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GluK2

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Target not currently curated in GtoImmuPdb

Target id: 451

Nomenclature: GluK2

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 1 908 6q16.3 GRIK2 glutamate ionotropic receptor kainate type subunit 2
Mouse 3 1 908 10 24.87 cM Grik2 glutamate receptor, ionotropic, kainate 2 (beta 2)
Rat 3 1 908 20q13 Grik2 glutamate ionotropic receptor kainate type subunit 2
Previous and Unofficial Names Click here for help
EAA4 | GLUK6 | GluR6 | MRT6 | glutamate receptor 6 | Glurbeta2 | glutamate receptor, ionotropic, kainate 2 | glutamate receptor, ionotropic, kainate 2 (beta 2) | glutamate receptor
Database Links Click here for help
Alphafold Q13002 (Hs), P39087 (Mm), P42260 (Rn)
ChEMBL Target CHEMBL3683 (Hs), CHEMBL3607 (Rn)
Ensembl Gene ENSG00000164418 (Hs), ENSMUSG00000056073 (Mm), ENSRNOG00000000368 (Rn)
Entrez Gene 2898 (Hs), 14806 (Mm), 54257 (Rn)
Human Protein Atlas ENSG00000164418 (Hs)
KEGG Gene hsa:2898 (Hs), mmu:14806 (Mm), rno:54257 (Rn)
OMIM 138244 (Hs)
Orphanet ORPHA205590 (Hs)
Pharos Q13002 (Hs)
RefSeq Nucleotide NM_021956 (Hs), NM_010349 (Mm), NM_019309 (Rn)
RefSeq Protein NP_068775 (Hs), NP_034479 (Mm), NP_062182 (Rn)
SynPHARM 83004 (in complex with kainate)
UniProtKB Q13002 (Hs), P39087 (Mm), P42260 (Rn)
Wikipedia GRIK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Electron density map of GluK2 desensitized state in complex with 2S,4R-4-methylglutamate
PDB Id:  4UQQ
Ligand:  SYM2081
Resolution:  0.0Å
Species:  Rat
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the ligand-binding and transmembrane domains of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344
PDB Id:  8FWS
Ligand:  BPAM344
Resolution:  3.23Å
Species:  Rat
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to two concanavalin A dimers. Composite map.
PDB Id:  9B36
Ligand:  BPAM344
Resolution:  4.29Å
Species:  Rat
References:  2
Natural/Endogenous Ligands Click here for help
L-glutamic acid

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]kainate Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Full agonist 8.2 pKd 10
⤷ pKd 8.2 (Kd 6.6x10-9 M) [10]
dysiherbaine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 8.9 pKi 8
⤷ pKi 8.9 (Ki 1.2x10-9 M) [8]
kainate Small molecule or natural product Click here for species-specific activity table Rn Agonist 7.8 – 8.4 pKi 1,10
⤷ pKi 7.8 – 8.4 (Ki 1.43x10-8 – 3.7x10-9 M) [1,10]
Description: Measured using kainic acid in rat forebrain homogenate.
SYM2081 Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.0 pKi 6
⤷ pKi 8.0 (Ki 1x10-8 M) [6]
SYM2081 Small molecule or natural product Click here for species-specific activity table Rn Agonist 7.8 – 8.0 pKi 7,10
⤷ pKi 7.8 – 8.0 (Ki 1.7x10-8 – 9.8x10-9 M) [7,10]
Description: Measuring displacement of [3H]kainate binding to recombinant rGluR6 receptors.
domoic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.7 pKi 1
⤷ pKi 7.7 (Ki 1.83x10-8 M) [1]
Description: Measuring displacement of [3H]Kainate binding by domoate.
kainate Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.3 – 7.5 pKi 1,9
⤷ pKi 7.3 – 7.5 (Ki 5.3x10-8 – 3.2x10-8 M) [1,9]
Description: Measured using kainic acid.
LY339434 Small molecule or natural product Click here for species-specific activity table Hs Agonist 4.8 – 4.9 pKi 9
⤷ pKi 4.8 – 4.9 (Ki 1.541x10-5 – 1.204x10-5 M) [9]
SYM2081 Small molecule or natural product Click here for species-specific activity table Rn Full agonist 7.7 pIC50 10
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [10]
[3H]SYM2081 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist - -
⤷
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
2,4-epi-neodysiherbaine Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
⤷
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
BPAM344 Small molecule or natural product Ligand has a PDB structure Hs Positive 4.1 pEC50 - no 4
⤷ pEC50 4.1 (EC50 7.9x10-5 M) [4]
Not voltage dependent
concanavalin A Peptide Click here for species-specific activity table Hs Positive - - - no
⤷
Not voltage dependent
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Mental retardation, autosomal recessive, 6; MRT6
Synonyms: Autosomal recessive non-syndromic intellectual disability [Orphanet: ORPHA88616]
OMIM: 611092
Orphanet: ORPHA88616

References

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1. Cantrell BE, Zimmerman DM, Monn JA, Kamboj RK, Hoo KH, Tizzano JP, Pullar IA, Farrell LN, Bleakman D. (1996) Synthesis of a series of aryl kainic acid analogs and evaluation in cells stably expressing the kainate receptor humGluR6. J Med Chem, 39 (19): 3617-24. [PMID:8809152]

2. Gangwar SP, Yelshanskaya MV, Nadezhdin KD, Yen LY, Newton TP, Aktolun M, Kurnikova MG, Sobolevsky AI. (2024) Kainate receptor channel opening and gating mechanism. Nature, 630 (8017): 762-768. [PMID:38778115]

3. Gangwar SP, Yen LY, Yelshanskaya MV, Sobolevsky AI. (2023) Positive and negative allosteric modulation of GluK2 kainate receptors by BPAM344 and antiepileptic perampanel. Cell Rep, 42 (2): 112124. [PMID:36857176]

4. Larsen AP, Fièvre S, Frydenvang K, Francotte P, Pirotte B, Kastrup JS, Mulle C. (2017) Identification and Structure-Function Study of Positive Allosteric Modulators of Kainate Receptors. Mol Pharmacol, 91 (6): 576-585. [PMID:28360094]

5. Meyerson JR, Kumar J, Chittori S, Rao P, Pierson J, Bartesaghi A, Mayer ML, Subramaniam S. (2014) Structural mechanism of glutamate receptor activation and desensitization. Nature, 514 (7522): 328-34. [PMID:25119039]

6. Pedregal C, Collado I, Escribano A, Ezquerra J, Domínguez C, Mateo AI, Rubio A, Baker SR, Goldsworthy J, Kamboj RK et al.. (2000) 4-Alkyl- and 4-cinnamylglutamic acid analogues are potent GluR5 kainate receptor agonists. J Med Chem, 43 (10): 1958-68. [PMID:10821708]

7. Sagot E, Pickering DS, Pu X, Umberti M, Stensbøl TB, Nielsen B, Chapelet M, Bolte J, Gefflaut T, Bunch L. (2008) Chemo-enzymatic synthesis of a series of 2,4-syn-functionalized (S)-glutamate analogues: new insight into the structure-activity relation of ionotropic glutamate receptor subtypes 5, 6, and 7. J Med Chem, 51 (14): 4093-103. [PMID:18578478]

8. Sakai R, Swanson GT, Shimamoto K, Green T, Contractor A, Ghetti A, Tamura-Horikawa Y, Oiwa C, Kamiya H. (2001) Pharmacological properties of the potent epileptogenic amino acid dysiherbaine, a novel glutamate receptor agonist isolated from the marine sponge Dysidea herbacea. J Pharmacol Exp Ther, 296 (2): 650-8. [PMID:11160654]

9. Small B, Thomas J, Kemp M, Hoo K, Ballyk B, Deverill M, Ogden AM, Rubio A, Pedregal C, Bleakman D. (1998) LY339434, a GluR5 kainate receptor agonist. Neuropharmacology, 37 (10-11): 1261-7. [PMID:9849663]

10. Zhou LM, Gu ZQ, Costa AM, Yamada KA, Mansson PE, Giordano T, Skolnick P, Jones KA. (1997) (2S,4R)-4-methylglutamic acid (SYM 2081): a selective, high-affinity ligand for kainate receptors. J Pharmacol Exp Ther, 280 (1): 422-7. [PMID:8996224]

Contributors

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