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P28472 (GBRB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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-3
Alternative name(s):
GABA(A) receptor subunit beta-3
Gene names
Name:GABRB3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length473 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

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

GABRB3 variants may be associated with insomnia, a condition of inability to initiate or maintain sleep [MIM:137192].

Involvement in disease

Epilepsy, childhood absence 5 (ECA5) [MIM:612269]: 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.9

Sequence similarities

Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB3 sub-subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Epilepsy
   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_processcochlea development

Inferred from electronic annotation. Source: Ensembl

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

signal transduction

Traceable author statement Ref.1. Source: ProtInc

synaptic transmission

Traceable author statement. Source: Reactome

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

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

Traceable author statement Ref.1. Source: ProtInc

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 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Isoforms differ in their signal region.
Isoform 1 (identifier: P28472-1)

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: P28472-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MWGLAGGRLFGIFSAPVLVAVVCCAQ → MCSGLLELLLPIWLSWTLGTRGSEPR
Isoform 3 (identifier: P28472-3)

The sequence of this isoform differs from the canonical sequence as follows:
     3-80: GLAGGRLFGI...SIDMVSEVNM → ATYQTEE
Note: No experimental confirmation available.
Isoform 4 (identifier: P28472-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 473448Gamma-aminobutyric acid receptor subunit beta-3
PRO_0000000462

Regions

Topological domain26 – 245220Extracellular Probable
Transmembrane246 – 26722Helical; Probable
Transmembrane271 – 29323Helical; Probable
Transmembrane305 – 32723Helical; Probable
Topological domain328 – 450123Cytoplasmic Probable
Transmembrane451 – 47222Helical; Probable

Amino acid modifications

Glycosylation331N-linked (GlcNAc...) Potential
Glycosylation1051N-linked (GlcNAc...) Potential
Glycosylation1741N-linked (GlcNAc...) Potential
Disulfide bond161 ↔ 175 By similarity

Natural variations

Alternative sequence1 – 8585Missing in isoform 4.
VSP_046676
Alternative sequence1 – 2626MWGLA…VCCAQ → MCSGLLELLLPIWLSWTLGT RGSEPR in isoform 2.
VSP_000088
Alternative sequence3 – 8078GLAGG…SEVNM → ATYQTEE in isoform 3.
VSP_046126
Natural variant321G → R in ECA5; the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. Ref.9
VAR_047957
Natural variant1731Q → L. Ref.5
Corresponds to variant rs17850679 [ dbSNP | Ensembl ].
VAR_047958
Natural variant2171R → H Found in a subject suffering from insomnia; functional analysis reveals a slower rate of the fast phase of desensitization compared with alpha1beta3gamma2S GABA(A) receptors; current deactivation is faster in the mutated receptors. Ref.8
VAR_047959
Isoform 2:
Natural variant111P → S in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type.
Corresponds to variant rs25409 [ dbSNP | Ensembl ].
Natural variant151S → F in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type.

Experimental info

Sequence conflict971L → H in BAH13811. Ref.2
Sequence conflict1931W → R in BAH11997. Ref.2

Sequences

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

Last modified December 1, 1992. Version 1.
Checksum: D63597F7FBC69E71

FASTA47354,116
        10         20         30         40         50         60 
MWGLAGGRLF GIFSAPVLVA VVCCAQSVND PGNMSFVKET VDKLLKGYDI RLRPDFGGPP 

        70         80         90        100        110        120 
VCVGMNIDIA SIDMVSEVNM DYTLTMYFQQ YWRDKRLAYS GIPLNLTLDN RVADQLWVPD 

       130        140        150        160        170        180 
TYFLNDKKSF VHGVTVKNRM IRLHPDGTVL YGLRITTTAA CMMDLRRYPL DEQNCTLEIE 

       190        200        210        220        230        240 
SYGYTTDDIE FYWRGGDKAV TGVERIELPQ FSIVEHRLVS RNVVFATGAY PRLSLSFRLK 

       250        260        270        280        290        300 
RNIGYFILQT YMPSILITIL SWVSFWINYD ASAARVALGI TTVLTMTTIN THLRETLPKI 

       310        320        330        340        350        360 
PYVKAIDMYL MGCFVFVFLA LLEYAFVNYI FFGRGPQRQK KLAEKTAKAK NDRSKSESNR 

       370        380        390        400        410        420 
VDAHGNILLT SLEVHNEMNE VSGGIGDTRN SAISFDNSGI QYRKQSMPRE GHGRFLGDRS 

       430        440        450        460        470 
LPHKKTHLRR RSSQLKIKIP DLTDVNAIDR WSRIVFPFTF SLFNLVYWLY YVN 

« Hide

Isoform 2 [UniParc].

Checksum: 3A7F9A0EB3537D5E
Show »

FASTA47354,379
Isoform 3 [UniParc].

Checksum: 5B5BB0E56D41435A
Show »

FASTA40246,740
Isoform 4 [UniParc].

Checksum: 6646C270C24396F2
Show »

FASTA38845,006

References

« Hide 'large scale' references
[1]"The GABAA receptor beta 3 subunit gene: characterization of a human cDNA from chromosome 15q11q13 and mapping to a region of conserved synteny on mouse chromosome 7."
Wagstaff J., Chaillet J.R., Lalande M.
Genomics 11:1071-1078(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"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 3 AND 4).
Tissue: Brain and Testis.
[3]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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].
[5]"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 1), VARIANT LEU-173.
Tissue: Eye.
[6]"A strong promoter element is located between alternative exons of a gene encoding the human gamma-aminobutyric acid-type A receptor beta 3 subunit (GABRB3)."
Kirkness E.F., Fraser C.M.
J. Biol. Chem. 268:4420-4428(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-80 (ISOFORMS 1 AND 2).
Tissue: Fibroblast.
[7]"Localization of the gene encoding the GABAA receptor beta 3 subunit to the Angelman/Prader-Willi region of human chromosome 15."
Wagstaff J., Knoll J.H.M., Fleming J., Kirkness E.F., Martin-Gallardo A., Greenberg F., Graham J.M. Jr., Menninger J., Ward D., Venter J.C., Lalande M.
Am. J. Hum. Genet. 49:330-337(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 81-153 AND 183-227.
[8]"Functional characterization of the new human GABA(A) receptor mutation beta3(R192H)."
Buhr A., Bianchi M.T., Baur R., Courtet P., Pignay V., Boulenger J.P., Gallati S., Hinkle D.J., Macdonald R.L., Sigel E.
Hum. Genet. 111:154-160(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-217, CHARACTERIZATION OF VARIANT HIS-217.
[9]"Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy."
Tanaka M., Olsen R.W., Medina M.T., Schwartz E., Alonso M.E., Duron R.M., Castro-Ortega R., Martinez-Juarez I.E., Pascual-Castroviejo I., Machado-Salas J., Silva R., Bailey J.N., Bai D., Ochoa A., Jara-Prado A., Pineda G., Macdonald R.L., Delgado-Escueta A.V.
Am. J. Hum. Genet. 82:1249-1261(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ECA5 ARG-32, VARIANTS ECA5 SER-11 AND PHE-15 (ISOFORM 2).
+Additional computationally mapped references.

Web resources

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M82919 mRNA. Translation: AAA52511.1.
AK295167 mRNA. Translation: BAH11997.1.
AK302822 mRNA. Translation: BAH13811.1.
AC009878 Genomic DNA. No translation available.
AC011196 Genomic DNA. No translation available.
AC104569 Genomic DNA. No translation available.
AC127511 Genomic DNA. No translation available.
AC135999 Genomic DNA. No translation available.
AC145167 Genomic DNA. No translation available.
AC145196 Genomic DNA. No translation available.
EU606048 Genomic DNA. No translation available.
CH471151 Genomic DNA. Translation: EAW57655.1.
BC010641 mRNA. Translation: AAH10641.1.
L04311 Genomic DNA. Translation: AAA52508.1.
L04311 Genomic DNA. Translation: AAA52507.1.
CCDSCCDS10018.1. [P28472-2]
CCDS10019.1. [P28472-1]
CCDS53920.1. [P28472-4]
CCDS53921.1. [P28472-3]
PIRA55275.
B45468.
RefSeqNP_000805.1. NM_000814.5. [P28472-1]
NP_001178249.1. NM_001191320.1. [P28472-4]
NP_001178250.1. NM_001191321.2. [P28472-3]
NP_001265560.1. NM_001278631.1. [P28472-4]
NP_068712.1. NM_021912.4. [P28472-2]
UniGeneHs.302352.
Hs.727263.

3D structure databases

ProteinModelPortalP28472.
SMRP28472. Positions 47-346.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108836. 5 interactions.
IntActP28472. 1 interaction.
STRING9606.ENSP00000299267.

Chemistry

BindingDBP28472.
ChEMBLCHEMBL2094121.
DrugBankDB00189. Ethchlorvynol.
DB00690. Flurazepam.
DB00186. Lorazepam.
DB00683. Midazolam.
GuidetoPHARMACOLOGY412.

PTM databases

PhosphoSiteP28472.

Polymorphism databases

DMDM120773.

Proteomic databases

MaxQBP28472.
PaxDbP28472.
PRIDEP28472.

Protocols and materials databases

DNASU2562.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000299267; ENSP00000299267; ENSG00000166206. [P28472-2]
ENST00000311550; ENSP00000308725; ENSG00000166206. [P28472-1]
ENST00000400188; ENSP00000383049; ENSG00000166206. [P28472-3]
ENST00000545868; ENSP00000439169; ENSG00000166206. [P28472-4]
GeneID2562.
KEGGhsa:2562.
UCSCuc001zaz.3. human. [P28472-1]
uc001zba.3. human. [P28472-2]
uc021sgg.1. human.

Organism-specific databases

CTD2562.
GeneCardsGC15M026788.
GeneReviewsGABRB3.
HGNCHGNC:4083. GABRB3.
MIM137192. gene+phenotype.
612269. phenotype.
neXtProtNX_P28472.
Orphanet106. Autism.
64280. Childhood absence epilepsy.
PharmGKBPA28497.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG77438.
HOVERGENHBG051707.
KOK05181.
OrthoDBEOG712TVZ.
PhylomeDBP28472.
TreeFamTF315453.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.
SignaLinkP28472.

Gene expression databases

ArrayExpressP28472.
BgeeP28472.
CleanExHS_GABRB3.
GenevestigatorP28472.

Family and domain databases

Gene3D2.70.170.10. 1 hit.
InterProIPR006028. GABAA/Glycine_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. 1 hit.
TIGRFAMsTIGR00860. LIC. 1 hit.
PROSITEPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGABRB3. human.
GeneWikiGABRB3.
GenomeRNAi2562.
NextBio10121.
PROP28472.
SOURCESearch...

Entry information

Entry nameGBRB3_HUMAN
AccessionPrimary (citable) accession number: P28472
Secondary accession number(s): B7Z2W1 expand/collapse secondary AC list , B7Z825, F5H3D2, H7BYV8, Q14352, Q96FM5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: July 9, 2014
This is version 148 of the entry and version 1 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM