Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Gamma-aminobutyric acid receptor subunit beta-3

Gene

GABRB3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei225Agonist1

GO - Molecular functioni

  • GABA-A receptor activity Source: UniProtKB
  • GABA-gated chloride ion channel activity Source: GO_Central
  • identical protein binding Source: IntAct

GO - Biological processi

  • cellular response to histamine Source: UniProtKB
  • chloride transmembrane transport Source: GO_Central
  • cochlea development Source: Ensembl
  • gamma-aminobutyric acid signaling pathway Source: UniProtKB
  • inhibitory postsynaptic potential Source: Ensembl
  • inner ear receptor cell development Source: Ensembl
  • innervation Source: Ensembl
  • negative regulation of neuron apoptotic process Source: Ensembl
  • palate development Source: UniProtKB
  • sensory perception of sound Source: Ensembl
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionChloride channel, Ion channel, Ligand-gated ion channel, Receptor
Biological processIon transport, Transport
LigandChloride

Enzyme and pathway databases

ReactomeiR-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-977441 GABA A receptor activation
SignaLinkiP28472

Protein family/group databases

TCDBi1.A.9.5.4 the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family

Names & Taxonomyi

Protein namesi
Recommended name:
Gamma-aminobutyric acid receptor subunit beta-3
Alternative name(s):
GABA(A) receptor subunit beta-3
Gene namesi
Name:GABRB3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000166206.13
HGNCiHGNC:4083 GABRB3
MIMi137192 gene+phenotype
neXtProtiNX_P28472

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 245Extracellular1 PublicationAdd BLAST220
Transmembranei246 – 267HelicalAdd BLAST22
Topological domaini268 – 270Cytoplasmic1 Publication3
Transmembranei271 – 293HelicalAdd BLAST23
Topological domaini294 – 304Extracellular1 PublicationAdd BLAST11
Transmembranei305 – 327HelicalAdd BLAST23
Topological domaini328 – 450Cytoplasmic1 PublicationAdd BLAST123
Transmembranei451 – 472HelicalAdd BLAST22

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasmic vesicle, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Epilepsy, childhood absence 5 (ECA5)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:612269
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04795732G → R in ECA5; the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. 2 PublicationsCorresponds to variant dbSNP:rs71651682Ensembl.1
Isoform 2 (identifier: P28472-2)
Natural varianti11P → S in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs25409Ensembl.1
Natural varianti15S → F in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. 1 Publication1
Epileptic encephalopathy, early infantile, 43 (EIEE43)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE43 inheritance is autosomal dominant.
See also OMIM:617113
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077076120D → N in EIEE43; no effect on localization to the plasma membrane; decreased GABA-gated chloride ion channel activity; decreased single channel open probability. 3 PublicationsCorresponds to variant dbSNP:rs886037938Ensembl.1
Natural variantiVAR_078223124L → F in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs1057519550Ensembl.1
Natural variantiVAR_078619138N → NH in EIEE43. 1 Publication1
Natural variantiVAR_077077157T → M in EIEE43; unknown pathological significance. 1 Publication1
Natural variantiVAR_077078182Y → F in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs886037939Ensembl.1
Natural variantiVAR_077079249Q → K in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs886037940Ensembl.1
Natural variantiVAR_078224254S → F in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs1057519549Ensembl.1
Natural variantiVAR_077080256L → Q in EIEE43. 1 Publication1
Natural variantiVAR_078719287T → I in EIEE43. 1 Publication1
Natural variantiVAR_077081293L → H in EIEE43; unknown pathological significance. 1 Publication1
Natural variantiVAR_077082305A → T in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs886037941Ensembl.1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi2562
GeneReviewsiGABRB3
MalaCardsiGABRB3
MIMi137192 gene+phenotype
612269 phenotype
617113 phenotype
OpenTargetsiENSG00000166206
Orphaneti106 Autism
64280 Childhood absence epilepsy
PharmGKBiPA28497

Chemistry databases

ChEMBLiCHEMBL1847
DrugBankiDB00659 Acamprosate
DB00546 Adinazolam
DB00404 Alprazolam
DB00543 Amoxapine
DB01558 Bromazepam
DB00237 Butabarbital
DB00241 Butalbital
DB00475 Chlordiazepoxide
DB01594 Cinolazepam
DB00349 Clobazam
DB01068 Clonazepam
DB00628 Clorazepate
DB01559 Clotiazepam
DB01189 Desflurane
DB00829 Diazepam
DB00228 Enflurane
DB01049 Ergoloid mesylate
DB01215 Estazolam
DB00402 Eszopiclone
DB00898 Ethanol
DB00189 Ethchlorvynol
DB00292 Etomidate
DB01567 Fludiazepam
DB01205 Flumazenil
DB00690 Flurazepam
DB06716 Fospropofol
DB01437 Glutethimide
DB00801 Halazepam
DB01159 Halothane
DB00753 Isoflurane
DB00602 Ivermectin
DB00186 Lorazepam
DB00371 Meprobamate
DB00463 Metharbital
DB01028 Methoxyflurane
DB01107 Methyprylon
DB00683 Midazolam
DB01595 Nitrazepam
DB00334 Olanzapine
DB00842 Oxazepam
DB00312 Pentobarbital
DB00592 Piperazine
DB01708 Prasterone
DB01588 Prazepam
DB00794 Primidone
DB00818 Propofol
DB01589 Quazepam
DB01236 Sevoflurane
DB00306 Talbutal
DB00231 Temazepam
DB11582 Thiocolchicoside
DB00273 Topiramate
DB00897 Triazolam
GuidetoPHARMACOLOGYi412

Polymorphism and mutation databases

BioMutaiGABRB3
DMDMi120773

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000000046226 – 473Gamma-aminobutyric acid receptor subunit beta-3Add BLAST448

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi33N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi105N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi161 ↔ 1751 Publication
Glycosylationi174N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP28472
PaxDbiP28472
PeptideAtlasiP28472
PRIDEiP28472

PTM databases

iPTMnetiP28472
PhosphoSitePlusiP28472

Expressioni

Gene expression databases

BgeeiENSG00000166206
CleanExiHS_GABRB3
ExpressionAtlasiP28472 baseline and differential
GenevisibleiP28472 HS

Interactioni

Subunit structurei

Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:22243422, PubMed:18281286, PubMed:18514161, PubMed:24909990). Can form functional homopentamers (in vitro) (PubMed:22303015). Interacts with UBQLN1 (By similarity). May interact with KIF21B (By similarity).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself5EBI-6258252,EBI-6258252

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi108836, 10 interactors
DIPiDIP-61029N
IntActiP28472, 1 interactor
STRINGi9606.ENSP00000299267

Chemistry databases

BindingDBiP28472

Structurei

Secondary structure

1473
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi34 – 45Combined sources12
Turni54 – 57Combined sources4
Beta strandi61 – 76Combined sources16
Turni77 – 80Combined sources4
Beta strandi81 – 93Combined sources13
Helixi95 – 97Combined sources3
Beta strandi106 – 108Combined sources3
Helixi110 – 115Combined sources6
Beta strandi121 – 123Combined sources3
Beta strandi126 – 131Combined sources6
Beta strandi134 – 136Combined sources3
Beta strandi138 – 143Combined sources6
Beta strandi147 – 160Combined sources14
Turni166 – 169Combined sources4
Beta strandi172 – 183Combined sources12
Turni186 – 188Combined sources3
Beta strandi189 – 193Combined sources5
Helixi196 – 198Combined sources3
Beta strandi199 – 201Combined sources3
Helixi203 – 205Combined sources3
Beta strandi209 – 225Combined sources17
Beta strandi228 – 241Combined sources14
Helixi244 – 249Combined sources6
Helixi251 – 262Combined sources12
Helixi263 – 266Combined sources4
Helixi272 – 295Combined sources24
Helixi305 – 330Combined sources26
Helixi447 – 471Combined sources25

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4COFX-ray2.97A/B/C/D/E26-332[»]
A/B/C/D/E447-473[»]
5O8FX-ray3.20A/B/C/D/E26-246[»]
5OJMX-ray3.30A/B/C/D/E26-242[»]
ProteinModelPortaliP28472
SMRiP28472
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni120 – 122Agonist binding3
Regioni180 – 182Agonist binding3
Regioni290 – 311Allosteric effector bindingAdd BLAST22

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3643 Eukaryota
ENOG410XPWH LUCA
GeneTreeiENSGT00760000118821
HOVERGENiHBG051707
InParanoidiP28472
KOiK05181
PhylomeDBiP28472
TreeFamiTF315453

Family and domain databases

Gene3Di2.70.170.10, 1 hit
InterProiView protein in InterPro
IPR006028 GABAA/Glycine_rcpt
IPR002289 GABAAb_rcpt
IPR006202 Neur_chan_lig-bd
IPR036734 Neur_chan_lig-bd_sf
IPR006201 Neur_channel
IPR036719 Neuro-gated_channel_TM_sf
IPR006029 Neurotrans-gated_channel_TM
IPR018000 Neurotransmitter_ion_chnl_CS
PANTHERiPTHR18945 PTHR18945, 1 hit
PfamiView protein in Pfam
PF02931 Neur_chan_LBD, 1 hit
PF02932 Neur_chan_memb, 1 hit
PRINTSiPR01160 GABAARBETA
PR00253 GABAARECEPTR
PR00252 NRIONCHANNEL
SUPFAMiSSF63712 SSF63712, 1 hit
SSF90112 SSF90112, 1 hit
TIGRFAMsiTIGR00860 LIC, 1 hit
PROSITEiView protein in PROSITE
PS00236 NEUROTR_ION_CHANNEL, 1 hit

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Isoforms differ in their signal region.
Isoform 1 (identifier: P28472-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MWGLAGGRLF GIFSAPVLVA VVCCAQSVND PGNMSFVKET VDKLLKGYDI
60 70 80 90 100
RLRPDFGGPP VCVGMNIDIA SIDMVSEVNM DYTLTMYFQQ YWRDKRLAYS
110 120 130 140 150
GIPLNLTLDN RVADQLWVPD TYFLNDKKSF VHGVTVKNRM IRLHPDGTVL
160 170 180 190 200
YGLRITTTAA CMMDLRRYPL DEQNCTLEIE SYGYTTDDIE FYWRGGDKAV
210 220 230 240 250
TGVERIELPQ FSIVEHRLVS RNVVFATGAY PRLSLSFRLK RNIGYFILQT
260 270 280 290 300
YMPSILITIL SWVSFWINYD ASAARVALGI TTVLTMTTIN THLRETLPKI
310 320 330 340 350
PYVKAIDMYL MGCFVFVFLA LLEYAFVNYI FFGRGPQRQK KLAEKTAKAK
360 370 380 390 400
NDRSKSESNR VDAHGNILLT SLEVHNEMNE VSGGIGDTRN SAISFDNSGI
410 420 430 440 450
QYRKQSMPRE GHGRFLGDRS LPHKKTHLRR RSSQLKIKIP DLTDVNAIDR
460 470
WSRIVFPFTF SLFNLVYWLY YVN
Length:473
Mass (Da):54,116
Last modified:December 1, 1992 - v1
Checksum:iD63597F7FBC69E71
GO
Isoform 2 (identifier: P28472-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MWGLAGGRLFGIFSAPVLVAVVCCAQ → MCSGLLELLLPIWLSWTLGTRGSEPR

Show »
Length:473
Mass (Da):54,379
Checksum:i3A7F9A0EB3537D5E
GO
Isoform 3 (identifier: P28472-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     3-80: GLAGGRLFGI...SIDMVSEVNM → ATYQTEE

Note: No experimental confirmation available.
Show »
Length:402
Mass (Da):46,740
Checksum:i5B5BB0E56D41435A
GO
Isoform 4 (identifier: P28472-4) [UniParc]FASTAAdd to basket

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

Show »
Length:388
Mass (Da):45,006
Checksum:i6646C270C24396F2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti97L → H in BAH13811 (PubMed:14702039).Curated1
Sequence conflicti193W → R in BAH11997 (PubMed:14702039).Curated1

Polymorphismi

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04795732G → R in ECA5; the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. 2 PublicationsCorresponds to variant dbSNP:rs71651682Ensembl.1
Natural variantiVAR_077076120D → N in EIEE43; no effect on localization to the plasma membrane; decreased GABA-gated chloride ion channel activity; decreased single channel open probability. 3 PublicationsCorresponds to variant dbSNP:rs886037938Ensembl.1
Natural variantiVAR_078223124L → F in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs1057519550Ensembl.1
Natural variantiVAR_078619138N → NH in EIEE43. 1 Publication1
Natural variantiVAR_077077157T → M in EIEE43; unknown pathological significance. 1 Publication1
Natural variantiVAR_047958173Q → L1 PublicationCorresponds to variant dbSNP:rs17850679Ensembl.1
Natural variantiVAR_077078182Y → F in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs886037939Ensembl.1
Natural variantiVAR_047959217R → 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. 1 PublicationCorresponds to variant dbSNP:rs121913125Ensembl.1
Natural variantiVAR_079429232R → Q Found in patients with Dravet syndrome; unknown pathological significance. 1 Publication1
Natural variantiVAR_077079249Q → K in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs886037940Ensembl.1
Natural variantiVAR_078224254S → F in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs1057519549Ensembl.1
Natural variantiVAR_077080256L → Q in EIEE43. 1 Publication1
Natural variantiVAR_078719287T → I in EIEE43. 1 Publication1
Natural variantiVAR_077081293L → H in EIEE43; unknown pathological significance. 1 Publication1
Natural variantiVAR_077082305A → T in EIEE43. 1 PublicationCorresponds to variant dbSNP:rs886037941Ensembl.1
Isoform 2 (identifier: P28472-2)
Natural varianti11P → S in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs25409Ensembl.1
Natural varianti15S → F in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0466761 – 85Missing in isoform 4. 1 PublicationAdd BLAST85
Alternative sequenceiVSP_0000881 – 26MWGLA…VCCAQ → MCSGLLELLLPIWLSWTLGT RGSEPR in isoform 2. CuratedAdd BLAST26
Alternative sequenceiVSP_0461263 – 80GLAGG…SEVNM → ATYQTEE in isoform 3. 1 PublicationAdd BLAST78

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS10018.1 [P28472-2]
CCDS10019.1 [P28472-1]
CCDS53920.1 [P28472-4]
CCDS53921.1 [P28472-3]
PIRiA55275
B45468
RefSeqiNP_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]
UniGeneiHs.302352
Hs.727263

Genome annotation databases

EnsembliENST00000299267; ENSP00000299267; ENSG00000166206 [P28472-2]
ENST00000311550; ENSP00000308725; ENSG00000166206 [P28472-1]
ENST00000400188; ENSP00000383049; ENSG00000166206 [P28472-3]
ENST00000545868; ENSP00000439169; ENSG00000166206 [P28472-4]
ENST00000622697; ENSP00000481004; ENSG00000166206 [P28472-4]
ENST00000628124; ENSP00000486819; ENSG00000166206 [P28472-4]
ENST00000636466; ENSP00000489768; ENSG00000166206 [P28472-4]
GeneIDi2562
KEGGihsa:2562
UCSCiuc001zaz.5 human [P28472-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiGBRB3_HUMAN
AccessioniPrimary (citable) accession number: P28472
Secondary accession number(s): B7Z2W1
, B7Z825, F5H3D2, H7BYV8, Q14352, Q96FM5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: March 28, 2018
This is version 186 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health