Reviewed,
UniProtKB/Swiss-Prot P28472 (GBRB3_HUMAN)
Last modified
June 16, 2009.
Version 96.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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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 |
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| 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 | 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 a cause of chonic insomnia. Insomnia is characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition. Defects in GABRB3 are the cause of childhood absence epilepsy type 5 (ECA5) [MIM:612269]. ECA5 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. Absence seizures may either remit or persist into adulthood. Ref.6 |
| Sequence similarities | Belongs to the ligand-gated ionic channel (TC 1.A.9) family. [View classification] |
Ontologies
Alternative products
| This entry describes 2 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 | |||||||||
Sequence annotation (Features) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
| Natural variant | 11 | 1 | P → S in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. dbSNP rs25409. | ||||||
| Natural variant | 15 | 1 | S → F in ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. | ||||||
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 | Probable | ||||||||
| Transmembrane | 271 – 293 | 23 | Probable | ||||||||
| Transmembrane | 305 – 327 | 23 | Probable | ||||||||
| Topological domain | 328 – 450 | 123 | Cytoplasmic Probable | ||||||||
| Transmembrane | 451 – 472 | 22 | 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 | |||||||
| Natural variant | 32 | 1 | G → R in ECA5; the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type. Ref.6 | VAR_047957 | |||||||
| Natural variant | 173 | 1 | Q → L: dbSNP rs17850679. Ref.2 | 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.5 | VAR_047959 | |||||||
Sequences
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References
| « Hide '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: 1664410] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "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], VARIANT LEU-173. Tissue: Eye. |
| [3] | "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: 8382702] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-80 (ISOFORMS 1 AND 2). Tissue: Fibroblast. |
| [4] | "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: 1714232] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 81-153 AND 183-227. |
| [5] | "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: 12189488] [Abstract] Cited for: VARIANT INSOMNIA HIS-217, CHARACTERIZATION OF VARIANT INSOMNIA HIS-217. |
| [6] | "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: 18514161] [Abstract] Cited for: VARIANT ECA5 ARG-32, VARIANTS ECA5 SER-11 AND PHE-15 (ISOFORM 2). |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| M82919 mRNA. Translation: AAA52511.1. BC010641 mRNA. Translation: AAH10641.1. L04311 Genomic DNA. Translation: AAA52508.1. L04311 Genomic DNA. Translation: AAA52507.1. | |
| IPI | IPI00003467. IPI00217235. |
| PIR | A55275. B45468. |
| RefSeq | NP_000805.1. NP_068712.1. |
| UniGene | Hs.302352 Hs.657298 |
3D structure databases | |
| ModBase | Search... |
PTM databases | |
| PhosphoSite | P28472. |
Proteomic databases | |
| PRIDE | P28472. |
Genome annotation databases | |
| Ensembl | ENSG00000166206. Homo sapiens. [Contig view] |
| GeneID | 2562. |
| KEGG | hsa:2562. |
Organism-specific databases | |
| GeneCards | GC15M024342. |
| H-InvDB | HIX0012052. |
| HGNC | HGNC:4083. GABRB3. |
| MIM | 137192. gene. 612269. phenotype. |
| Orphanet | 106. Autism. |
| PharmGKB | PA28497. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | P28472. |
Gene expression databases | |
| ArrayExpress | P28472. |
| Bgee | P28472. |
| CleanEx | HS_GABRB3. |
| GermOnline | ENSG00000166206. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR006028. GABAA_rcpt. IPR002289. GABAAb_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 | PR01160. GABAARBETA. PR00253. GABAARECEPTR. PR00252. NRIONCHANNEL. |
| TIGRFAMs | TIGR00860. LIC. 1 hit. |
| PROSITE | PS00236. NEUROTR_ION_CHANNEL. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00189. Ethchlorvynol. DB00690. Flurazepam. DB00186. Lorazepam. DB00683. Midazolam. |
| NextBio | 10121. |
| SOURCE | Search... |
Entry information
| Entry name | GBRB3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P28472 Secondary accession number(s): Q14352, Q96FM5 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 15 Human chromosome 15: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Protein Spotlight Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with


