GABA<sub>A</sub> receptor α1 subunit | GABA<sub>A</sub> receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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GABAA receptor α1 subunit

Target not currently curated in GtoImmuPdb

Target id: 404

Nomenclature: GABAA receptor α1 subunit

Family: GABAA receptors

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 456 5q34-q35 GABRA1 gamma-aminobutyric acid type A receptor subunit alpha1 3
Mouse 4 455 11 A5 Gabra1 gamma-aminobutyric acid (GABA) A receptor 9
Rat 4 455 10q21 Gabra1 gamma-aminobutyric acid type A receptor subunit alpha 1 13
Previous and Unofficial Names
EJM5 | gamma-aminobutyric acid receptor subunit alpha-1 | Gabra-1 | gamma-aminobutyric acid (GABA) A receptor, alpha 1 | gamma-aminobutyric acid (GABA) A receptor, subunit alpha 1 | gamma-aminobutyric acid (GABA) A receptor | gamma-aminobutyric acid type A receptor alpha1 subunit
Database Links
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL2093872 (Hs), CHEMBL2109244 (Hs), CHEMBL2109243 (Hs), CHEMBL1962 (Hs), CHEMBL3139 (Mm), CHEMBL2094133 (Mm), CHEMBL1907607 (Rn), CHEMBL343 (Rn)
DrugBank Target P14867 (Hs), P14867 (Hs)
Ensembl Gene ENSG00000022355 (Hs), ENSMUSG00000010803 (Mm), ENSRNOG00000003512 (Rn)
Entrez Gene 2554 (Hs), 14394 (Mm), 29705 (Rn)
Human Protein Atlas ENSG00000022355 (Hs)
KEGG Gene hsa:2554 (Hs), mmu:14394 (Mm), rno:29705 (Rn)
OMIM 137160 (Hs)
Orphanet ORPHA121989 (Hs)
Pharos P14867 (Hs)
RefSeq Nucleotide NM_000806 (Hs), NM_010250 (Mm), NM_183326 (Rn)
RefSeq Protein NP_000797 (Hs), NP_034380 (Mm), NP_899155 (Rn)
UniProtKB P14867 (Hs), P62812 (Mm), P62813 (Rn)
Wikipedia GABRA1 (Hs)
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
GABAA receptor β3 subunit
GABAA receptor γ2 subunit
GABAA receptor β2 subunit
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
5α-pregnan-3α-ol-20-one
tetrahydrodeoxycorticosterone
Zn2+

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CGS8216 Hs Inverse agonist 10.3 pKi 7
⤷ pKi 10.3 (Ki 5x10-11 M) [7]
ZK93423 Hs Partial agonist 9.0 pKi 2
⤷ pKi 9.0 (Ki 1x10-9 M) [2]
[3H]muscimol Hs Full agonist - -
⤷ [Binds to: GABA site]
isoguvacine Hs Full agonist - -
⤷ [Binds to: GABA site]
isonipecotic acid Hs Agonist - -
⤷ [Binds to: GABA site]
muscimol Hs Full agonist - -
⤷ [Binds to: GABA site]
piperidine-4-sulphonic acid Hs Full agonist - -
⤷ [Binds to: GABA site]
gaboxadol Hs Agonist - -
⤷ [Binds to: GABA site]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
bicuculline Hs Antagonist - -
⤷ [Binds to: GABA site]
[3H]gabazine Hs Antagonist - -
⤷ [Binds to: GABA site]
gabazine 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 Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
picrotoxin Hs - no - - - no
⤷
Not voltage dependent
TBPS Hs - no - - - no
⤷
Not voltage dependent
[35S]TBPS Hs - no - - - no
⤷ [Binds to: anion channel]
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
triazolam Hs Positive 9.0 pKd - no 6
⤷ pKd 9.0 (Kd 1x10-9 M) [6]
Not voltage dependent
Description: Binding affinity to GABAA α1β2γ2 receptor.
flumazenil Hs Antagonist 9.1 pKi - no 8
⤷ pKi 9.1 (Ki 8x10-10 M) [Binds to: benzodiazepine site] [8]
Not voltage dependent
Description: Affinity measured using α1β3γ2 receptors.
triazolam Hs Positive 9.1 pKi - no 7
⤷ pKi 9.1 (Ki 8x10-10 M) [7]
Not voltage dependent
Description: Binding affinity for human recombinant GABAA receptor α1β3&gamma,2.
clonazepam Hs Positive 8.9 pKi - no 10
⤷ pKi 8.9 (Ki 1.27x10-9 M) [10]
Not voltage dependent
Description: Assay using recombinant GABAA channels with subunit composition; α1β1γ2.
flunitrazepam Hs Positive 8.3 pKi - no 4
⤷ pKi 8.3 (Ki 5.2x10-9 M) [Binds to: benzodiazepine site] [4]
Not voltage dependent
Description: Assay using recombinant GABAA channels with subunit composition; α1β3γ2.
diazepam Hs Positive 7.8 pKi - no 10
⤷ pKi 7.8 (Ki 1.63x10-8 M) [Binds to: benzodiazepine site] [10]
Not voltage dependent
Description: Assay using recombinant GABAA channels with subunit composition; α1β1γ2.
zolpidem Hs Positive 7.4 – 7.7 pKi - no 5,11
⤷ pKi 7.4 – 7.7 (Ki 4.1x10-8 – 2.07x10-8 M) [5,11]
Not voltage dependent
Description: Assay using recombinant GABAA channels with subunit composition; α1β3γ2.
alprazolam Hs Positive 7.4 pEC50 - no 1
⤷ pEC50 7.4 (EC50 3.7x10-8 M) [Binds to: benzodiazepine site] [1]
Not voltage dependent
Zn2+ Hs Inhibition - - - no
⤷
Not voltage dependent
α3IA Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
α5IA Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
5α-pregnan-3α-ol-20-one Hs Potentiation - - - no
⤷
Not voltage dependent
bretazenil Hs Full agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
DMCM Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
indiplon Hs Full agonist - - - no
⤷ [Binds to: benzodiazepine site] high affinity
Not voltage dependent
L838417 Hs Antagonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
MRK016 Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
ocinaplon Hs Full agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
Ro15-4513 Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
Ro19-4603 Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
RO4938581 Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
tetrahydrodeoxycorticosterone Hs Potentiation - - - no
⤷
Not voltage dependent
TP003 Hs Antagonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
TPA023 Hs Antagonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
ZK93426 Hs Antagonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
[3H]flunitrazepam Hs Positive - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
[3H]zolpidem Hs Positive - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
[3H]CGS8216 Hs Mixed - - - no
⤷ [Binds to: benzodiazepine site] agonist and antagonist
Not voltage dependent
[11C]flumazenil 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 [12]. 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:  Epilepsy, idiopathic generalized, susceptibility to, 13; EIG13
Description: The OMIM entry for this diseases also represents juvenile myoclonic epilepsy type 5, and childhood absence epilepsy type 4, as they have been classed as subtypes of idiopathic generalized epilepsy. Please see the OMIM entry for more detailed information.
Synonyms: Childhood absence epilepsy [Orphanet: ORPHA64280] [Disease Ontology: DOID:1825]
Idiopathic generalized epilepsy [Disease Ontology: DOID:1827]
Juvenile myoclonic epilepsy [Orphanet: ORPHA307]
Disease Ontology: DOID:1827, DOID:1825
OMIM: 611136
Orphanet: ORPHA64280, ORPHA307

References

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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. Cox ED, Diaz-Arauzo H, Huang Q, Reddy MS, Ma C, Harris B, McKernan R, Skolnick P, Cook JM. (1998) Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABAA receptors. J. Med. Chem., 41 (14): 2537-52. [PMID:9651158]

3. 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]

4. Hadingham KL, Garrett EM, Wafford KA, Bain C, Heavens RP, Sirinathsinghji DJ, Whiting PJ. (1996) Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors. Mol. Pharmacol., 49 (2): 253-9. [PMID:8632757]

5. Hadingham KL, Wafford KA, Thompson SA, Palmer KJ, Whiting PJ. (1995) Expression and pharmacology of human GABAA receptors containing gamma 3 subunits. Eur. J. Pharmacol., 291 (3): 301-9. [PMID:8719414]

6. 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]

7. 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]

8. Huang Q, Liu R, Zhang P, He X, McKernan R, Gan T, Bennett DW, Cook JM. (1998) Predictive models for GABAA/benzodiazepine receptor subtypes: studies of quantitative structure-activity relationships for imidazobenzodiazepines at five recombinant GABAA/benzodiazepine receptor subtypes [alphaxbeta3gamma2 (x = 1-3, 5, and 6)] via comparative molecular field analysis. J. Med. Chem., 41 (21): 4130-42. [PMID:9767648]

9. 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. Genomics, 9 (2): 390-5. [PMID:1848528]

10. Pritchett DB, Lüddens H, Seeburg PH. (1989) Type I and type II GABAA-benzodiazepine receptors produced in transfected cells. Science, 245 (4924): 1389-92. [PMID:2551039]

11. Scholze P, Ebert V, Sieghart W. (1996) Affinity of various ligands for GABAA receptors containing alpha 4 beta 3 gamma 2, alpha 4 gamma 2, or alpha 1 beta 3 gamma 2 subunits. Eur. J. Pharmacol., 304 (1-3): 155-62. [PMID:8813598]

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

13. 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]

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