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glycine receptor α3 subunit

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Target id: 425

Nomenclature: glycine receptor α3 subunit

Family: Glycine receptors

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 464 4q34.1 GLRA3 glycine receptor alpha 3 9
Mouse 4 464 8 29.69 cM Glra3 glycine receptor, alpha 3 subunit 5
Rat 4 464 16p11 Glra3 glycine receptor, alpha 3 6
Previous and Unofficial Names Click here for help
glycine receptor
Database Links Click here for help
Alphafold O75311 (Hs), Q91XP5 (Mm), P24524 (Rn)
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL1075092 (Hs), CHEMBL4295912 (Mm), CHEMBL3392921 (Rn)
DrugBank Target O75311 (Hs)
Ensembl Gene ENSG00000145451 (Hs), ENSMUSG00000038257 (Mm), ENSRNOG00000049792 (Rn)
Entrez Gene 8001 (Hs), 110304 (Mm), 114516 (Rn)
Human Protein Atlas ENSG00000145451 (Hs)
KEGG Gene hsa:8001 (Hs), mmu:110304 (Mm), rno:114516 (Rn)
OMIM 600421 (Hs)
Pharos O75311 (Hs)
RefSeq Nucleotide NM_006529 (Hs), NM_080438 (Mm), NM_053724 (Rn)
RefSeq Protein NP_006520 (Hs), NP_536686 (Mm), NP_446176 (Rn)
UniProtKB O75311 (Hs), Q91XP5 (Mm), P24524 (Rn)
Wikipedia GLRA3 (Hs)
Functional Characteristics Click here for help
γ = 105 pS (main state); (+ β = 48 pS)
Natural/Endogenous Ligands Click here for help
Cu2+
glycine
Zn2+
Selective agonists (potency order) (Human)
glycine > β-alanine > taurine

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

Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
HU-210 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 pIC50
⤷ pIC50 7.3 (IC50 5x10-8 M)
WIN55212-2 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 pIC50
⤷ pIC50 7.0 (IC50 9.7x10-8 M)
onternabez Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.0 pIC50
⤷ pIC50 7.0 (IC50 9.7x10-8 M)
(12E,20Z,18S)-8-hydroxyvariabilin Small molecule or natural product Hs Antagonist 5.2 pIC50
⤷ pIC50 5.2 (IC50 7x10-6 M)
nifedipine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.5 pIC50
⤷ pIC50 4.5 (IC50 2.92x10-5 M)
strychnine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist - -
⤷
[3H]strychnine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive 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
picrotoxinin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - no 6.4 pIC50 - no
⤷ pIC50 6.4 (IC50 4.3x10-7 M)
Not voltage dependent
ginkgolide B Small molecule or natural product Click here for species-specific activity table Hs - no 5.7 pIC50 - no
⤷ pIC50 5.7 (IC50 1.8x10-6 M)
Not voltage dependent
picrotin Small molecule or natural product Click here for species-specific activity table Hs - no 5.2 pIC50 - no
⤷ pIC50 5.2 (IC50 6x10-6 M)
Not voltage dependent
picrotoxin Small molecule or natural product Click here for species-specific activity table Hs - no - - - no
⤷ block is weaker when β subunit is co-expressed
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
Δ9-tetrahydrocannabinol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Potentiation ~5.3 pEC50 - no
⤷ pEC50 ~5.3 (EC50 ~5x10-6 M) ~1500% potentiation
Not voltage dependent
Cu2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Inhibition 5.0 pIC50 - no
⤷ pIC50 5.0 (IC50 9x10-6 M) endogenous
Not voltage dependent
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Inhibition 3.8 pIC50 - no
⤷ pIC50 3.8 (IC50 1.5x10-4 M) endogenous
Not voltage dependent
Tissue Distribution Click here for help
Spinal cord (dorsal horn laminae 1 and 2)
Species:  Mouse
Technique:  Immunocytochemistry
References:  3
Retina (bipolar, amacrine and ganglion cells in inner plexiform layer)
Species:  Mouse
Technique:  Immunohistochemistry
References:  4
Retina (entire inner nuclear layer and in cells in the ganglion cell layer)
Species:  Rat
Technique:  In situ hybridisation
References:  2
Cochlea (Organ of Corti, spiral ganaglion neurons)
Species:  Rat
Technique:  RT-PCR
References:  1
Internal granule cell layer of olfactory bulb, infralimbic cortex, hippocampus (CA1, CA3 and dentate gyrus), hypothalamus, cerebellar granule cell layer
Species:  Rat
Technique:  In situ hybridisation
References:  7
Gene Expression and Pathophysiology Click here for help
GlyR α3 subunit knockout
Tissue or cell type: 
Pathophysiology:  Knockout mice displayed no overt behavioural phenotype. Notably, they did not exhibit startle symptoms and they displayed normal responses to tactile and acute inflammatory pain stimuli. However, mice deficient in GlyR α3 not only lacked the inhibition of glycinergic neurotransmission by prostaglandin E2 seen in wildtype mice but also showed a reduction in pain sensitization induced by spinal prostaglandin E2 injection or peripheral inflammation.
Species:  Mouse
Technique:  Gene targeting 'knockout' in embryonic stem cells
References:  3
Biologically Significant Variants Click here for help
Type:  mRNA editing
Species:  Rat
Description:  RNA editing results in a novel α3 subunit variant (α3-P185L) at which glycine demonstrates high potency.
References:  8
Type:  Splice variant
Species:  Human
Description:  The GlyR α3L splice variant, contains an additional 15 amino acids in the large intracellular M3-M4 domain relative to the α3K variant. They share similar distribution patterns. The α3K variant displays faster desensitisation.
Amino acids:  479
References:  9
General Comments
Two alternatively spliced human glycine receptor α3 subunits exist, provisionally termed α3L and α3S (or α3K). α3S differs from α3L (tabulated above) by deletion of 15 amino acid residues in the large intracellular loop between TM3 and TM4 [9]. In addition, RNA editing results in a novel α3 subunit (α3P185L) at which glycine demonstrates high agonist potency [8].

References

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1. Dlugaiczyk J, Singer W, Schick B, Iro H, Becker K, Becker CM, Zimmermann U, Rohbock K, Knipper M. (2008) Expression of glycine receptors and gephyrin in the rat cochlea. Histochem Cell Biol, 129 (4): 513-23. [PMID:18231803]

2. Greferath U, Brandstätter JH, Wässle H, Kirsch J, Kuhse J, Grünert U. (1994) Differential expression of glycine receptor subunits in the retina of the rat: a study using immunohistochemistry and in situ hybridization. Vis Neurosci, 11 (4): 721-9. [PMID:7918222]

3. Harvey RJ, Depner UB, Wässle H, Ahmadi S, Heindl C, Reinold H, Smart TG, Harvey K, Schütz B, Abo-Salem OM et al.. (2004) GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science, 304 (5672): 884-7. [PMID:15131310]

4. Haverkamp S, Müller U, Zeilhofer HU, Harvey RJ, Wässle H. (2004) Diversity of glycine receptors in the mouse retina: localization of the alpha2 subunit. J Comp Neurol, 477 (4): 399-411. [PMID:15329889]

5. Kingsmore SF, Suh D, Seldin MF. (1994) Genetic mapping of the glycine receptor alpha 3 subunit on mouse chromosome 8. Mamm Genome, 5 (12): 831-2. [PMID:7894176]

6. Kuhse J, Schmieden V, Betz H. (1990) Identification and functional expression of a novel ligand binding subunit of the inhibitory glycine receptor. J Biol Chem, 265 (36): 22317-20. [PMID:2176214]

7. Malosio ML, Marquèze-Pouey B, Kuhse J, Betz H. (1991) Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J, 10 (9): 2401-9. [PMID:1651228]

8. Meier JC, Henneberger C, Melnick I, Racca C, Harvey RJ, Heinemann U, Schmieden V, Grantyn R. (2005) RNA editing produces glycine receptor alpha3(P185L), resulting in high agonist potency. Nat Neurosci, 8 (6): 736-44. [PMID:15895087]

9. Nikolic Z, Laube B, Weber RG, Lichter P, Kioschis P, Poustka A, Mülhardt C, Becker CM. (1998) The human glycine receptor subunit alpha3. Glra3 gene structure, chromosomal localization, and functional characterization of alternative transcripts. J Biol Chem, 273 (31): 19708-14. [PMID:9677400]

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