Proteins > Gamma-aminobutyric acid receptor subunit alpha-4
Page last updated: 2024-08-07 16:43:56
Gamma-aminobutyric acid receptor subunit alpha-4
A gamma-aminobutyric acid receptor subunit alpha-4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P48169]
Synonyms
GABA(A) receptor subunit alpha-4
Research
Bioassay Publications (40)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 3 (7.50) | 18.7374 |
| 1990's | 6 (15.00) | 18.2507 |
| 2000's | 18 (45.00) | 29.6817 |
| 2010's | 11 (27.50) | 24.3611 |
| 2020's | 2 (5.00) | 2.80 |
Compounds (86)
Drugs with Inhibition Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| gamma-aminobutyric acid | Homo sapiens (human) | Ki | 0.1165 | 2 | 2 |
| phenytoin | Homo sapiens (human) | Ki | 100.0000 | 1 | 1 |
| clonazepam | Homo sapiens (human) | IC50 | 555,904.0000 | 1 | 1 |
| clonazepam | Homo sapiens (human) | Ki | 0.0008 | 1 | 1 |
| nordazepam | Homo sapiens (human) | IC50 | 106,414.0000 | 1 | 1 |
| diazepam | Homo sapiens (human) | IC50 | 41,198.3400 | 3 | 3 |
| diazepam | Homo sapiens (human) | Ki | 0.0100 | 2 | 2 |
| fipronil | Homo sapiens (human) | IC50 | 0.0023 | 1 | 1 |
| flumazenil | Homo sapiens (human) | Ki | 0.0052 | 4 | 29 |
| flunitrazepam | Homo sapiens (human) | IC50 | 263,027.0000 | 1 | 1 |
| fluoxetine | Homo sapiens (human) | IC50 | 5.2000 | 1 | 2 |
| hydroxyurea | Homo sapiens (human) | Ki | 113.0000 | 1 | 2 |
| isoguvacine | Homo sapiens (human) | Ki | 0.0550 | 1 | 2 |
| 4-piperidinecarboxylic acid | Homo sapiens (human) | Ki | 0.5056 | 1 | 2 |
| kynurenic acid | Homo sapiens (human) | IC50 | 2,900.0000 | 1 | 1 |
| muscimol | Homo sapiens (human) | IC50 | 0.0160 | 1 | 1 |
| muscimol | Homo sapiens (human) | Ki | 0.0085 | 2 | 2 |
| nitrazepam | Homo sapiens (human) | IC50 | 100,000.0000 | 1 | 1 |
| cm 7116 | Homo sapiens (human) | IC50 | 500,035.0000 | 1 | 1 |
| ro 15-4513 | Homo sapiens (human) | Ki | 0.0041 | 1 | 2 |
| temazepam | Homo sapiens (human) | IC50 | 62,517.3000 | 1 | 1 |
| zolpidem | Homo sapiens (human) | Ki | 2.3343 | 2 | 29 |
| triiodothyronine | Homo sapiens (human) | IC50 | 23.0000 | 1 | 1 |
| bicuculline | Homo sapiens (human) | IC50 | 15.0000 | 1 | 1 |
| flavone | Homo sapiens (human) | Ki | 0.5085 | 2 | 2 |
| chlordesmethyldiazepam | Homo sapiens (human) | IC50 | 277,952.0014 | 2 | 2 |
| 6-aminonicotinic acid | Homo sapiens (human) | Ki | 4.2369 | 1 | 2 |
| halazepam | Homo sapiens (human) | IC50 | 10,864.3000 | 1 | 1 |
| progabide | Homo sapiens (human) | Ki | 40.0000 | 1 | 1 |
| duloxetine | Homo sapiens (human) | IC50 | 0.0190 | 1 | 2 |
| norharman | Homo sapiens (human) | IC50 | 1.6218 | 1 | 1 |
| baicalin | Homo sapiens (human) | Ki | 77.6247 | 1 | 1 |
| 2-aminonicotinic acid | Homo sapiens (human) | Ki | 100.0000 | 1 | 1 |
| n-desmethylflunitrazepam | Homo sapiens (human) | IC50 | 25,003.5000 | 1 | 1 |
| 7-aminonitrazepam | Homo sapiens (human) | IC50 | 2,588.2100 | 1 | 1 |
| ro 20-1815 | Homo sapiens (human) | IC50 | 15,381.5000 | 1 | 1 |
| brexanolone | Homo sapiens (human) | IC50 | 0.0220 | 1 | 1 |
| 2,5-dihydro-2-(4-methoxyphenyl)-3h-pyrazolo(4,3-c)quinolin-3-one | Homo sapiens (human) | IC50 | 0.0001 | 1 | 1 |
| beta-carboline-3-carboxylic acid ethyl ester | Homo sapiens (human) | IC50 | 0.0050 | 1 | 1 |
| beta-carboline-3-carboxylic acid methyl ester | Homo sapiens (human) | IC50 | 0.0050 | 1 | 1 |
| ro 15-3505 | Homo sapiens (human) | Ki | 0.0008 | 1 | 1 |
| zk 93426 | Homo sapiens (human) | Ki | 0.1370 | 1 | 1 |
| 3-ethoxy-beta-carboline | Homo sapiens (human) | IC50 | 0.0240 | 1 | 1 |
| tert-butyl beta-carboline-3-carboxylate | Homo sapiens (human) | IC50 | 0.0100 | 1 | 1 |
| tert-butyl beta-carboline-3-carboxylate | Homo sapiens (human) | Ki | 1.0000 | 1 | 1 |
| 3',6-dinitroflavone | Homo sapiens (human) | Ki | 0.0120 | 1 | 1 |
| cgp 36742 | Homo sapiens (human) | IC50 | 508.0000 | 1 | 1 |
| pitrazepin | Homo sapiens (human) | IC50 | 0.2400 | 1 | 1 |
| 7-aminoclonazepam | Homo sapiens (human) | IC50 | 13,335.2000 | 1 | 1 |
| ro 5-3438 | Homo sapiens (human) | IC50 | 71,449.6000 | 1 | 1 |
| cocaine | Homo sapiens (human) | IC50 | 127.0000 | 1 | 1 |
| 6-bromoflavone | Homo sapiens (human) | Ki | 0.0708 | 1 | 1 |
| n-desmethylflunitrazepam | Homo sapiens (human) | IC50 | 666,807.0000 | 1 | 1 |
| ro 05-4082 | Homo sapiens (human) | IC50 | 454,988.0000 | 1 | 1 |
| l 364373 | Homo sapiens (human) | IC50 | 100.0000 | 1 | 1 |
| eszopiclone | Homo sapiens (human) | Ki | 0.1020 | 1 | 1 |
| 1-(1h-indol-3-ylcarbonyl)-n-(4-methoxybenzyl)formamide | Homo sapiens (human) | Ki | 0.1622 | 1 | 1 |
| 2-[(2-ethoxyphenoxy)-phenylmethyl]morpholine | Homo sapiens (human) | IC50 | 0.0110 | 1 | 2 |
| meclonazepam | Homo sapiens (human) | IC50 | 833,681.0000 | 1 | 1 |
| isothaz | Homo sapiens (human) | IC50 | 16.0000 | 1 | 1 |
| n-(indol-3-ylglyoxylyl)benzylamine | Homo sapiens (human) | Ki | 0.1202 | 1 | 1 |
| 6-bromo-3'-nitroflavone | Homo sapiens (human) | Ki | 0.0010 | 1 | 1 |
| 3-propoxy-beta-carboline | Homo sapiens (human) | IC50 | 0.0110 | 1 | 1 |
| 3-propoxy-beta-carboline | Homo sapiens (human) | Ki | 1.0000 | 1 | 1 |
| apigenin | Homo sapiens (human) | Ki | 3.0200 | 1 | 1 |
| harman | Homo sapiens (human) | IC50 | 12.3027 | 1 | 1 |
| amentoflavone | Homo sapiens (human) | Ki | 0.0060 | 2 | 2 |
| baicalein | Homo sapiens (human) | Ki | 5.6234 | 1 | 1 |
| chrysin | Homo sapiens (human) | Ki | 3.0200 | 1 | 1 |
| hispidulin | Homo sapiens (human) | Ki | 1.0000 | 1 | 1 |
| scutellarein | Homo sapiens (human) | Ki | 12.0226 | 1 | 1 |
| wogonin | Homo sapiens (human) | Ki | 2.0417 | 1 | 1 |
| cholesta-3,5-dien-7-one | Homo sapiens (human) | IC50 | 1.0000 | 1 | 1 |
| ry 80 | Homo sapiens (human) | Ki | 0.0246 | 4 | 9 |
| 1-Ethyl-9H-pyrido[3,4-b]indole | Homo sapiens (human) | IC50 | 251.1890 | 1 | 1 |
| ganaxolone | Homo sapiens (human) | IC50 | 0.0420 | 1 | 1 |
| mrk 016 | Homo sapiens (human) | Ki | 0.3950 | 1 | 1 |
| bis(7)-tacrine | Homo sapiens (human) | IC50 | 6.0000 | 1 | 1 |
| pwz-029 | Homo sapiens (human) | Ki | 0.1694 | 2 | 2 |
| naluzotan | Homo sapiens (human) | Ki | 2.0000 | 1 | 1 |
| basimglurant | Homo sapiens (human) | Ki | 3.1600 | 1 | 1 |
| ro 4956371 | Homo sapiens (human) | Ki | 3.1600 | 1 | 1 |
| mdv 3100 | Homo sapiens (human) | IC50 | 3.0000 | 1 | 1 |
| valproate sodium | Homo sapiens (human) | Ki | 100.0000 | 1 | 1 |
| apalutamide | Homo sapiens (human) | IC50 | 3.0000 | 1 | 1 |
| nitd 609 | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
Drugs with Activation Measurements
Drugs with Other Measurements
Five-Membered N-Heterocyclic Scaffolds as Novel Amino Bioisosteres at γ-Aminobutyric Acid (GABA) Type A Receptors and GABA Transporters.Journal of medicinal chemistry, , 06-27, Volume: 62, Issue:12, 2019
Synthesis and pharmacological evaluation of 6-aminonicotinic acid analogues as novel GABA(A) receptor agonists.European journal of medicinal chemistry, , Sep-12, Volume: 84, 2014
Design, Synthesis, and Pharmacological Evaluation of Fluorescent and Biotinylated Antagonists of ρ1 GABAC Receptors.ACS medicinal chemistry letters, , Apr-11, Volume: 4, Issue:4, 2013
p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol.Journal of medicinal chemistry, , Dec-08, Volume: 54, Issue:23, 2011
Novel gamma-aminobutyric acid rho1 receptor antagonists; synthesis, pharmacological activity and structure-activity relationships.Journal of medicinal chemistry, , Jul-10, Volume: 51, Issue:13, 2008
Bioisosteric determinants for subtype selectivity of ligands for heteromeric GABA(A) receptors.Bioorganic & medicinal chemistry letters, , Jun-18, Volume: 11, Issue:12, 2001
New anticonvulsants: Schiff bases of gamma-aminobutyric acid and gamma-aminobutyramide.Journal of medicinal chemistry, , Volume: 23, Issue:6, 1980
High affinity central benzodiazepine receptor ligands: synthesis and biological evaluation of a series of phenyltriazolobenzotriazindione derivatives.Journal of medicinal chemistry, , Apr-21, Volume: 48, Issue:8, 2005
Prediction of receptor properties and binding affinity of ligands to benzodiazepine/GABAA receptors using artificial neural networks.Journal of medicinal chemistry, , Feb-17, Volume: 38, Issue:4, 1995
2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization.Journal of medicinal chemistry, , Nov-03, Volume: 48, Issue:22, 2005
High affinity central benzodiazepine receptor ligands: synthesis and biological evaluation of a series of phenyltriazolobenzotriazindione derivatives.Journal of medicinal chemistry, , Apr-21, Volume: 48, Issue:8, 2005
Benzodiazepine receptor ligands. 7. Synthesis and pharmacological evaluation of new 3-esters of the 8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide. 3-(2-Thienylmethoxycarbonyl) derivative: an anxioselective agent in rodents.Journal of medicinal chemistry, , Dec-19, Volume: 45, Issue:26, 2002
Prediction of receptor properties and binding affinity of ligands to benzodiazepine/GABAA receptors using artificial neural networks.Journal of medicinal chemistry, , Feb-17, Volume: 38, Issue:4, 1995
Quinazolines and 1,4-benzodiazepines. 90. Structure-activity relationship between substituted 2-amino-N-(2-benzoyl-4-chlorophenyl)acetamides and 1,4-benzodiazepinones.Journal of medicinal chemistry, , Volume: 25, Issue:9, 1982
Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different.Journal of medicinal chemistry, , Nov-27, Volume: 51, Issue:22, 2008
High affinity central benzodiazepine receptor ligands: synthesis and biological evaluation of a series of phenyltriazolobenzotriazindione derivatives.Journal of medicinal chemistry, , Apr-21, Volume: 48, Issue:8, 2005
Benzodiazepine receptor ligands. 7. Synthesis and pharmacological evaluation of new 3-esters of the 8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide. 3-(2-Thienylmethoxycarbonyl) derivative: an anxioselective agent in rodents.Journal of medicinal chemistry, , Dec-19, Volume: 45, Issue:26, 2002
Synthesis and pharmacological evaluation of 6-aminonicotinic acid analogues as novel GABA(A) receptor agonists.European journal of medicinal chemistry, , Sep-12, Volume: 84, 2014
Design, Synthesis, and Pharmacological Evaluation of Fluorescent and Biotinylated Antagonists of ρ1 GABAC Receptors.ACS medicinal chemistry letters, , Apr-11, Volume: 4, Issue:4, 2013
2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization.Journal of medicinal chemistry, , Nov-03, Volume: 48, Issue:22, 2005
New anticonvulsants: Schiff bases of gamma-aminobutyric acid and gamma-aminobutyramide.Journal of medicinal chemistry, , Volume: 23, Issue:6, 1980
3D-QSAR model of flavonoids binding at benzodiazepine site in GABAA receptors.Journal of medicinal chemistry, , Jun-07, Volume: 44, Issue:12, 2001
Mixture-based synthetic combinatorial libraries.Journal of medicinal chemistry, , Sep-23, Volume: 42, Issue:19, 1999
Prediction of receptor properties and binding affinity of ligands to benzodiazepine/GABAA receptors using artificial neural networks.Journal of medicinal chemistry, , Feb-17, Volume: 38, Issue:4, 1995
Quinazolines and 1,4-benzodiazepines. 90. Structure-activity relationship between substituted 2-amino-N-(2-benzoyl-4-chlorophenyl)acetamides and 1,4-benzodiazepinones.Journal of medicinal chemistry, , Volume: 25, Issue:9, 1982
Neuroactive Steroids. 2. 3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one (SAGE-217): A Clinical Next Generation Neuroactive Steroid Positive Allosteric Modulator of the (γ-Aminobutyric Acid)Journal of medicinal chemistry, , 09-28, Volume: 60, Issue:18, 2017
Neuroactive Steroids. 1. Positive Allosteric Modulators of the (γ-Aminobutyric Acid)A Receptor: Structure-Activity Relationships of Heterocyclic Substitution at C-21.Journal of medicinal chemistry, , Apr-23, Volume: 58, Issue:8, 2015
Five-Membered N-Heterocyclic Scaffolds as Novel Amino Bioisosteres at γ-Aminobutyric Acid (GABA) Type A Receptors and GABA Transporters.Journal of medicinal chemistry, , 06-27, Volume: 62, Issue:12, 2019
Bioisosteric determinants for subtype selectivity of ligands for heteromeric GABA(A) receptors.Bioorganic & medicinal chemistry letters, , Jun-18, Volume: 11, Issue:12, 2001
Design, synthesis, and subtype selectivity of 3,6-disubstituted β-carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed toward agents for treatment of alcohol abuse.Bioorganic & medicinal chemistry, , Nov-01, Volume: 18, Issue:21, 2010
Three-dimensional quantitative structure-activity relationships from molecular similarity matrices and genetic neural networks. 2. Applications.Journal of medicinal chemistry, , Dec-19, Volume: 40, Issue:26, 1997
Design, synthesis, and subtype selectivity of 3,6-disubstituted β-carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed toward agents for treatment of alcohol abuse.Bioorganic & medicinal chemistry, , Nov-01, Volume: 18, Issue:21, 2010
Three-dimensional quantitative structure-activity relationships from molecular similarity matrices and genetic neural networks. 2. Applications.Journal of medicinal chemistry, , Dec-19, Volume: 40, Issue:26, 1997
A study of the structure-activity relationship of GABA(A)-benzodiazepine receptor bivalent ligands by conformational analysis with low temperature NMR and X-ray analysis.Bioorganic & medicinal chemistry, , Oct-01, Volume: 16, Issue:19, 2008
Determination of the stable conformation of GABA(A)-benzodiazepine receptor bivalent ligands by low temperature NMR and X-ray analysis.Bioorganic & medicinal chemistry letters, , Mar-22, Volume: 14, Issue:6, 2004
Synthesis, in vitro affinity, and efficacy of a bis 8-ethynyl-4H-imidazo[1,5a]- [1,4]benzodiazepine analogue, the first bivalent alpha5 subtype selective BzR/GABA(A) antagonist.Journal of medicinal chemistry, , Dec-18, Volume: 46, Issue:26, 2003
The GABA(A) receptor as a target for photochromic molecules.Bioorganic & medicinal chemistry, , Nov-15, Volume: 18, Issue:22, 2010
Selective influence on contextual memory: physiochemical properties associated with selectivity of benzodiazepine ligands at GABAA receptors containing the alpha5 subunit.Journal of medicinal chemistry, , Jul-10, Volume: 51, Issue:13, 2008
Enables
This protein enables 2 target(s):
| Target | Category | Definition |
|---|
| transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | molecular function | Any transmitter-gated ion channel activity that is involved in regulation of postsynaptic membrane potential. [GO_REF:0000061, GOC:TermGenie, PMID:20200227] |
| GABA-gated chloride ion channel activity | molecular function | Enables the transmembrane transfer of a chloride ion by a channel that opens when GABA has been bound by the channel complex or one of its constituent parts. [GOC:mtg_transport, ISBN:0815340729] |
Located In
This protein is located in 3 target(s):
| Target | Category | Definition |
|---|
| plasma membrane | cellular component | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363] |
| GABA-ergic synapse | cellular component | A synapse that uses GABA as a neurotransmitter. These synapses are typically inhibitory. [GOC:dos] |
| postsynaptic specialization membrane | cellular component | The membrane component of the postsynaptic specialization. This is the region of the postsynaptic membrane in which the population of neurotransmitter receptors involved in synaptic transmission are concentrated. [GOC:dos] |
Active In
This protein is active in 5 target(s):
| Target | Category | Definition |
|---|
| dendrite membrane | cellular component | The portion of the plasma membrane surrounding a dendrite. [GOC:mah] |
| plasma membrane | cellular component | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363] |
| postsynapse | cellular component | The part of a synapse that is part of the post-synaptic cell. [GOC:dos] |
| neuron projection | cellular component | A prolongation or process extending from a nerve cell, e.g. an axon or dendrite. [GOC:jl, http://www.cogsci.princeton.edu/~wn/] |
| synapse | cellular component | The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane. [GOC:aruk, ISBN:0198506732, PMID:24619342, PMID:29383328, PMID:31998110] |
Part Of
This protein is part of 3 target(s):
| Target | Category | Definition |
|---|
| GABA-A receptor complex | cellular component | A protein complex which is capable of GABA-A receptor activity. In human, it is usually composed of either two alpha, two beta and one gamma chain of the GABA-A receptor subunits or 5 chains of the GABA-A receptor subunits rho1-3 (formally known as GABA-C receptor). [GO_REF:0000088, GOC:bhm, GOC:TermGenie, PMID:18790874] |
| chloride channel complex | cellular component | An ion channel complex through which chloride ions pass. [GOC:mah] |
| transmembrane transporter complex | cellular component | A transmembrane protein complex which enables the transfer of a substance from one side of a membrane to the other. [GOC:bhm, GOC:TermGenie, PMID:18024586] |
Involved In
This protein is involved in 5 target(s):
| Target | Category | Definition |
|---|
| gamma-aminobutyric acid signaling pathway | biological process | The series of molecular signals generated by the binding of gamma-aminobutyric acid (GABA, 4-aminobutyrate), an amino acid which acts as a neurotransmitter in some organisms, to its receptor on the surface of a target cell. [GOC:mah] |
| synaptic transmission, GABAergic | biological process | The vesicular release of gamma-aminobutyric acid (GABA). from a presynapse, across a chemical synapse, the subsequent activation of GABA receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse. [GOC:dos, ISBN:0126603030] |
| chloride transmembrane transport | biological process | The process in which chloride is transported across a membrane. [GOC:TermGenie, GOC:vw] |
| inhibitory synapse assembly | biological process | The aggregation, arrangement and bonding together of a set of components to form an inhibitory synapse. [GO_REF:0000079, GOC:bf, GOC:PARL, GOC:TermGenie] |
| regulation of postsynaptic membrane potential | biological process | Any process that modulates the potential difference across a post-synaptic membrane. [GOC:dph, GOC:ef] |