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GluN2B

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Target not currently curated in GtoImmuPdb

Target id: 457

Nomenclature: GluN2B

Family: Ionotropic glutamate receptors

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 3 1 1484 12p13.1 GRIN2B glutamate ionotropic receptor NMDA type subunit 2B
Mouse 3 1 1482 6 66.38 cM Grin2b glutamate receptor, ionotropic, NMDA2B (epsilon 2)
Rat 3 1 1482 4q43 Grin2b glutamate ionotropic receptor NMDA type subunit 2B
Previous and Unofficial Names Click here for help
NMDAR2B | GluRepsilon2 | glutamate receptor, ionotropic, N-methyl D-aspartate 2B | glutamate receptor, ionotropic, NMDA2B (epsilon 2) | glutamate receptor
Database Links Click here for help
Alphafold Q13224 (Hs), Q01097 (Mm), Q00960 (Rn)
ChEMBL Target CHEMBL1904 (Hs), CHEMBL3442 (Mm), CHEMBL311 (Rn)
DrugBank Target Q13224 (Hs), Q13224 (Hs)
Ensembl Gene ENSG00000273079 (Hs), ENSMUSG00000030209 (Mm), ENSRNOG00000008766 (Rn)
Entrez Gene 2904 (Hs), 14812 (Mm), 24410 (Rn)
Human Protein Atlas ENSG00000273079 (Hs)
KEGG Gene hsa:2904 (Hs), mmu:14812 (Mm), rno:24410 (Rn)
OMIM 138252 (Hs)
Orphanet ORPHA266126 (Hs)
Pharos Q13224 (Hs)
RefSeq Nucleotide NM_000834 (Hs), NM_008171 (Mm), NM_012574 (Rn)
RefSeq Protein NP_000825 (Hs), NP_032197 (Mm), NP_036706 (Rn)
UniProtKB Q13224 (Hs), Q01097 (Mm), Q00960 (Rn)
Wikipedia GRIN2B (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of GluN1a/GluN2B NMDA Receptor Ion Channel
PDB Id:  4PE5
Resolution:  3.96Å
Species:  Rat
References:  8
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with ifenprodil
PDB Id:  3QEL
Ligand:  ifenprodil
Resolution:  2.6Å
Species:  Rat
References:  9
Natural/Endogenous Ligands Click here for help
D-aspartic acid
D-serine
glycine
L-aspartic acid
L-glutamic acid

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
glycine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist - -
⤷ [Binds to: glycine site] GluN2D > GluN2C > GluN2B > GluN2A
L-aspartic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist - -
⤷ [Binds to: glutamate site] GluN2D = GluN2B > GluN2C = GluN2A
(+)-HA966 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist - -
⤷ [Binds to: glycine site] GluN2B > GluN2A
(RS)-(tetrazol-5-yl)glycine Small molecule or natural product Click here for species-specific activity table Hs Full agonist - -
⤷ [Binds to: glutamate site] GluN2D > GluN2C = GluN2B > GluN2A
[3H]glycine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Agonist - -
⤷ [Binds to: glycine site]
D-serine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist - -
⤷ [Binds to: glycine site] GluN2D > GluN2C > GluN2B > GluN2A
homoquinolinic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist - -
⤷ [Binds to: glutamate site] GluN2B ≥ GluN2A ≥ GluN2D > GluN2C; partial agonist at GluN2A and GluN2C
NMDA Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist - -
⤷ [Binds to: glutamate site] GluN2D > GluN2C > GluN2B > GluN2A
D-aspartic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist - -
⤷ [Binds to: glutamate site] GluN2D > GluN2C = GluN2B > GluN2A
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
S-deschloroketamine Small molecule or natural product Hs Antagonist 5.4 pKd 1
⤷ pKd 5.4 (Kd 3.6x10-6 M) [1]
Description: Binding affinity for hGluN1/hGluN2B receptors expressed in HEK293 cells
5,7-dichlorokynurenic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist - -
⤷ [Binds to: glycine site]
[3H]CGP39653 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist - -
⤷ [Binds to: glutamate site]
[3H]CGP61594 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist - -
⤷ [Binds to: glycine site] photoaffinity ligand
[3H]CGS19755 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist - -
⤷ [Binds to: glutamate site]
[3H]CPP Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist - -
⤷ [Binds to: glutamate site]
[3H]L689560 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist - -
⤷ [Binds to: glycine site]
[3H]MDL105519 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist - -
⤷ [Binds to: glycine site]
CGP37849 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
⤷ [Binds to: glutamate site]
selfotel Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
⤷ [Binds to: glutamate site]
conantokin-G Peptide Click here for species-specific activity table Hs Antagonist - -
⤷ [Binds to: glutamate site] GluN2B > GluN2D = GluN2C = GluN2A
d-AP5 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
⤷ [Binds to: glutamate site]
d-CCPene Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
⤷ [Binds to: glutamate site] GluN2A = GluN2B > GluN2C = GluN2D
GV196771A Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
⤷ [Binds to: glycine site]
L689560 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
⤷ [Binds to: glycine site]
L701324 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
⤷ [Binds to: glycine site]
LY233053 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
⤷ [Binds to: glutamate site]
NVP-AAM077 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - - 4-6,11
⤷ [Binds to: glutamate site] GluN2A > GluN2B (human), but weakly selective for rat GluN2A versus GluN2B [4-6,11]
UBP141 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - - 10
⤷ [Binds to: glutamate site] GluN2D ≥ GluN2C > GluN2A ≥ GluN2B [10]
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
Mg2+ Click here for species-specific activity table Hs - no - - - no
⤷ GluN2A = GluN2B > GluN2C = GluN2D
Not voltage dependent
dizocilpine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - no - - - no
⤷
Not voltage dependent
[3H]dizocilpine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs - no - - - no
⤷ [Binds to: cation channel]
Not voltage dependent
amantadine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs - no - - - no
⤷ GluN2C = GluN2D ≥ GluN2B ≥ GluN2A
Not voltage dependent
ketamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs - no - - - no
⤷
Not voltage dependent
N1-dansyl-spermine Small molecule or natural product Click here for species-specific activity table Hs - no - - - no
⤷ GluN2A = GluN2B >> GluN2C = GluN2D
Not voltage dependent
phencyclidine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - no - - - no
⤷
Not voltage dependent
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
SAGE-718 Small molecule or natural product Click here for species-specific activity table Hs Positive 7.1 pEC50 - no 7
⤷ pEC50 7.1 (EC50 7.9x10-8 M) [7]
Not voltage dependent
Description: Value obtained using automated patch clamp electrophysiology in HEK293 cells stably expressing recombinant human GluN1/GluN2B Rs
onfasprodil Small molecule or natural product Hs Negative 8.1 pIC50 - no 3
⤷ pIC50 8.1 (IC50 8.3x10-9 M) [3]
Not voltage dependent
DQP-1105 Small molecule or natural product Click here for species-specific activity table Rn Negative 6.9 pIC50 - no 2
⤷ pIC50 6.9 (IC50 1.13x10-7 M) [2]
Not voltage dependent
Description: Measured using recombinant GluN1-1a NMDA subunits co-expressed with GluN2C subunits.
View species-specific allosteric modulator tables
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Mental retardation, autosomal dominant 6; MRD6
Synonyms: Autosomal dominant non-syndromic intellectual disability [Orphanet: ORPHA178469] [Disease Ontology: DOID:0060307]
Disease Ontology: DOID:0060307
OMIM: 613970
Orphanet: ORPHA178469

References

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1. Štefková-Mazochová K, Danda H, Dehaen W, Jurásek B, Šíchová K, Pinterová-Leca N, Mazoch V, Krausová BH, Kysilov B, Smejkalová T et al.. (2022) Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine in Wistar rats. Br J Pharmacol, 179 (1): 65-83. [PMID:34519023]

2. Acker TM, Yuan H, Hansen KB, Vance KM, Ogden KK, Jensen HS, Burger PB, Mullasseril P, Snyder JP, Liotta DC et al.. (2011) Mechanism for noncompetitive inhibition by novel GluN2C/D N-methyl-D-aspartate receptor subunit-selective modulators. Mol Pharmacol, 80 (5): 782-95. [PMID:21807990]

3. Anderson DR, Volkmann RA, Menniti FS. (2019) N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B. Patent number: US10239835B2. Assignee: Cadent Therapeutics Inc. Priority date: 26/09/2014. Publication date: 26/03/2019.

4. Auberson YP, Allgeier H, Bischoff S, Lingenhoehl K, Moretti R, Schmutz M. (2002) 5-Phosphonomethylquinoxalinediones as competitive NMDA receptor antagonists with a preference for the human 1A/2A, rather than 1A/2B receptor composition. Bioorg Med Chem Lett, 12 (7): 1099-102. [PMID:11909726]

5. Feng B, Tse HW, Skifter DA, Morley R, Jane DE, Monaghan DT. (2004) Structure-activity analysis of a novel NR2C/NR2D-preferring NMDA receptor antagonist: 1-(phenanthrene-2-carbonyl) piperazine-2,3-dicarboxylic acid. Br J Pharmacol, 141 (3): 508-16. [PMID:14718249]

6. Frizelle PA, Chen PE, Wyllie DJ. (2006) Equilibrium constants for (R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid (NVP-AAM077) acting at recombinant NR1/NR2A and NR1/NR2B N-methyl-D-aspartate receptors: Implications for studies of synaptic transmission. Mol Pharmacol, 70 (3): 1022-32. [PMID:16778008]

7. Hill MD, Blanco MJ, Salituro FG, Bai Z, Beckley JT, Ackley MA, Dai J, Doherty JJ, Harrison BL, Hoffmann EC et al.. (2022) SAGE-718: A First-in-Class N-Methyl-d-Aspartate Receptor Positive Allosteric Modulator for the Potential Treatment of Cognitive Impairment. J Med Chem, 65 (13): 9063-9075. [PMID:35785990]

8. Karakas E, Furukawa H. (2014) Crystal structure of a heterotetrameric NMDA receptor ion channel. Science, 344 (6187): 992-7. [PMID:24876489]

9. Karakas E, Simorowski N, Furukawa H. (2011) Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors. Nature, 475 (7355): 249-53. [PMID:21677647]

10. Morley RM, Tse HW, Feng B, Miller JC, Monaghan DT, Jane DE. (2005) Synthesis and pharmacology of N1-substituted piperazine-2,3-dicarboxylic acid derivatives acting as NMDA receptor antagonists. J Med Chem, 48 (7): 2627-37. [PMID:15801853]

11. Neyton J, Paoletti P. (2006) Relating NMDA receptor function to receptor subunit composition: limitations of the pharmacological approach. J Neurosci, 26 (5): 1331-3. [PMID:16452656]

Contributors

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