UniProt functional annotation for P47870



	UniProt functional annotation for P47870

UniProt code: P47870.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:8264558, PubMed:19763268, PubMed:27789573, PubMed:29950725). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:23909897, PubMed:25489750). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (By similarity). The alpha1/beta2/gamma2 receptor and the alpha2/beta2/gamma2 receptor exhibit synaptogenic activity (PubMed:23909897, PubMed:25489750). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity). {ECO:0000250|UniProtKB:P63137, ECO:0000250|UniProtKB:P63138, ECO:0000269|PubMed:19763268, ECO:0000269|PubMed:23909897, ECO:0000269|PubMed:25489750, ECO:0000269|PubMed:27789573, ECO:0000269|PubMed:29950725, ECO:0000269|PubMed:8264558}.

Activity regulation: Allosterically activated by benzodiazepines (PubMed:29950725). Allosterically activated by the anesthetic etomidate (By similarity). Inhibited by the antagonist bicuculline (PubMed:29950725). {ECO:0000250|UniProtKB:P0C2W5, ECO:0000269|PubMed:29950725}.

Subunit: Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:8264558, PubMed:29950725). Interacts with UBQLN1 (By similarity). Interacts with KCTD8, KCTD12 and KCTD16; this interaction determines the pharmacology and kinetics of the receptor response, the KCTD proteins markedly accelerating the GABA-B response, although to different extents (By similarity). May interact with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). {ECO:0000250|UniProtKB:P63138, ECO:0000269|PubMed:29950725, ECO:0000269|PubMed:8264558}.

Subcellular location: Cell junction, synapse, postsynaptic cell membrane {ECO:0000250|UniProtKB:P63137}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:19763268, ECO:0000269|PubMed:8264558}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P63138}.

Tissue specificity: Isoform 1 and isoform 2 show reduced expression in schizophrenic brain. Isoform 3 shows increased expression in schizophrenic and bipolar disorder brains while isoform 4 shows reduced expression. {ECO:0000269|PubMed:16983389, ECO:0000269|PubMed:19763268}.

Domain: The extracellular domain contributes to synaptic contact formation. {ECO:0000250|UniProtKB:P63137}.

Ptm: Glycosylated. {ECO:0000250|UniProtKB:P63137}.

Disease: Epileptic encephalopathy, infantile or early childhood, 2 (IECEE2) [MIM:617829]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE2 is an autosomal dominant condition with variable age at seizure onset, ranging from early infancy to 6 years. {ECO:0000269|PubMed:25124326, ECO:0000269|PubMed:27789573, ECO:0000269|PubMed:29100083}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB2 sub- subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:8264558, PubMed:19763268, PubMed:27789573, PubMed:29950725). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:23909897, PubMed:25489750). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (By similarity). The alpha1/beta2/gamma2 receptor and the alpha2/beta2/gamma2 receptor exhibit synaptogenic activity (PubMed:23909897, PubMed:25489750). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity). {ECO:0000250\|UniProtKB:P63137, ECO:0000250\|UniProtKB:P63138, ECO:0000269\|PubMed:19763268, ECO:0000269\|PubMed:23909897, ECO:0000269\|PubMed:25489750, ECO:0000269\|PubMed:27789573, ECO:0000269\|PubMed:29950725, ECO:0000269\|PubMed:8264558}.


Activity regulation:		Allosterically activated by benzodiazepines (PubMed:29950725). Allosterically activated by the anesthetic etomidate (By similarity). Inhibited by the antagonist bicuculline (PubMed:29950725). {ECO:0000250\|UniProtKB:P0C2W5, ECO:0000269\|PubMed:29950725}.
Subunit:		Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:8264558, PubMed:29950725). Interacts with UBQLN1 (By similarity). Interacts with KCTD8, KCTD12 and KCTD16; this interaction determines the pharmacology and kinetics of the receptor response, the KCTD proteins markedly accelerating the GABA-B response, although to different extents (By similarity). May interact with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). {ECO:0000250\|UniProtKB:P63138, ECO:0000269\|PubMed:29950725, ECO:0000269\|PubMed:8264558}.
Subcellular location:		Cell junction, synapse, postsynaptic cell membrane {ECO:0000250\|UniProtKB:P63137}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000269\|PubMed:19763268, ECO:0000269\|PubMed:8264558}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane {ECO:0000250\|UniProtKB:P63138}.
Tissue specificity:		Isoform 1 and isoform 2 show reduced expression in schizophrenic brain. Isoform 3 shows increased expression in schizophrenic and bipolar disorder brains while isoform 4 shows reduced expression. {ECO:0000269\|PubMed:16983389, ECO:0000269\|PubMed:19763268}.
Domain:		The extracellular domain contributes to synaptic contact formation. {ECO:0000250\|UniProtKB:P63137}.
Ptm:		Glycosylated. {ECO:0000250\|UniProtKB:P63137}.
Disease:		Epileptic encephalopathy, infantile or early childhood, 2 (IECEE2) [MIM:617829]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE2 is an autosomal dominant condition with variable age at seizure onset, ranging from early infancy to 6 years. {ECO:0000269\|PubMed:25124326, ECO:0000269\|PubMed:27789573, ECO:0000269\|PubMed:29100083}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB2 sub- subfamily. {ECO:0000305}.