P28472 (GBRB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gamma-aminobutyric acid receptor subunit beta-3

Alternative name(s):
GABA(A) receptor subunit beta-3

Gene names

Name:

GABRB3

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	473 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	Binds UBQLN1 By similarity. Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.
Subcellular location	Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.
Involvement in disease	Defects in GABRB3 are associated with chronic insomnia, a condition of inability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition. Epilepsy, childhood absence 5 (ECA5) [MIM:612269]: 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. Absence seizures may either remit or persist into adulthood. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB3 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 Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cochlea development Inferred from electronic annotation. Source: Compara inner ear receptor cell development Inferred from electronic annotation. Source: Compara innervation Inferred from electronic annotation. Source: Compara ion transmembrane transport Traceable author statement. Source: Reactome sensory perception of sound Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW 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 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]

Note: Isoforms differ in their signal region.

Isoform 1 (identifier: P28472-1)

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: P28472-2)

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

Isoform 3 (identifier: P28472-3)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 473	448	Gamma-aminobutyric acid receptor subunit beta-3		PRO_0000000462
Regions
	Topological domain	26 – 245	220	Extracellular Probable
	Transmembrane	246 – 267	22	Helical; Probable
	Transmembrane	271 – 293	23	Helical; Probable
	Transmembrane	305 – 327	23	Helical; Probable
	Topological domain	328 – 450	123	Cytoplasmic Probable
	Transmembrane	451 – 472	22	Helical; Probable
Amino acid modifications
	Glycosylation	33	1	N-linked (GlcNAc...) Potential
	Glycosylation	105	1	N-linked (GlcNAc...) Potential
	Glycosylation	174	1	N-linked (GlcNAc...) Potential
	Disulfide bond	161 ↔ 175		By similarity
Natural variations
	Alternative sequence	1 – 26	26	MWGLA…VCCAQ → MCSGLLELLLPIWLSWTLGT RGSEPR in isoform 2.		VSP_000088
	Alternative sequence	3 – 80	78	GLAGG…SEVNM → ATYQTEE in isoform 3.		VSP_046126
	Natural variant	32	1	G → R in ECA5; the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. Ref.9		VAR_047957
	Natural variant	173	1	Q → L. Ref.5 Corresponds to variant rs17850679 [ dbSNP | Ensembl ].		VAR_047958
	Natural variant	217	1	R → H in 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. Ref.8		VAR_047959
Isoform 2:
	Natural variant	11	1	P → S in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. Corresponds to variant rs25409 [ dbSNP | Ensembl ].
	Natural variant	15	1	S → F in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type.
Experimental info
	Sequence conflict	193	1	W → R in BAH11997. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: D63597F7FBC69E71	FASTA	473	54,116
	10 20 30 40 50 60 MWGLAGGRLF GIFSAPVLVA VVCCAQSVND PGNMSFVKET VDKLLKGYDI RLRPDFGGPP 70 80 90 100 110 120 VCVGMNIDIA SIDMVSEVNM DYTLTMYFQQ YWRDKRLAYS GIPLNLTLDN RVADQLWVPD 130 140 150 160 170 180 TYFLNDKKSF VHGVTVKNRM IRLHPDGTVL YGLRITTTAA CMMDLRRYPL DEQNCTLEIE 190 200 210 220 230 240 SYGYTTDDIE FYWRGGDKAV TGVERIELPQ FSIVEHRLVS RNVVFATGAY PRLSLSFRLK 250 260 270 280 290 300 RNIGYFILQT YMPSILITIL SWVSFWINYD ASAARVALGI TTVLTMTTIN THLRETLPKI 310 320 330 340 350 360 PYVKAIDMYL MGCFVFVFLA LLEYAFVNYI FFGRGPQRQK KLAEKTAKAK NDRSKSESNR 370 380 390 400 410 420 VDAHGNILLT SLEVHNEMNE VSGGIGDTRN SAISFDNSGI QYRKQSMPRE GHGRFLGDRS 430 440 450 460 470 LPHKKTHLRR RSSQLKIKIP DLTDVNAIDR WSRIVFPFTF SLFNLVYWLY YVN
	Isoform 2 [UniParc]. Checksum: 3A7F9A0EB3537D5E	FASTA	473	54,379
	10 20 30 40 50 60 MCSGLLELLL PIWLSWTLGT RGSEPRSVND PGNMSFVKET VDKLLKGYDI RLRPDFGGPP 70 80 90 100 110 120 VCVGMNIDIA SIDMVSEVNM DYTLTMYFQQ YWRDKRLAYS GIPLNLTLDN RVADQLWVPD 130 140 150 160 170 180 TYFLNDKKSF VHGVTVKNRM IRLHPDGTVL YGLRITTTAA CMMDLRRYPL DEQNCTLEIE 190 200 210 220 230 240 SYGYTTDDIE FYWRGGDKAV TGVERIELPQ FSIVEHRLVS RNVVFATGAY PRLSLSFRLK 250 260 270 280 290 300 RNIGYFILQT YMPSILITIL SWVSFWINYD ASAARVALGI TTVLTMTTIN THLRETLPKI 310 320 330 340 350 360 PYVKAIDMYL MGCFVFVFLA LLEYAFVNYI FFGRGPQRQK KLAEKTAKAK NDRSKSESNR 370 380 390 400 410 420 VDAHGNILLT SLEVHNEMNE VSGGIGDTRN SAISFDNSGI QYRKQSMPRE GHGRFLGDRS 430 440 450 460 470 LPHKKTHLRR RSSQLKIKIP DLTDVNAIDR WSRIVFPFTF SLFNLVYWLY YVN
	Isoform 3 [UniParc]. Checksum: 5B5BB0E56D41435A	FASTA	402	46,740
	10 20 30 40 50 60 MWATYQTEED YTLTMYFQQY WRDKRLAYSG IPLNLTLDNR VADQLWVPDT YFLNDKKSFV 70 80 90 100 110 120 HGVTVKNRMI RLHPDGTVLY GLRITTTAAC MMDLRRYPLD EQNCTLEIES YGYTTDDIEF 130 140 150 160 170 180 YWRGGDKAVT GVERIELPQF SIVEHRLVSR NVVFATGAYP RLSLSFRLKR NIGYFILQTY 190 200 210 220 230 240 MPSILITILS WVSFWINYDA SAARVALGIT TVLTMTTINT HLRETLPKIP YVKAIDMYLM 250 260 270 280 290 300 GCFVFVFLAL LEYAFVNYIF FGRGPQRQKK LAEKTAKAKN DRSKSESNRV DAHGNILLTS 310 320 330 340 350 360 LEVHNEMNEV SGGIGDTRNS AISFDNSGIQ YRKQSMPREG HGRFLGDRSL PHKKTHLRRR 370 380 390 400 SSQLKIKIPD LTDVNAIDRW SRIVFPFTFS LFNLVYWLYY VN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The GABAA receptor beta 3 subunit gene: characterization of a human cDNA from chromosome 15q11q13 and mapping to a region of conserved synteny on mouse chromosome 7." Wagstaff J., Chaillet J.R., Lalande M. Genomics 11:1071-1078(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[3]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1), VARIANT LEU-173. Tissue: Eye.
[6]	"A strong promoter element is located between alternative exons of a gene encoding the human gamma-aminobutyric acid-type A receptor beta 3 subunit (GABRB3)." Kirkness E.F., Fraser C.M. J. Biol. Chem. 268:4420-4428(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-80 (ISOFORMS 1 AND 2). Tissue: Fibroblast.
[7]	"Localization of the gene encoding the GABAA receptor beta 3 subunit to the Angelman/Prader-Willi region of human chromosome 15." Wagstaff J., Knoll J.H.M., Fleming J., Kirkness E.F., Martin-Gallardo A., Greenberg F., Graham J.M. Jr., Menninger J., Ward D., Venter J.C., Lalande M. Am. J. Hum. Genet. 49:330-337(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 81-153 AND 183-227.
[8]	"Functional characterization of the new human GABA(A) receptor mutation beta3(R192H)." Buhr A., Bianchi M.T., Baur R., Courtet P., Pignay V., Boulenger J.P., Gallati S., Hinkle D.J., Macdonald R.L., Sigel E. Hum. Genet. 111:154-160(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT INSOMNIA HIS-217, CHARACTERIZATION OF VARIANT INSOMNIA HIS-217.
[9]	"Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy." Tanaka M., Olsen R.W., Medina M.T., Schwartz E., Alonso M.E., Duron R.M., Castro-Ortega R., Martinez-Juarez I.E., Pascual-Castroviejo I., Machado-Salas J., Silva R., Bailey J.N., Bai D., Ochoa A., Jara-Prado A., Pineda G., Macdonald R.L., Delgado-Escueta A.V. Am. J. Hum. Genet. 82:1249-1261(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ECA5 ARG-32, VARIANTS ECA5 SER-11 AND PHE-15 (ISOFORM 2).
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Cross-references

Sequence databases
EMBL GenBank DDBJ	M82919 mRNA. Translation: AAA52511.1. AK295167 mRNA. Translation: BAH11997.1. 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.
IPI	IPI00003467. IPI00217235. IPI00873700.
PIR	A55275. B45468.
RefSeq	NP_000805.1. NM_000814.5. NP_001178249.1. NM_001191320.1. NP_001178250.1. NM_001191321.1. NP_068712.1. NM_021912.4.
UniGene	Hs.302352.
3D structure databases
ProteinModelPortal	P28472.
ModBase	Search...
Protein-protein interaction databases
IntAct	P28472. 1 interaction.
STRING	9606.ENSP00000299267.
PTM databases
PhosphoSite	P28472.
Polymorphism databases
DMDM	120773.
Proteomic databases
PaxDb	P28472.
PRIDE	P28472.
Protocols and materials databases
DNASU	2562.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299267; ENSP00000299267; ENSG00000166206. ENST00000311550; ENSP00000308725; ENSG00000166206. ENST00000400188; ENSP00000383049; ENSG00000166206.
GeneID	2562.
KEGG	hsa:2562.
UCSC	uc001zaz.3. human. uc001zba.3. human.
Organism-specific databases
CTD	2562.
GeneCards	GC15M026788.
HGNC	HGNC:4083. GABRB3.
MIM	137192. gene. 612269. phenotype.
neXtProt	NX_P28472.
Orphanet	106. Autism. 64280. Childhood absence epilepsy.
PharmGKB	PA28497.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG77438.
HOVERGEN	HBG051707.
KO	K05181.
OrthoDB	EOG45756F.
PhylomeDB	P28472.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P28472.
Bgee	P28472.
CleanEx	HS_GABRB3.
Genevestigator	P28472.
GermOnline	ENSG00000166206. Homo sapiens.
Family and domain databases
Gene3D	2.70.170.10. 1 hit.
InterPro	IPR006028. GABAA_rcpt. IPR002289. GABAAb_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	PR01160. GABAARBETA. PR00253. GABAARECEPTR. 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	P28472.
ChEMBL	CHEMBL1847.
ChiTaRS	GABRB3. human.
DrugBank	DB00189. Ethchlorvynol. DB00690. Flurazepam. DB00186. Lorazepam. DB00683. Midazolam.
GenomeRNAi	2562.
NextBio	10121.
SOURCE	Search...

Entry information

Entry name

GBRB3_HUMAN

Accession

Primary (citable) accession number: P28472
Secondary accession number(s): B7Z2W1 , H7BYV8, Q14352, Q96FM5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	May 1, 2013
This is version 134 of the entry and version 1 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.