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Reviewed, UniProtKB/Swiss-Prot P28472 (GBRB3_HUMAN)

Last modified June 16, 2009. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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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)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length473 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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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.

Involvement in disease

Defects in GABRB3 are a cause of chonic insomnia. Insomnia is characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition.

Defects in GABRB3 are the cause of childhood absence epilepsy type 5 (ECA5) [MIM:612269]. ECA5 is a subtype of idiopathic generalized epilepsy (IGE) 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. During adolescence, tonic-clonic and myoclonic seizures develop. Absence seizures may either remit or persist into adulthood. Ref.6

Sequence similarities

Belongs to the ligand-gated ionic channel (TC 1.A.9) family. [View classification]

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Alternative products

This entry describes 2 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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Natural variant111P → S in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. dbSNP rs25409.
Natural variant151S → F in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type.

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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 – 26722 Probable
Transmembrane271 – 29323 Probable
Transmembrane305 – 32723 Probable
Topological domain328 – 450123Cytoplasmic Probable
Transmembrane451 – 47222 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 – 2626MWGLA…VCCAQ → MCSGLLELLLPIWLSWTLGT RGSEPR in isoform 2.
VSP_000088
Natural variant321G → R in ECA5; the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. Ref.6
VAR_047957
Natural variant1731Q → L: dbSNP rs17850679. Ref.2
VAR_047958
Natural variant2171R → H in 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.5
VAR_047959

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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.

Checksum: 3A7F9A0EB3537D5E
Show »

FASTA47354,379

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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: 1664410] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-173.
Tissue: Eye.
[3]"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: 8382702] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-80 (ISOFORMS 1 AND 2).
Tissue: Fibroblast.
[4]"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: 1714232] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 81-153 AND 183-227.
[5]"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: 12189488] [Abstract]
Cited for: VARIANT INSOMNIA HIS-217, CHARACTERIZATION OF VARIANT INSOMNIA HIS-217.
[6]"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: 18514161] [Abstract]
Cited for: VARIANT ECA5 ARG-32, VARIANTS ECA5 SER-11 AND PHE-15 (ISOFORM 2).
+Additional computationally mapped references.

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Web resources

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

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Cross-references

Sequence databases

M82919 mRNA. Translation: AAA52511.1.
BC010641 mRNA. Translation: AAH10641.1.
L04311 Genomic DNA. Translation: AAA52508.1.
L04311 Genomic DNA. Translation: AAA52507.1.
IPIIPI00003467.
IPI00217235.
PIRA55275.
B45468.
RefSeqNP_000805.1.
NP_068712.1.
UniGeneHs.302352
Hs.657298

3D structure databases

ModBaseSearch...

PTM databases

PhosphoSiteP28472.

Proteomic databases

PRIDEP28472.

Genome annotation databases

EnsemblENSG00000166206. Homo sapiens. [Contig view]
GeneID2562.
KEGGhsa:2562.

Organism-specific databases

GeneCardsGC15M024342.
H-InvDBHIX0012052.
HGNCHGNC:4083. GABRB3.
MIM137192. gene.
612269. phenotype.
Orphanet106. Autism.
PharmGKBPA28497.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP28472.

Gene expression databases

ArrayExpressP28472.
BgeeP28472.
CleanExHS_GABRB3.
GermOnlineENSG00000166206. Homo sapiens.

Family and domain databases

InterProIPR006028. GABAA_rcpt.
IPR002289. GABAAb_rcpt.
IPR006029. Neu_channel_TM.
IPR006202. Neur_chan_lig_bd.
IPR006201. Neur_channel.
IPR018000. Neurotransmitter_ion_chnl_CS.
[Graphical view]
Gene3DG3DSA:2.70.170.10. Neur_chan_lig_bd. 1 hit.
PANTHERPTHR18945. Neur_channel. 1 hit.
PfamPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSPR01160. GABAARBETA.
PR00253. GABAARECEPTR.
PR00252. NRIONCHANNEL.
TIGRFAMsTIGR00860. LIC. 1 hit.
PROSITEPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00189. Ethchlorvynol.
DB00690. Flurazepam.
DB00186. Lorazepam.
DB00683. Midazolam.
NextBio10121.
SOURCESearch...

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Entry information

Entry nameGBRB3_HUMAN
AccessionPrimary (citable) accession number: P28472
Secondary accession number(s): Q14352, Q96FM5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: June 16, 2009
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 15

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents