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GABAA receptor α1 subunit

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Target not currently curated in GtoImmuPdb

Target id: 404

Nomenclature: GABAA receptor α1 subunit

Family: GABAA receptors

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 456 5q34 GABRA1 gamma-aminobutyric acid type A receptor subunit alpha1 3
Mouse 4 455 11 24.97 cM Gabra1 gamma-aminobutyric acid type A receptor subunit alpha 1 9
Rat 4 455 10q21 Gabra1 gamma-aminobutyric acid type A receptor subunit alpha 1 15
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold P14867 (Hs), P62812 (Mm), P62813 (Rn)
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL1962 (Hs), CHEMBL3139 (Mm), 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 Click here for help
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 Click here for help
GABA
5α-pregnan-3α-ol-20-one
tetrahydrodeoxycorticosterone
Zn2+

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CGS8216 Small molecule or natural product Click here for species-specific activity table Hs Inverse agonist 10.3 pKi 8
⤷ pKi 10.3 (Ki 5x10-11 M) [8]
ZK93423 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 9.0 pKi 2
⤷ pKi 9.0 (Ki 1x10-9 M) [2]
[3H]muscimol Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist - -
⤷ [Binds to: GABA site]
isoguvacine Small molecule or natural product Click here for species-specific activity table Hs Full agonist - -
⤷ [Binds to: GABA site]
isonipecotic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist - -
⤷ [Binds to: GABA site]
muscimol Small molecule or natural product Click here for species-specific activity table Hs Full agonist - -
⤷ [Binds to: GABA site]
piperidine-4-sulphonic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist - -
⤷ [Binds to: GABA site]
gaboxadol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure 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 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist - -
⤷ [Binds to: GABA site]
[3H]gabazine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist - -
⤷ [Binds to: GABA site]
gabazine Small molecule or natural product Click here for species-specific activity table 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 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs - no - - - no
⤷
Not voltage dependent
TBPS Small molecule or natural product Click here for species-specific activity table Hs - no - - - no
⤷
Not voltage dependent
[35S]TBPS Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive 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 Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table 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 Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.1 pKi - no 13
⤷ pKi 9.1 (Ki 8x10-10 M) [Binds to: benzodiazepine site] Antagonist at α1 receptors, but allosteric modulator at other subtypes. [13]
Not voltage dependent
Description: Affinity measured using α1β3γ2 receptors.
triazolam Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Positive 9.1 pKi - no 8
⤷ pKi 9.1 (Ki 8x10-10 M) [8]
Not voltage dependent
Description: Binding affinity for human recombinant GABAA receptor α1β3&gamma,2.
clonazepam Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Positive 8.9 pKi - no 10
⤷ pKi 8.9 (Ki 1.27x10-9 M) [Binds to: benzodiazepine site] [10]
Not voltage dependent
Description: Assay using recombinant GABAA channels with subunit composition; α1β1γ2.
flunitrazepam Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table 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 Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure 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 Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Positive 7.4 – 7.7 pKi - no 5,12-13
⤷ pKi 7.4 – 7.7 (Ki 4.1x10-8 – 2.07x10-8 M) At very low concentrations, zolpidem seems to be selective, overall it is partially selective [5,12-13]
Not voltage dependent
Description: Assay using recombinant GABAA channels with subunit composition; α1β3γ2.
alprazolam Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Positive 7.4 pEC50 - no 1
⤷ pEC50 7.4 (EC50 3.7x10-8 M) [Binds to: benzodiazepine site] [1]
Not voltage dependent
ganaxolone Small molecule or natural product Approved drug Hs Potentiation 6.6 pEC50 - no 7
⤷ pEC50 6.6 (EC50 2.6x10-7 M) [7]
Not voltage dependent
Description: Potentiation of GABA-activated currents in Xenopus oocytes expressing cloned human α1/β2/γ2L subunits of GABAA receptor
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Inhibition - - - no
⤷
Not voltage dependent
α3IA Small molecule or natural product Click here for species-specific activity table Hs Inverse agonist - - - no 13
⤷ [Binds to: benzodiazepine site] [13]
Not voltage dependent
α5IA Small molecule or natural product Click here for species-specific activity table Hs Inverse agonist - - - no 13
⤷ [Binds to: benzodiazepine site] [13]
Not voltage dependent
5α-pregnan-3α-ol-20-one Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Potentiation - - - no
⤷
Not voltage dependent
bretazenil Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
DMCM Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inverse agonist - - - no 11
⤷ [Binds to: benzodiazepine site] [11]
Not voltage dependent
indiplon Small molecule or natural product Hs Full agonist - - - no
⤷ [Binds to: benzodiazepine site] high affinity
Not voltage dependent
L838417 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - - - no 13
⤷ [Binds to: benzodiazepine site] [13]
Not voltage dependent
MRK016 Small molecule or natural product Click here for species-specific activity table Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
ocinaplon Small molecule or natural product Click here for species-specific activity table Hs Full agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
Ro15-4513 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
Ro19-4603 Small molecule or natural product Click here for species-specific activity table Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
RO4938581 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inverse agonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
tetrahydrodeoxycorticosterone Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Potentiation - - - no
⤷
Not voltage dependent
TP003 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
TPA023 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
ZK93426 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
[3H]flunitrazepam Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Positive - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
[3H]zolpidem Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Positive - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
[3H]CGS8216 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Mixed - - - no
⤷ [Binds to: benzodiazepine site] agonist and antagonist
Not voltage dependent
[11C]flumazenil 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 - - - no
⤷ [Binds to: benzodiazepine site]
Not voltage dependent
[18F]fluoroethylflumazenil Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs - - - - 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 [14]. The drug has been mapped to the relevant, experimental α subunit, and heteromeric partners are listed in the Associated Proteins table above. ZK93426 is a positive modulator of α1βγ2, α2βγ2, α3βγ2, and α4βγ2, and a weak inverse agonist at α5βγ2 receptors [13].
Clinically-Relevant Mutations and Pathophysiology Click here for help
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. Hogenkamp DJ, Tahir SH, Hawkinson JE, Upasani RB, Alauddin M, Kimbrough CL, Acosta-Burruel M, Whittemore ER, Woodward RM, Lan NC et al.. (1997) Synthesis and in vitro activity of 3 beta-substituted-3 alpha-hydroxypregnan-20-ones: allosteric modulators of the GABAA receptor. J Med Chem, 40 (1): 61-72. [PMID:9016329]

8. 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]

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. Ramerstorfer J, Furtmüller R, Vogel E, Huck S, Sieghart W. (2010) The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. Eur J Pharmacol, 636 (1-3): 18-27. [PMID:20303942]

12. 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]

13. Sieghart W, Savić MM. (2018) International Union of Basic and Clinical Pharmacology. CVI: GABAA Receptor Subtype- and Function-selective Ligands: Key Issues in Translation to Humans. Pharmacol Rev, 70 (4): 836-878. [PMID:30275042]

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

15. 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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