Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Gamma-aminobutyric acid receptor subunit alpha-1

Gene

GABRA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).By similarity

GO - Molecular functioni

  1. chloride channel activity Source: UniProtKB-KW
  2. drug binding Source: BHF-UCL
  3. extracellular ligand-gated ion channel activity Source: InterPro
  4. GABA-A receptor activity Source: ProtInc

GO - Biological processi

  1. cellular response to histamine Source: Ensembl
  2. gamma-aminobutyric acid signaling pathway Source: ProtInc
  3. ion transmembrane transport Source: Reactome
  4. synaptic transmission Source: Reactome
  5. synaptic transmission, GABAergic Source: BHF-UCL
  6. transmembrane transport Source: Reactome
  7. transport Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Chloride

Enzyme and pathway databases

ReactomeiREACT_24987. GABA A receptor activation.
REACT_25387. Ligand-gated ion channel transport.
REACT_267716. Orphan transporters.

Names & Taxonomyi

Protein namesi
Recommended name:
Gamma-aminobutyric acid receptor subunit alpha-1
Alternative name(s):
GABA(A) receptor subunit alpha-1
Gene namesi
Name:GABRA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:4075. GABRA1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 251224ExtracellularCuratedAdd
BLAST
Transmembranei252 – 27322HelicalCuratedAdd
BLAST
Transmembranei279 – 30022HelicalCuratedAdd
BLAST
Transmembranei313 – 33422HelicalCuratedAdd
BLAST
Topological domaini335 – 42187CytoplasmicCuratedAdd
BLAST
Transmembranei422 – 44322HelicalCuratedAdd
BLAST

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. chloride channel complex Source: UniProtKB-KW
  3. integral component of plasma membrane Source: BHF-UCL
  4. plasma membrane Source: Reactome
  5. postsynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Epilepsy, childhood absence 41 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood.

See also OMIM:611136
Epilepsy, idiopathic generalized 131 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures.

See also OMIM:611136
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti219 – 2191D → N in EIG13; the mutant protein is partially retained in the endoplasmic reticulum and has decreased expression at the plasma membrane; causes decreased current amplitude in response to GABA compared to wild-type and alters receptor gating kinetics including faster desensitization. 1 Publication
VAR_071810
Juvenile myoclonic epilepsy 51 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue.

See also OMIM:611136
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti322 – 3221A → D in EJM5. 1 Publication
VAR_013642
Epileptic encephalopathy, early infantile, 191 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA severe neurologic disorder characterized by onset of seizures in the first months of life and usually associated with EEG abnormalities. Affected infants have convulsive seizures (hemiclonic or generalized) that are often prolonged and triggered by fever. Other seizure types include focal, myoclonic, absence seizures, and drop attacks. Development is normal in the first year of life with later slowing and intellectual disability.

See also OMIM:615744
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti112 – 1121R → Q in EIEE19. 1 Publication
VAR_071809
Natural varianti251 – 2511G → S in EIEE19. 1 Publication
VAR_071811
Natural varianti306 – 3061K → T in EIEE19. 1 Publication
VAR_071812

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

MIMi611136. phenotype.
615744. phenotype.
Orphaneti64280. Childhood absence epilepsy.
33069. Dravet syndrome.
307. Juvenile myoclonic epilepsy.
PharmGKBiPA28489.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 456429Gamma-aminobutyric acid receptor subunit alpha-1PRO_0000000428Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence Analysis
Glycosylationi138 – 1381N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi166 ↔ 180By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP14867.
PRIDEiP14867.

PTM databases

PhosphoSiteiP14867.

Expressioni

Gene expression databases

BgeeiP14867.
CleanExiHS_GABRA1.
ExpressionAtlasiP14867. baseline and differential.
GenevestigatoriP14867.

Organism-specific databases

HPAiCAB022502.
HPA055746.

Interactioni

Subunit structurei

Interacts with TRAK1. Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains. Binds UBQLN1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi108828. 3 interactions.
IntActiP14867. 1 interaction.
STRINGi9606.ENSP00000023897.

Structurei

3D structure databases

ProteinModelPortaliP14867.
SMRiP14867. Positions 46-340.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG238757.
GeneTreeiENSGT00760000119010.
HOGENOMiHOG000231337.
HOVERGENiHBG051707.
InParanoidiP14867.
KOiK05175.
OMAiAPNIARD.
OrthoDBiEOG7JX342.
PhylomeDBiP14867.
TreeFamiTF315453.

Family and domain databases

Gene3Di2.70.170.10. 1 hit.
InterProiIPR006028. GABAA/Glycine_rcpt.
IPR001390. GABAAa_rcpt.
IPR005431. GABBAa1_rcpt.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
IPR018000. Neurotransmitter_ion_chnl_CS.
[Graphical view]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 2 hits.
[Graphical view]
PRINTSiPR01079. GABAARALPHA.
PR01614. GABAARALPHA1.
PR00253. GABAARECEPTR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P14867-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MRKSPGLSDC LWAWILLLST LTGRSYGQPS LQDELKDNTT VFTRILDRLL
60 70 80 90 100
DGYDNRLRPG LGERVTEVKT DIFVTSFGPV SDHDMEYTID VFFRQSWKDE
110 120 130 140 150
RLKFKGPMTV LRLNNLMASK IWTPDTFFHN GKKSVAHNMT MPNKLLRITE
160 170 180 190 200
DGTLLYTMRL TVRAECPMHL EDFPMDAHAC PLKFGSYAYT RAEVVYEWTR
210 220 230 240 250
EPARSVVVAE DGSRLNQYDL LGQTVDSGIV QSSTGEYVVM TTHFHLKRKI
260 270 280 290 300
GYFVIQTYLP CIMTVILSQV SFWLNRESVP ARTVFGVTTV LTMTTLSISA
310 320 330 340 350
RNSLPKVAYA TAMDWFIAVC YAFVFSALIE FATVNYFTKR GYAWDGKSVV
360 370 380 390 400
PEKPKKVKDP LIKKNNTYAP TATSYTPNLA RGDPGLATIA KSATIEPKEV
410 420 430 440 450
KPETKPPEPK KTFNSVSKID RLSRIAFPLL FGIFNLVYWA TYLNREPQLK

APTPHQ
Length:456
Mass (Da):51,802
Last modified:January 17, 2003 - v3
Checksum:iF81EC9ECBE64E94D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti122 – 1221W → R in CAA32874. (PubMed:2465923)Curated
Sequence conflicti128 – 14013Missing in CAA31925. (PubMed:2847710)CuratedAdd
BLAST
Sequence conflicti204 – 2041R → H in CAA31925. (PubMed:2847710)Curated
Sequence conflicti315 – 3151W → WDW in CAA31925. (PubMed:2847710)Curated
Sequence conflicti362 – 3654IKKN → FPNS in CAA31925. (PubMed:2847710)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti112 – 1121R → Q in EIEE19. 1 Publication
VAR_071809
Natural varianti219 – 2191D → N in EIG13; the mutant protein is partially retained in the endoplasmic reticulum and has decreased expression at the plasma membrane; causes decreased current amplitude in response to GABA compared to wild-type and alters receptor gating kinetics including faster desensitization. 1 Publication
VAR_071810
Natural varianti251 – 2511G → S in EIEE19. 1 Publication
VAR_071811
Natural varianti306 – 3061K → T in EIEE19. 1 Publication
VAR_071812
Natural varianti322 – 3221A → D in EJM5. 1 Publication
VAR_013642

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14766 mRNA. Translation: CAA32874.1.
CH471062 Genomic DNA. Translation: EAW61538.1.
CH471062 Genomic DNA. Translation: EAW61539.1.
BC030696 mRNA. Translation: AAH30696.1.
X13584 mRNA. Translation: CAA31925.1.
CCDSiCCDS4357.1.
PIRiA31588.
A60652.
RefSeqiNP_000797.2. NM_000806.5.
NP_001121115.1. NM_001127643.1.
NP_001121116.1. NM_001127644.1.
NP_001121117.1. NM_001127645.1.
NP_001121120.1. NM_001127648.1.
UniGeneiHs.175934.

Genome annotation databases

EnsembliENST00000023897; ENSP00000023897; ENSG00000022355.
ENST00000393943; ENSP00000377517; ENSG00000022355.
ENST00000428797; ENSP00000393097; ENSG00000022355.
ENST00000437025; ENSP00000415441; ENSG00000022355.
GeneIDi2554.
KEGGihsa:2554.
UCSCiuc003lyx.4. human.

Polymorphism databases

DMDMi27808653.

Cross-referencesi

Web resourcesi

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14766 mRNA. Translation: CAA32874.1.
CH471062 Genomic DNA. Translation: EAW61538.1.
CH471062 Genomic DNA. Translation: EAW61539.1.
BC030696 mRNA. Translation: AAH30696.1.
X13584 mRNA. Translation: CAA31925.1.
CCDSiCCDS4357.1.
PIRiA31588.
A60652.
RefSeqiNP_000797.2. NM_000806.5.
NP_001121115.1. NM_001127643.1.
NP_001121116.1. NM_001127644.1.
NP_001121117.1. NM_001127645.1.
NP_001121120.1. NM_001127648.1.
UniGeneiHs.175934.

3D structure databases

ProteinModelPortaliP14867.
SMRiP14867. Positions 46-340.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108828. 3 interactions.
IntActiP14867. 1 interaction.
STRINGi9606.ENSP00000023897.

Chemistry

BindingDBiP14867.
ChEMBLiCHEMBL2095172.
DrugBankiDB00659. Acamprosate.
DB00546. Adinazolam.
DB00404. Alprazolam.
DB01351. Amobarbital.
DB00543. Amoxapine.
DB01352. Aprobarbital.
DB01558. Bromazepam.
DB00237. Butabarbital.
DB00241. Butalbital.
DB01353. Butethal.
DB00475. Chlordiazepoxide.
DB01594. Cinolazepam.
DB00349. Clobazam.
DB01068. Clonazepam.
DB00628. Clorazepate.
DB01559. Clotiazepam.
DB01189. Desflurane.
DB00829. Diazepam.
DB00228. Enflurane.
DB01049. Ergoloid mesylate.
DB01215. Estazolam.
DB00402. Eszopiclone.
DB00898. Ethanol.
DB00189. Ethchlorvynol.
DB00292. Etomidate.
DB01567. Fludiazepam.
DB01205. Flumazenil.
DB00690. Flurazepam.
DB01381. Ginkgo biloba.
DB01437. Glutethimide.
DB00801. Halazepam.
DB01159. Halothane.
DB01354. Heptabarbital.
DB01355. Hexobarbital.
DB00753. Isoflurane.
DB01587. Ketazolam.
DB00186. Lorazepam.
DB00371. Meprobamate.
DB00474. Methohexital.
DB01028. Methoxyflurane.
DB00849. Methylphenobarbital.
DB01107. Methyprylon.
DB00683. Midazolam.
DB01595. Nitrazepam.
DB00334. Olanzapine.
DB00842. Oxazepam.
DB00312. Pentobarbital.
DB01174. Phenobarbital.
DB01588. Prazepam.
DB00794. Primidone.
DB00837. Progabide.
DB00818. Propofol.
DB01589. Quazepam.
DB01346. Quinidine barbiturate.
DB00418. Secobarbital.
DB01236. Sevoflurane.
DB00306. Talbutal.
DB00231. Temazepam.
DB01154. Thiamylal.
DB00599. Thiopental.
DB00273. Topiramate.
DB00897. Triazolam.
DB00962. Zaleplon.
DB00425. Zolpidem.
DB01198. Zopiclone.
GuidetoPHARMACOLOGYi404.

PTM databases

PhosphoSiteiP14867.

Polymorphism databases

DMDMi27808653.

Proteomic databases

PaxDbiP14867.
PRIDEiP14867.

Protocols and materials databases

DNASUi2554.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000023897; ENSP00000023897; ENSG00000022355.
ENST00000393943; ENSP00000377517; ENSG00000022355.
ENST00000428797; ENSP00000393097; ENSG00000022355.
ENST00000437025; ENSP00000415441; ENSG00000022355.
GeneIDi2554.
KEGGihsa:2554.
UCSCiuc003lyx.4. human.

Organism-specific databases

CTDi2554.
GeneCardsiGC05P161206.
HGNCiHGNC:4075. GABRA1.
HPAiCAB022502.
HPA055746.
MIMi137160. gene.
611136. phenotype.
615744. phenotype.
neXtProtiNX_P14867.
Orphaneti64280. Childhood absence epilepsy.
33069. Dravet syndrome.
307. Juvenile myoclonic epilepsy.
PharmGKBiPA28489.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG238757.
GeneTreeiENSGT00760000119010.
HOGENOMiHOG000231337.
HOVERGENiHBG051707.
InParanoidiP14867.
KOiK05175.
OMAiAPNIARD.
OrthoDBiEOG7JX342.
PhylomeDBiP14867.
TreeFamiTF315453.

Enzyme and pathway databases

ReactomeiREACT_24987. GABA A receptor activation.
REACT_25387. Ligand-gated ion channel transport.
REACT_267716. Orphan transporters.

Miscellaneous databases

GeneWikiiGamma-aminobutyric_acid_(GABA)_A_receptor,_alpha_1.
Gamma-aminobutyric_acid_receptor_subunit_alpha-1.
GenomeRNAii2554.
NextBioi10087.
PROiP14867.
SOURCEiSearch...

Gene expression databases

BgeeiP14867.
CleanExiHS_GABRA1.
ExpressionAtlasiP14867. baseline and differential.
GenevestigatoriP14867.

Family and domain databases

Gene3Di2.70.170.10. 1 hit.
InterProiIPR006028. GABAA/Glycine_rcpt.
IPR001390. GABAAa_rcpt.
IPR005431. GABBAa1_rcpt.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
IPR018000. Neurotransmitter_ion_chnl_CS.
[Graphical view]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 2 hits.
[Graphical view]
PRINTSiPR01079. GABAARALPHA.
PR01614. GABAARALPHA1.
PR00253. GABAARECEPTR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits."
    Schofield P.R., Pritchett D.B., Sontheimer H., Kettenmann H., Seeburg P.H.
    FEBS Lett. 244:361-364(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  4. "Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor."
    Garrett K.M., Duman R.S., Saito N., Blume A.J., Vitek M.P., Tallman J.F.
    Biochem. Biophys. Res. Commun. 156:1039-1045(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-365.
    Tissue: Cerebellum.
  5. "Novel alpha1 and gamma2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy."
    Lachance-Touchette P., Brown P., Meloche C., Kinirons P., Lapointe L., Lacasse H., Lortie A., Carmant L., Bedford F., Bowie D., Cossette P.
    Eur. J. Neurosci. 34:237-249(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN EIG13, VARIANT EIG13 ASN-219, CHARACTERIZATION OF VARIANT EIG13 ASN-219.
  6. Cited for: INVOLVEMENT IN EIEE19, VARIANTS EIEE19 GLN-112; SER-251 AND THR-306.
  7. Cited for: VARIANT EJM5 ASP-322.
  8. "A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy."
    Maljevic S., Krampfl K., Cobilanschi J., Tilgen N., Beyer S., Weber Y.G., Schlesinger F., Ursu D., Melzer W., Cossette P., Bufler J., Lerche H., Heils A.
    Ann. Neurol. 59:983-987(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN ECA4.

Entry informationi

Entry nameiGBRA1_HUMAN
AccessioniPrimary (citable) accession number: P14867
Secondary accession number(s): D3DQK6, Q8N629
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 17, 2003
Last modified: January 7, 2015
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.