2A subunits in which this single cysteine was replaced by an alanine, the effect of endogenous NO was lost [10].
  • Using site-directed mutagenesis, we have identified three C-terminal tyrosine residues of NR2A that are required for Src's modulation of the zinc sensitivity of NMDA receptors [11].
  • 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 [12].
  • In studying chimeras of NR2A and NR2C subunits of the NMDA receptor, we have found that glycine-independent desensitization depends on two regions of the extracellular N-terminal domain [13].

Chemical compound and disease context of GRIN2A

  • In contrast, ischemia of longer duration (up to 30 min) caused an immediate decrease in the protein levels as well as tyrosine phosphorylation of both NR2A and NR2B subunits which was accompanied by the marked attenuation of the association with their investigated molecular partners--PSD-95 and NRTKs [14].

Biological context of GRIN2A


Anatomical context of GRIN2A


Associations of GRIN2A with chemical compounds

  • The glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the NMDA receptor, resides in this region and a recent study has reported an association between this gene and ADHD [5].
  • The GRIN2A (glutamate receptor, ionotropic, N-methyl D-aspartate 2A) gene that encodes the N-methyl D-aspartate receptor subunit 2A (NMDA2A) maps to this region of linkage [15].
  • Analysis of correlation between serum D-serine levels and functional promoter polymorphisms of GRIN2A and GRIN2B genes [20].
  • Although the carboxy(C)-terminal domain of the NR2A subunit contains potential tyrosine phosphorylation sites, the mechanisms by which Src modulates synaptic plasticity and NMDA receptor currents is not fully understood [11].
  • Glycine antagonist sites with low and intermediate affinity for [3H]CGP 61594 were detected also in situ by radioligand binding in brain areas predominantly expressing the NR2A and NR2C subunits, respectively [21].

Physical interactions of GRIN2A

  • We have localized regions in the S1 binding domain of both subunits required for the transmission of allosteric signals from the glutamate binding NR2A subunit to the glycine binding NR1 subunit [22].
  • Ser39 phosphorylation does not interfere with SAP97 capability to bind NR2A [23].

Regulatory relationships of GRIN2A

  • In contrast to the null effects of con-G and Ala/con-G at a NR1a/NR2A-containing receptor, some inhibition ( approximately 40%) of NMDA-evoked currents was effected by these peptides in cells expressing NR1b/NR2A [24].
  • Thus, CaMKII-dependent phosphorylation of SAP97 in different time frames and locations within the neurons controls both NR2A trafficking and insertion [23].
  • However, NR2A/B and 8-OHdG immunoreactivities were enhanced in CA1 over 24 h after ischemia although NR1 immunoreactivity was decreased [25].

Other interactions of GRIN2A

  • HS patients, by comparison, showed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NMDA-mediated pyramidal neuron responses should be reduced in HS patients compared with non-HS cases [26].
  • Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell [26].
  • In addition, GRIN2A and GRM6 loci were successfully localized on Chr 10 linkage maps by linkage analyses [27].
  • We conclude that replication is required and that further work examining for association of GRIN2A polymorphisms with ADHD is warranted [15].
  • HS patients, by contrast, showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases [26].

Analytical, diagnostic and therapeutic context of GRIN2A

  • Recently, we identified a variable (GT)n repeat in the promoter region of the NMDA NR2A subunit gene (GRIN2A), and showed its association with schizophrenia in a case-control study, together with a correlation between the length of the repeat and severity of chronic outcome [28].
  • Immunoblotting of the double immunopurified NR2A/NR2B(FLAG)-containing material demonstrated the presence of anti-NR1, anti-NR2A, anti-FLAG, and, more important, anti-c-Myc antibody immunoreactivities [29].
  • Amino acid residues positioned at or near the narrow constriction that interact with intracellular Mg2+ were identified in recombinant NR1-NR2A channels expressed in Xenopus oocytes or human embryonic kidney (HEK) 293 cells [30].
  • The oligomerization status of the co-expressed NR1a constructs and NR2A subunits was investigated using a non-denaturing gel electrophoresis system (blue native-polyacrylamide gel electrophoresis) and sucrose density gradient centrifugation [31].
  • Western blot analysis confirmed a lower expression of the NR2A and NR2B isoforms at the protein level [32].


  1. Distribution of the N-methyl-D-aspartate glutamate receptor subunit NR2A in control and amyotrophic lateral sclerosis spinal cord. Samarasinghe, S., Virgo, L., de Belleroche, J. Brain Res. (1996) [Pubmed]
  2. Expression of N-methyl-D-aspartate receptors using vaccinia virus causes excitotoxic death in human kidney cells. García-Gallo, M., Behrens, M.M., Renart, J., Díaz-Guerra, M. J. Cell. Biochem. (1999) [Pubmed]
  3. 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]
  4. Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke. Dambinova, S.A., Khounteev, G.A., Izykenova, G.A., Zavolokov, I.G., Ilyukhina, A.Y., Skoromets, A.A. Clin. Chem. (2003) [Pubmed]
  5. Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region. Adams, J., Crosbie, J., Wigg, K., Ickowicz, A., Pathare, T., Roberts, W., Malone, M., Schachar, R., Tannock, R., Kennedy, J.L., Barr, C.L. Mol. Psychiatry (2004) [Pubmed]
  6. 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]
  7. 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]
  8. Genetic analysis of a functional GRIN2A promoter (GT)n repeat in bipolar disorder pedigrees in humans. Itokawa, M., Yamada, K., Iwayama-Shigeno, Y., Ishitsuka, Y., Detera-Wadleigh, S., Yoshikawa, T. Neurosci. Lett. (2003) [Pubmed]
  9. Receptor compartmentalization and trafficking at glutamate synapses: a developmental proposal. van Zundert, B., Yoshii, A., Constantine-Paton, M. Trends Neurosci. (2004) [Pubmed]
  10. Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation. Choi, Y.B., Tenneti, L., Le, D.A., Ortiz, J., Bai, G., Chen, H.S., Lipton, S.A. Nat. Neurosci. (2000) [Pubmed]
  11. Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition. Zheng, F., Gingrich, M.B., Traynelis, S.F., Conn, P.J. Nat. Neurosci. (1998) [Pubmed]
  12. NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Barria, A., Malinow, R. Neuron (2005) [Pubmed]
  13. Glycine-independent NMDA receptor desensitization: localization of structural determinants. Villarroel, A., Regalado, M.P., Lerma, J. Neuron (1998) [Pubmed]
  14. Transient forebrain ischemia effects interaction of Src, FAK, and PYK2 with the NR2B subunit of N-methyl-D-aspartate receptor in gerbil hippocampus. Zalewska, T., Ziemka-Nałecz, M., Domańska-Janik, K. Brain Res. (2005) [Pubmed]
  15. Follow-up of genetic linkage findings on chromosome 16p13: evidence of association of N-methyl-D aspartate glutamate receptor 2A gene polymorphism with ADHD. Turic, D., Langley, K., Mills, S., Stephens, M., Lawson, D., Govan, C., Williams, N., Van Den Bree, M., Craddock, N., Kent, L., Owen, M., O'Donovan, M., Thapar, A. Mol. Psychiatry (2004) [Pubmed]
  16. A microsatellite repeat in the promoter of the N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia. Itokawa, M., Yamada, K., Yoshitsugu, K., Toyota, T., Suga, T., Ohba, H., Watanabe, A., Hattori, E., Shimizu, H., Kumakura, T., Ebihara, M., Meerabux, J.M., Toru, M., Yoshikawa, T. Pharmacogenetics (2003) [Pubmed]
  17. Neuronal and glial localization of NR1 and NR2A/B subunits of the NMDA receptor in the human cerebral cortex. Conti, F., Barbaresi, P., Melone, M., Ducati, A. Cereb. Cortex (1999) [Pubmed]
  18. Cloning, functional coexpression, and pharmacological characterisation of human cDNAs encoding NMDA receptor NR1 and NR2A subunits. Le Bourdellès, B., Wafford, K.A., Kemp, J.A., Marshall, G., Bain, C., Wilcox, A.S., Sikela, J.M., Whiting, P.J. J. Neurochem. (1994) [Pubmed]
  19. Development of N-methyl-D-aspartate receptor subunit immunoreactivity in the neonatal gerbil cochlear nucleus. Joelson, D., Schwartz, I.R. Microsc. Res. Tech. (1998) [Pubmed]
  20. 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]
  21. 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]
  22. Intersubunit cooperativity in the NMDA receptor. Regalado, M.P., Villarroel, A., Lerma, J. Neuron (2001) [Pubmed]
  23. Dual role of CaMKII-dependent SAP97 phosphorylation in mediating trafficking and insertion of NMDA receptor subunit NR2A. Mauceri, D., Gardoni, F., Marcello, E., Di Luca, M. J. Neurochem. (2007) [Pubmed]
  24. The amino acid residue at sequence position 5 in the conantokin peptides partially governs subunit-selective antagonism of recombinant N-methyl-D-aspartate receptors. Klein, R.C., Prorok, M., Galdzicki, Z., Castellino, F.J. J. Biol. Chem. (2001) [Pubmed]
  25. The alterations of N-Methyl-D-aspartate receptor expressions and oxidative DNA damage in the CA1 area at the early time after ischemia-reperfusion insult. Won, M.H., Kang, T., Park, S., Jeon, G., Kim, Y., Seo, J.H., Choi, E., Chung, M., Cho, S.S. Neurosci. Lett. (2001) [Pubmed]
  26. 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]
  27. Gene mapping of NMDA receptors and metabotropic glutamate receptors in the rat (Rattus norvegicus). Kuramoto, T., Maihara, T., Masu, M., Nakanishi, S., Serikawa, T. Genomics (1994) [Pubmed]
  28. Extended analyses support the association of a functional (GT)n polymorphism in the GRIN2A promoter with Japanese schizophrenia. Iwayama-Shigeno, Y., Yamada, K., Itokawa, M., Toyota, T., Meerabux, J.M., Minabe, Y., Mori, N., Inada, T., Yoshikawa, T. Neurosci. Lett. (2005) [Pubmed]
  29. 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]
  30. Intracellular Mg2+ interacts with structural determinants of the narrow constriction contributed by the NR1-subunit in the NMDA receptor channel. Wollmuth, L.P., Kuner, T., Sakmann, B. J. Physiol. (Lond.) (1998) [Pubmed]
  31. Identification of molecular determinants that are important in the assembly of N-methyl-D-aspartate receptors. Meddows, E., Le Bourdelles, B., Grimwood, S., Wafford, K., Sandhu, S., Whiting, P., McIlhinney, R.A. J. Biol. Chem. (2001) [Pubmed]
  32. 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]
WikiGenes - Universities