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glycine receptor β subunit

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Not curated in GtoImmuPdb

Target id: 427

Nomenclature: glycine receptor β subunit

Family: Glycine receptors

Annotation status:  image of a blue circle Annotated and reviewed, awaiting update  » Email us

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 497 4q32.1 GLRB glycine receptor beta 7
Mouse 4 496 3 35.71 cM Glrb glycine receptor, beta subunit 12
Rat 4 496 2q33 Glrb glycine receptor, beta 6
Previous and Unofficial Names Click here for help
spa | glycine receptor
Database Links Click here for help
Alphafold P48167 (Hs), P48168 (Mm), P20781 (Rn)
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL2363052 (Hs), CHEMBL4296075 (Hs), CHEMBL4106144 (Hs), CHEMBL3392921 (Rn)
DrugBank Target P48167 (Hs)
Ensembl Gene ENSG00000109738 (Hs), ENSMUSG00000028020 (Mm), ENSRNOG00000010199 (Rn)
Entrez Gene 2743 (Hs), 14658 (Mm), 25456 (Rn)
Human Protein Atlas ENSG00000109738 (Hs)
KEGG Gene hsa:2743 (Hs), mmu:14658 (Mm), rno:25456 (Rn)
OMIM 138492 (Hs)
Orphanet ORPHA122182 (Hs)
Pharos P48167 (Hs)
RefSeq Nucleotide NM_000824 (Hs), NM_010298 (Mm), NM_053296 (Rn)
RefSeq Protein NP_000815 (Hs), NP_034428 (Mm), NP_445748 (Rn)
UniProtKB P48167 (Hs), P48168 (Mm), P20781 (Rn)
Wikipedia GLRB (Hs)
Natural/Endogenous Ligands Click here for help
glycine
Zn2+

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
tropisetron Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.3 pKi
⤷ pKi 5.3 (Ki 5.4x10-6 M) when co-expressed with the α2 subunit
pregnenolone sulphate Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.0 – 5.6 pKi
⤷ pKi 5.6 (Ki 2.7x10-6 M) when co-expressed with the α1 subunit
pKi 5.0 (Ki 1.01x10-5 M) when co-expressed with the α2 subunit
nifedipine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.9 – 5.9 pIC50
⤷ pIC50 5.9 (IC50 1.2x10-6 M) when co-expressed with the α1 subunit
pIC50 4.9 (IC50 1.14x10-5 M) when co-expressed with the α3 subunit
bilobalide Small molecule or natural product Click here for species-specific activity table Hs Antagonist 3.7 – 4.3 pIC50
⤷ pIC50 4.3 (IC50 5x10-5 M) when co-expressed with the α2 subunit
pIC50 3.7 (IC50 2.04x10-4 M) when co-expressed with the α1 subunit
ginkgolide X Small molecule or natural product Click here for species-specific activity table Hs Antagonist >3.5 pIC50
⤷ pIC50 >3.5 (IC50 <3x10-4 M) when co-expressed with the α2 subunit
pIC50 >3.5 (IC50 <3x10-4 M) when co-expressed with the α1 subunit
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
ginkgolide B Small molecule or natural product Click here for species-specific activity table Hs - no 5.6 – 6.9 pIC50 - no
⤷ pIC50 6.1 – 6.9 (IC50 8x10-7 – 1.4x10-7 M) when co-expressed with the α2 subunit
Not voltage dependent
pIC50 6.3 (IC50 5.5x10-7 M) when co-expressed with the α3 subunit
Not voltage dependent
pIC50 5.6 – 6.7 (IC50 2.5x10-6 – 1.8x10-7 M) when co-expressed with the α1 subunit
Not voltage dependent
cyanotriphenylborate Small molecule or natural product Rn - no 5.1 – 5.6 pIC50 - no 17
⤷ pIC50 5.6 (IC50 2.8x10-6 M) when co-expressed with the human α1 subunit [17]
Not voltage dependent
pIC50 5.1 (IC50 7.5x10-6 M) when co-expressed with the human α2 subunit [17]
Not voltage dependent
picrotoxinin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - no 4.6 – 5.1 pIC50 - no
⤷ pIC50 5.1 (IC50 8.9x10-6 M) when co-expressed with the α3 subunit
Not voltage dependent
pIC50 4.6 (IC50 2.7x10-5 M) when co-expressed with the α1 subunit
Not voltage dependent
picrotin Small molecule or natural product Click here for species-specific activity table Hs - no 4.6 pIC50 - no
⤷ pIC50 4.6 (IC50 2.7x10-5 M) when co-expressed with the α1 subunit
Not voltage dependent
pIC50 4.6 (IC50 2.4x10-5 M) when co-expressed with the α3 subunit
Not voltage dependent
picrotoxin Small molecule or natural product Click here for species-specific activity table Hs - no 3.7 – 4.5 pIC50 - no
⤷ pIC50 4.5 (IC50 2.97x10-5 M) when co-expressed with the α2 subunit
Not voltage dependent
pIC50 3.7 (IC50 2.19x10-4 M) when co-expressed with the α1 subunit
Not voltage dependent
View species-specific channel blocker tables
Allosteric Modulators
Key to terms and symbols 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 Inhibition 3.7 – 4.9 pIC50 - no
⤷ pIC50 4.9 (IC50 1.3x10-5 M) endogenous; when co-expressed with the α1 subunit
Not voltage dependent
pIC50 3.7 (IC50 1.8x10-4 M) endogenous; when co-expressed with the α2 subunit
Not voltage dependent
Tissue Distribution Click here for help
Retina (inner plexiform layer)
Species:  Mouse
Technique:  Immunocytochemistry
References:  15
Retina (entire inner nuclear layer and cells in the ganglion cell layer)
Species:  Rat
Technique:  In situ hybridisation, immunohistochemistry
References:  5
Kupffer cells, neutrophils and macrophages
Species:  Rat
Technique:  RT-PCR
References:  3
Cochlea (Organ of Corti, spiral ganglion neurons)
Species:  Rat
Technique:  RT-PCR
References:  2
Neural stem progenitor cells
Species:  Rat
Technique:  RT-PCR
References:  13
Wide distribution throughout spinal cord and brain
Species:  Rat
Technique:  In situ hybridisation
References:  10
Tissue Distribution Comments
    The receptor has been detected in other tissues in porcine (pig) for example:
  • detected in retina (subset of cones) using single cell RT-PCR and immunocytochemistry [1,4].
  • detected in sperm using western blots [11].
Physiological Consequences of Altering Gene Expression Click here for help
The spastic mouse exhibits a hyperekplexia phenotype. It is caused by a 7.1 kb line-1 insert into the β subunit that results in aberrant splicing and reduction in functional receptor expression
Species:  Mouse
Tissue: 
Technique:  Naturally occcuring line-1 insertion mutation into the β subunit
References:  8-9,12
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Hyperekplexia 2; HKPX2
Synonyms: Hereditary hyperekplexia [Orphanet: ORPHA3197]
OMIM: 614619
Orphanet: ORPHA3197
Comments:  Human hyperekplexia is caused by simultaneous occurrence on separate alleles of a GlyR β subunit missense mutation (G229D) that modestly reduces the glycine sensitivity of α1β GlyRs and a β subunit splice variant that excises exon 5. When present on a single allele, the individual mutations result in no phenotype.
References:  16
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human G229D 16
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Mouse
Description:  A GlyR β subunit variant, βΔ7 lacks exon 7 which encodes a stretch of 50 amino acids that includes all of the first transmembrane domain. In vitro studies suggest that the protein integrates into the plasma membrane and forms complexes with α1 subunits, but electrophysiological studies suggest that α1βΔ7 heteromers may not be functional.
References:  14

References

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1. Balse E, Tessier LH, Forster V, Roux MJ, Sahel JA, Picaud S. (2006) Glycine receptors in a population of adult mammalian cones. J Physiol (Lond.), 571 (Pt 2): 391-401. [PMID:16396929]

2. 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]

3. 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]

4. Ge LH, Lee SC, Liu J, Yang XL. (2007) Glycine receptors are functionally expressed on bullfrog retinal cone photoreceptors. Neuroscience, 146 (1): 427-34. [PMID:17346892]

5. 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]

6. Grenningloh G, Pribilla I, Prior P, Multhaup G, Beyreuther K, Taleb O, Betz H. (1990) Cloning and expression of the 58 kd beta subunit of the inhibitory glycine receptor. Neuron, 4 (6): 963-70. [PMID:2163264]

7. Handford CA, Lynch JW, Baker E, Webb GC, Ford JH, Sutherland GR, Schofield PR. (1996) The human glycine receptor beta subunit: primary structure, functional characterisation and chromosomal localisation of the human and murine genes. Brain Res Mol Brain Res, 35 (1-2): 211-9. [PMID:8717357]

8. Hartenstein B, Schenkel J, Kuhse J, Besenbeck B, Kling C, Becker CM, Betz H, Weiher H. (1996) Low level expression of glycine receptor beta subunit transgene is sufficient for phenotype correction in spastic mice. EMBO J, 15 (6): 1275-82. [PMID:8635460]

9. Kingsmore SF, Giros B, Suh D, Bieniarz M, Caron MG, Seldin MF. (1994) Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat Genet, 7 (2): 136-41. [PMID:7920630]

10. Malosio ML, Grenningloh G, Kuhse J, Schmieden V, Schmitt B, Prior P, Betz H. (1991) Alternative splicing generates two variants of the alpha 1 subunit of the inhibitory glycine receptor. J Biol Chem, 266 (4): 2048-53. [PMID:1703526]

11. Melendrez CS, Meizel S. (1996) Immunochemical identification of the glycine receptor/Cl-channel in porcine sperm. Biochem Biophys Res Commun, 223 (3): 675-8. [PMID:8687455]

12. Mülhardt C, Fischer M, Gass P, Simon-Chazottes D, Guénet JL, Kuhse J, Betz H, Becker CM. (1994) The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element. Neuron, 13 (4): 1003-15. [PMID:7946325]

13. 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]

14. Oertel J, Villmann C, Kettenmann H, Kirchhoff F, Becker CM. (2007) A novel glycine receptor beta subunit splice variant predicts an unorthodox transmembrane topology. Assembly into heteromeric receptor complexes. J Biol Chem, 282 (5): 2798-807. [PMID:17145751]

15. Pinto LH, Grünert U, Studholme K, Yazulla S, Kirsch J, Becker CM. (1994) Glycine receptors in the retinas of normal and spastic mutant mice. Invest Ophthalmol Vis Sci, 35 (10): 3633-9. [PMID:8088953]

16. Rees MI, Lewis TM, Kwok JB, Mortier GR, Govaert P, Snell RG, Schofield PR, Owen MJ. (2002) Hyperekplexia associated with compound heterozygote mutations in the beta-subunit of the human inhibitory glycine receptor (GLRB). Hum Mol Genet, 11 (7): 853-60. [PMID:11929858]

17. 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]

Contributors

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Citation information

Joseph. W. Lynch.

Last modified on 10/11/2014.

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