P31644 · GBRA5_HUMAN
- ProteinGamma-aminobutyric acid receptor subunit alpha-5
- GeneGABRA5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids462 (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 (PubMed:14993607, PubMed:29961870, PubMed:30140029, PubMed:31056671).
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:30140029).
When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:14993607, PubMed:30140029).
GABAARs containing alpha-5/GABRA5 subunits are mainly extrasynaptic and contribute to the tonic GABAergic inhibition in the hippocampus (By similarity).
Extrasynaptic alpha-5-containing GABAARs in CA1 pyramidal neurons play a role in learning and memory processes (By similarity).
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:30140029).
When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:14993607, PubMed:30140029).
GABAARs containing alpha-5/GABRA5 subunits are mainly extrasynaptic and contribute to the tonic GABAergic inhibition in the hippocampus (By similarity).
Extrasynaptic alpha-5-containing GABAARs in CA1 pyramidal neurons play a role in learning and memory processes (By similarity).
Catalytic activity
- chloride(in) = chloride(out)
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-5
- Alternative names
Gene names
- Community suggested namesGABRA5
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP31644
- 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 | 32-260 | Extracellular | ||||
Sequence: QMPTSSVKDETNDNITIFTRILDGLLDGYDNRLRPGLGERITQVRTDIYVTSFGPVSDTEMEYTIDVFFRQSWKDERLRFKGPMQRLPLNNLLASKIWTPDTFFHNGKKSIAHNMTTPNKLLRLEDDGTLLYTMRLTISAECPMQLEDFPMDAHACPLKFGSYAYPNSEVVYVWTNGSTKSVVVAEDGSRLNQYHLMGQTVGTENISTSTGEYTIMTAHFHLKRKIGYF | ||||||
Transmembrane | 261-281 | Helical | ||||
Sequence: VIQTYLPCIMTVILSQVSFWL | ||||||
Topological domain | 282-286 | Cytoplasmic | ||||
Sequence: NRESV | ||||||
Transmembrane | 287-308 | Helical | ||||
Sequence: PARTVFGVTTVLTMTTLSISAR | ||||||
Topological domain | 309-318 | Extracellular | ||||
Sequence: NSLPKVAYAT | ||||||
Transmembrane | 319-340 | Helical | ||||
Sequence: AMDWFIAVCYAFVFSALIEFAT | ||||||
Topological domain | 341-427 | Cytoplasmic | ||||
Sequence: VNYFTKRGWAWDGKKALEAAKIKKKREVILNKSTNAFTTGKMSHPPNIPKEQTPAGTSNTTSVSVKPSEEKTSESKKTYNSISKIDK | ||||||
Transmembrane | 428-448 | Helical | ||||
Sequence: MSRIVFPVLFGTFNLVYWATY | ||||||
Topological domain | 449-462 | Extracellular | ||||
Sequence: LNREPVIKGAASPK |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Developmental and epileptic encephalopathy 79 (DEE79)
- Note
- DescriptionA form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE79 is an autosomal dominant form characterized by onset of refractory seizures in the first months of life. Brain imaging may show hypomyelination, cerebral atrophy and thinning of the corpus callosum.
- See alsoMIM:618559
Natural variants in DEE79
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_083201 | 294 | V>F | in DEE79; decreased subcellular localization to the cell membrane resulting in altered protein localization to the synapse and altered gamma-aminobutyric acid signaling pathway | |
VAR_083202 | 294 | V>L | in DEE79; increased affinity to GABA; decreased maximal GABA-evoked current density | |
VAR_083203 | 413 | S>F | in DEE79; decreased subcellular localization to the cell membrane resulting in altered protein localization to the synapse and altered gamma-aminobutyric acid signaling pathway; the mutant subunit decreases the trafficking of the partnering GABRB3 subunit to the cell membrane with no effect on other subunits |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_083201 | 294 | in DEE79; decreased subcellular localization to the cell membrane resulting in altered protein localization to the synapse and altered gamma-aminobutyric acid signaling pathway | |||
Sequence: V → F | ||||||
Natural variant | VAR_083202 | 294 | in DEE79; increased affinity to GABA; decreased maximal GABA-evoked current density | |||
Sequence: V → L | ||||||
Natural variant | VAR_083203 | 413 | in DEE79; decreased subcellular localization to the cell membrane resulting in altered protein localization to the synapse and altered gamma-aminobutyric acid signaling pathway; the mutant subunit decreases the trafficking of the partnering GABRB3 subunit to the cell membrane with no effect on other subunits | |||
Sequence: S → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 608 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-31 | |||||
Sequence: MDNGMFSGFIMIKNLLLFCISMNLSSHFGFS | ||||||
Chain | PRO_0000000444 | 32-462 | Gamma-aminobutyric acid receptor subunit alpha-5 | |||
Sequence: QMPTSSVKDETNDNITIFTRILDGLLDGYDNRLRPGLGERITQVRTDIYVTSFGPVSDTEMEYTIDVFFRQSWKDERLRFKGPMQRLPLNNLLASKIWTPDTFFHNGKKSIAHNMTTPNKLLRLEDDGTLLYTMRLTISAECPMQLEDFPMDAHACPLKFGSYAYPNSEVVYVWTNGSTKSVVVAEDGSRLNQYHLMGQTVGTENISTSTGEYTIMTAHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGWAWDGKKALEAAKIKKKREVILNKSTNAFTTGKMSHPPNIPKEQTPAGTSNTTSVSVKPSEEKTSESKKTYNSISKIDKMSRIVFPVLFGTFNLVYWATYLNREPVIKGAASPK | ||||||
Glycosylation | 45 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 145 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 173↔187 | |||||
Sequence: CPMQLEDFPMDAHAC | ||||||
Glycosylation | 207 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 236 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Cross-link | 355 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K |
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) chains, each subunit exhibiting distinct physiological and pharmacological properties.
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 377-408 | Polar residues | ||||
Sequence: FTTGKMSHPPNIPKEQTPAGTSNTTSVSVKPS | ||||||
Region | 377-412 | Disordered | ||||
Sequence: FTTGKMSHPPNIPKEQTPAGTSNTTSVSVKPSEEKT |
Domain
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. GABRA5 sub-subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length462
- Mass (Da)52,146
- Last updated1993-07-01 v1
- Checksum260A8B554113AFF9
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 377-408 | Polar residues | ||||
Sequence: FTTGKMSHPPNIPKEQTPAGTSNTTSVSVKPS |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L08485 EMBL· GenBank· DDBJ | AAA58490.1 EMBL· GenBank· DDBJ | mRNA | ||
AK290453 EMBL· GenBank· DDBJ | BAF83142.1 EMBL· GenBank· DDBJ | mRNA | ||
BT009830 EMBL· GenBank· DDBJ | AAP88832.1 EMBL· GenBank· DDBJ | mRNA | ||
BC111979 EMBL· GenBank· DDBJ | AAI11980.1 EMBL· GenBank· DDBJ | mRNA | ||
BC113422 EMBL· GenBank· DDBJ | AAI13423.1 EMBL· GenBank· DDBJ | mRNA | ||
AF061785 EMBL· GenBank· DDBJ | AAC31809.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF228447 EMBL· GenBank· DDBJ | AAF62508.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF228448 EMBL· GenBank· DDBJ | AAF62509.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF228449 EMBL· GenBank· DDBJ | AAF62510.1 EMBL· GenBank· DDBJ | Genomic DNA |