UniProt functional annotation for P28472



	UniProt functional annotation for P28472

UniProt code: P28472.

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:18514161, PubMed:22303015, PubMed:26950270, PubMed:22243422, PubMed:24909990). 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: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/beta3/gamma2 receptor exhibits synaptogenic activity (PubMed:25489750). The alpha2/beta3/gamma2 receptor shows very little or no synaptogenic activity (By similarity). Functions also as histamine receptor and mediates cellular responses to histamine (PubMed:18281286). Plays an important role in somatosensation and in the production of antinociception (By similarity). {ECO:0000250|UniProtKB:P63080, ECO:0000269|PubMed:18281286, ECO:0000269|PubMed:18514161, ECO:0000269|PubMed:22243422, ECO:0000269|PubMed:22303015, ECO:0000269|PubMed:24909990, ECO:0000269|PubMed:25489750, ECO:0000269|PubMed:26950270}.

Subunit: Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:22243422, PubMed:18281286, PubMed:18514161, PubMed:24909990). Can form functional homopentamers (in vitro) (PubMed:22303015). Interacts with UBQLN1 (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). Interacts with LHFPL4 (By similarity). Interacts with GIT1; this interaction is required for synaptic GABRB3 surface stability and inhibitory synapse strength (By similarity). {ECO:0000250|UniProtKB:P63079, ECO:0000250|UniProtKB:P63080, ECO:0000269|PubMed:18281286, ECO:0000269|PubMed:18514161, ECO:0000269|PubMed:22243422, ECO:0000269|PubMed:22303015, ECO:0000269|PubMed:24909990}.

Subcellular location: Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein {ECO:0000269|PubMed:24909990}. Cell membrane {ECO:0000269|PubMed:18281286, ECO:0000269|PubMed:18514161, ECO:0000269|PubMed:22243422, ECO:0000269|PubMed:22303015, ECO:0000269|PubMed:24909990, ECO:0000269|PubMed:26950270}; Multi-pass membrane protein {ECO:0000269|PubMed:24909990}. Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P63079}.

Polymorphism: GABRB3 variants may be associated with insomnia, a condition of inability to initiate or maintain sleep [MIM:137192].

Disease: 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. {ECO:0000269|PubMed:18514161, ECO:0000269|PubMed:22303015}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Disease: Developmental and epileptic encephalopathy 43 (DEE43) [MIM:617113]: 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. DEE43 inheritance is autosomal dominant. {ECO:0000269|PubMed:23934111, ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:26950270, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27476654, ECO:0000269|PubMed:27864847}. 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. GABRB3 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:18514161, PubMed:22303015, PubMed:26950270, PubMed:22243422, PubMed:24909990). 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: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/beta3/gamma2 receptor exhibits synaptogenic activity (PubMed:25489750). The alpha2/beta3/gamma2 receptor shows very little or no synaptogenic activity (By similarity). Functions also as histamine receptor and mediates cellular responses to histamine (PubMed:18281286). Plays an important role in somatosensation and in the production of antinociception (By similarity). {ECO:0000250\|UniProtKB:P63080, ECO:0000269\|PubMed:18281286, ECO:0000269\|PubMed:18514161, ECO:0000269\|PubMed:22243422, ECO:0000269\|PubMed:22303015, ECO:0000269\|PubMed:24909990, ECO:0000269\|PubMed:25489750, ECO:0000269\|PubMed:26950270}.


Subunit:		Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:22243422, PubMed:18281286, PubMed:18514161, PubMed:24909990). Can form functional homopentamers (in vitro) (PubMed:22303015). Interacts with UBQLN1 (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). Interacts with LHFPL4 (By similarity). Interacts with GIT1; this interaction is required for synaptic GABRB3 surface stability and inhibitory synapse strength (By similarity). {ECO:0000250\|UniProtKB:P63079, ECO:0000250\|UniProtKB:P63080, ECO:0000269\|PubMed:18281286, ECO:0000269\|PubMed:18514161, ECO:0000269\|PubMed:22243422, ECO:0000269\|PubMed:22303015, ECO:0000269\|PubMed:24909990}.
Subcellular location:		Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein {ECO:0000269\|PubMed:24909990}. Cell membrane {ECO:0000269\|PubMed:18281286, ECO:0000269\|PubMed:18514161, ECO:0000269\|PubMed:22243422, ECO:0000269\|PubMed:22303015, ECO:0000269\|PubMed:24909990, ECO:0000269\|PubMed:26950270}; Multi-pass membrane protein {ECO:0000269\|PubMed:24909990}. Cytoplasmic vesicle membrane {ECO:0000250\|UniProtKB:P63079}.
Polymorphism:		GABRB3 variants may be associated with insomnia, a condition of inability to initiate or maintain sleep [MIM:137192].
Disease:		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. {ECO:0000269\|PubMed:18514161, ECO:0000269\|PubMed:22303015}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease:		Developmental and epileptic encephalopathy 43 (DEE43) [MIM:617113]: 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. DEE43 inheritance is autosomal dominant. {ECO:0000269\|PubMed:23934111, ECO:0000269\|PubMed:25356899, ECO:0000269\|PubMed:26950270, ECO:0000269\|PubMed:26993267, ECO:0000269\|PubMed:27476654, ECO:0000269\|PubMed:27864847}. 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. GABRB3 sub- subfamily. {ECO:0000305}.