UniProt functional annotation for P19491



	UniProt functional annotation for P19491

UniProt code: P19491.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

Function: Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate. Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (PubMed:16037816). {ECO:0000269|PubMed:12015593, ECO:0000269|PubMed:12501192, ECO:0000269|PubMed:12730367, ECO:0000269|PubMed:12872125, ECO:0000269|PubMed:15591246, ECO:0000269|PubMed:16037816, ECO:0000269|PubMed:16192394, ECO:0000269|PubMed:16483599, ECO:0000269|PubMed:17018279, ECO:0000269|PubMed:19265014, ECO:0000269|PubMed:19946266, ECO:0000269|PubMed:20547133, ECO:0000269|PubMed:21172611, ECO:0000269|PubMed:21317873, ECO:0000269|PubMed:21846932, ECO:0000269|PubMed:9351977}.

Subunit: Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. May interact with MPP4. Forms a ternary complex with GRIP1 and CSPG4 (By similarity). Interacts with ATAD1 in an ATP-dependent manner. ATAD1-catalyzed ATP hydrolysis disrupts binding to ATAD1 and to GRIP1 and leads to AMPAR complex disassembly. Interacts with NSF via its C- terminus. Interacts with CACNG2, PRKCABP and GRIP2 (PubMed:27756895). Part of a complex containing GRIA2, NSF and NAPA and/or NAPB. Interacts with PICK1 (via PDZ domain) (By similarity). Interacts with GRIA1 and SYNDIG1. Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (By similarity). Interacts with LRFN1. Found in a complex with GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5. Interacts with OLFM2 (By similarity). Interacts with AP4B1, AP4E1 and AP4M1; probably indirect it mediates the somatodendritic localization of GRIA2 in neurons (By similarity). Forms a complex with NSG1, GRIA2 and STX12; controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (PubMed:16037816). Interacts with IQSEC1; the interaction is required for ARF6 activation (PubMed:20547133). {ECO:0000250|UniProtKB:P23819, ECO:0000269|PubMed:10027300, ECO:0000269|PubMed:10414981, ECO:0000269|PubMed:12015593, ECO:0000269|PubMed:12501192, ECO:0000269|PubMed:16037816, ECO:0000269|PubMed:16483599, ECO:0000269|PubMed:16630835, ECO:0000269|PubMed:16793768, ECO:0000269|PubMed:18817736, ECO:0000269|PubMed:19234459, ECO:0000269|PubMed:19265014, ECO:0000269|PubMed:19946266, ECO:0000269|PubMed:20547133, ECO:0000269|PubMed:21317873, ECO:0000269|PubMed:21496646, ECO:0000269|PubMed:27756895, ECO:0000269|PubMed:9069286, ECO:0000269|PubMed:9697855, ECO:0000269|PubMed:9804426}.

Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P23819}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P23819}. Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Cell junction, synapse, postsynaptic density membrane {ECO:0000250|UniProtKB:P23819}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P23819}. Note=Interaction with CACNG2, CNIH2 and CNIH3 promotes cell surface expression (By similarity). Displays a somatodendritic localization and is excluded from axons in neurons (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P23819}.

Tissue specificity: Detected in forebrain. Detected in dendrites of neuronal cells. Expressed in the pyramidal cell layers of CA1 and CA3 and in the granule cell layer of the dentate gyrus (PubMed:12657670). {ECO:0000269|PubMed:12657670, ECO:0000269|PubMed:14687553, ECO:0000269|PubMed:15240807, ECO:0000269|PubMed:9697855}.

Developmental stage: Detected at low levels in newborns. Levels increase strongly and are highest in hippocampus from 8 to 14 day old animals. Detected at intermediate levels at day 42 (at protein level). {ECO:0000269|PubMed:14687553}.

Induction: Down-regulated in the pyramidal cell layer of CA1 in the hippocampus by global ischemia. {ECO:0000269|PubMed:12657670}.

Domain: The M4 transmembrane segment mediates tetramerization and is required for cell surface expression. {ECO:0000250}.

Ptm: Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-610 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-836 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity). {ECO:0000250}.

Ptm: Phosphorylation at Tyr-876 is required forc interaction with IQSEC1 and ARF6 activation. {ECO:0000269|PubMed:20547133}.

Rna editing: Modified_positions=607 {ECO:0000269|PubMed:1717158}; Note=Fully edited in the brain. Heteromerically expressed edited GLUR2 (R) receptor complexes are impermeable to calcium, whereas the unedited (Q) forms are highly permeable to divalent ions (By similarity). {ECO:0000250};

Miscellaneous: The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate.

Similarity: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA2 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate. Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (PubMed:16037816). {ECO:0000269\|PubMed:12015593, ECO:0000269\|PubMed:12501192, ECO:0000269\|PubMed:12730367, ECO:0000269\|PubMed:12872125, ECO:0000269\|PubMed:15591246, ECO:0000269\|PubMed:16037816, ECO:0000269\|PubMed:16192394, ECO:0000269\|PubMed:16483599, ECO:0000269\|PubMed:17018279, ECO:0000269\|PubMed:19265014, ECO:0000269\|PubMed:19946266, ECO:0000269\|PubMed:20547133, ECO:0000269\|PubMed:21172611, ECO:0000269\|PubMed:21317873, ECO:0000269\|PubMed:21846932, ECO:0000269\|PubMed:9351977}.


Subunit:		Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. May interact with MPP4. Forms a ternary complex with GRIP1 and CSPG4 (By similarity). Interacts with ATAD1 in an ATP-dependent manner. ATAD1-catalyzed ATP hydrolysis disrupts binding to ATAD1 and to GRIP1 and leads to AMPAR complex disassembly. Interacts with NSF via its C- terminus. Interacts with CACNG2, PRKCABP and GRIP2 (PubMed:27756895). Part of a complex containing GRIA2, NSF and NAPA and/or NAPB. Interacts with PICK1 (via PDZ domain) (By similarity). Interacts with GRIA1 and SYNDIG1. Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (By similarity). Interacts with LRFN1. Found in a complex with GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5. Interacts with OLFM2 (By similarity). Interacts with AP4B1, AP4E1 and AP4M1; probably indirect it mediates the somatodendritic localization of GRIA2 in neurons (By similarity). Forms a complex with NSG1, GRIA2 and STX12; controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (PubMed:16037816). Interacts with IQSEC1; the interaction is required for ARF6 activation (PubMed:20547133). {ECO:0000250\|UniProtKB:P23819, ECO:0000269\|PubMed:10027300, ECO:0000269\|PubMed:10414981, ECO:0000269\|PubMed:12015593, ECO:0000269\|PubMed:12501192, ECO:0000269\|PubMed:16037816, ECO:0000269\|PubMed:16483599, ECO:0000269\|PubMed:16630835, ECO:0000269\|PubMed:16793768, ECO:0000269\|PubMed:18817736, ECO:0000269\|PubMed:19234459, ECO:0000269\|PubMed:19265014, ECO:0000269\|PubMed:19946266, ECO:0000269\|PubMed:20547133, ECO:0000269\|PubMed:21317873, ECO:0000269\|PubMed:21496646, ECO:0000269\|PubMed:27756895, ECO:0000269\|PubMed:9069286, ECO:0000269\|PubMed:9697855, ECO:0000269\|PubMed:9804426}.
Subcellular location:		Cell membrane {ECO:0000250\|UniProtKB:P23819}; Multi-pass membrane protein {ECO:0000250\|UniProtKB:P23819}. Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Cell junction, synapse, postsynaptic density membrane {ECO:0000250\|UniProtKB:P23819}; Multi-pass membrane protein {ECO:0000250\|UniProtKB:P23819}. Note=Interaction with CACNG2, CNIH2 and CNIH3 promotes cell surface expression (By similarity). Displays a somatodendritic localization and is excluded from axons in neurons (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:P23819}.
Tissue specificity:		Detected in forebrain. Detected in dendrites of neuronal cells. Expressed in the pyramidal cell layers of CA1 and CA3 and in the granule cell layer of the dentate gyrus (PubMed:12657670). {ECO:0000269\|PubMed:12657670, ECO:0000269\|PubMed:14687553, ECO:0000269\|PubMed:15240807, ECO:0000269\|PubMed:9697855}.
Developmental stage:		Detected at low levels in newborns. Levels increase strongly and are highest in hippocampus from 8 to 14 day old animals. Detected at intermediate levels at day 42 (at protein level). {ECO:0000269\|PubMed:14687553}.
Induction:		Down-regulated in the pyramidal cell layer of CA1 in the hippocampus by global ischemia. {ECO:0000269\|PubMed:12657670}.
Domain:		The M4 transmembrane segment mediates tetramerization and is required for cell surface expression. {ECO:0000250}.
Ptm:		Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-610 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-836 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity). {ECO:0000250}.
Ptm:		Phosphorylation at Tyr-876 is required forc interaction with IQSEC1 and ARF6 activation. {ECO:0000269\|PubMed:20547133}.
Rna editing:		Modified_positions=607 {ECO:0000269\|PubMed:1717158}; Note=Fully edited in the brain. Heteromerically expressed edited GLUR2 (R) receptor complexes are impermeable to calcium, whereas the unedited (Q) forms are highly permeable to divalent ions (By similarity). {ECO:0000250};
Miscellaneous:		The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate.
Similarity:		Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA2 subfamily. {ECO:0000305}.