P14867 (GBRA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gamma-aminobutyric acid receptor subunit alpha-1

Alternative name(s):
GABA(A) receptor subunit alpha-1

Gene names

Name:

GABRA1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	456 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 junction › synapse › postsynaptic 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 process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Disease	Disease mutation Epilepsy
Domain	Signal Transmembrane Transmembrane helix
Ligand	Chloride
Molecular function	Chloride channel Ion channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	gamma-aminobutyric acid signaling pathway Traceable author statement Ref.1. Source: ProtInc ion transmembrane transport Traceable author statement. Source: Reactome synaptic transmission, GABAergic Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GABA-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 456	429	Gamma-aminobutyric acid receptor subunit alpha-1		PRO_0000000428
Regions
	Topological domain	28 – 251	224	Extracellular Probable
	Transmembrane	252 – 273	22	Helical; Probable
	Transmembrane	279 – 300	22	Helical; Probable
	Transmembrane	313 – 334	22	Helical; Probable
	Topological domain	335 – 421	87	Cytoplasmic Probable
	Transmembrane	422 – 443	22	Helical; Probable
Amino acid modifications
	Glycosylation	38	1	N-linked (GlcNAc...) Potential
	Glycosylation	138	1	N-linked (GlcNAc...) Potential
	Disulfide bond	166 ↔ 180		By similarity
Natural variations
	Natural variant	322	1	A → D in EJM5. Ref.5		VAR_013642
Experimental info
	Sequence conflict	122	1	W → R in CAA32874. Ref.1
	Sequence conflict	128 – 140	13	Missing in CAA31925. Ref.4
	Sequence conflict	204	1	R → H in CAA31925. Ref.4
	Sequence conflict	315	1	W → WDW in CAA31925. Ref.4
	Sequence conflict	362 – 365	4	IKKN → FPNS in CAA31925. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P14867 [UniParc]. Last modified January 17, 2003. Version 3. Checksum: F81EC9ECBE64E94D	FASTA	456	51,802
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00295235.
PIR	A31588. A60652.
RefSeq	NP_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.
UniGene	Hs.175934.
3D structure databases
ProteinModelPortal	P14867.
SMR	P14867. Positions 43-341.
ModBase	Search...
Protein-protein interaction databases
IntAct	P14867. 1 interaction.
STRING	9606.ENSP00000023897.
PTM databases
PhosphoSite	P14867.
Polymorphism databases
DMDM	27808653.
Proteomic databases
PaxDb	P14867.
PRIDE	P14867.
Protocols and materials databases
DNASU	2554.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000023897; ENSP00000023897; ENSG00000022355. ENST00000393943; ENSP00000377517; ENSG00000022355. ENST00000420560; ENSP00000408041; ENSG00000022355. ENST00000428797; ENSP00000393097; ENSG00000022355. ENST00000437025; ENSP00000415441; ENSG00000022355. ENST00000444819; ENSP00000414232; ENSG00000022355.
GeneID	2554.
KEGG	hsa:2554.
UCSC	uc003lyx.4. human.
Organism-specific databases
CTD	2554.
GeneCards	GC05P161206.
HGNC	HGNC:4075. GABRA1.
HPA	CAB001963. CAB022502.
MIM	137160. gene. 611136. phenotype.
neXtProt	NX_P14867.
Orphanet	64280. Childhood absence epilepsy. 307. Juvenile myoclonic epilepsy.
PharmGKB	PA28489.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG238757.
HOGENOM	HOG000231337.
HOVERGEN	HBG051707.
InParanoid	P14867.
KO	K05175.
OMA	APNIARD.
OrthoDB	EOG7JX342.
PhylomeDB	P14867.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P14867.
Bgee	P14867.
CleanEx	HS_GABRA1.
Genevestigator	P14867.
Family and domain databases
Gene3D	2.70.170.10. 1 hit.
InterPro	IPR006028. GABAA_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]
PANTHER	PTHR18945. PTHR18945. 1 hit.
Pfam	PF02931. Neur_chan_LBD. 1 hit. PF02932. Neur_chan_memb. 2 hits. [Graphical view]
PRINTS	PR01079. GABAARALPHA. PR01614. GABAARALPHA1. PR00253. GABAARECEPTR. PR00252. NRIONCHANNEL.
SUPFAM	SSF63712. SSF63712. 1 hit. SSF90112. SSF90112. 1 hit.
TIGRFAMs	TIGR00860. LIC. 1 hit.
PROSITE	PS00236. NEUROTR_ION_CHANNEL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P14867.
ChEMBL	CHEMBL2095172.
DrugBank	DB00404. 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.
GeneWiki	Gamma-aminobutyric_acid_(GABA)_A_receptor,_alpha_1. Gamma-aminobutyric_acid_receptor_subunit_alpha-1.
GenomeRNAi	2554.
NextBio	10087.
PRO	P14867.
SOURCE	Search...

Entry information

Entry name

GBRA1_HUMAN

Accession

Primary (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:	November 13, 2013
This is version 153 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.