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GRIN2B
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<h2 id="nmda-receptors">NMDA receptors</h2> <p><i>N</i>-methyl-D-aspartate (<a href="/facts/NMDA_receptor/BqMhXEbU">NMDA</a>) receptors are a class of <a href="/facts/Ionotropic_glutamate_receptor/RqSxqHqF">ionotropic glutamate receptors</a>. The NMDA receptor channel has been shown to be involved in <a href="/facts/Long-term_potentiation/AbuJmBeo">long-term potentiation</a>, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heterotetramers composed of two molecules of the key receptor subunit NMDAR1 (<a href="/facts/GRIN1/buPGUcXF">GRIN1</a>) and two drawn from one or more of the four NMDAR2 subunits: NMDAR2A (<a href="/facts/GRIN2A/KE9KrAEj">GRIN2A</a>), NMDAR2B (GRIN2B), NMDAR2C (<a href="/facts/GRIN2C/J4f62bfV">GRIN2C</a>), and NMDAR2D (<a href="/facts/GRIN2D/K05cp0zL">GRIN2D</a>). The NR2 subunit acts as the agonist binding site for <a href="/facts/Glutamic_acid/7oXbNcvu">glutamate</a>, one of the predominant excitatory neurotransmitter receptors in the mammalian brain.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> </p> <h2 id="function">Function</h2> <p>NR2B has been associated with age- and <a href="/facts/Visual_system/QVcuA27K">visual</a>-experience-dependent plasticity in the <a href="/facts/Neocortex/YEVjPgGK">neocortex</a> of <a href="/facts/Rat/5rn6uEKM">rats</a>, where an increased NR2B/NR2A ratio correlates directly with the stronger excitatory LTP in young animals. This is thought to contribute to experience-dependent refinement of developing <a href="/facts/Cortex_(anatomy)/cFCCqbUR">cortical</a> circuits.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> </p><p>Engineered to overexpress GRIN2B in their brains, mice and rats exhibit improved mental function. The "Doogie" mouse performed twice as well on one learning test.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p> <h2 id="ligands">Ligands</h2> <ul><li><a href="/facts/Besonprodil/MexaKbLx">Besonprodil</a></li> <li><a href="/facts/CERC-301/f4KXS6Qm">CERC-301</a>, a selective NR2B receptor antagonist</li> <li><a href="/facts/Eliprodil/LcJTSPe8">Eliprodil</a></li> <li><a href="/facts/Ethanol/3lCLfBSP">Ethanol</a> - apparent induction of dephosphorylation of the NR2B Tyr1472 residue by <a href="/facts/STriatal-Enriched_protein_tyrosine_Phosphatase/K31hn17w">STEP</a>, leading to reduced receptor function</li> <li><a href="/facts/Ifenprodil/SqWzThA5">Ifenprodil</a></li> <li><a href="/facts/Rislenemdaz/f4KXS6Qm">Rislenemdaz</a></li> <li><a href="/facts/EVT-101/rfb27Ymg">EVT-101</a>, a selective NR2B receptor antagonist. This compound was tested as a potentially fast-acting antidepressant.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> In 2011 it was voluntarily withdrawn from a Phase II clinical study in treatment-resistant depression due to an unsatisfactory toxicity profile.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a></li> <li><a href="/facts/Felbamate/LxFRqrFr">Felbamate</a>, an anticonvulsant that is also a <a href="/facts/Positive_allosteric_modulator/Gg1It5Cj">positive allosteric modulator</a> for the <a href="/facts/GABAA_receptor/6G4rAGb3">GABAA receptor</a></li> <li>Ro-25-6981 (also known as MI-4), a selective NR2B receptor antagonist</li> <li><a href="/facts/Traxoprodil/klMtgXpM">Traxoprodil</a>, a selective NR2B receptor antagonist</li> <li><a href="/facts/Toluene/Pzdt8dwD">Toluene</a> - noncompetitive antagonist</li></ul> <h2 id="interactions">Interactions</h2> <p>GRIN2B has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with: </p> <ul><li><a href="/facts/Actinin,_alpha_2/N0kgqzL2">Actinin, alpha 2</a>,<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a></li> <li><a href="/facts/DLG2/Ap0FIEGD">DLG2</a>,<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a></li> <li><a href="/facts/DLG3/Iz8MeFY6">DLG3</a>,<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a><a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a></li> <li><a href="/facts/DLG4/d23IStkv">DLG4</a>,<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a><a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a><a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a><a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a><a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a><a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a></li> <li><a href="/facts/EXOC4/8JsKleN1">EXOC4</a>,<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a></li> <li><a href="/facts/LIN7B/FwXrWXd9">LIN7B</a>,<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> and</li> <li><a href="/facts/RICS_(gene)/uwcuDWnK">RICS</a>.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a></li></ul> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/NMDA_receptor/BqMhXEbU">NMDA receptor</a></li> <li><a href="/facts/Glutamate_receptor/MGwpHHUA">Glutamate receptor</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Schröder HC, Perovic S, Kavsan V, Ushijima H, Müller WE (1998). "Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death". <i>Neurotoxicology</i>. 19 (4–5): 683–8. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9745929">9745929</a>.</li> <li>Nagy J (June 2004). "The NR2B subtype of NMDA receptor: a potential target for the treatment of alcohol dependence". <i>Current Drug Targets. CNS and Neurological Disorders</i>. 3 (3): 169–79. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.2174%2F1568007043337409">10.2174/1568007043337409</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15180478">15180478</a>.</li> <li>King JE, Eugenin EA, Buckner CM, Berman JW (April 2006). <a href="https://doi.org/10.1016%2Fj.micinf.2005.11.014">"HIV tat and neurotoxicity"</a>. <i>Microbes and Infection</i>. 8 (5): 1347–57. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2Fj.micinf.2005.11.014">10.1016/j.micinf.2005.11.014</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16697675">16697675</a>.</li> <li>Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (September 1995). "Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95". <i>Science</i>. 269 (5231): 1737–40. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1995Sci...269.1737K">1995Sci...269.1737K</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1126%2Fscience.7569905">10.1126/science.7569905</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7569905">7569905</a>.</li> <li>Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (March 1995). "Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity". <i>Annals of Neurology</i>. 37 (3): 373–80. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Fana.410370314">10.1002/ana.410370314</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7695237">7695237</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:24405132">24405132</a>.</li> <li>Mandich P, Schito AM, Bellone E, Antonacci R, Finelli P, Rocchi M, Ajmar F (July 1994). "Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12". <i>Genomics</i>. 22 (1): 216–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fgeno.1994.1366">10.1006/geno.1994.1366</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7959773">7959773</a>.</li> <li>Adams SL, Foldes RL, Kamboj RK (January 1995). "Human N-methyl-D-aspartate receptor modulatory subunit hNR3: cloning and sequencing of the cDNA and primary structure of the protein". <i>Biochimica et Biophysica Acta</i>. 1260 (1): 105–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0167-4781%2894%2900189-a">10.1016/0167-4781(94)00189-a</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7999784">7999784</a>.</li> <li>Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY (March 1994). "Changing subunit composition of heteromeric NMDA receptors during development of rat cortex". <i>Nature</i>. 368 (6467): 144–7. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1994Natur.368..144S">1994Natur.368..144S</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F368144a0">10.1038/368144a0</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8139656">8139656</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:4332025">4332025</a>.</li> <li>Roche KW, Raymond LA, Blackstone C, Huganir RL (April 1994). <a href="https://doi.org/10.1016%2FS0021-9258%2817%2932623-6">"Transmembrane topology of the glutamate receptor subunit GluR6"</a>. <i>The Journal of Biological Chemistry</i>. 269 (16): 11679–82. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0021-9258%2817%2932623-6">10.1016/S0021-9258(17)32623-6</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8163463">8163463</a>.</li> <li>Lannuzel A, Lledo PM, Lamghitnia HO, Vincent JD, Tardieu M (November 1995). "HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i increase, alter [Ca2+]i homeostasis and induce neurotoxicity in human embryonic neurons". <i>The European Journal of Neuroscience</i>. 7 (11): 2285–93. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1111%2Fj.1460-9568.1995.tb00649.x">10.1111/j.1460-9568.1995.tb00649.x</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8563977">8563977</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:27201873">27201873</a>.</li> <li>Corasaniti MT, Melino G, Navarra M, Garaci E, Finazzi-Agrò A, Nisticò G (September 1995). "Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is prevented by NMDA receptor antagonists and inhibitors of nitric oxide and cyclooxygenase". <i>Neurodegeneration</i>. 4 (3): 315–21. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F1055-8330%2895%2990021-7">10.1016/1055-8330(95)90021-7</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8581564">8581564</a>.</li> <li>Niethammer M, Kim E, Sheng M (April 1996). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6578538">"Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases"</a>. <i>The Journal of Neuroscience</i>. 16 (7): 2157–63. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1523%2FJNEUROSCI.16-07-02157.1996">10.1523/JNEUROSCI.16-07-02157.1996</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6578538">6578538</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8601796">8601796</a>.</li> <li>Pittaluga A, Pattarini R, Severi P, Raiteri M (May 1996). "Human brain N-methyl-D-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120". <i>AIDS</i>. 10 (5): 463–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1097%2F00002030-199605000-00003">10.1097/00002030-199605000-00003</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8724036">8724036</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:1669986">1669986</a>.</li> <li>Hess SD, Daggett LP, Crona J, Deal C, Lu CC, Urrutia A, Chavez-Noriega L, Ellis SB, Johnson EC, Veliçelebi G (August 1996). "Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors". <i>The Journal of Pharmacology and Experimental Therapeutics</i>. 278 (2): 808–16. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8768735">8768735</a>.</li> <li>Müller BM, Kistner U, Kindler S, Chung WJ, Kuhlendahl S, Fenster SD, Lau LF, Veh RW, Huganir RL, Gundelfinger ED, Garner CC (August 1996). <a href="https://doi.org/10.1016%2FS0896-6273%2800%2980157-9">"SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo"</a>. <i>Neuron</i>. 17 (2): 255–65. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0896-6273%2800%2980157-9">10.1016/S0896-6273(00)80157-9</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8780649">8780649</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:18715321">18715321</a>.</li> <li>Wu P, Price P, Du B, Hatch WC, Terwilliger EF (April 1996). "Direct cytotoxicity of HIV-1 envelope protein gp120 on human NT neurons". <i>NeuroReport</i>. 7 (5): 1045–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1097%2F00001756-199604100-00018">10.1097/00001756-199604100-00018</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8804048">8804048</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:21018147">21018147</a>.</li> <li>Bennett BA, Rusyniak DE, Hollingsworth CK (December 1995). "HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures". <i>Brain Research</i>. 705 (1–2): 168–76. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0006-8993%2895%2901166-8">10.1016/0006-8993(95)01166-8</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8821747">8821747</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:32822686">32822686</a>.</li> <li>Toggas SM, Masliah E, Mucke L (January 1996). "Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine". <i>Brain Research</i>. 706 (2): 303–7. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0006-8993%2895%2901197-8">10.1016/0006-8993(95)01197-8</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8822372">8822372</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:44260060">44260060</a>.</li> <li>Dreyer EB, Lipton SA (December 1995). "The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid". <i>The European Journal of Neuroscience</i>. 7 (12): 2502–7. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1111%2Fj.1460-9568.1995.tb01048.x">10.1111/j.1460-9568.1995.tb01048.x</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8845955">8845955</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:7370984">7370984</a>.</li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (May 1992). "Heteromeric NMDA receptors: molecular and functional distinction of subtypes". Science. 256 (5060): 1217–21. Bibcode:1992Sci...256.1217M. doi:10.1126/science.256.5060.1217. PMID 1350383. S2CID 989677. <a href="/wiki/Bibcode_(identifier)" target="_blank">/wiki/Bibcode_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"Entrez Gene: GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2904" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2904</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Yoshimura Y, Ohmura T, Komatsu Y (July 2003). "Two forms of synaptic plasticity with distinct dependence on age, experience, and NMDA receptor subtype in rat visual cortex". The Journal of Neuroscience. 23 (16): 6557–66. doi:10.1523/JNEUROSCI.23-16-06557.2003. PMC 6740618. PMID 12878697. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740618" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740618</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Liu G, Tsien JZ (September 1999). "Genetic enhancement of learning and memory in mice". Nature. 401 (6748): 63–9. Bibcode:1999Natur.401...63T. doi:10.1038/43432. PMID 10485705. S2CID 481884. <a href="/wiki/Bibcode_(identifier)" target="_blank">/wiki/Bibcode_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Wang D, Cui Z, Zeng Q, Kuang H, Wang LP, Tsien JZ, Cao X (October 2009). "Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats". PLOS ONE. 4 (10): e7486. Bibcode:2009PLoSO...4.7486W. doi:10.1371/journal.pone.0007486. PMC 2759522. 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