UniProt functional annotation for P42260



	UniProt functional annotation for P42260

UniProt code: P42260.

Organism: Rattus norvegicus (Rat).

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

Function: Ionotropic glutamate receptor. 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 (PubMed:17115050, PubMed:17486098). Modulates cell surface expression of NETO2 (By similarity). {ECO:0000250|UniProtKB:P39087, ECO:0000269|PubMed:17115050, ECO:0000269|PubMed:17486098}.

Function: Independent of its ionotropic glutamate receptor activity, acts as a thermoreceptor conferring sensitivity to cold temperatures (By similarity). Functions in dorsal root ganglion neurons (By similarity). {ECO:0000250|UniProtKB:P39087}.

Activity regulation: Cold receptor activity activated by temperatures between 10-19 degrees Celsius. {ECO:0000250|UniProtKB:P39087}.

Subunit: Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Assembles into a kainate-gated homomeric channel that does not bind AMPA (By similarity). GRIK2 associated to GRIK5 forms functional channels that can be gated by AMPA. Interacts with DLG4. Interacts with NETO2. Interacts (via C-terminus) with KLHL17 (via kelch repeats); the interaction targets GRIK2 for degradation via ubiquitin-proteasome pathway. {ECO:0000250, ECO:0000269|PubMed:11744724, ECO:0000269|PubMed:15677325, ECO:0000269|PubMed:17062563, ECO:0000269|PubMed:17115050, ECO:0000269|PubMed:19217376, ECO:0000269|PubMed:21791290}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:17486098}; Multi-pass membrane protein {ECO:0000269|PubMed:17486098}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000269|PubMed:17486098}; Multi-pass membrane protein {ECO:0000269|PubMed:17486098}.

Tissue specificity: Highest expression is found in the olfactory lobe, piriform cortex, dentate gyrus, hippocampus, granular cell layer of the cerebellum, and in caudate-putamen.

Ptm: Sumoylation mediates kainate receptor-mediated endocytosis and regulates synaptic transmission. Sumoylation is enhanced by PIAS3 and desumoylated by SENP1. {ECO:0000269|PubMed:17486098}.

Ptm: Ubiquitinated. Ubiquitination regulates the GRIK2 levels at the synapse by leading kainate receptor degradation through proteasome. {ECO:0000269|PubMed:17062563}.

Ptm: Phosphorylated by PKC at Ser-868 upon agonist activation, this directly enhance sumoylation. {ECO:0000250}.

Rna editing: Modified_positions=567 {ECO:0000269|PubMed:7681676}, 571 {ECO:0000269|PubMed:7681676}, 621 {ECO:0000269|PubMed:7681676}; Note=Partially edited. The presence of Gln at position 621 (non-edited) determines channels with low calcium permeability, whereas an arginine residue (edited) determines a higher calcium permeability especially if the preceding sites are fully edited. This receptor is nearly completely edited in all gray matter structures (90% of the receptors).;

Miscellaneous: The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate > quisqualate > glutamate. It does not bind AMPA without coexpression with GRIK5.

Similarity: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK2 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:		Ionotropic glutamate receptor. 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 (PubMed:17115050, PubMed:17486098). Modulates cell surface expression of NETO2 (By similarity). {ECO:0000250\|UniProtKB:P39087, ECO:0000269\|PubMed:17115050, ECO:0000269\|PubMed:17486098}.



Function:		Independent of its ionotropic glutamate receptor activity, acts as a thermoreceptor conferring sensitivity to cold temperatures (By similarity). Functions in dorsal root ganglion neurons (By similarity). {ECO:0000250\|UniProtKB:P39087}.


Activity regulation:		Cold receptor activity activated by temperatures between 10-19 degrees Celsius. {ECO:0000250\|UniProtKB:P39087}.
Subunit:		Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Assembles into a kainate-gated homomeric channel that does not bind AMPA (By similarity). GRIK2 associated to GRIK5 forms functional channels that can be gated by AMPA. Interacts with DLG4. Interacts with NETO2. Interacts (via C-terminus) with KLHL17 (via kelch repeats); the interaction targets GRIK2 for degradation via ubiquitin-proteasome pathway. {ECO:0000250, ECO:0000269\|PubMed:11744724, ECO:0000269\|PubMed:15677325, ECO:0000269\|PubMed:17062563, ECO:0000269\|PubMed:17115050, ECO:0000269\|PubMed:19217376, ECO:0000269\|PubMed:21791290}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:17486098}; Multi-pass membrane protein {ECO:0000269\|PubMed:17486098}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000269\|PubMed:17486098}; Multi-pass membrane protein {ECO:0000269\|PubMed:17486098}.
Tissue specificity:		Highest expression is found in the olfactory lobe, piriform cortex, dentate gyrus, hippocampus, granular cell layer of the cerebellum, and in caudate-putamen.
Ptm:		Sumoylation mediates kainate receptor-mediated endocytosis and regulates synaptic transmission. Sumoylation is enhanced by PIAS3 and desumoylated by SENP1. {ECO:0000269\|PubMed:17486098}.
Ptm:		Ubiquitinated. Ubiquitination regulates the GRIK2 levels at the synapse by leading kainate receptor degradation through proteasome. {ECO:0000269\|PubMed:17062563}.
Ptm:		Phosphorylated by PKC at Ser-868 upon agonist activation, this directly enhance sumoylation. {ECO:0000250}.
Rna editing:		Modified_positions=567 {ECO:0000269\|PubMed:7681676}, 571 {ECO:0000269\|PubMed:7681676}, 621 {ECO:0000269\|PubMed:7681676}; Note=Partially edited. The presence of Gln at position 621 (non-edited) determines channels with low calcium permeability, whereas an arginine residue (edited) determines a higher calcium permeability especially if the preceding sites are fully edited. This receptor is nearly completely edited in all gray matter structures (90% of the receptors).;
Miscellaneous:		The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate > quisqualate > glutamate. It does not bind AMPA without coexpression with GRIK5.
Similarity:		Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK2 subfamily. {ECO:0000305}.