UniProt functional annotation for P18507



	UniProt functional annotation for P18507

UniProt code: P18507.

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:2538761, 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, PubMed:27864268). 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 alpha1/beta3/gamma2 receptor exhibit synaptogenic activity (PubMed:23909897, PubMed:25489750). The alpha2/beta2/gamma2 receptor exhibits synatogenic activity whereas 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 (By similarity). {ECO:0000250|UniProtKB:P22723, ECO:0000269|PubMed:23909897, ECO:0000269|PubMed:2538761, ECO:0000269|PubMed:25489750, ECO:0000269|PubMed:27864268, ECO:0000269|PubMed:29950725}.

Activity regulation: Allosterically activated by benzodiazepines (PubMed:2538761, PubMed:29950725). Activated by pentobarbitol (By similarity). Inhibited by the antagonist bicuculline (PubMed:29950725). Inhibited by zinc ions (PubMed:27864268). {ECO:0000250|UniProtKB:P18508, ECO:0000269|PubMed:2538761, ECO:0000269|PubMed:27864268, ECO:0000269|PubMed:29950725}.

Subunit: Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:2538761, PubMed:29950725). Interacts with GABARAP (PubMed:9892355). Interacts 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 SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology (By similarity). {ECO:0000250|UniProtKB:P18508, ECO:0000250|UniProtKB:P22723, ECO:0000269|PubMed:2538761, ECO:0000269|PubMed:29950725, ECO:0000269|PubMed:9892355}.

Subcellular location: Cell junction, synapse, postsynaptic cell membrane {ECO:0000269|PubMed:2538761}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:2538761, ECO:0000269|PubMed:27864268}; Multi-pass membrane protein {ECO:0000255}. Cell projection, dendrite {ECO:0000250|UniProtKB:P22723}. Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P18508}.

Domain: The extracellular domain contributes to synaptic contact formation. {ECO:0000250|UniProtKB:P22723}.

Ptm: Glycosylated. {ECO:0000250|UniProtKB:P22723}.

Ptm: Palmitoylated by ZDHHC3/GODZ; required for the accumulation of GABA(A) receptors at the postsynaptic membrane of inhibitory GABAergic synapses. {ECO:0000250|UniProtKB:P22723}.

Disease: Developmental and epileptic encephalopathy 74 (DEE74) [MIM:618396]: A form of epileptic encephalopathy, a heterogeneous group of severe early-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. DEE74 is an autosomal dominant form with onset in the first year of life. {ECO:0000269|PubMed:27864268}. Note=The gene represented in this entry is involved in disease pathogenesis.

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. {ECO:0000269|PubMed:11326275}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Disease: Febrile seizures, familial, 8 (FEB8) [MIM:607681]: 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. {ECO:0000269|PubMed:16924025}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Generalized epilepsy with febrile seizures plus 3 (GEFS+3) [MIM:607681]: 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. {ECO:0000269|PubMed:11326274, ECO:0000269|PubMed:23708187}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: This subunit carries the benzodiazepine binding site.

Similarity: 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. {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:2538761, 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, PubMed:27864268). 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 alpha1/beta3/gamma2 receptor exhibit synaptogenic activity (PubMed:23909897, PubMed:25489750). The alpha2/beta2/gamma2 receptor exhibits synatogenic activity whereas 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 (By similarity). {ECO:0000250\|UniProtKB:P22723, ECO:0000269\|PubMed:23909897, ECO:0000269\|PubMed:2538761, ECO:0000269\|PubMed:25489750, ECO:0000269\|PubMed:27864268, ECO:0000269\|PubMed:29950725}.


Activity regulation:		Allosterically activated by benzodiazepines (PubMed:2538761, PubMed:29950725). Activated by pentobarbitol (By similarity). Inhibited by the antagonist bicuculline (PubMed:29950725). Inhibited by zinc ions (PubMed:27864268). {ECO:0000250\|UniProtKB:P18508, ECO:0000269\|PubMed:2538761, ECO:0000269\|PubMed:27864268, ECO:0000269\|PubMed:29950725}.
Subunit:		Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:2538761, PubMed:29950725). Interacts with GABARAP (PubMed:9892355). Interacts 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 SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology (By similarity). {ECO:0000250\|UniProtKB:P18508, ECO:0000250\|UniProtKB:P22723, ECO:0000269\|PubMed:2538761, ECO:0000269\|PubMed:29950725, ECO:0000269\|PubMed:9892355}.
Subcellular location:		Cell junction, synapse, postsynaptic cell membrane {ECO:0000269\|PubMed:2538761}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000269\|PubMed:2538761, ECO:0000269\|PubMed:27864268}; Multi-pass membrane protein {ECO:0000255}. Cell projection, dendrite {ECO:0000250\|UniProtKB:P22723}. Cytoplasmic vesicle membrane {ECO:0000250\|UniProtKB:P18508}.
Domain:		The extracellular domain contributes to synaptic contact formation. {ECO:0000250\|UniProtKB:P22723}.
Ptm:		Glycosylated. {ECO:0000250\|UniProtKB:P22723}.
Ptm:		Palmitoylated by ZDHHC3/GODZ; required for the accumulation of GABA(A) receptors at the postsynaptic membrane of inhibitory GABAergic synapses. {ECO:0000250\|UniProtKB:P22723}.
Disease:		Developmental and epileptic encephalopathy 74 (DEE74) [MIM:618396]: A form of epileptic encephalopathy, a heterogeneous group of severe early-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. DEE74 is an autosomal dominant form with onset in the first year of life. {ECO:0000269\|PubMed:27864268}. Note=The gene represented in this entry is involved in disease pathogenesis.
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. {ECO:0000269\|PubMed:11326275}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease:		Febrile seizures, familial, 8 (FEB8) [MIM:607681]: 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. {ECO:0000269\|PubMed:16924025}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Generalized epilepsy with febrile seizures plus 3 (GEFS+3) [MIM:607681]: 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. {ECO:0000269\|PubMed:11326274, ECO:0000269\|PubMed:23708187}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		This subunit carries the benzodiazepine binding site.
Similarity:		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. {ECO:0000305}.