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P18507 (GBRG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 154. 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 gamma-2
Alternative name(s):
GABA(A) receptor subunit gamma-2
Gene names
Name:GABRG2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length467 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

Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Interacts with GABARAP. Ref.6

Subcellular location

Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.

Post-translational modification

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

Involvement in disease

Epilepsy, childhood absence 2 (ECA2) [MIM:607681]: 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. Some individuals manifest febrile seizures. Absence seizures may either remit or persist into adulthood.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.8

Febrile seizures, familial, 8 (FEB8) [MIM:611277]: Seizures 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Generalized epilepsy with febrile seizures plus 3 (GEFS+3) [MIM:611277]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Severe myoclonic epilepsy in infancy (SMEI) [MIM:607208]: A rare disorder characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development delay is observed around the second year of life. Some patients manifest a borderline disease phenotype and do not necessarily fulfill all diagnostic criteria for core SMEI. SMEI is considered to be the most severe phenotype within the spectrum of generalized epilepsies with febrile seizures-plus.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Miscellaneous

This subunit carries the benzodiazepine binding site.

Sequence similarities

Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG2 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
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult behavior

Inferred from electronic annotation. Source: Ensembl

gamma-aminobutyric acid signaling pathway

Traceable author statement Ref.1. Source: ProtInc

ion transmembrane transport

Traceable author statement. Source: Reactome

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

synaptic transmission, GABAergic

Inferred from sequence or structural similarity. Source: BHF-UCL

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

chloride channel complex

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from electronic annotation. Source: Ensembl

dendrite membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

inhibitory synapse

Inferred from electronic annotation. Source: Ensembl

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

Inferred from electronic annotation. Source: Ensembl

benzodiazepine 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 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P18507-1)

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: P18507-2)

The sequence of this isoform differs from the canonical sequence as follows:
     376-376: P → PLLRMFSFK
Isoform 3 (identifier: P18507-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3939 Potential
Chain40 – 467428Gamma-aminobutyric acid receptor subunit gamma-2
PRO_0000000477

Regions

Topological domain40 – 273234Extracellular Probable
Transmembrane274 – 29623Helical; Probable
Transmembrane300 – 32223Helical; Probable
Transmembrane334 – 35623Helical; Probable
Topological domain357 – 44387Cytoplasmic Probable
Transmembrane444 – 46623Helical; Probable
Region425 – 44218Interaction with GABARAP Potential

Amino acid modifications

Glycosylation521N-linked (GlcNAc...) Potential
Glycosylation1291N-linked (GlcNAc...) Potential
Glycosylation2471N-linked (GlcNAc...) Potential
Disulfide bond190 ↔ 204 By similarity

Natural variations

Alternative sequence2111Y → WSRSIAQAGMCSGVISAHYS LRFWGSTDPPTLASRVAGIS D in isoform 3.
VSP_047323
Alternative sequence3761P → PLLRMFSFK in isoform 2 and isoform 3.
VSP_041124
Natural variant791N → S Found in a patient with generalized tonic-clonic seizures. Ref.10
VAR_065226
Natural variant821R → Q in ECA2 and FEB8; abolishes in vitro sensitivity to diazepam. Ref.8
Corresponds to variant rs28933070 [ dbSNP | Ensembl ].
VAR_014265
Natural variant1771R → G in FEB8. Ref.9
VAR_038602
Natural variant3281K → M in GEFS+3. Ref.7
VAR_014266
Natural variant3571H → R. Ref.4
Corresponds to variant rs17855003 [ dbSNP | Ensembl ].
VAR_065163

Experimental info

Sequence conflict1201T → M in CAA33437. Ref.1
Sequence conflict1811T → S in CAA33437. Ref.1
Sequence conflict384 – 3852Missing no nucleotide entry Ref.5
Sequence conflict3991E → D no nucleotide entry Ref.5
Sequence conflict438 – 4392IA → RI no nucleotide entry Ref.5

Sequences

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

Last modified October 17, 2006. Version 2.
Checksum: 7450DFE1157C9224

FASTA46754,162
        10         20         30         40         50         60 
MSSPNIWSTG SSVYSTPVFS QKMTVWILLL LSLYPGFTSQ KSDDDYEDYA SNKTWVLTPK 

        70         80         90        100        110        120 
VPEGDVTVIL NNLLEGYDNK LRPDIGVKPT LIHTDMYVNS IGPVNAINME YTIDIFFAQT 

       130        140        150        160        170        180 
WYDRRLKFNS TIKVLRLNSN MVGKIWIPDT FFRNSKKADA HWITTPNRML RIWNDGRVLY 

       190        200        210        220        230        240 
TLRLTIDAEC QLQLHNFPMD EHSCPLEFSS YGYPREEIVY QWKRSSVEVG DTRSWRLYQF 

       250        260        270        280        290        300 
SFVGLRNTTE VVKTTSGDYV VMSVYFDLSR RMGYFTIQTY IPCTLIVVLS WVSFWINKDA 

       310        320        330        340        350        360 
VPARTSLGIT TVLTMTTLST IARKSLPKVS YVTAMDLFVS VCFIFVFSAL VEYGTLHYFV 

       370        380        390        400        410        420 
SNRKPSKDKD KKKKNPAPTI DIRPRSATIQ MNNATHLQER DEEYGYECLD GKDCASFFCC 

       430        440        450        460 
FEDCRTGAWR HGRIHIRIAK MDSYARIFFP TAFCLFNLVY WVSYLYL 

« Hide

Isoform 2 [UniParc].

Checksum: DE142F62846576DF
Show »

FASTA47555,186
Isoform 3 [UniParc].

Checksum: C450709F7B8F9DD1
Show »

FASTA51559,344

References

« Hide 'large scale' references
[1]"Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology."
Pritchett D.B., Sontheimer H., Shivers B.D., Ymer S., Kettenmann H., Schofield P.R., Seeburg P.H.
Nature 338:582-585(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"Complete genomic sequence of 195 Kb of human DNA containing the gene GABRG2."
Jiang S., Yu J., Wang J., Tan Z., Xue H., Feng G., He L., Yang H.
DNA Seq. 11:373-382(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORMS 1 AND 2), VARIANT ARG-357.
Tissue: Brain.
[5]"Antibodies to the human gamma 2 subunit of the gamma-aminobutyric acidA/benzodiazepine receptor."
Khan Z.U., Fernando L.P., Escriba P., Busquets X., Mallet J., Miralles C.P., Filla M., De Blas A.L.
J. Neurochem. 60:961-971(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 357-443 (ISOFORM 1).
Tissue: Brain cortex.
[6]"GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton."
Wang H., Bedford F.K., Brandon N.J., Moss S.J., Olsen R.W.
Nature 397:69-72(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GABARAP.
[7]"First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene."
Baulac S., Huberfeld G., Gourfinkel-An I., Mitropoulou G., Beranger A., Prud'homme J.-F., Baulac M., Brice A., Bruzzone R., LeGuern E.
Nat. Genet. 28:46-48(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GEFS+3 MET-328.
[8]"Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures."
Wallace R.H., Marini C., Petrou S., Harkin L.A., Bowser D.N., Panchal R.G., Williams D.A., Sutherland G.R., Mulley J.C., Scheffer I.E., Berkovic S.F.
Nat. Genet. 28:49-52(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ECA2/FEB8 GLN-82.
[9]"A novel GABRG2 mutation associated with febrile seizures."
Audenaert D., Schwartz E., Claeys K.G., Claes L., Deprez L., Suls A., Van Dyck T., Lagae L., Van Broeckhoven C., Macdonald R.L., De Jonghe P.
Neurology 67:687-690(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FEB8 GLY-177.
[10]"Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies."
Shi X., Huang M.C., Ishii A., Yoshida S., Okada M., Morita K., Nagafuji H., Yasumoto S., Kaneko S., Kojima T., Hirose S.
J. Hum. Genet. 55:375-378(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-79.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS03905.
RefSeqNP_000807.2. NM_000816.3.
NP_944493.2. NM_198903.2.
NP_944494.1. NM_198904.2.
UniGeneHs.7195.

3D structure databases

ProteinModelPortalP18507.
SMRP18507. Positions 65-467.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108840. 2 interactions.
STRING9606.ENSP00000410732.

Chemistry

BindingDBP18507.
ChEMBLCHEMBL2094130.
GuidetoPHARMACOLOGY414.

PTM databases

PhosphoSiteP18507.

Polymorphism databases

DMDM116242488.

Proteomic databases

PaxDbP18507.
PRIDEP18507.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356592; ENSP00000349000; ENSG00000113327. [P18507-2]
ENST00000361925; ENSP00000354651; ENSG00000113327. [P18507-1]
ENST00000414552; ENSP00000410732; ENSG00000113327. [P18507-3]
GeneID2566.
KEGGhsa:2566.
UCSCuc003lyy.4. human. [P18507-2]
uc003lyz.4. human. [P18507-1]

Organism-specific databases

CTD2566.
GeneCardsGC05P161494.
HGNCHGNC:4087. GABRG2.
MIM137164. gene.
604233. phenotype.
607208. phenotype.
607681. phenotype.
611277. phenotype.
neXtProtNX_P18507.
Orphanet64280. Childhood absence epilepsy.
33069. Dravet syndrome.
36387. Generalized epilepsy with febrile seizures-plus context.
PharmGKBPA28501.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238757.
HOGENOMHOG000231337.
HOVERGENHBG051707.
KOK05186.
OMAGFTSQKS.
OrthoDBEOG7JX342.
PhylomeDBP18507.
TreeFamTF315453.

Enzyme and pathway databases

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

Gene expression databases

ArrayExpressP18507.
BgeeP18507.
CleanExHS_GABRG2.
GenevestigatorP18507.

Family and domain databases

Gene3D2.70.170.10. 1 hit.
InterProIPR006028. GABAA_rcpt.
IPR005439. GABBAg2_rcpt.
IPR005437. GABBAg_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]
PRINTSPR00253. GABAARECEPTR.
PR01620. GABAARGAMMA.
PR01622. GABAARGAMMA2.
PR00252. NRIONCHANNEL.
SUPFAMSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsTIGR00860. LIC. 1 hit.
PROSITEPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGABRG2.
GenomeRNAi2566.
NextBio10145.
PROP18507.
SOURCESearch...

Entry information

Entry nameGBRG2_HUMAN
AccessionPrimary (citable) accession number: P18507
Secondary accession number(s): F5HB82 expand/collapse secondary AC list , Q6GRL6, Q6PCC3, Q9UDB3, Q9UN15
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 154 of the entry and version 2 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 5

Human chromosome 5: entries, gene names and cross-references to MIM