Nomenclature: β

Family: Glycine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 497 4q31.3 GLRB glycine receptor, beta 7
Mouse 4 496 3 36.0 cM Glrb glycine receptor, beta subunit 12
Rat 4 496 2q33 Glrb glycine receptor, beta 6
Previous and Unofficial Names
Glycine receptor beta
glycine receptor 58 kDa subunit
glycine receptor subunit beta
glycine receptor, beta
glycine receptor, beta subunit
AI853901
spa
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
glycine
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
tropisetron Hs Antagonist 5.3 pKi
pKi 5.3 (Ki 5.4x10-6 M) when co-expressed with the α2 subunit
pregnenolone sulphate 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 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 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 Hs Antagonist >3.5 pIC50
pIC50 >3.5 (IC50 <3x10-4 M) when co-expressed with the α1 subunit
pIC50 >3.5 (IC50 <3x10-4 M) when co-expressed with the α2 subunit
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
ginkgolide B Hs - no 5.6 – 6.9 pIC50 - no
pIC50 6.1 – 6.9 (IC50 1.4x10-7 – 8x10-7 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 1.8x10-7 – 2.5x10-6 M) when co-expressed with the α1 subunit
Not voltage dependent
cyanotriphenylborate 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 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 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 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 Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
Zn2+ 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
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
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
Disease:  Hyperekplexia 2
OMIM:  614619
Orphanet:  3197
Comments: 
References:  16
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human G229D 16
Biologically Significant Variants
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

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. Neuroscience146 (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. Neuron4 (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. Neuron13 (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. U.S.A.91 (19): 8950-4. [PMID:8090751]

To cite this database page, please use the following:

Joseph. W. Lynch.
Glycine receptors: β. Last modified on 16/05/2014. Accessed on 25/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=427.

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