Reviewed, UniProtKB/Swiss-Prot P18507 (GBRG2_HUMAN)

Names and origin

Protein names

Recommended name:
    Gamma-aminobutyric acid receptor subunit gamma-2
Alternative name(s):
    GABA(A) receptor subunit gamma-2

Gene names

Name:

GABRG2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.4
Subcellular location	Cell junction › synapse › postsynaptic 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	Defects in GABRG2 are the cause of childhood absence epilepsy type 2 (ECA2) [MIM:607681]. ECA2 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. Some individuals manifest ECA2 occurring in combination with febrile convulsions [MIM:611277]. Ref.6 Defects in GABRG2 are the cause of familial febrile convulsions type 8 (FEB8) [MIM:611277]. A febrile convulsion is defined as a seizure event in infancy or childhood, usually occurring between 6 months and 6 years of age, associated with fever but without any evidence of intracranial infection or defined pathologic or traumatic cause. Febrile convulsions affect 5-12% of infants and children up to 6 years of age. There is epidemiological evidence that febrile seizures are associated with subsequent afebrile and unprovoked seizures in 2% to 7% of patients. Ref.7 Defects in GABRG2 are the cause of generalized epilepsy with febrile seizures plus type 3 (GEFS+3) [MIM:604233]. Generalized epilepsy with febrile seizures-plus refers to 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. GEFS+ is a disease combining febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. Ref.5 Defects in GABRG2 are a cause of severe myoclonic epilepsy in infancy (SMEI) [MIM:607208]; also called Dravet syndrome. SMEI is 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. SMEI is considered to be the most severe phenotype within the spectrum of generalized epilepsies with febrile seizures-plus.
Miscellaneous	This subunit carries the benzodiazepine binding site.
Sequence similarities	Belongs to the ligand-gated ionic channel (TC 1.A.9) family. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Disease	Disease mutation Epilepsy
Domain	Signal Transmembrane
Ligand	Chloride
Molecular function	Chloride channel Ionic channel
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Gene Ontology (GO)
Biological process	chloride transport Inferred from electronic annotation. Source: InterPro gamma-aminobutyric acid signaling pathway Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	benzodiazepine receptor activity Ref.1 Traceable author statement. Source: ProtInc chloride channel activity Inferred from electronic annotation. Source: UniProtKB-KW chloride ion binding Inferred from electronic annotation. Source: UniProtKB-KW extracellular ligand-gated ion channel activity Inferred from electronic annotation. Source: InterPro protein binding Ref.4 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 39	39	Potential
	Chain	40 – 467	428	Gamma-aminobutyric acid receptor subunit gamma-2		PRO_0000000477
Regions
	Topological domain	40 – 273	234	Extracellular Probable
	Transmembrane	274 – 296	23	Probable
	Transmembrane	300 – 322	23	Probable
	Transmembrane	334 – 356	23	Probable
	Topological domain	357 – 443	87	Cytoplasmic Probable
	Transmembrane	444 – 466	23	Probable
	Region	425 – 442	18	Interaction with GABARAP Potential
Amino acid modifications
	Glycosylation	52	1	N-linked (GlcNAc...) Potential
	Glycosylation	129	1	N-linked (GlcNAc...) Potential
	Glycosylation	247	1	N-linked (GlcNAc...) Potential
	Disulfide bond	190 ↔ 204		By similarity
Natural variations
	Natural variant	82	1	R → Q in ECA2 and FEB8; abolishes in vitro sensitivity to diazepam.		VAR_014265
	Natural variant	177	1	R → G in FEB8. Ref.7		VAR_038602
	Natural variant	328	1	K → M in GEFS+3. Ref.5		VAR_014266
Experimental info
	Sequence conflict	120	1	T → M in CAA33437. Ref.1
	Sequence conflict	181	1	T → S in CAA33437. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P18507-1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 7450DFE1157C9224	FASTA	467	54,162
	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

References

	« Hide 'large scale' referencesShow '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: 2538761] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 11328646] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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].
[4]	"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: 9892355] [Abstract] Cited for: INTERACTION WITH GABARAP.
[5]	"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: 11326274] [Abstract] Cited for: VARIANT GEFS+3 MET-328.
[6]	"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: 11326275] [Abstract] Cited for: VARIANT ECA2/FEB8 GLN-82.
[7]	"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: 16924025] [Abstract] Cited for: VARIANT FEB8 GLY-177.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Cross-references

Sequence databases
EMBLGenBankDDBJ	X15376 mRNA. Translation: CAA33437.1. AF165124 Genomic DNA. Translation: AAD50273.1. BC069348 mRNA. Translation: AAH69348.1. BC074795 mRNA. Translation: AAH74795.1.
IPI	IPI00000023.
PIR	S03905.
RefSeq	NP_000807.2.
UniGene	Hs.7195
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	P18507.
Genome annotation databases
Ensembl	ENSG00000113327. Homo sapiens. [Contig view]
GeneID	2566.
KEGG	hsa:2566.
Organism-specific databases
GeneCards	GC05P161427.
H-InvDB	HIX0024813.
HGNC	HGNC:4087. GABRG2.
MIM	137164. gene. 604233. phenotype. 607208. phenotype. 607681. phenotype. 611277. phenotype.
Orphanet	33069. Dravet syndrome. 64280. Epilepsy, childhood absence. 36387. Generalized epilepsy with febrile seizures-plus context.
PharmGKB	PA28501.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P18507.
Gene expression databases
ArrayExpress	P18507.
Bgee	P18507.
CleanEx	HS_GABRG2.
GermOnline	ENSG00000113327. Homo sapiens.
Family and domain databases
InterPro	IPR006028. GABAA_rcpt. IPR005439. GABBAg2_rcpt. IPR005437. GABBAg_rcpt. IPR006029. Neu_channel_TM. IPR006202. Neur_chan_lig_bd. IPR006201. Neur_channel. IPR018000. Neurotransmitter_ion_chnl_CS. [Graphical view]
Gene3D	G3DSA:2.70.170.10. Neur_chan_lig_bd. 1 hit.
PANTHER	PTHR18945. Neur_channel. 1 hit.
Pfam	PF02931. Neur_chan_LBD. 1 hit. PF02932. Neur_chan_memb. 1 hit. [Graphical view]
PRINTS	PR00253. GABAARECEPTR. PR01620. GABAARGAMMA. PR01622. GABAARGAMMA2. PR00252. NRIONCHANNEL.
TIGRFAMs	TIGR00860. LIC. 1 hit.
PROSITE	PS00236. NEUROTR_ION_CHANNEL. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	10145.
SOURCE	Search...

Entry information

Entry name

GBRG2_HUMAN

Accession

Primary (citable) accession number: P18507
Secondary accession number(s): Q6GRL6, Q9UN15

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	October 17, 2006
Last modified:	June 16, 2009
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)