GRIN2B

GRIN2B
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	5EWM, 5EWL, 5EWJ
Identifiers
Aliases	GRIN2B, GluN2B, MRD6, NMDAR2B, NR2B, hNR3, EIEE27, glutamate ionotropic receptor NMDA type subunit 2B, NR3, DEE27
External IDs	OMIM: 138252 MGI: 95821 HomoloGene: 646 GeneCards: GRIN2B
Gene location (Human)
Chr.	Chromosome 12 (human)[1]
End	13,982,002 bp[1]
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)[2]
End	136,150,509 bp[2]
RNA expression pattern
	Top expressed in
	Brodmann area 23; ; sural nerve; ; middle temporal gyrus; ; corpus callosum; ; prefrontal cortex; ; nucleus accumbens; ; endothelial cell; ; dorsolateral prefrontal cortex; ; entorhinal cortex; ; superior frontal gyrus;
	Top expressed in
	olfactory tubercle; ; lateral geniculate nucleus; ; superior frontal gyrus; ; subiculum; ; seminiferous tubule; ; nucleus accumbens; ; Region I of hippocampus proper; ; supraoptic nucleus; ; ventromedial nucleus; ; medial dorsal nucleus;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	zinc ion binding; glycine binding; metal ion binding; ion channel activity; protein binding; ionotropic glutamate receptor activity; extracellularly glutamate-gated ion channel activity; NMDA glutamate receptor activity; glutamate binding; glutamate-gated calcium ion channel activity; amyloid-beta binding; signaling receptor activity;
Cellular component	integral component of membrane; postsynaptic membrane; membrane; synapse; NMDA selective glutamate receptor complex; cell surface; cell junction; neuron projection; intracellular anatomical structure; integral component of plasma membrane; postsynaptic density; plasma membrane; cytoplasm; synaptic membrane; postsynaptic density membrane;
Biological process	glutamate receptor signaling pathway; ephrin receptor signaling pathway; ion transport; MAPK cascade; learning or memory; response to ethanol; chemical synaptic transmission; ionotropic glutamate receptor signaling pathway; excitatory postsynaptic potential; regulation of ion transmembrane transport; transport; calcium-mediated signaling; protein heterotetramerization; regulation of molecular function; calcium ion transmembrane import into cytosol; multicellular organism development; brain development; regulation of synaptic plasticity; long-term potentiation; excitatory chemical synaptic transmission; positive regulation of neuron death; negative regulation of dendritic spine maintenance; positive regulation of cysteine-type endopeptidase activity; regulation of NMDA receptor activity;
	Sources:Amigo / QuickGO
Orthologs
	2904
	14812
	ENSG00000273079
	ENSMUSG00000030209
	Q13224
	Q01097
	NM_000834
	NM_008171; NM_001363750
	NP_000825
	NP_032197; NP_001350679
	Wikidata
View/Edit Human	View/Edit Mouse

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.[5]

NMDA receptors

N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. The 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 heterotetramers composed of two molecules of the key receptor subunit NMDAR1 (GRIN1) and two drawn from one or more of the four NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D). The NR2 subunit acts as the agonist binding site for glutamate, one of the predominant excitatory neurotransmitter receptors in the mammalian brain.[6]

Function

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.[7]

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.[8][9]

Ligands

Besonprodil
CERC-301, a selective NR2B receptor antagonist
Eliprodil
Ethanol - apparent induction of dephosphorylation of the NR2B Tyr1472 residue by STEP, leading to reduced receptor function
Ifenprodil
Rislenemdaz
Evt 101, a selective NR2B receptor antagonist. This compound was tested as a potentially fast-acting antidepressant.[10] In 2011 it was voluntarily withdrawn from a Phase II clinical study in treatment-resistant depression due to an unsatisfactory toxicity profile.[11]
Felbamate, an anticonvulsant that is also a positive allosteric modulator for the GABA_A receptor
Ro-25-6981 (also known as MI-4), a selective NR2B receptor antagonist
Traxoprodil, a selective NR2B receptor antagonist
Toluene - noncompetitive antagonist

Interactions

GRIN2B has been shown to interact with:

Actinin, alpha 2,[12]
DLG2,[13][14]
DLG3,[13][14][15][16]
DLG4,[13][14][15][16][17][18]
EXOC4,[15]
LIN7B,[19] and
RICS.[20]

References

GRCh38: Ensembl release 89: ENSG00000273079 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000030209 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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.
"Entrez Gene: GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B".
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.
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.
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. PMID 19838302.
"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.
"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.
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. Bibcode:1997Natur.385..439W. doi:10.1038/385439a0. PMID 9009191. S2CID 4266742.
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". American Journal of Physiology. Cell Physiology. 282 (6): C1396–403. doi:10.1152/ajpcell.00615.2001. PMID 11997254.
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.
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". Nature Cell Biology. 5 (6): 520–30. doi:10.1038/ncb990. PMID 12738960. S2CID 13444388.
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". The Journal of Biological Chemistry. 277 (24): 21697–711. doi:10.1074/jbc.M112339200. PMID 11937501.
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. S2CID 16068361.
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. Bibcode:1995Sci...269.1737K. doi:10.1126/science.7569905. PMID 7569905.
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". The Journal of Neuroscience. 19 (11): 4189–99. doi:10.1523/JNEUROSCI.19-11-04189.1999. PMC 6782594. PMID 10341223.
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". Molecular Biology of the Cell. 14 (7): 2921–34. doi:10.1091/mbc.E02-09-0623. PMC 165687. PMID 12857875.

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 (June 2004). "The NR2B subtype of NMDA receptor: a potential target for the treatment of alcohol dependence". Current Drug Targets. CNS and Neurological Disorders. 3 (3): 169–79. doi:10.2174/1568007043337409. PMID 15180478.
King JE, Eugenin EA, Buckner CM, Berman JW (April 2006). "HIV tat and neurotoxicity". Microbes and Infection. 8 (5): 1347–57. doi:10.1016/j.micinf.2005.11.014. PMID 16697675.
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. Bibcode:1995Sci...269.1737K. doi:10.1126/science.7569905. PMID 7569905.
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". Annals of Neurology. 37 (3): 373–80. doi:10.1002/ana.410370314. PMID 7695237. S2CID 24405132.
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". Genomics. 22 (1): 216–8. doi:10.1006/geno.1994.1366. PMID 7959773.
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". Biochimica et Biophysica 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 (March 1994). "Changing subunit composition of heteromeric NMDA receptors during development of rat cortex". Nature. 368 (6467): 144–7. Bibcode:1994Natur.368..144S. doi:10.1038/368144a0. PMID 8139656. S2CID 4332025.
Roche KW, Raymond LA, Blackstone C, Huganir RL (April 1994). "Transmembrane topology of the glutamate receptor subunit GluR6". The Journal of Biological Chemistry. 269 (16): 11679–82. doi:10.1016/S0021-9258(17)32623-6. PMID 8163463.
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". The European Journal of Neuroscience. 7 (11): 2285–93. doi:10.1111/j.1460-9568.1995.tb00649.x. PMID 8563977. S2CID 27201873.
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". Neurodegeneration. 4 (3): 315–21. doi:10.1016/1055-8330(95)90021-7. PMID 8581564.
Niethammer M, Kim E, Sheng M (April 1996). "Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases". The Journal of Neuroscience. 16 (7): 2157–63. doi:10.1523/JNEUROSCI.16-07-02157.1996. PMC 6578538. PMID 8601796.
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". AIDS. 10 (5): 463–8. doi:10.1097/00002030-199605000-00003. PMID 8724036. S2CID 1669986.
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". The Journal of Pharmacology and Experimental Therapeutics. 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 (August 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. S2CID 18715321.
Wu P, Price P, Du B, Hatch WC, Terwilliger EF (April 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. S2CID 21018147.
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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000273079 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000030209 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1350383-5] 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.

[6] "Entrez Gene: GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B".

[7] 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.

[tang1999-8] 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.

[9] 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. PMID 19838302.

[urlThe_Effects_of_a_Novel_NMDA_NR2B-Subtype_Selective_Antagonist,_EVT_101,_on_Brain_Function_-_Full_Text_View_-_ClinicalTrials.gov-10] "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.

[urlPhase_II_study_with_NR2B_sub-type_selective_NMDA_antagonist_in_treatment-resistant_depression_voluntarily_terminated.-11] "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.

[pmid9009191-12] 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. Bibcode:1997Natur.385..439W. doi:10.1038/385439a0. PMID 9009191. S2CID 4266742.

[pmid11997254-13] 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". American Journal of Physiology. Cell Physiology. 282 (6): C1396–403. doi:10.1152/ajpcell.00615.2001. PMID 11997254.

[pmid9278515-14] 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.

[pmid12738960-15] 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". Nature Cell Biology. 5 (6): 520–30. doi:10.1038/ncb990. PMID 12738960. S2CID 13444388.

[pmid11937501-16] 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". The Journal of Biological Chemistry. 277 (24): 21697–711. doi:10.1074/jbc.M112339200. PMID 11937501.

[pmid9581762-17] 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. S2CID 16068361.

[pmid7569905-18] 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. Bibcode:1995Sci...269.1737K. doi:10.1126/science.7569905. PMID 7569905.

[pmid10341223-19] 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". The Journal of Neuroscience. 19 (11): 4189–99. doi:10.1523/JNEUROSCI.19-11-04189.1999. PMC 6782594. PMID 10341223.

[pmid12857875-20] 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". Molecular Biology of the Cell. 14 (7): 2921–34. doi:10.1091/mbc.E02-09-0623. PMC 165687. PMID 12857875.