Protein Details: Gamma-aminobutyric acid receptor subunit alpha-4

Protein ID

ICDB_Pro_0551

Protein Name

Gamma-aminobutyric acid receptor subunit alpha-4

Gene Name

GABRA4

Organism

Homo sapiens (Human)

Length

554 amino acids

AlphaFoldDB

AF-P48169-F1-model_v4.pdb

Function

Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA);a major inhibitory neurotransmitter in the brain. GABA-gated chloride channels;also named GABA(A) receptors (GABAAR);consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s). When activated by GABA;GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. GABAARs containing alpha-4 are predominantly extrasynaptic;contributing to tonic inhibition in dentate granule cells and thalamic relay neurons (By similarity). Extrasynaptic alpha-4-containing GABAARs control levels of excitability and network activity (By similarity). GABAAR containing alpha-4-beta-3-delta subunits can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits;which may be involved in the regulation of sleep and wakefulness.

Sequence

MVSAKKVPAIALSAGVSFALLRFLCLAVCLNESPGQNQKEEKLCTENFTRILDSLLDGYDNRLRPGFGGPVTEVKTDIYVTSFGPVSDVEMEYTMDVFFRQTWIDKRLKYDGPIEILRLNNMMVTKVWTPDTFFRNGKKSVSHNMTAPNKLFRIMRNGTILYTMRLTISAECPMRLVDFPMDGHACPLKFGSYAYPKSEMIYTWTKGPEKSVEVPKESSSLVQYDLIGQTVSSETIKSITGEYIVMTVYFHLRRKMGYFMIQTYIPCIMTVILSQVSFWINKESVPARTVFGITTVLTMTTLSISARHSLPKVSYATAMDWFIAVCFAFVFSALIEFAAVNYFTNIQMEKAKRKTSKPPQEVPAAPVQREKHPEAPLQNTNANLNMRKRTNALVHSESDVGNRTEVGNHSSKSSTVVQESSKGTPRSYLASSPNPFSRANAAETISAARALPSASPTSIRTGYMPRKASVGSASTRHVFGSRLQRIKTTVNTIGATGKLSATPPPSAPPPSGSGTSKIDKYARILFPVTFGAFNMVYWVVYLSKDTMEKSESLM

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

BINDING 100; /ligand="4-aminobutanoate": "ligand shared with the neighboring beta subunit"; BINDING 163; /ligand="4-aminobutanoate": "ligand shared with the neighboring beta subunit"

Disease

Rare Genetic Epilepsy and Autism Spectrum Disorder

Location

Expressed in the brain

DOI ID

10.1016/0922-4106(95)90072-1; 10.1038/ng1285; 10.1038/nature03466; 10.1101/gr.2596504; 10.1016/0888-7543(95)80178-o; 10.1038/s41586-022-04517-3; 10.1126/science.1133427

RefSeq

NP_000800.2; NP_001191195.1; NP_001191196.1

Feature