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glycine receptor α2 subunit

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Target not currently curated in GtoImmuPdb

Target id: 424

Nomenclature: glycine receptor α2 subunit

Family: Glycine receptors

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 452 Xp22.2 GLRA2 glycine receptor alpha 2 3
Mouse 4 452 X 76.75 cM Glra2 glycine receptor, alpha 2 subunit 8
Rat 4 452 Xq14 Glra2 glycine receptor, alpha 2 5
Previous and Unofficial Names Click here for help
GLR | Glycine receptor alpha 2 subunit (glycine receptor neonatal) | glycine receptor strychnine-binding subunit | RNNEOGLY | glycine receptor, alpha 2 | glycine receptor
Database Links Click here for help
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Functional Characteristics Click here for help
γ = 111 pS (main state); (+ β = 54 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
pregnenolone sulphate Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.3 pKi
pKi 5.3 (Ki 5.5x10-6 M)
tropisetron Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.9 pKi
pKi 4.9 (Ki 1.3x10-5 M)
HU-210 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.0 pIC50
pIC50 7.0 (IC50 9x10-8 M)
WIN55212-2 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.7 pIC50
pIC50 6.7 (IC50 2.2x10-7 M)
HU-308 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pIC50
pIC50 6.0 (IC50 1.1x10-6 M)
ginkgolide X Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.6 pIC50
pIC50 5.6 (IC50 2.8x10-6 M)
bilobalide Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.1 pIC50
pIC50 5.1 (IC50 8x10-6 M)
colchicine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 4.2 pIC50
pIC50 4.2 (IC50 6.4x10-5 M)
5,7-dichlorokynurenic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 3.7 pIC50
pIC50 3.7 (IC50 1.88x10-4 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 - -
PMBA Small molecule or natural product Click here for species-specific activity table 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 4.1x10-7 M)
Not voltage dependent
picrotoxin Small molecule or natural product Click here for species-specific activity table Hs - no 5.6 pIC50 - no
pIC50 5.6 (IC50 2.3x10-6 M)
Not voltage dependent
ginkgolide B Small molecule or natural product Click here for species-specific activity table Hs - no 4.9 – 5.4 pIC50 - no
pIC50 4.9 – 5.4 (IC50 1.14x10-5 – 3.7x10-6 M)
Not voltage dependent
picrotin Small molecule or natural product Click here for species-specific activity table Hs - no 4.9 pIC50 - no
pIC50 4.9 (IC50 1.31x10-5 M)
Not voltage dependent
cyanotriphenylborate Small molecule or natural product Click here for species-specific activity table Hs - no >4.7 pIC50 - no 11
pIC50 >4.7 (IC50 <2x10-5 M) [11]
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
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Potentiation 6.3 pEC50 - no
pEC50 6.3 (EC50 5.4x10-7 M) endogenous; not affected by β subunit co-expression
Not voltage dependent
Δ9-tetrahydrocannabinol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Potentiation ~6.0 pEC50 - no
pEC50 ~6.0 (EC50 ~1x10-6 M) ~230% potentiation
Not voltage dependent
Cu2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Inhibition 4.8 pIC50 - no
pIC50 4.8 (IC50 1.7x10-5 M) endogenous
Not voltage dependent
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Inhibition 3.4 pIC50 - no
pIC50 3.4 (IC50 3.6x10-4 M) endogenous
Not voltage dependent
Tissue Distribution Click here for help
Retina (bipolar cells, amacrine cells and some ganglion cells in inner plexiform layer)
Species:  Mouse
Technique:  Immunocytochemistry
References:  4
Neural stem progenitor cells
Species:  Rat
Technique:  RT-PCR
References:  10
Tenia tecta, piriform cortex, infralimbic cortex, layer VI cerebral cortex, hippocampus (CA1, CA2, CA4 and dentate gyrus), geniculate and supergeniculate nuclei, dorsal horn of spinal cord
Species:  Rat
Technique:  In situ hybridisation
References:  7
Retina (amacrine cells in inner half of the inner nuclear layer and nearly all cells in the ganglion cell layer)
Species:  Rat
Technique:  In situ hybridisation
References:  2
Neutrophils and macrophages
Species:  Rat
Technique:  RT-PCR
References:  1
Gene Expression and Pathophysiology Click here for help
GlyR α2 knockout mice
Tissue or cell type:  embryonic stem cells
Pathophysiology:  Knock out mice displayed no overt behavioural phenotype or neuroanatomical changes. In particular they did not exhibit startle symptoms. However, cortical neurons were no longer responsive to applied glycine.
Species:  Mouse
Technique:  gene targeting ' gene knockout' in embryonic stem cells, whole cell patch-clamp electrophysiology
References:  13
Targeted knockdown of α2 GlyR
Tissue or cell type:  embryonic cells
Pathophysiology:  Targeted knockdown of α2 GlyR decreased the number of photoreceptors while increasing the number of other retinal cell types.
Species:  Mouse
Technique:  siRNA interference
References:  12
Gain-of-function experiments to increase expression of α2
Tissue or cell type:  embryonic cells
Pathophysiology:  Enhanced α2 GlyR expression induced exit from mitosis, and results in an increase in rod photoreceptor numbers
Species:  Mouse
Technique:  retroviral mediated gene transfer
References:  12
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  GlyR α2A and α2B splice variants differ by an adjacent dual amino acid substitution in the N-terminal domain (V58I, T59A). The α2B subunit exhibited significantly higher glycine sensitivity and is expressed at higher levels in the adult rat.
References:  5,9
Type:  Splice variant
Species:  Rat
Description:  The GlyR α2N splice variant lacks exon 3 and hence is not expressed.
References:  6
General Comments
The rat glycine receptor α2 subunit exists as two splice variants (α2A and α2B) that differ by a dual, adjacent amino acid substitution from α2A(V58,T59) to α2B(I58,A59) in the N-terminal extracellular domain [5].

References

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1. Froh M, Thurman RG, Wheeler MD. (2002) Molecular evidence for a glycine-gated chloride channel in macrophages and leukocytes. Am J Physiol Gastrointest Liver Physiol, 283 (4): G856-63. [PMID:12223345]

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. Grenningloh G, Schmieden V, Schofield PR, Seeburg PH, Siddique T, Mohandas TK, Becker CM, Betz H. (1990) Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO J, 9 (3): 771-6. [PMID:2155780]

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. Kuhse J, Kuryatov A, Maulet Y, Malosio ML, Schmieden V, Betz H. (1991) Alternative splicing generates two isoforms of the alpha 2 subunit of the inhibitory glycine receptor. FEBS Lett, 283 (1): 73-7. [PMID:1645300]

6. Kumar DV, Nighorn A, St John PA. (2002) Role of Nova-1 in regulating alpha2N, a novel glycine receptor splice variant, in developing spinal cord neurons. J Neurobiol, 52 (2): 156-65. [PMID:12124753]

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. Matzenbach B, Maulet Y, Sefton L, Courtier B, Avner P, Guénet JL, Betz H. (1994) Structural analysis of mouse glycine receptor alpha subunit genes. Identification and chromosomal localization of a novel variant. J Biol Chem, 269 (4): 2607-12. [PMID:7507926]

9. Miller PS, Harvey RJ, Smart TG. (2004) Differential agonist sensitivity of glycine receptor alpha2 subunit splice variants. Br J Pharmacol, 143 (1): 19-26. [PMID:15302677]

10. Nguyen L, Malgrange B, Belachew S, Rogister B, Rocher V, Moonen G, Rigo JM. (2002) Functional glycine receptors are expressed by postnatal nestin-positive neural stem/progenitor cells. Eur J Neurosci, 15 (8): 1299-305. [PMID:11994124]

11. Rundström N, Schmieden V, Betz H, Bormann J, Langosch D. (1994) Cyanotriphenylborate: subtype-specific blocker of glycine receptor chloride channels. Proc Natl Acad Sci USA, 91 (19): 8950-4. [PMID:8090751]

12. Young TL, Cepko CL. (2004) A role for ligand-gated ion channels in rod photoreceptor development. Neuron, 41 (6): 867-79. [PMID:15046720]

13. Young-Pearse TL, Ivic L, Kriegstein AR, Cepko CL. (2006) Characterization of mice with targeted deletion of glycine receptor alpha 2. Mol Cell Biol, 26 (15): 5728-34. [PMID:16847326]

Contributors

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