UniProt functional annotation for Q00959



	UniProt functional annotation for Q00959

UniProt code: Q00959.

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+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have lower sensitivity to glutamate and faster deactivation kinetics than channels formed by GRIN1 and GRIN2B (PubMed:28384476). Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity). {ECO:0000250|UniProtKB:P35436, ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:16281028, ECO:0000269|PubMed:23625947, ECO:0000269|PubMed:24462099, ECO:0000269|PubMed:26679993, ECO:0000269|PubMed:27618671, ECO:0000269|PubMed:27916457, ECO:0000269|PubMed:28384476, ECO:0000269|PubMed:28468946, ECO:0000269|PubMed:28760974, ECO:0000269|PubMed:8428958}.

Activity regulation: Channel activity is inhibited by nM concentrations of Zn(2+). {ECO:0000269|PubMed:27916457}.

Subunit: Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:1350383, PubMed:8428958, PubMed:28384476, PubMed:16281028, PubMed:23625947, PubMed:24462099, PubMed:27618671, PubMed:27916457, PubMed:28468946, PubMed:28760974, Ref.27). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (PubMed:11160393, PubMed:11588171, PubMed:12391275, PubMed:11929923). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Found in a complex with GRIN1, GRIN3A and PPP2CB (PubMed:11588171). Found in a complex with GRIN1 and GRIN3B (PubMed:14602821). Interacts with AIP1 (PubMed:9694864). Interacts with HIP1 and NETO1. 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 PDZ domains of PATJ and DLG4 (PubMed:7569905, PubMed:9647694). Interacts with LRFN2 (PubMed:16495444). Interacts with RPH3A and DLG4; this ternary complex regulates NMDA receptor composition at postsynaptic membranes (PubMed:26679993). Interacts with SORCS2 (By similarity). Interacts with ARC; preventing ARC oligomerization (PubMed:31080121). {ECO:0000250|UniProtKB:P35436, ECO:0000269|PubMed:11160393, ECO:0000269|PubMed:11588171, ECO:0000269|PubMed:11929923, ECO:0000269|PubMed:12391275, ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:14602821, ECO:0000269|PubMed:16281028, ECO:0000269|PubMed:16495444, ECO:0000269|PubMed:23625947, ECO:0000269|PubMed:24462099, ECO:0000269|PubMed:26679993, ECO:0000269|PubMed:27618671, ECO:0000269|PubMed:27916457, ECO:0000269|PubMed:28384476, ECO:0000269|PubMed:28468946, ECO:0000269|PubMed:28760974, ECO:0000269|PubMed:31080121, ECO:0000269|PubMed:7569905, ECO:0000269|PubMed:8428958, ECO:0000269|PubMed:9647694, ECO:0000269|PubMed:9694864, ECO:0000269|Ref.27, ECO:0000305}.

Subcellular location: Cell projection, dendritic spine {ECO:0000269|PubMed:26679993}. Cell membrane {ECO:0000269|PubMed:11160393, ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:14602821, ECO:0000269|PubMed:16281028, ECO:0000269|PubMed:23625947, ECO:0000269|PubMed:24462099, ECO:0000269|PubMed:27618671, ECO:0000269|PubMed:27916457, ECO:0000269|PubMed:28384476, ECO:0000269|PubMed:28468946, ECO:0000269|PubMed:28760974, ECO:0000269|PubMed:8428958}; Multi-pass membrane protein {ECO:0000305}. Cell junction, synapse {ECO:0000250|UniProtKB:P35436}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000269|PubMed:26679993, ECO:0000269|PubMed:9509416}; Multi-pass membrane protein {ECO:0000305}. Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P35436}. Note=Expression at the dendrite cell membrane and at synapses is regulated by SORCS2 and the retromer complex. {ECO:0000250|UniProtKB:P35436}.

Tissue specificity: Detected in brain cortex, olfactory bulb, hippocampus including the dentate gyrus, striatum, thalamus, superior colliculus, inferior colliculus, midbrain and cerebellum (at protein level) (PubMed:22960932, PubMed:9509416). Detected in brain cortex, hypothalamus and cerebellum (PubMed:1350383). {ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:22960932, ECO:0000269|PubMed:9509416}.

Developmental stage: Expressed during postnatal days P3 to P60, with increased expression after postnatal day 3. {ECO:0000269|PubMed:22960932}.

Domain: Contains an N-terminal domain, a ligand-binding domain and a transmembrane domain. Agonist binding to the extracellular ligand- binding domains triggers channel gating. {ECO:0000305|PubMed:16281028}.

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:B7ZSK1}.

Similarity: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2A/GRIN2A 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+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have lower sensitivity to glutamate and faster deactivation kinetics than channels formed by GRIN1 and GRIN2B (PubMed:28384476). Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity). {ECO:0000250\|UniProtKB:P35436, ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:16281028, ECO:0000269\|PubMed:23625947, ECO:0000269\|PubMed:24462099, ECO:0000269\|PubMed:26679993, ECO:0000269\|PubMed:27618671, ECO:0000269\|PubMed:27916457, ECO:0000269\|PubMed:28384476, ECO:0000269\|PubMed:28468946, ECO:0000269\|PubMed:28760974, ECO:0000269\|PubMed:8428958}.


Activity regulation:		Channel activity is inhibited by nM concentrations of Zn(2+). {ECO:0000269\|PubMed:27916457}.
Subunit:		Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:1350383, PubMed:8428958, PubMed:28384476, PubMed:16281028, PubMed:23625947, PubMed:24462099, PubMed:27618671, PubMed:27916457, PubMed:28468946, PubMed:28760974, Ref.27). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (PubMed:11160393, PubMed:11588171, PubMed:12391275, PubMed:11929923). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Found in a complex with GRIN1, GRIN3A and PPP2CB (PubMed:11588171). Found in a complex with GRIN1 and GRIN3B (PubMed:14602821). Interacts with AIP1 (PubMed:9694864). Interacts with HIP1 and NETO1. 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 PDZ domains of PATJ and DLG4 (PubMed:7569905, PubMed:9647694). Interacts with LRFN2 (PubMed:16495444). Interacts with RPH3A and DLG4; this ternary complex regulates NMDA receptor composition at postsynaptic membranes (PubMed:26679993). Interacts with SORCS2 (By similarity). Interacts with ARC; preventing ARC oligomerization (PubMed:31080121). {ECO:0000250\|UniProtKB:P35436, ECO:0000269\|PubMed:11160393, ECO:0000269\|PubMed:11588171, ECO:0000269\|PubMed:11929923, ECO:0000269\|PubMed:12391275, ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:14602821, ECO:0000269\|PubMed:16281028, ECO:0000269\|PubMed:16495444, ECO:0000269\|PubMed:23625947, ECO:0000269\|PubMed:24462099, ECO:0000269\|PubMed:26679993, ECO:0000269\|PubMed:27618671, ECO:0000269\|PubMed:27916457, ECO:0000269\|PubMed:28384476, ECO:0000269\|PubMed:28468946, ECO:0000269\|PubMed:28760974, ECO:0000269\|PubMed:31080121, ECO:0000269\|PubMed:7569905, ECO:0000269\|PubMed:8428958, ECO:0000269\|PubMed:9647694, ECO:0000269\|PubMed:9694864, ECO:0000269\|Ref.27, ECO:0000305}.
Subcellular location:		Cell projection, dendritic spine {ECO:0000269\|PubMed:26679993}. Cell membrane {ECO:0000269\|PubMed:11160393, ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:14602821, ECO:0000269\|PubMed:16281028, ECO:0000269\|PubMed:23625947, ECO:0000269\|PubMed:24462099, ECO:0000269\|PubMed:27618671, ECO:0000269\|PubMed:27916457, ECO:0000269\|PubMed:28384476, ECO:0000269\|PubMed:28468946, ECO:0000269\|PubMed:28760974, ECO:0000269\|PubMed:8428958}; Multi-pass membrane protein {ECO:0000305}. Cell junction, synapse {ECO:0000250\|UniProtKB:P35436}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000269\|PubMed:26679993, ECO:0000269\|PubMed:9509416}; Multi-pass membrane protein {ECO:0000305}. Cytoplasmic vesicle membrane {ECO:0000250\|UniProtKB:P35436}. Note=Expression at the dendrite cell membrane and at synapses is regulated by SORCS2 and the retromer complex. {ECO:0000250\|UniProtKB:P35436}.
Tissue specificity:		Detected in brain cortex, olfactory bulb, hippocampus including the dentate gyrus, striatum, thalamus, superior colliculus, inferior colliculus, midbrain and cerebellum (at protein level) (PubMed:22960932, PubMed:9509416). Detected in brain cortex, hypothalamus and cerebellum (PubMed:1350383). {ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:22960932, ECO:0000269\|PubMed:9509416}.
Developmental stage:		Expressed during postnatal days P3 to P60, with increased expression after postnatal day 3. {ECO:0000269\|PubMed:22960932}.
Domain:		Contains an N-terminal domain, a ligand-binding domain and a transmembrane domain. Agonist binding to the extracellular ligand- binding domains triggers channel gating. {ECO:0000305\|PubMed:16281028}.
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:B7ZSK1}.
Similarity:		Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2A/GRIN2A subfamily. {ECO:0000305}.