P62812 · GBRA1_MOUSE
- ProteinGamma-aminobutyric acid receptor subunit alpha-1
- GeneGabra1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids455 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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) (PubMed:27129275).
When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (By similarity).
Alpha-1/GABRA1-containing GABAARs are largely synaptic (By similarity).
Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity).
GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:27129275).
GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity).
GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity).
Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (PubMed:25348603).
Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (PubMed:16945976, PubMed:25422464).
When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (By similarity).
Alpha-1/GABRA1-containing GABAARs are largely synaptic (By similarity).
Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity).
GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:27129275).
GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity).
GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity).
Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (PubMed:25348603).
Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (PubMed:16945976, PubMed:25422464).
Catalytic activity
- chloride(in) = chloride(out)
Activity regulation
Allosterically activated by benzodiazepines, the neuroanesthetic alphaxalone and pentobarbital (By similarity).
Inhibited by the antagonist bicuculline (By similarity).
Potentiated by histamine (By similarity).
Inhibited by the antagonist bicuculline (By similarity).
Potentiated by histamine (By similarity).
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGamma-aminobutyric acid receptor subunit alpha-1
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP62812
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Postsynaptic cell membrane ; Multi-pass membrane protein
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 28-252 | Extracellular | ||||
Sequence: QPSQDELKDNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMTTHFHLKRKIGYF | ||||||
Transmembrane | 253-273 | Helical | ||||
Sequence: VIQTYLPCIMTVILSQVSFWL | ||||||
Topological domain | 274-278 | Cytoplasmic | ||||
Sequence: NRESV | ||||||
Transmembrane | 279-300 | Helical | ||||
Sequence: PARTVFGVTTVLTMTTLSISAR | ||||||
Topological domain | 301-310 | Extracellular | ||||
Sequence: NSLPKVAYAT | ||||||
Transmembrane | 311-332 | Helical | ||||
Sequence: AMDWFIAVCYAFVFSALIEFAT | ||||||
Topological domain | 333-420 | Cytoplasmic | ||||
Sequence: VNYFTKRGYAWDGKSVVPEKPKKVKDPLIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKIDR | ||||||
Transmembrane | 421-440 | Helical | ||||
Sequence: LSRIAFPLLFGIFNLVYWAT | ||||||
Topological domain | 441-455 | Extracellular | ||||
Sequence: YLNREPQLKAPTPHQ |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Gene knockdown in orbitofrontal prefrontal cortex results in an inability of mice to select actions based on their consequences, developing instead habit-like behavioral inflexibility.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 8 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-27 | |||||
Sequence: MKKSRGLSDYLWAWTLILSTLSGRSYG | ||||||
Chain | PRO_0000000429 | 28-455 | Gamma-aminobutyric acid receptor subunit alpha-1 | |||
Sequence: QPSQDELKDNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDPLIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKIDRLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ | ||||||
Glycosylation | 37 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 137 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 165↔179 | |||||
Sequence: CPMHLEDFPMDAHAC |
Post-translational modification
Glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Heteropentamer, formed by a combination of alpha (GABRA1-6), beta (GABRB1-3), gamma (GABRG1-3), delta (GABRD), epsilon (GABRE), rho (GABRR1-3), pi (GABRP) and theta (GABRQ) subunits, each subunit exhibiting distinct physiological and pharmacological properties (PubMed:25422464).
Interacts with UBQLN1 (By similarity).
Interacts with TRAK1 (PubMed:16380713).
Interacts with KIF21B (By similarity).
Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity).
Interacts with LHFPL4 (By similarity).
Interacts with NLGN2 (By similarity).
Interacts with SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology (PubMed:31601770).
Interacts with UBQLN1 (By similarity).
Interacts with TRAK1 (PubMed:16380713).
Interacts with KIF21B (By similarity).
Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity).
Interacts with LHFPL4 (By similarity).
Interacts with NLGN2 (By similarity).
Interacts with SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology (PubMed:31601770).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Domain
The extracellular domain contributes to synaptic contact formation.
The GABA-binding pockets are located at the interface between neighboring alpha and beta subunits.
GABAARs subunits share a common topological structure: a peptide sequence made up of a long extracellular N-terminal, four transmembrane domains, intracellular or cytoplasmic domain located between the third and the fourth transmembrane domains.
Sequence similarities
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA1 sub-subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length455
- Mass (Da)51,754
- Last updated2004-08-16 v1
- ChecksumA270B43423B4086E
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E9PXL4 | E9PXL4_MOUSE | Gabra1 | 132 | ||
A0A0U1RQ83 | A0A0U1RQ83_MOUSE | Gabra1 | 114 | ||
A0A0U1RPE4 | A0A0U1RPE4_MOUSE | Gabra1 | 302 | ||
E9Q2L8 | E9Q2L8_MOUSE | Gabra1 | 91 | ||
A0A140LJE7 | A0A140LJE7_MOUSE | Gabra1 | 167 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M86566 EMBL· GenBank· DDBJ | AAB59634.1 EMBL· GenBank· DDBJ | mRNA | ||
M63436 EMBL· GenBank· DDBJ | AAA37654.1 EMBL· GenBank· DDBJ | mRNA | ||
X61430 EMBL· GenBank· DDBJ | CAA43672.1 EMBL· GenBank· DDBJ | mRNA |