UniProt functional annotation for P35439



	UniProt functional annotation for P35439

UniProt code: P35439.

Organism: Rattus norvegicus (Rat).

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

Function: Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:1350383, PubMed:1834949, PubMed:1388270, PubMed:8428958, PubMed:18177891, PubMed:28384476, PubMed:15996549, PubMed:24876489, PubMed:27135925, PubMed:27618671, PubMed:28468946). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:28384476). {ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:1388270, ECO:0000269|PubMed:15996549, ECO:0000269|PubMed:18177891, ECO:0000269|PubMed:1834949, ECO:0000269|PubMed:24876489, ECO:0000269|PubMed:27135925, ECO:0000269|PubMed:27618671, ECO:0000269|PubMed:28384476, ECO:0000269|PubMed:28468946, ECO:0000269|PubMed:8428958}.

Subunit: Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:18177891, PubMed:28384476, PubMed:16281028, PubMed:15996549, PubMed:21389213, PubMed:24876489, PubMed:27135925, PubMed:28468946, Ref.32). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), an epsilon subunit, plus GRIN3A or GRIN3B (in vitro) (PubMed:11160393, PubMed:11929923, PubMed:12391275). In vivo, the subunit composition may vary in function of the expression levels of the different subunits (Probable). Found in a complex with GRIN2A or GRIN2B, GRIN3A and PPP2CB (PubMed:11588171). Found in a complex with GRIN2A or GRIN2B and GRIN3B (By similarity). 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 DLG4 and MPDZ (PubMed:15312654). Interacts with LRFN1 and LRFN2 (PubMed:16495444, PubMed:16630835). Interacts with MYZAP (PubMed:18849881). Found in a complex with DLG4 and PRR7 (PubMed:27458189). Found in a complex with GRIN2B and PRR7 (PubMed:27458189). Interacts with PRR7; the interaction is reduced following NMDA receptor activity (PubMed:27458189). {ECO:0000250|UniProtKB:P35438, ECO:0000269|PubMed:11160393, ECO:0000269|PubMed:11588171, ECO:0000269|PubMed:11929923, ECO:0000269|PubMed:12391275, ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:15312654, ECO:0000269|PubMed:15996549, ECO:0000269|PubMed:16281028, ECO:0000269|PubMed:16495444, ECO:0000269|PubMed:16630835, ECO:0000269|PubMed:18177891, ECO:0000269|PubMed:18849881, ECO:0000269|PubMed:21389213, ECO:0000269|PubMed:24876489, ECO:0000269|PubMed:27135925, ECO:0000269|PubMed:27458189, ECO:0000269|PubMed:27618671, ECO:0000269|PubMed:28384476, ECO:0000269|PubMed:28468946, ECO:0000269|PubMed:8428958, ECO:0000269|Ref.32, ECO:0000305}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:1388270, ECO:0000269|PubMed:15996549, ECO:0000269|PubMed:18177891, ECO:0000269|PubMed:1834949, ECO:0000269|PubMed:21389213, ECO:0000269|PubMed:24876489, ECO:0000269|PubMed:27135925, ECO:0000269|PubMed:27618671, ECO:0000269|PubMed:28384476, ECO:0000269|PubMed:28468946, ECO:0000269|PubMed:8428958}; Multi-pass membrane protein {ECO:0000269|PubMed:24876489, ECO:0000269|PubMed:27135925}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000250}. Note=Enriched in postsynaptic plasma membrane and postsynaptic densities. {ECO:0000250}.

Tissue specificity: Detected throughout the brain, in brain cortex, cerebellum, thalamus and olfactory bulb. {ECO:0000269|PubMed:1350383}.

Domain: A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter. {ECO:0000250|UniProtKB:A0A1L8F5J9}.

Ptm: NMDA is probably regulated by C-terminal phosphorylation of an isoform of NR1 by PKC. Dephosphorylated on Ser-897 probably by protein phosphatase 2A (PPP2CB). Its phosphorylated state is influenced by the formation of the NMDAR-PPP2CB complex and the NMDAR channel activity. {ECO:0000269|PubMed:11588171, ECO:0000269|PubMed:15936117}.

Similarity: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR1/GRIN1 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:		Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:1350383, PubMed:1834949, PubMed:1388270, PubMed:8428958, PubMed:18177891, PubMed:28384476, PubMed:15996549, PubMed:24876489, PubMed:27135925, PubMed:27618671, PubMed:28468946). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:28384476). {ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:1388270, ECO:0000269\|PubMed:15996549, ECO:0000269\|PubMed:18177891, ECO:0000269\|PubMed:1834949, ECO:0000269\|PubMed:24876489, ECO:0000269\|PubMed:27135925, ECO:0000269\|PubMed:27618671, ECO:0000269\|PubMed:28384476, ECO:0000269\|PubMed:28468946, ECO:0000269\|PubMed:8428958}.


Subunit:		Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:18177891, PubMed:28384476, PubMed:16281028, PubMed:15996549, PubMed:21389213, PubMed:24876489, PubMed:27135925, PubMed:28468946, Ref.32). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), an epsilon subunit, plus GRIN3A or GRIN3B (in vitro) (PubMed:11160393, PubMed:11929923, PubMed:12391275). In vivo, the subunit composition may vary in function of the expression levels of the different subunits (Probable). Found in a complex with GRIN2A or GRIN2B, GRIN3A and PPP2CB (PubMed:11588171). Found in a complex with GRIN2A or GRIN2B and GRIN3B (By similarity). 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 DLG4 and MPDZ (PubMed:15312654). Interacts with LRFN1 and LRFN2 (PubMed:16495444, PubMed:16630835). Interacts with MYZAP (PubMed:18849881). Found in a complex with DLG4 and PRR7 (PubMed:27458189). Found in a complex with GRIN2B and PRR7 (PubMed:27458189). Interacts with PRR7; the interaction is reduced following NMDA receptor activity (PubMed:27458189). {ECO:0000250\|UniProtKB:P35438, ECO:0000269\|PubMed:11160393, ECO:0000269\|PubMed:11588171, ECO:0000269\|PubMed:11929923, ECO:0000269\|PubMed:12391275, ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:15312654, ECO:0000269\|PubMed:15996549, ECO:0000269\|PubMed:16281028, ECO:0000269\|PubMed:16495444, ECO:0000269\|PubMed:16630835, ECO:0000269\|PubMed:18177891, ECO:0000269\|PubMed:18849881, ECO:0000269\|PubMed:21389213, ECO:0000269\|PubMed:24876489, ECO:0000269\|PubMed:27135925, ECO:0000269\|PubMed:27458189, ECO:0000269\|PubMed:27618671, ECO:0000269\|PubMed:28384476, ECO:0000269\|PubMed:28468946, ECO:0000269\|PubMed:8428958, ECO:0000269\|Ref.32, ECO:0000305}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:1388270, ECO:0000269\|PubMed:15996549, ECO:0000269\|PubMed:18177891, ECO:0000269\|PubMed:1834949, ECO:0000269\|PubMed:21389213, ECO:0000269\|PubMed:24876489, ECO:0000269\|PubMed:27135925, ECO:0000269\|PubMed:27618671, ECO:0000269\|PubMed:28384476, ECO:0000269\|PubMed:28468946, ECO:0000269\|PubMed:8428958}; Multi-pass membrane protein {ECO:0000269\|PubMed:24876489, ECO:0000269\|PubMed:27135925}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000250}. Note=Enriched in postsynaptic plasma membrane and postsynaptic densities. {ECO:0000250}.
Tissue specificity:		Detected throughout the brain, in brain cortex, cerebellum, thalamus and olfactory bulb. {ECO:0000269\|PubMed:1350383}.
Domain:		A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter. {ECO:0000250\|UniProtKB:A0A1L8F5J9}.
Ptm:		NMDA is probably regulated by C-terminal phosphorylation of an isoform of NR1 by PKC. Dephosphorylated on Ser-897 probably by protein phosphatase 2A (PPP2CB). Its phosphorylated state is influenced by the formation of the NMDAR-PPP2CB complex and the NMDAR channel activity. {ECO:0000269\|PubMed:11588171, ECO:0000269\|PubMed:15936117}.
Similarity:		Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR1/GRIN1 subfamily. {ECO:0000305}.