P18507 (GBRG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.5
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	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.7 Familial febrile convulsions 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.8 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.6 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 process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Epilepsy
Domain	Signal Transmembrane Transmembrane helix
Ligand	Chloride
Molecular function	Chloride channel Ion channel
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	gamma-aminobutyric acid signaling pathway Traceable author statement Ref.1. Source: ProtInc ion transmembrane transport Traceable author statement. Source: Reactome synaptic transmission, GABAergic Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW dendrite membrane Inferred from sequence or structural similarity. Source: BHF-UCL integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GABA-A receptor activity Inferred from electronic annotation. Source: InterPro 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 2 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

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	Helical; Probable
	Transmembrane	300 – 322	23	Helical; Probable
	Transmembrane	334 – 356	23	Helical; Probable
	Topological domain	357 – 443	87	Cytoplasmic Probable
	Transmembrane	444 – 466	23	Helical; 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
	Alternative sequence	376	1	P → PLLRMFSFK in isoform 2.		VSP_041124
	Natural variant	79	1	N → S Found in a patient with generalized tonic-clonic seizures. Ref.9		VAR_065226
	Natural variant	82	1	R → Q in ECA2 and FEB8; abolishes in vitro sensitivity to diazepam. Ref.7 Corresponds to variant rs28933070 [ dbSNP | Ensembl ].		VAR_014265
	Natural variant	177	1	R → G in FEB8. Ref.8		VAR_038602
	Natural variant	328	1	K → M in GEFS+3. Ref.6		VAR_014266
	Natural variant	357	1	H → R. Ref.3 Corresponds to variant rs17855003 [ dbSNP | Ensembl ].		VAR_065163
Experimental info
	Sequence conflict	120	1	T → M in CAA33437. Ref.1
	Sequence conflict	181	1	T → S in CAA33437. Ref.1
	Sequence conflict	384 – 385	2	Missing no nucleotide entry Ref.4
	Sequence conflict	399	1	E → D no nucleotide entry Ref.4
	Sequence conflict	438 – 439	2	IA → RI no nucleotide entry Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: DE142F62846576DF	FASTA	475	55,186
	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 KKKKNPLLRM FSFKAPTIDI RPRSATIQMN NATHLQERDE EYGYECLDGK 430 440 450 460 470 DCASFFCCFE DCRTGAWRHG RIHIRIAKMD SYARIFFPTA FCLFNLVYWV SYLYL

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] [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 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.
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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. BC059389 mRNA. Translation: AAH59389.1. BC069348 mRNA. Translation: AAH69348.1. BC074795 mRNA. Translation: AAH74795.1.
IPI	IPI00000023. IPI00419200.
PIR	S03905.
RefSeq	NP_000807.2. NM_000816.3. NP_944494.1. NM_198904.2.
UniGene	Hs.7195.
3D structure databases
ProteinModelPortal	P18507.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000410732.
PTM databases
PhosphoSite	P18507.
Polymorphism databases
DMDM	116242488.
Proteomic databases
PaxDb	P18507.
PRIDE	P18507.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000356592; ENSP00000349000; ENSG00000113327. ENST00000361925; ENSP00000354651; ENSG00000113327.
GeneID	2566.
KEGG	hsa:2566.
UCSC	uc003lyy.4. human. uc003lyz.4. human.
Organism-specific databases
CTD	2566.
GeneCards	GC05P161494.
HGNC	HGNC:4087. GABRG2.
MIM	137164. gene. 604233. phenotype. 607208. phenotype. 607681. phenotype. 611277. phenotype.
neXtProt	NX_P18507.
Orphanet	64280. Childhood absence epilepsy. 33069. Dravet syndrome. 36387. Generalized epilepsy with febrile seizures-plus context.
PharmGKB	PA28501.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG238757.
HOGENOM	HOG000231337.
HOVERGEN	HBG051707.
KO	K05186.
OrthoDB	EOG44BB25.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P18507.
Bgee	P18507.
CleanEx	HS_GABRG2.
Genevestigator	P18507.
GermOnline	ENSG00000113327. Homo sapiens.
Family and domain databases
Gene3D	2.70.170.10. 1 hit.
InterPro	IPR006028. 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]
PANTHER	PTHR18945. PTHR18945. 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.
SUPFAM	SSF90112. Neu_channel_TM. 1 hit. SSF63712. Neur_chan_LBD. 1 hit.
TIGRFAMs	TIGR00860. LIC. 1 hit.
PROSITE	PS00236. NEUROTR_ION_CHANNEL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P18507.
ChEMBL	CHEMBL1788.
GenomeRNAi	2566.
NextBio	10145.
SOURCE	Search...

Entry information

Entry name

GBRG2_HUMAN

Accession

Primary (citable) accession number: P18507
Secondary accession number(s): Q6GRL6 , Q6PCC3, Q9UDB3, Q9UN15

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 144 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.