Protein Details: Gamma-aminobutyric acid receptor subunit beta-3

Protein ID

ICDB_Pro_0461

Protein Name

Gamma-aminobutyric acid receptor subunit beta-3

Gene Name

GABRB3

Organism

Homo sapiens (Human)

Length

473 amino acids

AlphaFoldDB

AF-P28472-F1-model_v4.pdb

Function

Beta 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). GABAARs containing beta-3/GABRB3 subunit are found at both synaptic and extrasynaptic sites (By similarity). When activated by GABA;GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential;thereby reducing nerve transmission. GABAARs containing alpha-1 and beta-3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation. Extrasynaptic beta-3 receptors contribute to the tonic GABAergic inhibition (By similarity). GABAARs containing alpha-1;beta-3 and epsilon subunits may also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Beta-containing GABAARs 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. Plays an important role in somatosensation and in the production of antinociception (By similarity).

Sequence

MWGLAGGRLFGIFSAPVLVAVVCCAQSVNDPGNMSFVKETVDKLLKGYDIRLRPDFGGPPVCVGMNIDIASIDMVSEVNMDYTLTMYFQQYWRDKRLAYSGIPLNLTLDNRVADQLWVPDTYFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIESYGYTTDDIEFYWRGGDKAVTGVERIELPQFSIVEHRLVSRNVVFATGAYPRLSLSFRLKRNIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKIPYVKAIDMYLMGCFVFVFLALLEYAFVNYIFFGRGPQRQKKLAEKTAKAKNDRSKSESNRVDAHGNILLTSLEVHNEMNEVSGGIGDTRNSAISFDNSGIQYRKQSMPREGHGRFLGDRSLPHKKTHLRRRSSQLKIKIPDLTDVNAIDRWSRIVFPFTFSLFNLVYWLYYVN

PDB Structures

4COF 5O8F 5OJM 6A96 6HUG 6HUJ 6HUK 6HUO 6HUP 6I53 6QFA 7PBD 7PBZ 7PC0 7QN5 7QN6 7QN7 7QN8 7QN9 7QNA 7QNB 7QNC 7QND 7QNE 8PVB

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

BINDING 120..122; /ligand="benzamidine" : "agonist"; BINDING 122; /ligand="4-aminobutanoate": "ligand shared with the neighboring alpha subunit"; /note="in chain A"; /evidence="ECO:0000269|PubMed:35355020;ECO:0007744|PDB:7QN7"; BINDING 122; /ligand="histamine": "ligand shared between two neighboring beta subunits"; /note="in chain B"; /evidence="ECO:0000269|PubMed:35355020;ECO:0007744|PDB:7QN7"; BINDING 180..182; /ligand="benzamidine" : "agonist"; /evidence="ECO:0000269|PubMed:24909990;ECO:0007744|PDB:4COF"; BINDING 180; /ligand="4-aminobutanoate": "ligand shared with the neighboring alpha subunit"; /note="in chain A"; /evidence="ECO:0000269|PubMed:35355020;ECO:0007744|PDB:7QN7"; BINDING 181..182; /ligand="histamine": "ligand shared between two neighboring beta subunits"; /note="in chain B"; /evidence="ECO:0000269|PubMed:35355020;ECO:0007744|PDB:7QN7"; BINDING 182; /ligand="4-aminobutanoate": "ligand shared with the neighboring alpha subunit"; /note="in chain A"; /evidence="ECO:0000269|PubMed:30140029;ECO:0007744|PDB:6A96"; BINDING 225; /ligand="benzamidine" : "agonist"; BINDING 227; /ligand="4-aminobutanoate": "ligand shared with the neighboring alpha subunit"; /note="in chain A"; /evidence="ECO:0000269|PubMed:30140029;ECO:0000269|PubMed:35355020;ECO:0007744|PDB:6A96;ECO:0007744|PDB:7QN7"; BINDING 227; /ligand="histamine": "ligand shared between two neighboring beta subunits"; /note="in chain B"

Disease

Epilepsy;Childhood Absence 5 and Developmental And Epileptic Encephalopathy 43

Location

DOI ID

10.1016/0888-7543(91)90034-c; 10.1038/ng1285; 10.1038/nature04601; 10.1101/gr.2596504; 10.1016/s0021-9258(18)53626-7; 10.1073/pnas.0307231101; 10.1074/jbc.m709993200; 10.1021/bi201772m; 10.3791/52115; 10.1038/nature13293; 10.1038/s41422-018-0077-8; 10.1038/s41586-018-0833-4; 10.1038/s41586-022-04517-3; 10.1007/s00439-002-0766-7; 10.1016/j.ajhg.2008.04.020; 10.1074/jbc.m111.332528; 10.1038/nature12439; 10.1371/journal.pgen.1004772; 10.1016/j.ajhg.2016.06.003; 10.1002/ana.24631; 10.1136/jmedgenet-2015-103263; 10.1002/ajmg.a.38282; 10.1002/humu.23149

RefSeq

NP_000805.1 [P28472-1]; NP_001178249.1 [P28472-4]; NP_001178250.1 [P28472-3]; NP_001265560.1 [P28472-4]; NP_068712.1 [P28472-2]