P47869 (GBRA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gamma-aminobutyric acid receptor subunit alpha-2

Alternative name(s):
GABA(A) receptor subunit alpha-2

Gene names

Name:

GABRA2

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 › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	451 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.
Subcellular location	Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.
Polymorphism	Genetic variations in GABRA2 determine the genetic susceptibility to alcoholism [MIM:103780].
Sequence similarities	Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA2 sub-subfamily. [View classification]
Sequence caution	The sequence BAD92532.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
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 Inferred from mutant phenotype Ref.1. Source: UniProtKB ion transmembrane transport Traceable author statement. Source: Reactome neurotransmitter transport Inferred from mutant phenotype Ref.1. Source: UniProtKB regulation of neurotransmitter levels Inferred from mutant phenotype Ref.1. Source: UniProtKB
Cellular_component	axon Inferred from electronic annotation. Source: Compara cell junction Inferred from electronic annotation. Source: UniProtKB-KW chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW integral to synaptic vesicle membrane Inferred from direct assay Ref.1. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GABA-A receptor activity Inferred from electronic annotation. Source: InterPro benzodiazepine receptor activity Inferred from mutant phenotype Ref.1. Source: UniProtKB chloride channel activity Inferred from electronic annotation. Source: UniProtKB-KW 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 – 28	28	Potential
	Chain	29 – 451	423	Gamma-aminobutyric acid receptor subunit alpha-2		PRO_0000000433
Regions
	Topological domain	29 – 251	223	Extracellular Probable
	Transmembrane	252 – 273	22	Helical; Probable
	Transmembrane	279 – 300	22	Helical; Probable
	Transmembrane	313 – 334	22	Helical; Probable
	Topological domain	335 – 419	85	Cytoplasmic Probable
	Transmembrane	420 – 441	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
Experimental info
	Sequence conflict	10 – 11	2	MQ → IE in AAB27278. Ref.1
	Sequence conflict	343	1	A → T in AAB27278. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P47869 [UniParc]. Last modified February 20, 2007. Version 2. Checksum: 43F9F708B5A00FFD	FASTA	451	51,326
	10 20 30 40 50 60 MKTKLNIYNM QFLLFVFLVW DPARLVLANI QEDEAKNNIT IFTRILDRLL DGYDNRLRPG 70 80 90 100 110 120 LGDSITEVFT NIYVTSFGPV SDTDMEYTID VFFRQKWKDE RLKFKGPMNI LRLNNLMASK 130 140 150 160 170 180 IWTPDTFFHN GKKSVAHNMT MPNKLLRIQD DGTLLYTMRL TVQAECPMHL EDFPMDAHSC 190 200 210 220 230 240 PLKFGSYAYT TSEVTYIWTY NASDSVQVAP DGSRLNQYDL LGQSIGKETI KSSTGEYTVM 250 260 270 280 290 300 TAHFHLKRKI GYFVIQTYLP CIMTVILSQV SFWLNRESVP ARTVFGVTTV LTMTTLSISA 310 320 330 340 350 360 RNSLPKVAYA TAMDWFIAVC YAFVFSALIE FATVNYFTKR GWAWDGKSVV NDKKKEKASV 370 380 390 400 410 420 MIQNNAYAVA VANYAPNLSK DPVLSTISKS ATTPEPNKKP ENKPAEAKKT FNSVSKIDRM 430 440 450 SRIVFPVLFG TFNLVYWATY LNREPVLGVS P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors." Hadingham K.L., Wingrove P., le Bourdelles B., Palmer K.J., Ragan C.I., Whiting P.J. Mol. Pharmacol. 43:970-975(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations." Edenberg H.J., Dick D.M., Xuei X., Tian H., Almasy L., Bauer L.O., Crowe R.R., Goate A., Hesselbrock V., Jones K., Kwon J., Li T.-K., Nurnberger J.I. Jr., O'Connor S.J., Reich T., Rice J., Schuckit M.A., Porjesz B., Foroud T., Begleiter H. Am. J. Hum. Genet. 74:705-714(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Cross-references

Sequence databases
EMBL GenBank DDBJ	S62907 mRNA. Translation: AAB27278.1. AB209295 mRNA. Translation: BAD92532.1. Different initiation.
IPI	IPI00026631.
PIR	I57947.
RefSeq	NP_000798.2. NM_000807.2. NP_001107647.1. NM_001114175.1.
UniGene	Hs.116250.
3D structure databases
ProteinModelPortal	P47869.
ModBase	Search...
Protein-protein interaction databases
IntAct	P47869. 1 interaction.
STRING	9606.ENSP00000348897.
Protein family/group databases
TCDB	1.A.9.5.2. neurotransmitter receptor, cys loop, ligand-gated ion channel (LIC) family.
PTM databases
PhosphoSite	P47869.
Polymorphism databases
DMDM	126302547.
Proteomic databases
PaxDb	P47869.
PRIDE	P47869.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000356504; ENSP00000348897; ENSG00000151834. ENST00000381620; ENSP00000371033; ENSG00000151834. ENST00000510861; ENSP00000421828; ENSG00000151834. ENST00000514090; ENSP00000421300; ENSG00000151834.
GeneID	2555.
KEGG	hsa:2555.
UCSC	uc003gxc.3. human.
Organism-specific databases
CTD	2555.
GeneCards	GC04M046167.
HGNC	HGNC:4076. GABRA2.
HPA	HPA014261.
MIM	103780. phenotype. 137140. gene.
neXtProt	NX_P47869.
PharmGKB	PA28490.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG238757.
HOGENOM	HOG000231337.
HOVERGEN	HBG051707.
InParanoid	P47869.
KO	K05175.
OrthoDB	EOG4ZS935.
PhylomeDB	P47869.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P47869.
Bgee	P47869.
CleanEx	HS_GABRA2.
Genevestigator	P47869.
GermOnline	ENSG00000151834. Homo sapiens.
Family and domain databases
Gene3D	2.70.170.10. 1 hit.
InterPro	IPR006028. GABAA_rcpt. IPR001390. GABAAa_rcpt. IPR005432. GABBAa2_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. PR01615. GABAARALPHA2. PR00253. GABAARECEPTR. PR00252. NRIONCHANNEL.
SUPFAM	SSF90112. Neu_channel_TM. 1 hit. SSF63712. Neur_chan_LBD. 1 hit.
TIGRFAMs	TIGR00860. LIC. 1 hit.
PROSITE	PS00236. NEUROTR_ION_CHANNEL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P47869.
ChEMBL	CHEMBL4956.
ChiTaRS	GABRA2. human.
DrugBank	DB00404. Alprazolam. DB01558. Bromazepam. DB00829. Diazepam. DB00189. Ethchlorvynol. DB01567. Fludiazepam. DB01544. Flunitrazepam. DB00690. Flurazepam. DB00186. Lorazepam. DB00371. Meprobamate. DB00683. Midazolam.
GenomeRNAi	2555.
NextBio	10091.
SOURCE	Search...

Entry information

Entry name

GBRA2_HUMAN

Accession

Primary (citable) accession number: P47869
Secondary accession number(s): Q59G14

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 20, 2007
Last modified:	May 1, 2013
This is version 125 of the entry and version 2 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.