P47870 (GBRB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

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

Gene names

Name:

GABRB2

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	512 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	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 junction › synapse › postsynaptic 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 process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Ligand	Chloride
Molecular function	Chloride channel Ion channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cochlea development Inferred from electronic annotation. Source: Compara gamma-aminobutyric acid signaling pathway Traceable author statement Ref.1. Source: ProtInc inner ear receptor cell development Inferred from electronic annotation. Source: Compara innervation Inferred from electronic annotation. Source: Compara ion transmembrane transport Traceable author statement. Source: Reactome sensory perception of sound Inferred from electronic annotation. Source: Compara 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 cytosol Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GABA-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: Compara
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	By similarity
	Chain	26 – 512	487	Gamma-aminobutyric acid receptor subunit beta-2		PRO_0000000459
Regions
	Topological domain	26 – 244	219	Extracellular Probable
	Transmembrane	245 – 266	22	Helical; Probable
	Transmembrane	270 – 292	23	Helical; Probable
	Transmembrane	304 – 326	23	Helical; Probable
	Topological domain	327 – 489	163	Cytoplasmic Probable
	Transmembrane	490 – 511	22	Helical; Probable
Amino acid modifications
	Modified residue	434	1	Phosphotyrosine By similarity
	Modified residue	441	1	Phosphotyrosine By similarity
	Glycosylation	32	1	N-linked (GlcNAc...) Potential
	Glycosylation	104	1	N-linked (GlcNAc...) Potential
	Glycosylation	173	1	N-linked (GlcNAc...) Potential
	Disulfide bond	160 ↔ 174		By similarity
	Cross-link	45		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.8
Natural variations
	Alternative sequence	1 – 63	63	Missing in isoform 3.		VSP_038823
	Alternative sequence	360 – 397	38	Missing in isoform 2 and isoform 4.		VSP_038825
	Alternative sequence	360 – 376	17	IFYKD…YRSLW → VNSEGKPSLLLKLMEEC in isoform 3.		VSP_038824
	Alternative sequence	377 – 512	136	Missing in isoform 3.		VSP_038828
	Alternative sequence	410	1	E → D in isoform 4.		VSP_038826
	Alternative sequence	411 – 512	102	Missing in isoform 4.		VSP_038827
Experimental info
	Mutagenesis	389	1	T → A: Displays reduced current rundown following repeated receptor activation. Ref.3
	Sequence conflict	336	1	Q → L in BAF82419. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) (Beta-2L) [UniParc]. Last modified March 23, 2010. Version 2. Checksum: C390A0C92815DD89	FASTA	512	59,150
	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
	Isoform 2 (Short) (Beta-2S) [UniParc]. Checksum: 1390A982EB616332	FASTA	474	54,606
	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 EKMRLDVNKM 370 380 390 400 410 420 DPHENILLST LEIKNEMATS EAVMGLGDPR STMLAYDASS IQYRKAGLPR HSFGRNALER 430 440 450 460 470 HVAQKKSRLR RRASQLKITI PDLTDVNAID RWSRIFFPVV FSFFNIVYWL YYVN
	Isoform 3 (Beta-2S1) [UniParc]. Checksum: 5914B38B94A611B2	FASTA	313	36,086
	10 20 30 40 50 60 MNIDIASIDM VSEVNMDYTL TMYFQQAWRD KRLSYNVIPL NLTLDNRVAD QLWVPDTYFL 70 80 90 100 110 120 NDKKSFVHGV TVKNRMIRLH PDGTVLYGLR ITTTAACMMD LRRYPLDEQN CTLEIESYGY 130 140 150 160 170 180 TTDDIEFYWR GDDNAVTGVT KIELPQFSIV DYKLITKKVV FSTGSYPRLS LSFKLKRNIG 190 200 210 220 230 240 YFILQTYMPS ILITILSWVS FWINYDASAA RVALGITTVL TMTTINTHLR ETLPKIPYVK 250 260 270 280 290 300 AIDMYLMGCF VFVFMALLEY ALVNYIFFGR GPQRQKKAAE KAASANNEKM RLDVNKVNSE 310 GKPSLLLKLM EEC
	Isoform 4 (Beta-2S2) [UniParc]. Checksum: 0550692E2DD2662C	FASTA	372	42,741
	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 EKMRLDVNKM 370 DPHENILLST LD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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.
IPI	IPI00026639. IPI00216394. IPI00954901. IPI00955985.
PIR	I52656.
RefSeq	NP_000804.1. NM_000813.2. NP_068711.1. NM_021911.2.
UniGene	Hs.303527.
3D structure databases
ProteinModelPortal	P47870.
SMR	P47870. Positions 46-329.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-268409.
STRING	9606.ENSP00000274547.
Protein family/group databases
TCDB	1.A.9.5.2. neurotransmitter receptor, cys loop, ligand-gated ion channel (LIC) family.
PTM databases
PhosphoSite	P47870.
Polymorphism databases
DMDM	292495010.
Proteomic databases
PaxDb	P47870.
PeptideAtlas	P47870.
PRIDE	P47870.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000274547; ENSP00000274547; ENSG00000145864. ENST00000353437; ENSP00000274546; ENSG00000145864. ENST00000393959; ENSP00000377531; ENSG00000145864. ENST00000520240; ENSP00000429320; ENSG00000145864.
GeneID	2561.
KEGG	hsa:2561.
UCSC	uc003lyr.1. human. uc003lys.1. human. uc021yhg.1. human.
Organism-specific databases
CTD	2561.
GeneCards	GC05M160715.
HGNC	HGNC:4082. GABRB2.
HPA	CAB001964.
MIM	600232. gene.
neXtProt	NX_P47870.
PharmGKB	PA28496.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG77438.
HOVERGEN	HBG051707.
KO	K05181.
OMA	TSSIQYR.
OrthoDB	EOG45756F.
PhylomeDB	P47870.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P47870.
Bgee	P47870.
CleanEx	HS_GABRB2.
Genevestigator	P47870.
GermOnline	ENSG00000145864. Homo sapiens.
Family and domain databases
Gene3D	2.70.170.10. 1 hit.
InterPro	IPR006028. 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]
PANTHER	PTHR18945. PTHR18945. 1 hit.
Pfam	PF02931. Neur_chan_LBD. 1 hit. PF02932. Neur_chan_memb. 1 hit. [Graphical view]
PRINTS	PR01160. GABAARBETA. 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	P47870.
ChEMBL	CHEMBL1920.
DrugBank	DB00189. Ethchlorvynol. DB00690. Flurazepam. DB00186. Lorazepam. DB00683. Midazolam.
GenomeRNAi	2561.
NextBio	10115.
SOURCE	Search...

Entry information

Entry name

GBRB2_HUMAN

Accession

Primary (citable) accession number: P47870
Secondary accession number(s): A8K115 , A8K1A0, D1LYT0, D1LYT1, Q16323, Q4FZB2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	March 23, 2010
Last modified:	May 1, 2013
This is version 124 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.