Nomenclature: α1

Family: GABAA receptors

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation. 

Contents

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 456 5q34-q35 GABRA1 gamma-aminobutyric acid (GABA) A receptor, alpha 1 2
Mouse 4 455 11 A5 Gabra1 gamma-aminobutyric acid (GABA) A receptor, subunit alpha 1 5
Rat 4 455 10q21 Gabra1 gamma-aminobutyric acid (GABA) A receptor, alpha 1 8
Previous and Unofficial Names
EJM5
GABA(A) receptor, alpha 1
GABA(A) receptor subunit alpha-1
gamma-aminobutyric acid (GABA-A) receptor subunit alpha 1
gamma-aminobutyric acid (GABA-A) receptor, subunit alpha 1
gamma-aminobutyric acid A receptor, alpha 1
gamma-aminobutyric acid receptor subunit alpha-1
GABAA alpha 1
Gabra-1
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
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
β3
γ2
β2
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Not determined
Associated Protein Comments
Heteromeric GABAA receptors can be formed from the proteins listed in the table above. These receptors generally consist of 2 α, 2 β and 1 γ subunit. Examples of GABAA receptors containing the α1 subunit include α1β3γ3 and α1β2γ2.
Natural/Endogenous Ligands
GABA
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
piperidine-4-sulphonic acid Hs Full agonist - -
[Binds to: GABA site]
isonipecotic acid Hs Agonist - -
[Binds to: GABA site]
gaboxadol Hs Agonist - -
[Binds to: GABA site]
isoguvacine Hs Full agonist - -
[Binds to: GABA site]
muscimol Hs Full agonist - -
[Binds to: GABA site]
[3H]muscimol Hs Full agonist - -
[Binds to: GABA site]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]gabazine Hs Antagonist - -
[Binds to: GABA site]
gabazine Hs Antagonist - -
[Binds to: GABA site]
bicuculline Hs Antagonist - -
[Binds to: GABA site]
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
[35S]TBPS Hs - no - - - no
[Binds to: anion channel]
Not voltage dependent
picrotoxin Hs - no - - - no

Not voltage dependent
TBPS Hs - no - - - no

Not voltage dependent
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
triazolam Hs Positive 9.0 pKd - no 3
pKd 9.0 (Kd 1x10-9 M) [3]
Not voltage dependent
Description: Binding affinity to GABAA α1β2γ2 receptor.
triazolam Hs Positive 9.1 pKi - no 4
pKi 9.1 (Ki 8x10-10 M) [4]
Not voltage dependent
Description: Binding affinity for human recombinant GABAA receptor α1β3&gamma,2.
clonazepam Hs Positive 8.9 pKi - no 6
pKi 8.9 (Ki 1.27x10-9 M) [6]
Not voltage dependent
Description: Assay using recombinant GABAA channels with subunit composition; α1β1γ2.
alprazolam Hs Positive 7.43 pEC50 - no 1
pEC50 7.43 (EC50 3.7x10-8 M) [Binds to: benzodiazepine site] [1]
Not voltage dependent
[3H]flunitrazepam Hs - - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
MRK016 Hs Inverse agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
5α-pregnan-3α-ol-20-one Hs Potentiation - - - no

Not voltage dependent
Ro15-4513 Hs Inverse agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
[3H]zolpidem Hs - - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
α5IA Hs Inverse agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
Ro19-4603 Hs Inverse agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
tetrahydrodeoxycorticosterone Hs Potentiation - - - no

Not voltage dependent
diazepam Hs Full agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
α3IA Hs Inverse agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
[3H]CGS8216 Hs Mixed - - - no
[Binds to: benzodiazepine site] agonist and antagonist
Not voltage dependent
flunitrazepam Hs Full agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
indiplon Hs Full agonist - - - no
[Binds to: benzodiazepine site] high affinity
Not voltage dependent
zaleplon Hs Full agonist - - - no
[Binds to: benzodiazepine site] high affinity
Not voltage dependent
RO4938581 Hs Inverse agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
zolpidem Hs Full agonist - - - no
[Binds to: benzodiazepine site] high affinity
Not voltage dependent
flumazenil Hs Antagonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
TP003 Hs Antagonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
bretazenil Hs Full agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
[11C]flumazenil Hs Antagonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
ZK93426 Hs Antagonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
Zn2+ Hs Inhibition - - - no

Not voltage dependent
DMCM Hs Inverse agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
TPA023 Hs Antagonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
ocinaplon Hs Full agonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
L838417 Hs Antagonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
[18F]fluoroethylflumazenil Hs Antagonist - - - no
[Binds to: benzodiazepine site]
Not voltage dependent
Allosteric Modulator Comments
Triazolam binds to the benzodiazepine binding site of the heteromeric GABAA receptor, binding at the extracellular interface between the α and γ subunits [7]. The drug has been mapped to the relevant, experimental α subunit, and heteromeric partners are listed in the Associated Proteins table above .
Clinically-Relevant Mutations and Pathophysiology
Disease:  Juvenile myoclonic epilepsy, susceptibility to, 5; EJM5
OMIM:  611136
Orphanet:  307
References: 
Mutations not determined
Disease:  Childhood absence epilepsy, suceptibility to, 4; ECA4
OMIM:  611136
Orphanet:  64280
References: 
Mutations not determined

REFERENCES

1. Albaugh PA, Marshall L, Gregory J, White G, Hutchison A, Ross PC, Gallagher DW, Tallman JF, Crago M, Cassella JV. (2002) Synthesis and biological evaluation of 7,8,9,10-tetrahydroimidazo[1,2-c]pyrido[3,4-e]pyrimdin-5(6H)-ones as functionally selective ligands of the benzodiazepine receptor site on the GABA(A) receptor. J. Med. Chem.45 (23): 5043-51. [PMID:12408715]

2. Garrett KM, Duman RS, Saito N, Blume AJ, Vitek MP, Tallman JF. (1988) Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor. Biochem. Biophys. Res. Commun.156 (2): 1039-45. [PMID:2847710]

3. Harris D, Clayton T, Cook J, Sahbaie P, Halliwell RF, Furtmüller R, Huck S, Sieghart W, DeLorey TM. (2008) Selective influence on contextual memory: physiochemical properties associated with selectivity of benzodiazepine ligands at GABAA receptors containing the alpha5 subunit. J. Med. Chem.51 (13): 3788-803. [PMID:18537233]

4. Huang Q, He X, Ma C, Liu R, Yu S, Dayer CA, Wenger GR, McKernan R, Cook JM. (2000) Pharmacophore/receptor models for GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) via a comprehensive ligand-mapping approach. J. Med. Chem.43 (1): 71-95. [PMID:10633039]

5. Keir WJ, Kozak CA, Chakraborti A, Deitrich RA, Sikela JM. (1991) The cDNA sequence and chromosomal location of the murine GABAA alpha 1 receptor gene. Genomics9 (2): 390-5. [PMID:1848528]

6. Pritchett DB, Lüddens H, Seeburg PH. (1989) Type I and type II GABAA-benzodiazepine receptors produced in transfected cells. Science245 (4924): 1389-92. [PMID:2551039]

7. Sigel E, Buhr A. (1997) The benzodiazepine binding site of GABAA receptors. Trends Pharmacol. Sci.18 (11): 425-9. [PMID:9426470]

8. Wieland HA, Lüddens H, Seeburg PH. (1992) A single histidine in GABAA receptors is essential for benzodiazepine agonist binding. J. Biol. Chem.267 (3): 1426-9. [PMID:1346133]

To cite this database page, please use the following:

Richard Olsen, John A. Peters, Tim G. Hales, Werner Sieghart, Uwe Rudolph, Jeremy J. Lambert, Delia Belelli, Bernhard Luscher.
GABAA receptors: α1. Last modified on 15/05/2014. Accessed on 31/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=404.

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