Top ▲

GluA4

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 447

Nomenclature: GluA4

Family: Ionotropic glutamate receptors

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 3 1 902 11q22.3 GRIA4 glutamate ionotropic receptor AMPA type subunit 4
Mouse 3 1 902 9 2.46 cM Gria4 glutamate receptor, ionotropic, AMPA4 (alpha 4)
Rat 3 1 902 8q11 Gria4 glutamate ionotropic receptor AMPA type subunit 4
Previous and Unofficial Names Click here for help
GluR4 | GluRD | AMPA-selective glutamate receptor 4 | glutamate receptor 4 | spkw1 | glutamate receptor, ionotropic, AMPA 4 | glutamate receptor
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
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
(S)-5-fluorowillardiine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist - -
[3H]AMPA Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Agonist - -
AMPA Small molecule or natural product Click here for species-specific activity table Hs Full agonist - -
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ATPO Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
GYKI53655 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
GYKI53784 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
active isomer, non-competitive
tezampanel Small molecule or natural product Click here for species-specific activity table Hs Antagonist - -
NBQX Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist - -
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
extracellular argiotoxin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - no - - - no

Not voltage dependent
extracellular joro toxin Small molecule or natural product Click here for species-specific activity table Hs - no - - - no
selective for channels lacking GluA2
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
LY392098 Small molecule or natural product Click here for species-specific activity table Hs Positive 6.7 pEC50 - no 8
pEC50 6.7 (EC50 2x10-7 M) [8]
Not voltage dependent
LY404187 Small molecule or natural product Click here for species-specific activity table Hs Positive 6.7 pEC50 - no 8
pEC50 6.7 (EC50 2.1x10-7 M) [8]
Not voltage dependent
cyclothiazide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Positive 5.4 pEC50 - no 8
pEC50 5.4 (EC50 3.91x10-6 M) [8]
Not voltage dependent
aniracetam Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Positive - - - no

Not voltage dependent
CX516 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Positive - - - no

Not voltage dependent
CX546 Small molecule or natural product Click here for species-specific activity table Hs Positive - - - no

Not voltage dependent
IDRA-21 Small molecule or natural product Click here for species-specific activity table Hs Positive - - - no

Not voltage dependent
LY503430 Small molecule or natural product Click here for species-specific activity table Hs Positive - - - no

Not voltage dependent
piracetam Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Positive - - - no

Not voltage dependent
S18986 Small molecule or natural product Click here for species-specific activity table Hs Positive - - - no

Not voltage dependent
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Rat
Description:  ‘flip’ isoform
Nucleotide accession: 
Protein accession: 
References:  9-12
Type:  Splice variant
Species:  Mouse
Description:  ‘flip’ isoform
Nucleotide accession: 
Protein accession: 
References:  4,6
Type:  Splice variant
Species:  Rat
Description:  'flop’ isoform
Nucleotide accession: 
Protein accession: 
References:  9-12
Type:  Splice variant
Species:  Mouse
Description:  ‘flop’ isoform
Nucleotide accession: 
Protein accession: 
References:  4,6
Type:  Splice variant
Species:  Human
Description:  Human ‘long’ isoform (flop)
Nucleotide accession: 
Protein accession: 
References:  1,7
Type:  Splice variant
Species:  Human
Description:  Human ‘long’ isoform (flip)
Nucleotide accession: 
Protein accession: 
References:  1,7
Type:  Splice variant
Species:  Human
Description:  ‘flop’ isoform
Nucleotide accession: 
Protein accession: 
References:  1,3,7
Type:  Splice variant
Species:  Human
Description:  ‘flip’ isoform
Nucleotide accession: 
Protein accession: 
References:  1,7
Biologically Significant Variant Comments
GluA4 exists as alternatively spliced ‘flip’ and ‘flop’ isoforms which differ with respect to a cassette of 35 amino acids in the extracellular loop between M3 and M4 [3,11]. Tetrameric receptors assembled from the ‘flip’ isoform enter the desensitized state more slowly, and recover more quickly, than those formed from the ‘flop’ isoform [4,9]. RNA editing (AGA->IGA) occurs at a codon for arginine (unedited), or glycine (edited) at a locus with the extracellular loop that immediately precedes the alternatively spliced ‘flip’ and ‘flop’ modules. Edited channels recover from desensitization at a faster rate than those that are unedited [6].

The human GluA4 subunit may exist as ‘short’ and ‘long’ splice variants that differ in their C terminal sequence [2,5].

References

Show »

1. Fletcher EJ, Nutt SL, Hoo KH, Elliott CE, Korczak B, McWhinnie EA, Kamboj RK. (1995) Cloning, expression and pharmacological characterization of a human glutamate receptor: hGluR4. Recept Channels, 3 (1): 21-31. [PMID:8589990]

2. Gallo V, Upson LM, Hayes WP, Vyklicky L, Winters CA, Buonanno A. (1992) Molecular cloning and development analysis of a new glutamate receptor subunit isoform in cerebellum. J Neurosci, 12 (3): 1010-23. [PMID:1372042]

3. Keinänen K, Wisden W, Sommer B, Werner P, Herb A, Verdoorn TA, Sakmann B, Seeburg PH. (1990) A family of AMPA-selective glutamate receptors. Science, 249 (4968): 556-60. [PMID:2166337]

4. Koike M, Tsukada S, Tsuzuki K, Kijima H, Ozawa S. (2000) Regulation of kinetic properties of GluR2 AMPA receptor channels by alternative splicing. J Neurosci, 20 (6): 2166-74. [PMID:10704491]

5. Köhler M, Kornau HC, Seeburg PH. (1994) The organization of the gene for the functionally dominant alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit GluR-B. J Biol Chem, 269 (26): 17367-70. [PMID:7545935]

6. Lomeli H, Mosbacher J, Melcher T, Höger T, Geiger JR, Kuner T, Monyer H, Higuchi M, Bach A, Seeburg PH. (1994) Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science, 266 (5191): 1709-13. [PMID:7992055]

7. McNamara JO, Eubanks JH, McPherson JD, Wasmuth JJ, Evans GA, Heinemann SF. (1992) Chromosomal localization of human glutamate receptor genes. J Neurosci, 12 (7): 2555-62. [PMID:1319477]

8. Miu P, Jarvie KR, Radhakrishnan V, Gates MR, Ogden A, Ornstein PL, Zarrinmayeh H, Ho K, Peters D, Grabell J et al.. (2001) Novel AMPA receptor potentiators LY392098 and LY404187: effects on recombinant human AMPA receptors in vitro. Neuropharmacology, 40 (8): 976-83. [PMID:11406188]

9. Mosbacher J, Schoepfer R, Monyer H, Burnashev N, Seeburg PH, Ruppersberg JP. (1994) A molecular determinant for submillisecond desensitization in glutamate receptors. Science, 266 (5187): 1059-62. [PMID:7973663]

10. Sakimura K, Morita T, Kushiya E, Mishina M. (1992) Primary structure and expression of the gamma 2 subunit of the glutamate receptor channel selective for kainate. Neuron, 8 (2): 267-74. [PMID:1310861]

11. Sommer B, Keinänen K, Verdoorn TA, Wisden W, Burnashev N, Herb A, Köhler M, Takagi T, Sakmann B, Seeburg PH. (1990) Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. Science, 249 (4976): 1580-5. [PMID:1699275]

12. Sommer B, Köhler M, Sprengel R, Seeburg PH. (1991) RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell, 67 (1): 11-9. [PMID:1717158]

Contributors

Show »

How to cite this page