UniProt functional annotation for P23415



	UniProt functional annotation for P23415

UniProt code: P23415.

Organism: Homo sapiens (Human).

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

Function: Glycine receptors are ligand-gated chloride channels (PubMed:23994010, PubMed:25730860). Channel opening is triggered by extracellular glycine (PubMed:2155780, PubMed:7920629, PubMed:14551753, PubMed:16144831, PubMed:22715885, PubMed:22973015, PubMed:25973519, PubMed:9009272). Channel opening is also triggered by taurine and beta- alanine (PubMed:16144831, PubMed:9009272). Channel characteristics depend on the subunit composition; heteropentameric channels are activated by lower glycine levels and display faster desensitization (PubMed:14551753). Plays an important role in the down-regulation of neuronal excitability (PubMed:8298642, PubMed:9009272). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Channel activity is potentiated by ethanol (PubMed:25973519). Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (By similarity). {ECO:0000250|UniProtKB:Q64018, ECO:0000269|PubMed:14551753, ECO:0000269|PubMed:16144831, ECO:0000269|PubMed:2155780, ECO:0000269|PubMed:22715885, ECO:0000269|PubMed:22973015, ECO:0000269|PubMed:23994010, ECO:0000269|PubMed:25445488, ECO:0000269|PubMed:25730860, ECO:0000269|PubMed:25973519, ECO:0000269|PubMed:7920629, ECO:0000269|PubMed:7925268, ECO:0000269|PubMed:9009272, ECO:0000305|PubMed:8298642}.

Activity regulation: Channel activity is potentiated by nanomolar concentrations of Zn(2+); half-maximal activation is observed with 37 nM Zn(2+) (PubMed:16144831). Inhibited by higher Zn(2+) levels; haf- maximal inhibition occurs at 20 uM Zn(2+) (PubMed:16144831). Inhibited by strychnine (PubMed:2155780, PubMed:16144831, PubMed:25445488). Inhibited by lindane (PubMed:25445488). Inhibited by picrotoxin (PubMed:22715885, PubMed:23994010, PubMed:25730860). Strychnine binding locks the channel in a closed conformation and prevents channel opening in response to extracellular glycine (By similarity). {ECO:0000250|UniProtKB:O93430, ECO:0000269|PubMed:16144831, ECO:0000269|PubMed:2155780, ECO:0000269|PubMed:22715885, ECO:0000269|PubMed:23994010, ECO:0000269|PubMed:25445488, ECO:0000269|PubMed:25730860}.

Biophysicochemical properties: Kinetic parameters: Note=A concentration of about 0.02 mM glycine results in half-maximal channel conductance for homopentamers. A concentration of 0.018 mM glycine results in half-maximal channel conductance for homopentamers upon heterologous expression in cultured human embryonic kidney cells (PubMed:9009272). A concentration of 0.027 mM glycine results in half-maximal channel conductance for homopentamers upon heterologous expression in cultured human embryonic kidney cells (PubMed:7920629). {ECO:0000269|PubMed:7920629, ECO:0000269|PubMed:9009272};

Subunit: Homopentamer (in vitro) (PubMed:22715885, PubMed:22973015, PubMed:23994010, PubMed:25730860). Interacts with GLRB to form heteropentameric channels; this is probably the predominant form in vivo (PubMed:22715885, PubMed:22973015, PubMed:25445488). Heteropentamer composed of two GLRA1 and three GLRB (PubMed:22715885). Heteropentamer composed of three GLRA1 and two GLRB (PubMed:22973015). Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different (PubMed:14551753, PubMed:22715885, PubMed:22973015, PubMed:25445488, PubMed:23994010, PubMed:25730860). {ECO:0000269|PubMed:14551753, ECO:0000269|PubMed:22715885, ECO:0000269|PubMed:22973015, ECO:0000269|PubMed:23994010, ECO:0000269|PubMed:25445488, ECO:0000269|PubMed:25730860}.

Subcellular location: Cell junction, synapse, postsynaptic cell membrane {ECO:0000250|UniProtKB:Q64018}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q64018}. Cell junction, synapse {ECO:0000250|UniProtKB:Q64018}. Perikaryon {ECO:0000250|UniProtKB:Q64018}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q64018}. Cell membrane {ECO:0000269|PubMed:14551753, ECO:0000269|PubMed:16144831, ECO:0000269|PubMed:2155780, ECO:0000269|PubMed:22715885, ECO:0000269|PubMed:22973015, ECO:0000269|PubMed:24108130, ECO:0000269|PubMed:25445488, ECO:0000269|PubMed:25730860, ECO:0000269|PubMed:25973519, ECO:0000269|PubMed:7920629, ECO:0000269|PubMed:7925268, ECO:0000269|PubMed:9009272}; Multi-pass membrane protein {ECO:0000269|PubMed:23994010, ECO:0000269|PubMed:25730860, ECO:0000305|PubMed:2155780}.

Domain: The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. In the absence of the extracellular domain, the channel is in a constitutively open conformation (PubMed:23994010). Channel opening is effected by an outward rotation of the transmembrane domains that increases the diameter of the pore (By similarity). {ECO:0000250|UniProtKB:O93430, ECO:0000269|PubMed:23994010}.

Disease: Hyperekplexia 1 (HKPX1) [MIM:149400]: A neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli. {ECO:0000269|PubMed:10514101, ECO:0000269|PubMed:24108130, ECO:0000269|PubMed:25730860, ECO:0000269|PubMed:7611730, ECO:0000269|PubMed:7881416, ECO:0000269|PubMed:7925268, ECO:0000269|PubMed:7981700, ECO:0000269|PubMed:8298642, ECO:0000269|PubMed:8571969, ECO:0000269|PubMed:8733061, ECO:0000269|PubMed:9009272, ECO:0000269|PubMed:9067762, ECO:0000269|PubMed:9920650, ECO:0000269|Ref.18}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: The alpha subunit binds strychnine. {ECO:0000269|PubMed:2155780}.

Similarity: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRA1 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:		Glycine receptors are ligand-gated chloride channels (PubMed:23994010, PubMed:25730860). Channel opening is triggered by extracellular glycine (PubMed:2155780, PubMed:7920629, PubMed:14551753, PubMed:16144831, PubMed:22715885, PubMed:22973015, PubMed:25973519, PubMed:9009272). Channel opening is also triggered by taurine and beta- alanine (PubMed:16144831, PubMed:9009272). Channel characteristics depend on the subunit composition; heteropentameric channels are activated by lower glycine levels and display faster desensitization (PubMed:14551753). Plays an important role in the down-regulation of neuronal excitability (PubMed:8298642, PubMed:9009272). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Channel activity is potentiated by ethanol (PubMed:25973519). Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (By similarity). {ECO:0000250\|UniProtKB:Q64018, ECO:0000269\|PubMed:14551753, ECO:0000269\|PubMed:16144831, ECO:0000269\|PubMed:2155780, ECO:0000269\|PubMed:22715885, ECO:0000269\|PubMed:22973015, ECO:0000269\|PubMed:23994010, ECO:0000269\|PubMed:25445488, ECO:0000269\|PubMed:25730860, ECO:0000269\|PubMed:25973519, ECO:0000269\|PubMed:7920629, ECO:0000269\|PubMed:7925268, ECO:0000269\|PubMed:9009272, ECO:0000305\|PubMed:8298642}.


Activity regulation:		Channel activity is potentiated by nanomolar concentrations of Zn(2+); half-maximal activation is observed with 37 nM Zn(2+) (PubMed:16144831). Inhibited by higher Zn(2+) levels; haf- maximal inhibition occurs at 20 uM Zn(2+) (PubMed:16144831). Inhibited by strychnine (PubMed:2155780, PubMed:16144831, PubMed:25445488). Inhibited by lindane (PubMed:25445488). Inhibited by picrotoxin (PubMed:22715885, PubMed:23994010, PubMed:25730860). Strychnine binding locks the channel in a closed conformation and prevents channel opening in response to extracellular glycine (By similarity). {ECO:0000250\|UniProtKB:O93430, ECO:0000269\|PubMed:16144831, ECO:0000269\|PubMed:2155780, ECO:0000269\|PubMed:22715885, ECO:0000269\|PubMed:23994010, ECO:0000269\|PubMed:25445488, ECO:0000269\|PubMed:25730860}.
Biophysicochemical properties:		Kinetic parameters: Note=A concentration of about 0.02 mM glycine results in half-maximal channel conductance for homopentamers. A concentration of 0.018 mM glycine results in half-maximal channel conductance for homopentamers upon heterologous expression in cultured human embryonic kidney cells (PubMed:9009272). A concentration of 0.027 mM glycine results in half-maximal channel conductance for homopentamers upon heterologous expression in cultured human embryonic kidney cells (PubMed:7920629). {ECO:0000269\|PubMed:7920629, ECO:0000269\|PubMed:9009272};
Subunit:		Homopentamer (in vitro) (PubMed:22715885, PubMed:22973015, PubMed:23994010, PubMed:25730860). Interacts with GLRB to form heteropentameric channels; this is probably the predominant form in vivo (PubMed:22715885, PubMed:22973015, PubMed:25445488). Heteropentamer composed of two GLRA1 and three GLRB (PubMed:22715885). Heteropentamer composed of three GLRA1 and two GLRB (PubMed:22973015). Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different (PubMed:14551753, PubMed:22715885, PubMed:22973015, PubMed:25445488, PubMed:23994010, PubMed:25730860). {ECO:0000269\|PubMed:14551753, ECO:0000269\|PubMed:22715885, ECO:0000269\|PubMed:22973015, ECO:0000269\|PubMed:23994010, ECO:0000269\|PubMed:25445488, ECO:0000269\|PubMed:25730860}.
Subcellular location:		Cell junction, synapse, postsynaptic cell membrane {ECO:0000250\|UniProtKB:Q64018}; Multi-pass membrane protein {ECO:0000250\|UniProtKB:Q64018}. Cell junction, synapse {ECO:0000250\|UniProtKB:Q64018}. Perikaryon {ECO:0000250\|UniProtKB:Q64018}. Cell projection, dendrite {ECO:0000250\|UniProtKB:Q64018}. Cell membrane {ECO:0000269\|PubMed:14551753, ECO:0000269\|PubMed:16144831, ECO:0000269\|PubMed:2155780, ECO:0000269\|PubMed:22715885, ECO:0000269\|PubMed:22973015, ECO:0000269\|PubMed:24108130, ECO:0000269\|PubMed:25445488, ECO:0000269\|PubMed:25730860, ECO:0000269\|PubMed:25973519, ECO:0000269\|PubMed:7920629, ECO:0000269\|PubMed:7925268, ECO:0000269\|PubMed:9009272}; Multi-pass membrane protein {ECO:0000269\|PubMed:23994010, ECO:0000269\|PubMed:25730860, ECO:0000305\|PubMed:2155780}.
Domain:		The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. In the absence of the extracellular domain, the channel is in a constitutively open conformation (PubMed:23994010). Channel opening is effected by an outward rotation of the transmembrane domains that increases the diameter of the pore (By similarity). {ECO:0000250\|UniProtKB:O93430, ECO:0000269\|PubMed:23994010}.
Disease:		Hyperekplexia 1 (HKPX1) [MIM:149400]: A neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli. {ECO:0000269\|PubMed:10514101, ECO:0000269\|PubMed:24108130, ECO:0000269\|PubMed:25730860, ECO:0000269\|PubMed:7611730, ECO:0000269\|PubMed:7881416, ECO:0000269\|PubMed:7925268, ECO:0000269\|PubMed:7981700, ECO:0000269\|PubMed:8298642, ECO:0000269\|PubMed:8571969, ECO:0000269\|PubMed:8733061, ECO:0000269\|PubMed:9009272, ECO:0000269\|PubMed:9067762, ECO:0000269\|PubMed:9920650, ECO:0000269\|Ref.18}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		The alpha subunit binds strychnine. {ECO:0000269\|PubMed:2155780}.
Similarity:		Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRA1 sub-subfamily. {ECO:0000305}.