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P14867 (GBRA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 161. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gamma-aminobutyric acid receptor subunit alpha-1
Alternative name(s):
GABA(A) receptor subunit alpha-1
Gene names
Name:GABRA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length456 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

Subunit structure

Binds UBQLN1 By similarity. Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Interacts with TRAK1 By similarity.

Subcellular location

Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.

Involvement in disease

Epilepsy, childhood absence 4 (ECA4) [MIM:611136]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.6

Juvenile myoclonic epilepsy 5 (EJM5) [MIM:611136]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.5

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. [View classification]

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   DiseaseDisease mutation
Epilepsy
   DomainSignal
Transmembrane
Transmembrane helix
   LigandChloride
   Molecular functionChloride channel
Ion channel
Ligand-gated ion channel
Receptor
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processgamma-aminobutyric acid signaling pathway

Traceable author statement Ref.1. Source: ProtInc

ion transmembrane transport

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement. Source: Reactome

synaptic transmission, GABAergic

Inferred from sequence or structural similarity. Source: BHF-UCL

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

chloride channel complex

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionGABA-A receptor activity

Traceable author statement Ref.1. Source: ProtInc

chloride channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

drug binding

Inferred from sequence or structural similarity. Source: BHF-UCL

extracellular ligand-gated ion channel activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 456429Gamma-aminobutyric acid receptor subunit alpha-1
PRO_0000000428

Regions

Topological domain28 – 251224Extracellular Probable
Transmembrane252 – 27322Helical; Probable
Transmembrane279 – 30022Helical; Probable
Transmembrane313 – 33422Helical; Probable
Topological domain335 – 42187Cytoplasmic Probable
Transmembrane422 – 44322Helical; Probable

Amino acid modifications

Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation1381N-linked (GlcNAc...) Potential
Disulfide bond166 ↔ 180 By similarity

Natural variations

Natural variant3221A → D in EJM5. Ref.5
VAR_013642

Experimental info

Sequence conflict1221W → R in CAA32874. Ref.1
Sequence conflict128 – 14013Missing in CAA31925. Ref.4
Sequence conflict2041R → H in CAA31925. Ref.4
Sequence conflict3151W → WDW in CAA31925. Ref.4
Sequence conflict362 – 3654IKKN → FPNS in CAA31925. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P14867 [UniParc].

Last modified January 17, 2003. Version 3.
Checksum: F81EC9ECBE64E94D

FASTA45651,802
        10         20         30         40         50         60 
MRKSPGLSDC LWAWILLLST LTGRSYGQPS LQDELKDNTT VFTRILDRLL DGYDNRLRPG 

        70         80         90        100        110        120 
LGERVTEVKT DIFVTSFGPV SDHDMEYTID VFFRQSWKDE RLKFKGPMTV LRLNNLMASK 

       130        140        150        160        170        180 
IWTPDTFFHN GKKSVAHNMT MPNKLLRITE DGTLLYTMRL TVRAECPMHL EDFPMDAHAC 

       190        200        210        220        230        240 
PLKFGSYAYT RAEVVYEWTR EPARSVVVAE DGSRLNQYDL LGQTVDSGIV QSSTGEYVVM 

       250        260        270        280        290        300 
TTHFHLKRKI GYFVIQTYLP CIMTVILSQV SFWLNRESVP ARTVFGVTTV LTMTTLSISA 

       310        320        330        340        350        360 
RNSLPKVAYA TAMDWFIAVC YAFVFSALIE FATVNYFTKR GYAWDGKSVV PEKPKKVKDP 

       370        380        390        400        410        420 
LIKKNNTYAP TATSYTPNLA RGDPGLATIA KSATIEPKEV KPETKPPEPK KTFNSVSKID 

       430        440        450 
RLSRIAFPLL FGIFNLVYWA TYLNREPQLK APTPHQ 

« Hide

References

« Hide 'large scale' references
[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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy."
Cossette P., Liu L., Brisebois K., Dong H., Lortie A., Vanasse M., Saint-Hilaire J.-M., Carmant L., Verner A., Lu W.-Y., Tian Wang Y., Rouleau G.A.
Nat. Genet. 31:184-189(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EJM5 ASP-322.
[6]"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.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS4357.1.
PIRA31588.
A60652.
RefSeqNP_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.
UniGeneHs.175934.

3D structure databases

ProteinModelPortalP14867.
SMRP14867. Positions 43-341.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108828. 3 interactions.
IntActP14867. 1 interaction.
STRING9606.ENSP00000023897.

Chemistry

BindingDBP14867.
ChEMBLCHEMBL1962.
DrugBankDB00404. Alprazolam.
DB00237. Butabarbital.
DB00241. Butalbital.
DB01353. Butethal.
DB00475. Chlordiazepoxide.
DB00349. Clobazam.
DB01068. Clonazepam.
DB00628. Clorazepate.
DB01189. Desflurane.
DB00829. Diazepam.
DB00228. Enflurane.
DB00898. Ethanol.
DB00189. Ethchlorvynol.
DB00292. Etomidate.
DB01205. Flumazenil.
DB00690. Flurazepam.
DB00801. Halazepam.
DB01159. Halothane.
DB01355. Hexobarbital.
DB00753. Isoflurane.
DB00186. Lorazepam.
DB00371. Meprobamate.
DB00463. Metharbital.
DB00474. Methohexital.
DB01028. Methoxyflurane.
DB00849. Methylphenobarbital.
DB01107. Methyprylon.
DB00683. Midazolam.
DB01595. Nitrazepam.
DB00842. Oxazepam.
DB00312. Pentobarbital.
DB01174. Phenobarbital.
DB00466. Picrotoxin.
DB01588. Prazepam.
DB00794. Primidone.
DB00837. Progabide.
DB00818. Propofol.
DB01589. Quazepam.
DB00418. Secobarbital.
DB01236. Sevoflurane.
DB00306. Talbutal.
DB01154. Thiamylal.
DB00599. Thiopental.
DB00273. Topiramate.
DB00962. Zaleplon.
DB00425. Zolpidem.
GuidetoPHARMACOLOGY404.

PTM databases

PhosphoSiteP14867.

Polymorphism databases

DMDM27808653.

Proteomic databases

PaxDbP14867.
PRIDEP14867.

Protocols and materials databases

DNASU2554.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000023897; ENSP00000023897; ENSG00000022355.
ENST00000393943; ENSP00000377517; ENSG00000022355.
ENST00000420560; ENSP00000408041; ENSG00000022355.
ENST00000428797; ENSP00000393097; ENSG00000022355.
ENST00000437025; ENSP00000415441; ENSG00000022355.
ENST00000444819; ENSP00000414232; ENSG00000022355.
GeneID2554.
KEGGhsa:2554.
UCSCuc003lyx.4. human.

Organism-specific databases

CTD2554.
GeneCardsGC05P161206.
HGNCHGNC:4075. GABRA1.
HPACAB022502.
HPA055746.
MIM137160. gene.
611136. phenotype.
neXtProtNX_P14867.
Orphanet64280. Childhood absence epilepsy.
307. Juvenile myoclonic epilepsy.
PharmGKBPA28489.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238757.
HOGENOMHOG000231337.
HOVERGENHBG051707.
InParanoidP14867.
KOK05175.
OMAAPNIARD.
OrthoDBEOG7JX342.
PhylomeDBP14867.
TreeFamTF315453.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP14867.
BgeeP14867.
CleanExHS_GABRA1.
GenevestigatorP14867.

Family and domain databases

Gene3D2.70.170.10. 1 hit.
InterProIPR006028. 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]
PANTHERPTHR18945. PTHR18945. 1 hit.
PfamPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 2 hits.
[Graphical view]
PRINTSPR01079. GABAARALPHA.
PR01614. GABAARALPHA1.
PR00253. GABAARECEPTR.
PR00252. NRIONCHANNEL.
SUPFAMSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsTIGR00860. LIC. 1 hit.
PROSITEPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGamma-aminobutyric_acid_(GABA)_A_receptor,_alpha_1.
Gamma-aminobutyric_acid_receptor_subunit_alpha-1.
GenomeRNAi2554.
NextBio10087.
PROP14867.
SOURCESearch...

Entry information

Entry nameGBRA1_HUMAN
AccessionPrimary (citable) accession number: P14867
Secondary accession number(s): D3DQK6, Q8N629
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 17, 2003
Last modified: July 9, 2014
This is version 161 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM