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P47870 (GBRB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. 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 beta-2
Alternative name(s):
GABA(A) receptor subunit beta-2
Gene names
Name:GABRB2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length512 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

Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Binds UBQLN1. Interacts with KCTD8, KCTD12 and KCTD16; this interaction determines the pharmacology and kinetics of the receptor response, the KCTD proteins markedly accelerating the GABA-B response, although to different extents By similarity.

Subcellular location

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

Tissue specificity

Isoform 1 and isoform 2 show reduced expression in schizophrenic brain. Isoform 3 shows increased expression in schizophrenic and bipolar disorder brains while isoform 4 shows reduced expression. Ref.3 Ref.7

Sequence similarities

Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB2 sub-subfamily. [View classification]

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
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcochlea development

Inferred from electronic annotation. Source: Ensembl

gamma-aminobutyric acid signaling pathway

Traceable author statement Ref.1. Source: ProtInc

inner ear receptor cell development

Inferred from electronic annotation. Source: Ensembl

innervation

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Traceable author statement. Source: Reactome

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

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

cytosol

Inferred from electronic annotation. Source: Ensembl

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionGABA-A receptor activity

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

chloride channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

inhibitory extracellular ligand-gated ion channel activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P47870-2)

Also known as: Long; Beta-2L;

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: P47870-1)

Also known as: Short; Beta-2S;

The sequence of this isoform differs from the canonical sequence as follows:
     360-397: Missing.
Isoform 3 (identifier: P47870-3)

Also known as: Beta-2S1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-63: Missing.
     360-376: IFYKDIKQNGTQYRSLW → VNSEGKPSLLLKLMEEC
     377-512: Missing.
Isoform 4 (identifier: P47870-4)

Also known as: Beta-2S2;

The sequence of this isoform differs from the canonical sequence as follows:
     360-397: Missing.
     410-410: E → D
     411-512: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 By similarity
Chain26 – 512487Gamma-aminobutyric acid receptor subunit beta-2
PRO_0000000459

Regions

Topological domain26 – 244219Extracellular Probable
Transmembrane245 – 26622Helical; Probable
Transmembrane270 – 29223Helical; Probable
Transmembrane304 – 32623Helical; Probable
Topological domain327 – 489163Cytoplasmic Probable
Transmembrane490 – 51122Helical; Probable

Amino acid modifications

Modified residue4411Phosphotyrosine By similarity
Glycosylation321N-linked (GlcNAc...) Potential
Glycosylation1041N-linked (GlcNAc...) Potential
Glycosylation1731N-linked (GlcNAc...) Potential
Disulfide bond160 ↔ 174 By similarity
Cross-link45Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.8

Natural variations

Alternative sequence1 – 6363Missing in isoform 3.
VSP_038823
Alternative sequence360 – 39738Missing in isoform 2 and isoform 4.
VSP_038825
Alternative sequence360 – 37617IFYKD…YRSLW → VNSEGKPSLLLKLMEEC in isoform 3.
VSP_038824
Alternative sequence377 – 512136Missing in isoform 3.
VSP_038828
Alternative sequence4101E → D in isoform 4.
VSP_038826
Alternative sequence411 – 512102Missing in isoform 4.
VSP_038827

Experimental info

Mutagenesis3891T → A: Displays reduced current rundown following repeated receptor activation. Ref.3
Sequence conflict3361Q → L in BAF82419. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) (Beta-2L) [UniParc].

Last modified March 23, 2010. Version 2.
Checksum: C390A0C92815DD89

FASTA51259,150
        10         20         30         40         50         60 
MWRVRKRGYF GIWSFPLIIA AVCAQSVNDP SNMSLVKETV DRLLKGYDIR LRPDFGGPPV 

        70         80         90        100        110        120 
AVGMNIDIAS IDMVSEVNMD YTLTMYFQQA WRDKRLSYNV IPLNLTLDNR VADQLWVPDT 

       130        140        150        160        170        180 
YFLNDKKSFV HGVTVKNRMI RLHPDGTVLY GLRITTTAAC MMDLRRYPLD EQNCTLEIES 

       190        200        210        220        230        240 
YGYTTDDIEF YWRGDDNAVT GVTKIELPQF SIVDYKLITK KVVFSTGSYP RLSLSFKLKR 

       250        260        270        280        290        300 
NIGYFILQTY MPSILITILS WVSFWINYDA SAARVALGIT TVLTMTTINT HLRETLPKIP 

       310        320        330        340        350        360 
YVKAIDMYLM GCFVFVFMAL LEYALVNYIF FGRGPQRQKK AAEKAASANN EKMRLDVNKI 

       370        380        390        400        410        420 
FYKDIKQNGT QYRSLWDPTG NLSPTRRTTN YDFSLYTMDP HENILLSTLE IKNEMATSEA 

       430        440        450        460        470        480 
VMGLGDPRST MLAYDASSIQ YRKAGLPRHS FGRNALERHV AQKKSRLRRR ASQLKITIPD 

       490        500        510 
LTDVNAIDRW SRIFFPVVFS FFNIVYWLYY VN 

« Hide

Isoform 2 (Short) (Beta-2S) [UniParc].

Checksum: 1390A982EB616332
Show »

FASTA47454,606
Isoform 3 (Beta-2S1) [UniParc].

Checksum: 5914B38B94A611B2
Show »

FASTA31336,086
Isoform 4 (Beta-2S2) [UniParc].

Checksum: 0550692E2DD2662C
Show »

FASTA37242,741

References

« Hide 'large scale' references
[1]"Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors."
Hadingham K.L., Wingrove P.B., Wafford K.A., Bain C., Kemp J.A., Palmer K.J., Wilson A.W., Wilcox A.S., Sikela J.M., Ragan C.I.
Mol. Pharmacol. 44:1211-1218(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Brain.
[2]"Cloning, sequence analysis and expression of two forms of mRNA coding for the human beta 2 subunit of the GABAA receptor."
McKinley D.D., Lennon D.J., Carter D.B.
Brain Res. Mol. Brain Res. 28:175-179(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain.
[3]"Alternative-splicing in the exon-10 region of GABA(A) receptor beta(2) subunit gene: relationships between novel isoforms and psychotic disorders."
Zhao C., Xu Z., Wang F., Chen J., Ng S.K., Wong P.W., Yu Z., Pun F.W., Ren L., Lo W.S., Tsang S.Y., Xue H.
PLoS ONE 4:E6977-E6977(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), TISSUE SPECIFICITY, MUTAGENESIS OF THR-389, ALTERNATIVE SPLICING.
Tissue: Brain.
[4]"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] (ISOFORM 2).
Tissue: Brain.
[5]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].
[6]"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] (ISOFORM 2).
[7]"Two isoforms of GABA(A) receptor beta2 subunit with different electrophysiological properties: Differential expression and genotypical correlations in schizophrenia."
Zhao C., Xu Z., Chen J., Yu Z., Tong K.L., Lo W.S., Pun F.W., Ng S.K., Tsang S.Y., Xue H.
Mol. Psychiatry 11:1092-1105(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry."
Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.
Proteomics 7:868-874(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-45.
Tissue: Mammary cancer.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S67368 mRNA. Translation: AAB29370.1.
S77554 mRNA. Translation: AAB33983.1.
S77553 mRNA. Translation: AAB33982.1.
GU086163 mRNA. Translation: ACY69094.1.
GU086164 mRNA. Translation: ACY69095.1.
AK289730 mRNA. Translation: BAF82419.1.
AK289815 mRNA. Translation: BAF82504.1.
CH471062 Genomic DNA. Translation: EAW61543.1.
BC099705 mRNA. Translation: AAH99705.1.
BC099719 mRNA. Translation: AAH99719.1.
BC105639 mRNA. Translation: AAI05640.1.
PIRI52656.
RefSeqNP_000804.1. NM_000813.2.
NP_068711.1. NM_021911.2.
UniGeneHs.303527.

3D structure databases

ProteinModelPortalP47870.
SMRP47870. Positions 46-331.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108835. 4 interactions.
IntActP47870. 1 interaction.
MINTMINT-268409.
STRING9606.ENSP00000274547.

Chemistry

BindingDBP47870.
ChEMBLCHEMBL2093872.
DrugBankDB00189. Ethchlorvynol.
DB00690. Flurazepam.
DB00186. Lorazepam.
DB00683. Midazolam.
GuidetoPHARMACOLOGY411.

Protein family/group databases

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

PTM databases

PhosphoSiteP47870.

Polymorphism databases

DMDM292495010.

Proteomic databases

PaxDbP47870.
PeptideAtlasP47870.
PRIDEP47870.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000274547; ENSP00000274547; ENSG00000145864. [P47870-2]
ENST00000353437; ENSP00000274546; ENSG00000145864. [P47870-1]
ENST00000393959; ENSP00000377531; ENSG00000145864. [P47870-2]
ENST00000520240; ENSP00000429320; ENSG00000145864. [P47870-1]
GeneID2561.
KEGGhsa:2561.
UCSCuc003lyr.1. human. [P47870-1]
uc003lys.1. human. [P47870-2]
uc021yhg.1. human. [P47870-3]

Organism-specific databases

CTD2561.
GeneCardsGC05M160715.
HGNCHGNC:4082. GABRB2.
HPACAB001964.
MIM600232. gene.
neXtProtNX_P47870.
PharmGKBPA28496.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG77438.
HOVERGENHBG051707.
KOK05181.
OMATSSIQYR.
OrthoDBEOG712TVZ.
PhylomeDBP47870.
TreeFamTF315453.

Enzyme and pathway databases

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

Gene expression databases

ArrayExpressP47870.
BgeeP47870.
CleanExHS_GABRB2.
GenevestigatorP47870.

Family and domain databases

Gene3D2.70.170.10. 1 hit.
InterProIPR006028. GABAA_rcpt.
IPR002289. GABAAb_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. 1 hit.
[Graphical view]
PRINTSPR01160. GABAARBETA.
PR00253. GABAARECEPTR.
PR00252. NRIONCHANNEL.
SUPFAMSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 2 hits.
TIGRFAMsTIGR00860. LIC. 1 hit.
PROSITEPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGABRB2.
GenomeRNAi2561.
NextBio10115.
PROP47870.
SOURCESearch...

Entry information

Entry nameGBRB2_HUMAN
AccessionPrimary (citable) accession number: P47870
Secondary accession number(s): A8K115 expand/collapse secondary AC list , A8K1A0, D1LYT0, D1LYT1, Q16323, Q4FZB2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: March 23, 2010
Last modified: April 16, 2014
This is version 133 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 5

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