UniProt functional annotation for Q00960



	UniProt functional annotation for Q00960

UniProt code: Q00960.

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:19910922, PubMed:21677647, PubMed:24876489, PubMed:27135925, PubMed:27916457). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable). In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity (By similarity). {ECO:0000250|UniProtKB:Q01097, ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:19910922, ECO:0000269|PubMed:21677647, ECO:0000269|PubMed:24876489, ECO:0000269|PubMed:27135925, ECO:0000269|PubMed:27916457, ECO:0000305}.

Activity regulation: Channel activity is inhibited by micromolar levels of zinc ions (PubMed:19910922). Channel activity is inhibited by ifenprodil (PubMed:19910922, PubMed:21677647). {ECO:0000269|PubMed:19910922, ECO:0000269|PubMed:21677647}.

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:19910922, PubMed:21677647, PubMed:24876489, PubMed:27135925, PubMed:27916457). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B. In vivo, the subunit composition may depend on the expression levels of the different subunits. Found in a complex with GRIN1, GRIN3A and PPP2CB. Found in a complex with GRIN1 and GRIN3B. Interacts with MAGI3. Interacts with HIP1 and NETO1. Interacts with PDZ domains of PATJ, DLG3 and DLG4. Interacts with DAPK1 (By similarity). Found in a complex with GRIN1 and PRR7 (PubMed:27458189). Interacts with PRR7 (PubMed:27458189). Interacts with CAMK2A (By similarity). Interacts with ARC; preventing ARC oligomerization (PubMed:31080121). Interacts with TMEM25 (By similarity). {ECO:0000250|UniProtKB:Q01097, ECO:0000250|UniProtKB:Q13224, ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:19910922, ECO:0000269|PubMed:21677647, ECO:0000269|PubMed:24876489, ECO:0000269|PubMed:27135925, ECO:0000269|PubMed:27458189, ECO:0000269|PubMed:27916457, ECO:0000269|PubMed:28283559, ECO:0000269|PubMed:31080121}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:19910922, ECO:0000269|PubMed:21677647, ECO:0000269|PubMed:24876489, ECO:0000269|PubMed:27135925, ECO:0000269|PubMed:27916457}; Multi-pass membrane protein {ECO:0000269|PubMed:24876489, ECO:0000269|PubMed:27135925}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000269|PubMed:7513428, ECO:0000269|PubMed:9509416}; Multi-pass membrane protein {ECO:0000269|PubMed:24876489, ECO:0000269|PubMed:27135925}. Late endosome {ECO:0000250|UniProtKB:Q01097}. Lysosome {ECO:0000250|UniProtKB:Q01097}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q01097}. Note=Co-localizes with the motor protein KIF17 along microtubules. {ECO:0000250|UniProtKB:Q01097}.

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

Developmental stage: Expressed during postnatal days P3 to P60, with decreased expression after postnatal day 14. {ECO:0000269|PubMed:22960932}.

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:0000305|PubMed:24876489}.

Ptm: Phosphorylated on tyrosine residues (PubMed:7513428). Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity (By similarity). {ECO:0000250|UniProtKB:Q01097, ECO:0000269|PubMed:7513428}.

Similarity: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2B/GRIN2B 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:19910922, PubMed:21677647, PubMed:24876489, PubMed:27135925, PubMed:27916457). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable). In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity (By similarity). {ECO:0000250\|UniProtKB:Q01097, ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:19910922, ECO:0000269\|PubMed:21677647, ECO:0000269\|PubMed:24876489, ECO:0000269\|PubMed:27135925, ECO:0000269\|PubMed:27916457, ECO:0000305}.


Activity regulation:		Channel activity is inhibited by micromolar levels of zinc ions (PubMed:19910922). Channel activity is inhibited by ifenprodil (PubMed:19910922, PubMed:21677647). {ECO:0000269\|PubMed:19910922, ECO:0000269\|PubMed:21677647}.
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:19910922, PubMed:21677647, PubMed:24876489, PubMed:27135925, PubMed:27916457). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B. In vivo, the subunit composition may depend on the expression levels of the different subunits. Found in a complex with GRIN1, GRIN3A and PPP2CB. Found in a complex with GRIN1 and GRIN3B. Interacts with MAGI3. Interacts with HIP1 and NETO1. Interacts with PDZ domains of PATJ, DLG3 and DLG4. Interacts with DAPK1 (By similarity). Found in a complex with GRIN1 and PRR7 (PubMed:27458189). Interacts with PRR7 (PubMed:27458189). Interacts with CAMK2A (By similarity). Interacts with ARC; preventing ARC oligomerization (PubMed:31080121). Interacts with TMEM25 (By similarity). {ECO:0000250\|UniProtKB:Q01097, ECO:0000250\|UniProtKB:Q13224, ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:19910922, ECO:0000269\|PubMed:21677647, ECO:0000269\|PubMed:24876489, ECO:0000269\|PubMed:27135925, ECO:0000269\|PubMed:27458189, ECO:0000269\|PubMed:27916457, ECO:0000269\|PubMed:28283559, ECO:0000269\|PubMed:31080121}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:1350383, ECO:0000269\|PubMed:19910922, ECO:0000269\|PubMed:21677647, ECO:0000269\|PubMed:24876489, ECO:0000269\|PubMed:27135925, ECO:0000269\|PubMed:27916457}; Multi-pass membrane protein {ECO:0000269\|PubMed:24876489, ECO:0000269\|PubMed:27135925}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000269\|PubMed:7513428, ECO:0000269\|PubMed:9509416}; Multi-pass membrane protein {ECO:0000269\|PubMed:24876489, ECO:0000269\|PubMed:27135925}. Late endosome {ECO:0000250\|UniProtKB:Q01097}. Lysosome {ECO:0000250\|UniProtKB:Q01097}. Cytoplasm, cytoskeleton {ECO:0000250\|UniProtKB:Q01097}. Note=Co-localizes with the motor protein KIF17 along microtubules. {ECO:0000250\|UniProtKB:Q01097}.
Tissue specificity:		Expressed in the hippocampus including the dentate gyrus (at protein level) (PubMed:22960932). Detected in adult olfactory bulb, brain cortex, hippocampus, striatum, thalamus, superior colliculus, with much lower levels in inferior colliculus, midbrain and cerebellum. {ECO:0000269\|PubMed:22960932, ECO:0000269\|PubMed:9509416}.
Developmental stage:		Expressed during postnatal days P3 to P60, with decreased expression after postnatal day 14. {ECO:0000269\|PubMed:22960932}.
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:0000305\|PubMed:24876489}.
Ptm:		Phosphorylated on tyrosine residues (PubMed:7513428). Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity (By similarity). {ECO:0000250\|UniProtKB:Q01097, ECO:0000269\|PubMed:7513428}.
Similarity:		Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2B/GRIN2B subfamily. {ECO:0000305}.