P34903 · GBRA3_HUMAN
- ProteinGamma-aminobutyric acid receptor subunit alpha-3
- GeneGABRA3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids492 (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:16412217, PubMed:29053855).
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) (By similarity).
When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:16412217, PubMed:29053855).
Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (PubMed:16412217, PubMed:29053855).
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) (By similarity).
When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:16412217, PubMed:29053855).
Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (PubMed:16412217, PubMed:29053855).
Catalytic activity
- chloride(in) = chloride(out)
Activity regulation
Potentiated by etomidate, propofol, pregnanolone and flurazepam.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chloride channel complex | |
Cellular Component | dendrite membrane | |
Cellular Component | GABA-A receptor complex | |
Cellular Component | neuron projection | |
Cellular Component | plasma membrane | |
Cellular Component | postsynapse | |
Cellular Component | postsynaptic membrane | |
Cellular Component | synapse | |
Cellular Component | transmembrane transporter complex | |
Molecular Function | benzodiazepine receptor activity | |
Molecular Function | GABA-A receptor activity | |
Molecular Function | GABA-gated chloride ion channel activity | |
Biological Process | chloride transmembrane transport | |
Biological Process | gamma-aminobutyric acid signaling pathway | |
Biological Process | inhibitory synapse assembly | |
Biological Process | regulation of postsynaptic membrane potential | |
Biological Process | synaptic transmission, GABAergic |
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-3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP34903
- 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 | 29-274 | Extracellular | ||||
Sequence: QGESRRQEPGDFVKQDIGGLSPKHAPDIPDDSTDNITIFTRILDRLLDGYDNRLRPGLGDAVTEVKTDIYVTSFGPVSDTDMEYTIDVFFRQTWHDERLKFDGPMKILPLNNLLASKIWTPDTFFHNGKKSVAHNMTTPNKLLRLVDNGTLLYTMRLTIHAECPMHLEDFPMDVHACPLKFGSYAYTTAEVVYSWTLGKNKSVEVAQDGSRLNQYDLLGHVVGTEIIRSSTGEYVVMTTHFHLKRK | ||||||
Transmembrane | 275-295 | Helical | ||||
Sequence: IGYFVIQTYLPCIMTVILSQV | ||||||
Topological domain | 296-305 | Cytoplasmic | ||||
Sequence: SFWLNRESVP | ||||||
Transmembrane | 306-325 | Helical | ||||
Sequence: ARTVFGVTTVLTMTTLSISA | ||||||
Topological domain | 326-336 | Extracellular | ||||
Sequence: RNSLPKVAYAT | ||||||
Transmembrane | 337-357 | Helical | ||||
Sequence: AMDWFIAVCYAFVFSALIEFA | ||||||
Topological domain | 358-457 | Cytoplasmic | ||||
Sequence: TVNYFTKRSWAWEGKKVPEALEMKKKTPAAPAKKTSTTFNIVGTTYPINLAKDTEFSTISKGAAPSASSTPTIIASPKATYVQDSPTETKTYNSVSKVDK | ||||||
Transmembrane | 458-478 | Helical | ||||
Sequence: ISRIIFPVLFAIFNLVYWATY | ||||||
Topological domain | 479-492 | Extracellular | ||||
Sequence: VNRESAIKGMIRKQ |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features (EPILX2)
- Note
- DescriptionA neurologic disorder characterized by variable combinations of epileptic seizure, and a varying degree of intellectual disability and developmental delay. Some patients have dysmorphic facial features or mild skeletal anomalies. In general, males are more severely affected than females, although there is evidence for incomplete penetrance in both sexes.
- See alsoMIM:301091
Natural variants in EPILX2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_087846 | 166 | T>M | in EPILX2 | |
VAR_087847 | 242 | Q>L | in EPILX2; uncertain significance | |
VAR_087848 | 336 | T>M | in EPILX2; uncertain significance | |
VAR_087849 | 474 | Y>C | in EPILX2 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_087845 | 47 | found in a patient with autism spectrum disorder and no epileptic seizures; uncertain significance | |||
Sequence: G → R | ||||||
Natural variant | VAR_087846 | 166 | in EPILX2 | |||
Sequence: T → M | ||||||
Natural variant | VAR_087847 | 242 | in EPILX2; uncertain significance | |||
Sequence: Q → L | ||||||
Natural variant | VAR_087848 | 336 | in EPILX2; uncertain significance | |||
Sequence: T → M | ||||||
Natural variant | VAR_087849 | 474 | in EPILX2 | |||
Sequence: Y → C |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 491 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, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-28 | UniProt | |||||
Sequence: MIITQTSHCYMTSLGILFLINILPGTTG | |||||||
Chain | PRO_0000000437 | 29-492 | UniProt | Gamma-aminobutyric acid receptor subunit alpha-3 | |||
Sequence: QGESRRQEPGDFVKQDIGGLSPKHAPDIPDDSTDNITIFTRILDRLLDGYDNRLRPGLGDAVTEVKTDIYVTSFGPVSDTDMEYTIDVFFRQTWHDERLKFDGPMKILPLNNLLASKIWTPDTFFHNGKKSVAHNMTTPNKLLRLVDNGTLLYTMRLTIHAECPMHLEDFPMDVHACPLKFGSYAYTTAEVVYSWTLGKNKSVEVAQDGSRLNQYDLLGHVVGTEIIRSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRSWAWEGKKVPEALEMKKKTPAAPAKKTSTTFNIVGTTYPINLAKDTEFSTISKGAAPSASSTPTIIASPKATYVQDSPTETKTYNSVSKVDKISRIIFPVLFAIFNLVYWATYVNRESAIKGMIRKQ | |||||||
Glycosylation | 63 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 163 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 176 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 191↔205 | UniProt | |||||
Sequence: CPMHLEDFPMDVHAC | |||||||
Glycosylation | 228 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue | 426 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 427 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 433 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 433 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 442 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 442 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
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 (PubMed:16412217).
Binds UBQLN1 (By similarity).
Interacts with GPHN (PubMed:26613940).
Binds UBQLN1 (By similarity).
Interacts with GPHN (PubMed:26613940).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 28-54 | Disordered | ||||
Sequence: GQGESRRQEPGDFVKQDIGGLSPKHAP |
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. GABRA3 sub-subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length492
- Mass (Da)55,165
- Last updated1994-02-01 v1
- Checksum23A7390C9822691F
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 180 | in Ref. 3; AAH28629 | ||||
Sequence: L → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S62908 EMBL· GenBank· DDBJ | AAB27279.1 EMBL· GenBank· DDBJ | mRNA | ||
AF166361 EMBL· GenBank· DDBJ | AAG12455.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF165901 EMBL· GenBank· DDBJ | AAG12455.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF165902 EMBL· GenBank· DDBJ | AAG12455.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF165903 EMBL· GenBank· DDBJ | AAG12455.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF165904 EMBL· GenBank· DDBJ | AAG12455.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF165905 EMBL· GenBank· DDBJ | AAG12455.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF165906 EMBL· GenBank· DDBJ | AAG12455.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF166359 EMBL· GenBank· DDBJ | AAG12455.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF166360 EMBL· GenBank· DDBJ | AAG12455.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC028629 EMBL· GenBank· DDBJ | AAH28629.1 EMBL· GenBank· DDBJ | mRNA |