GRIN2B

Glutamate receptor, ionotropic, N-methyl D-aspartate 2B
Rendering based on PDB 1S11​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1S11​, 1S2S​, 2IPV​
Identifiers
Symbols	GRIN2B ; EIEE27; GluN2B; MRD6; NMDAR2B; NR2B; hNR3
External IDs	OMIM: 138252 MGI: 95821 HomoloGene: 646 IUPHAR: 457 ChEMBL: 1904 GeneCards: GRIN2B Gene
Gene ontology Molecular function • NMDA glutamate receptor activity • extracellular-glutamate-gated ion channel activity • calcium channel activity • protein binding • zinc ion binding • glycine binding Cellular component • plasma membrane • integral component of plasma membrane • synaptic vesicle • cell surface • NMDA selective glutamate receptor complex • cell junction • neuron projection • postsynaptic membrane • neuronal postsynaptic density Biological process • behavioral fear response • in utero embryonic development • startle response • suckling behavior • transport • glutamate receptor signaling pathway • synaptic transmission • axon guidance • sensory organ development • learning or memory • learning • memory • regulation of protein kinase A signaling • ionotropic glutamate receptor signaling pathway • response to ethanol • ephrin receptor signaling pathway • behavioral response to pain • detection of mechanical stimulus involved in sensory perception of pain • excitatory postsynaptic potential • long-term synaptic potentiation • calcium ion transmembrane transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2904	14812
Ensembl	ENSG00000273079	ENSMUSG00000030209
UniProt	Q13224	Q01097
RefSeq (mRNA)	NM_000834	NM_008171
RefSeq (protein)	NP_000825	NP_032197
Location (UCSC)	Chr 12: 13.54 – 13.98 Mb	Chr 6: 135.71 – 136.17 Mb
PubMed search

Glutamate [NMDA] receptor subunit epsilon-2 also known as N-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B) is a protein that in humans is encoded by the GRIN2B gene.^[1]

Function

N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA receptor channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heteromers composed of the key receptor subunit NMDAR1 (GRIN1) and 1 or more of the 4 NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D). The NR2 subunit acts as the agonist binding site for glutamate. This receptor is the predominant excitatory neurotransmitter receptor in the mammalian brain.^[2]

NR2B has been associated with age and visual experience dependent plasticity in the neocortex of rats, 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 cortical circuits.^[3]

Ligands

• Besonprodil
• CERC-301 selective NR2B receptor antagonist
• Eliprodil
• Evt 101, a selective NR2B receptor antagonist, was tested as a potentially fast acting antidepressant.^[4]

In 2011 it was voluntarily withdrawn from a Phase II clinical study in treatment-resistant depression due to an unsatisfactory toxicity profile.^[5]

• Ro-25-6981 (also known as MI-4) - selective NR2B receptor antagonist
• Traxoprodil selective NR2B receptor antagonist

Interactions

GRIN2B has been shown to interact with:

• Actinin, alpha 2,^[6]
• DLG2,^[7][8]
• DLG3,^{[7][8][9][10]}
• DLG4,^{[7][8][9][10][11][12]}
• EXOC4,^[9]
• LIN7B,^[13] and
• RICS.^[14]

See also

• NMDA receptor
• Glutamate receptor

References

1. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (Jun 1992). "Heteromeric NMDA receptors: molecular and functional distinction of subtypes". Science 256 (5060): 1217–21. doi:10.1126/science.256.5060.1217. PMID 1350383.
2. "Entrez Gene: GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B".
3. Yoshimura, Yumiko; Ohmura, Tomohisa; Komatsu, Yukio (2003-07-23). "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): 6557–6566. ISSN 0270-6474. PMID 12878697.
4. "The Effects of a Novel NMDA NR2B-Subtype Selective Antagonist, EVT 101, on Brain Function". NCT00526968. ClinicalTrials.gov. 2008-02-14. Retrieved 2010-08-19.
5. "Phase II study with NR2B sub-type selective NMDA antagonist in treatment-resistant depression voluntarily terminated". evotec.com. 2011-05-18. Retrieved 2015-08-24.
6. Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M (January 1997). "Competitive binding of alpha-actinin and calmodulin to the NMDA receptor". Nature 385 (6615): 439–42. doi:10.1038/385439a0. PMID 9009191.
7. Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y (June 2002). "Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses". Am. J. Physiol., Cell Physiol. 282 (6): C1396–403. doi:10.1152/ajpcell.00615.2001. PMID 11997254.
8. Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Südhof TC (September 1997). "Binding of neuroligins to PSD-95". Science 277 (5331): 1511–5. doi:10.1126/science.277.5331.1511. PMID 9278515.
9. Sans N, Prybylowski K, Petralia RS, Chang K, Wang YX, Racca C, Vicini S, Wenthold RJ (June 2003). "NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex". Nat. Cell Biol. 5 (6): 520–30. doi:10.1038/ncb990. PMID 12738960.
10. Lim IA, Hall DD, Hell JW (June 2002). "Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102". J. Biol. Chem. 277 (24): 21697–711. doi:10.1074/jbc.M112339200. PMID 11937501.
11. Niethammer M, Valtschanoff JG, Kapoor TM, Allison DW, Weinberg RJ, Craig AM, Sheng M (April 1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90". Neuron 20 (4): 693–707. doi:10.1016/s0896-6273(00)81009-0. PMID 9581762.
12. Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (September 1995). "Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95". Science 269 (5231): 1737–40. doi:10.1126/science.7569905. PMID 7569905.
13. Jo K, Derin R, Li M, Bredt DS (June 1999). "Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex". J. Neurosci. 19 (11): 4189–99. PMID 10341223.
14. Nakazawa T, Watabe AM, Tezuka T, Yoshida Y, Yokoyama K, Umemori H, Inoue A, Okabe S, Manabe T, Yamamoto T (July 2003). "p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPases, is involved in the N-methyl-d-aspartate receptor signaling". Mol. Biol. Cell 14 (7): 2921–34. doi:10.1091/mbc.E02-09-0623. PMC 165687. PMID 12857875.

Further reading

• Schröder HC, Perovic S, Kavsan V, Ushijima H, Müller WE (1998). "Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death". Neurotoxicology 19 (4-5): 683–8. PMID 9745929.
• Nagy J (2004). "The NR2B subtype of NMDA receptor: a potential target for the treatment of alcohol dependence". Curr Drug Targets CNS Neurol Disord 3 (3): 169–79. doi:10.2174/1568007043337409. PMID 15180478.
• King JE, Eugenin EA, Buckner CM, Berman JW (2006). "HIV tat and neurotoxicity". Microbes Infect. 8 (5): 1347–57. doi:10.1016/j.micinf.2005.11.014. PMID 16697675.
• Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (1995). "Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95". Science 269 (5231): 1737–40. doi:10.1126/science.7569905. PMID 7569905.
• Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (1995). "Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity". Ann. Neurol. 37 (3): 373–80. doi:10.1002/ana.410370314. PMID 7695237.
• Mandich P, Schito AM, Bellone E, Antonacci R, Finelli P, Rocchi M, Ajmar F (1994). "Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12". Genomics 22 (1): 216–8. doi:10.1006/geno.1994.1366. PMID 7959773.
• Adams SL, Foldes RL, Kamboj RK (1995). "Human N-methyl-D-aspartate receptor modulatory subunit hNR3: cloning and sequencing of the cDNA and primary structure of the protein". Biochim. Biophys. Acta 1260 (1): 105–8. doi:10.1016/0167-4781(94)00189-a. PMID 7999784.
• Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY (1994). "Changing subunit composition of heteromeric NMDA receptors during development of rat cortex". Nature 368 (6467): 144–7. doi:10.1038/368144a0. PMID 8139656.
• Roche KW, Raymond LA, Blackstone C, Huganir RL (1994). "Transmembrane topology of the glutamate receptor subunit GluR6". J. Biol. Chem. 269 (16): 11679–82. PMID 8163463.
• Lannuzel A, Lledo PM, Lamghitnia HO, Vincent JD, Tardieu M (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". Eur. J. Neurosci. 7 (11): 2285–93. doi:10.1111/j.1460-9568.1995.tb00649.x. PMID 8563977.
• Corasaniti MT, Melino G, Navarra M, Garaci E, Finazzi-Agrò A, Nisticò G (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". Neurodegeneration 4 (3): 315–21. doi:10.1016/1055-8330(95)90021-7. PMID 8581564.
• Niethammer M, Kim E, Sheng M (1996). "Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases". J. Neurosci. 16 (7): 2157–63. PMID 8601796.
• Pittaluga A, Pattarini R, Severi P, Raiteri M (1996). "Human brain N-methyl-D-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120". AIDS 10 (5): 463–8. doi:10.1097/00002030-199605000-00003. PMID 8724036.
• Hess SD, Daggett LP, Crona J, Deal C, Lu CC, Urrutia A, Chavez-Noriega L, Ellis SB, Johnson EC, Veliçelebi G (1996). "Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors". J. Pharmacol. Exp. Ther. 278 (2): 808–16. PMID 8768735.
• Müller BM, Kistner U, Kindler S, Chung WJ, Kuhlendahl S, Fenster SD, Lau LF, Veh RW, Huganir RL, Gundelfinger ED, Garner CC (1996). "SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo". Neuron 17 (2): 255–65. doi:10.1016/S0896-6273(00)80157-9. PMID 8780649.
• Wu P, Price P, Du B, Hatch WC, Terwilliger EF (1996). "Direct cytotoxicity of HIV-1 envelope protein gp120 on human NT neurons". NeuroReport 7 (5): 1045–9. doi:10.1097/00001756-199604100-00018. PMID 8804048.
• Bennett BA, Rusyniak DE, Hollingsworth CK (1995). "HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures". Brain Res. 705 (1-2): 168–76. doi:10.1016/0006-8993(95)01166-8. PMID 8821747.
• Toggas SM, Masliah E, Mucke L (1996). "Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine". Brain Res. 706 (2): 303–7. doi:10.1016/0006-8993(95)01197-8. PMID 8822372.
• Dreyer EB, Lipton SA (1995). "The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid". Eur. J. Neurosci. 7 (12): 2502–7. doi:10.1111/j.1460-9568.1995.tb01048.x. PMID 8845955.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.