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P47869 (GBRA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gamma-aminobutyric acid receptor subunit alpha-2
Alternative name(s):
GABA(A) receptor subunit alpha-2
Gene names
Name:GABRA2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length451 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 junctionsynapsepostsynaptic 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 processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
   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

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

synaptic transmission

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

chloride channel complex

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of 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_functionGABA-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...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P47869-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P47869-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: MKTKLNIYNM...SFGPVSDTDM → MRLKITLPSLREFLTDFWMVTIIGLDQDWE
     353-353: K → KSPSIKAEGITLTYNSVKAILQGAKLIWSKYIAFSWPSLFQEKTLEYLEKWMDCLTFKQSS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 451423Gamma-aminobutyric acid receptor subunit alpha-2
PRO_0000000433

Regions

Topological domain29 – 251223Extracellular Probable
Transmembrane252 – 27322Helical; Probable
Transmembrane279 – 30022Helical; Probable
Transmembrane313 – 33422Helical; Probable
Topological domain335 – 41985Cytoplasmic Probable
Transmembrane420 – 44122Helical; Probable

Amino acid modifications

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

Natural variations

Alternative sequence1 – 8585MKTKL…SDTDM → MRLKITLPSLREFLTDFWMV TIIGLDQDWE in isoform 2.
VSP_054277
Alternative sequence3531K → KSPSIKAEGITLTYNSVKAI LQGAKLIWSKYIAFSWPSLF QEKTLEYLEKWMDCLTFKQS S in isoform 2.
VSP_054278

Experimental info

Sequence conflict10 – 112MQ → IE in AAB27278. Ref.1
Sequence conflict3431A → T in AAB27278. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 20, 2007. Version 2.
Checksum: 43F9F708B5A00FFD

FASTA45151,326
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 040306CCB7836206
Show »

FASTA45652,064

References

« Hide '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] (ISOFORM 1).
Tissue: Brain.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Amygdala, Brain and Cerebellum.
[4]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] (ISOFORM 1).
Tissue: Brain.
[5]Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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.
AK125179 mRNA. Translation: BAG54159.1.
AK289662 mRNA. Translation: BAF82351.1.
AK293466 mRNA. Translation: BAH11514.1.
AB209295 mRNA. Translation: BAD92532.1. Different initiation.
AC084352 Genomic DNA. No translation available.
AC093745 Genomic DNA. No translation available.
AC095060 Genomic DNA. No translation available.
AC104072 Genomic DNA. No translation available.
CH471069 Genomic DNA. Translation: EAW93022.1.
CCDSCCDS3471.1.
PIRI57947.
RefSeqNP_000798.2. NM_000807.2. [P47869-1]
NP_001107647.1. NM_001114175.1. [P47869-1]
NP_001273756.1. NM_001286827.1. [P47869-2]
XP_006714065.1. XM_006714002.1. [P47869-1]
UniGeneHs.116250.

3D structure databases

ProteinModelPortalP47869.
SMRP47869. Positions 43-359.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108829. 2 interactions.
IntActP47869. 1 interaction.
STRING9606.ENSP00000348897.

Chemistry

BindingDBP47869.
ChEMBLCHEMBL2094130.
DrugBankDB00404. Alprazolam.
DB01558. Bromazepam.
DB00829. Diazepam.
DB00189. Ethchlorvynol.
DB01567. Fludiazepam.
DB01544. Flunitrazepam.
DB00690. Flurazepam.
DB00186. Lorazepam.
DB00371. Meprobamate.
DB00683. Midazolam.
GuidetoPHARMACOLOGY405.

Protein family/group databases

TCDB1.A.9.5.2. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

PTM databases

PhosphoSiteP47869.

Polymorphism databases

DMDM126302547.

Proteomic databases

PaxDbP47869.
PRIDEP47869.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356504; ENSP00000348897; ENSG00000151834.
ENST00000381620; ENSP00000371033; ENSG00000151834.
ENST00000510861; ENSP00000421828; ENSG00000151834.
ENST00000514090; ENSP00000421300; ENSG00000151834.
ENST00000540012; ENSP00000444409; ENSG00000151834.
GeneID2555.
KEGGhsa:2555.
UCSCuc003gxc.3. human. [P47869-1]

Organism-specific databases

CTD2555.
GeneCardsGC04M046167.
HGNCHGNC:4076. GABRA2.
HPAHPA014261.
MIM103780. phenotype.
137140. gene.
neXtProtNX_P47869.
PharmGKBPA28490.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238757.
HOGENOMHOG000231337.
HOVERGENHBG051707.
InParanoidP47869.
KOK05175.
OrthoDBEOG7JX342.
PhylomeDBP47869.
TreeFamTF315453.

Enzyme and pathway databases

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

Gene expression databases

ArrayExpressP47869.
BgeeP47869.
CleanExHS_GABRA2.
GenevestigatorP47869.

Family and domain databases

Gene3D2.70.170.10. 1 hit.
InterProIPR006028. GABAA/Glycine_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]
PANTHERPTHR18945. PTHR18945. 1 hit.
PfamPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 2 hits.
[Graphical view]
PRINTSPR01079. GABAARALPHA.
PR01615. GABAARALPHA2.
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

ChiTaRSGABRA2. human.
GeneWikiGABRA2.
GenomeRNAi2555.
NextBio10091.
PROP47869.
SOURCESearch...

Entry information

Entry nameGBRA2_HUMAN
AccessionPrimary (citable) accession number: P47869
Secondary accession number(s): A8K0U7, B7Z1H8, Q59G14
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 20, 2007
Last modified: July 9, 2014
This is version 137 of the entry and version 2 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 chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM