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; OMA:GRIN2B - orthologs
Gene location (Human)
Chr.	Chromosome 12 (human)
End	13,982,002 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	136,150,509 bp
RNA expression pattern
	Top expressed in
	buccal mucosa cell; ; Brodmann area 23; ; sural nerve; ; middle temporal gyrus; ; primary visual cortex; ; corpus callosum; ; prefrontal cortex; ; nucleus accumbens; ; endothelial cell; ; dorsolateral prefrontal cortex;
	Top expressed in
	lateral septal nucleus; ; olfactory tubercle; ; lateral geniculate nucleus; ; dentate gyrus of hippocampal formation granule cell; ; anterior amygdaloid area; ; superior frontal gyrus; ; subiculum; ; seminiferous tubule; ; nucleus accumbens; ; primary visual cortex;
	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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000273079 – Ensembl, May 2017
^ ^a ^b ^c 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.
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^ "Entrez Gene: GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B".
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^ 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.
^ ^a ^b ^c 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.
^ ^a ^b ^c 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.
^ ^a ^b ^c 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.
^ ^a ^b 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.

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