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Protein

Gamma-aminobutyric acid receptor subunit gamma-2

Gene

GABRG2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.1 Publication

Miscellaneous

This subunit carries the benzodiazepine binding site.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChloride channel, Ion channel
Biological processIon transport, Transport
LigandChloride

Enzyme and pathway databases

ReactomeiR-HSA-112314. Neurotransmitter receptors and postsynaptic signal transmission.
R-HSA-975298. Ligand-gated ion channel transport.
R-HSA-977441. GABA A receptor activation.

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 gamma-2
Alternative name(s):
GABA(A) receptor subunit gamma-2
Gene namesi
Name:GABRG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113327.14.
HGNCiHGNC:4087. GABRG2.

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 domaini40 – 273ExtracellularCuratedAdd BLAST234
Transmembranei274 – 296HelicalCuratedAdd BLAST23
Transmembranei300 – 322HelicalCuratedAdd BLAST23
Transmembranei334 – 356HelicalCuratedAdd BLAST23
Topological domaini357 – 443CytoplasmicCuratedAdd BLAST87
Transmembranei444 – 466HelicalCuratedAdd BLAST23

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Epilepsy, childhood absence 2 (ECA2)1 Publication
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. Some individuals manifest febrile seizures. Absence seizures may either remit or persist into adulthood.
See also OMIM:607681
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01426582R → Q in ECA2 and FEB8; abolishes in vitro sensitivity to diazepam. 1 PublicationCorresponds to variant dbSNP:rs28933070Ensembl.1
Febrile seizures, familial, 8 (FEB8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSeizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy.
See also OMIM:611277
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01426582R → Q in ECA2 and FEB8; abolishes in vitro sensitivity to diazepam. 1 PublicationCorresponds to variant dbSNP:rs28933070Ensembl.1
Natural variantiVAR_038602177R → G in FEB8. 1 PublicationCorresponds to variant dbSNP:rs267606837Ensembl.1
Generalized epilepsy with febrile seizures plus 3 (GEFS+3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity.
See also OMIM:611277
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078620323R → Q in GEFS+3. 1 PublicationCorresponds to variant dbSNP:rs397514737Ensembl.1
Natural variantiVAR_014266328K → M in GEFS+3. 1 PublicationCorresponds to variant dbSNP:rs121909672Ensembl.1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi2566.
MalaCardsiGABRG2.
MIMi604233. phenotype.
607681. phenotype.
611277. phenotype.
OpenTargetsiENSG00000113327.
Orphaneti64280. Childhood absence epilepsy.
33069. Dravet syndrome.
36387. Generalized epilepsy with febrile seizures-plus.
PharmGKBiPA28501.

Chemistry databases

ChEMBLiCHEMBL2111392.
DrugBankiDB00659. Acamprosate.
DB00546. Adinazolam.
DB06579. Adipiplon.
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.
DB00189. Ethchlorvynol.
DB00292. Etomidate.
DB01567. Fludiazepam.
DB01205. Flumazenil.
DB00690. Flurazepam.
DB01381. Ginkgo biloba.
DB01437. Glutethimide.
DB00801. Halazepam.
DB01159. Halothane.
DB00753. Isoflurane.
DB00186. Lorazepam.
DB00371. Meprobamate.
DB00463. Metharbital.
DB01028. Methoxyflurane.
DB01107. Methyprylon.
DB00683. Midazolam.
DB01595. Nitrazepam.
DB00334. Olanzapine.
DB00842. Oxazepam.
DB00312. Pentobarbital.
DB01708. Prasterone.
DB01588. Prazepam.
DB00794. Primidone.
DB00818. Propofol.
DB01589. Quazepam.
DB01236. Sevoflurane.
DB00306. Talbutal.
DB00231. Temazepam.
DB11582. Thiocolchicoside.
DB00273. Topiramate.
DB00897. Triazolam.

Polymorphism and mutation databases

BioMutaiGABRG2.
DMDMi116242488.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 39Sequence analysisAdd BLAST39
ChainiPRO_000000047740 – 467Gamma-aminobutyric acid receptor subunit gamma-2Add BLAST428

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi52N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi129N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi190 ↔ 204By similarity
Glycosylationi247N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Palmitoylated by ZDHHC3/GODZ; which may affect presynaptic clustering and/or cell surface stability.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

EPDiP18507.
PeptideAtlasiP18507.
PRIDEiP18507.
TopDownProteomicsiP18507-2. [P18507-2]

PTM databases

iPTMnetiP18507.
PhosphoSitePlusiP18507.
SwissPalmiP18507.

Expressioni

Gene expression databases

BgeeiENSG00000113327.
CleanExiHS_GABRG2.
ExpressionAtlasiP18507. baseline and differential.
GenevisibleiP18507. HS.

Interactioni

Subunit structurei

Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:2538761). Interacts with GABARAP (PubMed:9892355). Interacts with KIF21B (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GABARAPO951663EBI-15096952,EBI-712001

Protein-protein interaction databases

BioGridi108840. 15 interactors.
CORUMiP18507.
IntActiP18507. 1 interactor.

Chemistry databases

BindingDBiP18507.

Structurei

3D structure databases

ProteinModelPortaliP18507.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni425 – 442Interaction with GABARAPSequence analysisAdd BLAST18

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00760000119010.
HOGENOMiHOG000231337.
HOVERGENiHBG051707.
InParanoidiP18507.
KOiK05186.
OMAiSATIQMN.
OrthoDBiEOG091G0805.
PhylomeDBiP18507.
TreeFamiTF315453.

Family and domain databases

Gene3Di1.20.58.390. 1 hit.
2.70.170.10. 1 hit.
InterProiView protein in InterPro
IPR006028. GABAA/Glycine_rcpt.
IPR005439. GABBAg2_rcpt.
IPR005437. GABBAg_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.
PRINTSiPR00253. GABAARECEPTR.
PR01620. GABAARGAMMA.
PR01622. GABAARGAMMA2.
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 (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P18507-1) [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
MSSPNIWSTG SSVYSTPVFS QKMTVWILLL LSLYPGFTSQ KSDDDYEDYA
60 70 80 90 100
SNKTWVLTPK VPEGDVTVIL NNLLEGYDNK LRPDIGVKPT LIHTDMYVNS
110 120 130 140 150
IGPVNAINME YTIDIFFAQT WYDRRLKFNS TIKVLRLNSN MVGKIWIPDT
160 170 180 190 200
FFRNSKKADA HWITTPNRML RIWNDGRVLY TLRLTIDAEC QLQLHNFPMD
210 220 230 240 250
EHSCPLEFSS YGYPREEIVY QWKRSSVEVG DTRSWRLYQF SFVGLRNTTE
260 270 280 290 300
VVKTTSGDYV VMSVYFDLSR RMGYFTIQTY IPCTLIVVLS WVSFWINKDA
310 320 330 340 350
VPARTSLGIT TVLTMTTLST IARKSLPKVS YVTAMDLFVS VCFIFVFSAL
360 370 380 390 400
VEYGTLHYFV SNRKPSKDKD KKKKNPAPTI DIRPRSATIQ MNNATHLQER
410 420 430 440 450
DEEYGYECLD GKDCASFFCC FEDCRTGAWR HGRIHIRIAK MDSYARIFFP
460
TAFCLFNLVY WVSYLYL
Length:467
Mass (Da):54,162
Last modified:October 17, 2006 - v2
Checksum:i7450DFE1157C9224
GO
Isoform 2 (identifier: P18507-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     376-376: P → PLLRMFSFK

Show »
Length:475
Mass (Da):55,186
Checksum:iDE142F62846576DF
GO
Isoform 3 (identifier: P18507-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     211-211: Y → WSRSIAQAGMCSGVISAHYSLRFWGSTDPPTLASRVAGISD
     376-376: P → PLLRMFSFK

Note: No experimental confirmation available.
Show »
Length:515
Mass (Da):59,344
Checksum:iC450709F7B8F9DD1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti120T → M in CAA33437 (PubMed:2538761).Curated1
Sequence conflicti181T → S in CAA33437 (PubMed:2538761).Curated1
Sequence conflicti384 – 385Missing no nucleotide entry (PubMed:8382267).Curated2
Sequence conflicti399E → D no nucleotide entry (PubMed:8382267).Curated1
Sequence conflicti438 – 439IA → RI no nucleotide entry (PubMed:8382267).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06522679N → S Found in a patient with generalized tonic-clonic seizures. 1 PublicationCorresponds to variant dbSNP:rs112894280Ensembl.1
Natural variantiVAR_01426582R → Q in ECA2 and FEB8; abolishes in vitro sensitivity to diazepam. 1 PublicationCorresponds to variant dbSNP:rs28933070Ensembl.1
Natural variantiVAR_07181383P → S Found in a patient with idiopathic generalized epilepsy; unknown pathological significance; the currents elicited by mutant receptors are indistinguishable from wild-type; no difference in sensitivity of the mutant receptors to the allosteric regulators zinc and benzodiazepine diazepam compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs587777365Ensembl.1
Natural variantiVAR_038602177R → G in FEB8. 1 PublicationCorresponds to variant dbSNP:rs267606837Ensembl.1
Natural variantiVAR_078226274Y → C Probable disease-associated mutation found in a patient with generalized epilepsy with myoclonic atonic seizures, cognitive impairment and behavioral disorder. 1 Publication1
Natural variantiVAR_078620323R → Q in GEFS+3. 1 PublicationCorresponds to variant dbSNP:rs397514737Ensembl.1
Natural variantiVAR_014266328K → M in GEFS+3. 1 PublicationCorresponds to variant dbSNP:rs121909672Ensembl.1
Natural variantiVAR_065163357H → R1 PublicationCorresponds to variant dbSNP:rs17855003Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047323211Y → WSRSIAQAGMCSGVISAHYS LRFWGSTDPPTLASRVAGIS D in isoform 3. Curated1
Alternative sequenceiVSP_041124376P → PLLRMFSFK in isoform 2 and isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X15376 mRNA. Translation: CAA33437.1.
AF165124 Genomic DNA. Translation: AAD50273.1.
AC008611 Genomic DNA. No translation available.
AC091926 Genomic DNA. No translation available.
AC091984 Genomic DNA. No translation available.
BC059389 mRNA. Translation: AAH59389.1.
BC069348 mRNA. Translation: AAH69348.1.
BC074795 mRNA. Translation: AAH74795.1.
CCDSiCCDS4358.1. [P18507-1]
CCDS4359.1. [P18507-2]
CCDS47333.1. [P18507-3]
PIRiS03905.
RefSeqiNP_000807.2. NM_000816.3. [P18507-1]
NP_944493.2. NM_198903.2. [P18507-3]
NP_944494.1. NM_198904.2. [P18507-2]
UniGeneiHs.7195.

Genome annotation databases

EnsembliENST00000414552; ENSP00000410732; ENSG00000113327. [P18507-3]
ENST00000639111; ENSP00000492125; ENSG00000113327. [P18507-2]
ENST00000639213; ENSP00000491909; ENSG00000113327. [P18507-1]
GeneIDi2566.
KEGGihsa:2566.
UCSCiuc003lyy.5. human. [P18507-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiGBRG2_HUMAN
AccessioniPrimary (citable) accession number: P18507
Secondary accession number(s): F5HB82
, Q6GRL6, Q6PCC3, Q9UDB3, Q9UN15
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: October 17, 2006
Last modified: October 25, 2017
This is version 190 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  6. SIMILARITY comments
    Index of protein domains and families