Protein: Glutamate receptor ionotropic, NMDA 2A (GluN2A) (Glutamate [NMDA] receptor subunit epsilon-1) (N-methyl D-aspartate receptor subtype 2A) (NMDAR2A) (NR2A) (hNR2A) (Q12879)
Organism: Homo sapiens (Human)
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. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity).
Subcellular location: Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q00959}. Cell membrane {ECO:0000269|PubMed:23933820, ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:27839871, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:28242877, ECO:0000269|PubMed:38538865, ECO:0000269|PubMed:8768735}; Multi-pass membrane protein {ECO:0000269|PubMed:34186027}. Synapse {ECO:0000250|UniProtKB:P35436}. Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q00959}; Multi-pass membrane protein {ECO:0000269|PubMed:34186027}. 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}.
Sequence: MGRVGYWTLLVLPALLVWRGPAPSAAAEKGPPALNIAVMLGHSHDVTERELRTLWGPEQAAGLPLDVNVVALLMNRTDPKSLITHVCDLMSGARIHGLVFGDDTDQEAVAQMLDFISSHTFVPILGIHGGASMIMADKDPTSTFFQFGASIQQQATVMLKIMQDYDWHVFSLVTTIFPGYREFISFVKTTVDNSFVGWDMQNVITLDTSFEDAKTQVQLKKIHSSVILLYCSKDEAVLILSEARSLGLTGYDFFWIVPSLVSGNTELIPKEFPSGLISVSYDDWDYSLEARVRDGIGILTTAASSMLEKFSYIPEAKASCYGQMERPEVPMHTLHPFMVNVTWDGKDLSFTEEGYQVHPRLVVIVLNKDREWEKVGKWENHTLSLRHAVWPRYKSFSDCEPDDNHLSIVTLEEAPFVIVEDIDPLTETCVRNTVPCRKFVKINNSTNEGMNVKKCCKGFCIDILKKLSRTVKFTYDLYLVTNGKHGKKVNNVWNGMIGEVVYQRAVMAVGSLTINEERSEVVDFSVPFVETGISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIVSAIAVFVFEYFSPVGYNRNLAKGKAPHGPSFTIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVWAFFAVIFLASYTANLAAFMIQEEFVDQVTGLSDKKFQRPHDYSPPFRFGTVPNGSTERNIRNNYPYMHQYMTKFNQKGVEDALVSLKTGKLDAFIYDAAVLNYKAGRDEGCKLVTIGSGYIFATTGYGIALQKGSPWKRQIDLALLQFVGDGEMEELETLWLTGICHNEKNEVMSSQLDIDNMAGVFYMLAAAMALSLITFIWEHLFYWKLRFCFTGVCSDRPGLLFSISRGIYSCIHGVHIEEKKKSPDFNLTGSQSNMLKLLRSAKNISSMSNMNSSRMDSPKRAADFIQRGSLIMDMVSDKGNLMYSDNRSFQGKESIFGDNMNELQTFVANRQKDNLNNYVFQGQHPLTLNESNPNTVEVAVSTESKANSRPRQLWKKSVDSIRQDSLSQNPVSQRDEATAENRTHSLKSPRYLPEEMAHSDISETSNRATCHREPDNSKNHKTKDNFKRSVASKYPKDCSEVERTYLKTKSSSPRDKIYTIDGEKEPGFHLDPPQFVENVTLPENVDFPDPYQDPSENFRKGDSTLPMNRNPLHNEEGLSNNDQYKLYSKHFTLKDKGSPHSETSERYRQNSTHCRSCLSNMPTYSGHFTMRSPFKCDACLRMGNLYDIDEDQMLQETGNPATGEQVYQQDWAQNNALQLQKNKLRISRQHSYDNIVDKPRELDLSRPSRSISLKDRERLLEGNFYGSLFSVPSSKLSGKKSSLFPQGLEDSKRSKSLLPDHTSDNPFLHSHRDDQRLVIGRCPSDPYKHSLPSQAVNDSYLRSSLRSTASYCSRDSRGHNDVYISEHVMPYAANKNNMYSTPRVLNSCSNRRVYKKMPSIESDV
InterPro domains: - IPR001508: Ionotropic glutamate receptor, metazoa (family) [473-841]
- IPR001320: Ionotropic glutamate receptor, C-terminal (domain) [431-828]
- IPR015683: Ionotropic glutamate receptor (family) [111-889]
- IPR001828: Receptor, ligand binding region (domain) [106-280]
- IPR019594: Ionotropic glutamate receptor, L-glutamate and glycine-binding domain (domain) [439-539]
- IPR018884: Glutamate [NMDA] receptor, epsilon subunit, C-terminal (domain) [839-1464]
- IPR028082: Periplasmic binding protein-like I (homologous_superfamily) [34-391]
Interaction partners: - Glutamate receptor ionotropic, NMDA 1
- Glutamate receptor ionotropic, NMDA 2B
- Glutamate receptor ionotropic, NMDA 3A
- Disks large homolog 4
- Glutamate receptor ionotropic, NMDA 2C
- Glutamate receptor ionotropic, NMDA 2D
- Disks large homolog 3
- Glutamate receptor ionotropic, NMDA 3B
- Disks large homolog 2
- Tyrosine-protein kinase Fyn
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0060089 (molecular transducer activity), GO:0005488 (binding), GO:0005215 (transporter activity), GO:0036094 (small molecule binding), GO:0022857 (transmembrane transporter activity), GO:0038023 (signaling receptor activity), GO:0043167 (ion binding), GO:0005515 (protein binding), GO:0015075 (monoatomic ion transmembrane transporter activity), GO:0043168 (anion binding), GO:0043169 (cation binding), GO:0022803 (passive transmembrane transporter activity), GO:0030594 (neurotransmitter receptor activity), GO:0004888 (transmembrane signaling receptor activity), GO:1901702 (salt transmembrane transporter activity), GO:0043177 (organic acid binding), GO:0015318 (inorganic molecular entity transmembrane transporter activity), GO:0015267 (channel activity), GO:0008324 (monoatomic cation transmembrane transporter activity), GO:0016594 (glycine binding), GO:0008066 (glutamate receptor activity), GO:0031406 (carboxylic acid binding), GO:0005216 (monoatomic ion channel activity), GO:0022890 (inorganic cation transmembrane transporter activity), GO:0015085 (calcium ion transmembrane transporter activity), GO:0022835 (transmitter-gated channel activity), GO:0004972 (NMDA glutamate receptor activity), GO:0022824 (transmitter-gated monoatomic ion channel activity), GO:0005262 (calcium channel activity), GO:0016597 (amino acid binding), GO:0046873 (metal ion transmembrane transporter activity), GO:0005261 (monoatomic cation channel activity), GO:0004970 (ionotropic glutamate receptor activity), GO:0022839 (monoatomic ion gated channel activity), GO:0022836 (gated channel activity), GO:0005244 (voltage-gated monoatomic ion channel activity), GO:0099094 (ligand-gated monoatomic cation channel activity), GO:0022834 (ligand-gated channel activity), GO:0015276 (ligand-gated monoatomic ion channel activity), GO:0022832 (voltage-gated channel activity), GO:0099604 (ligand-gated calcium channel activity), GO:0099507 (ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential), GO:0005230 (extracellular ligand-gated monoatomic ion channel activity)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0051234 (establishment of localization), GO:0051716 (cellular response to stimulus), GO:0055085 (transmembrane transport), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0050794 (regulation of cellular process), GO:0007166 (cell surface receptor signaling pathway), GO:0034220 (monoatomic ion transmembrane transport), GO:0098660 (inorganic ion transmembrane transport), GO:0006810 (transport), GO:0098655 (monoatomic cation transmembrane transport), GO:0071702 (organic substance transport), GO:0007215 (glutamate receptor signaling pathway), GO:0098662 (inorganic cation transmembrane transport), GO:0006811 (monoatomic ion transport), GO:0070588 (calcium ion transmembrane transport), GO:0006816 (calcium ion transport), GO:0006812 (monoatomic cation transport), GO:0097553 (calcium ion transmembrane import into cytosol), GO:0030001 (metal ion transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0071944 (cell periphery), GO:0098796 (membrane protein complex), GO:0030054 (cell junction), GO:0031984 (organelle subcompartment), GO:1990351 (transporter complex), GO:0098794 (postsynapse), GO:0043235 (receptor complex), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0098802 (plasma membrane signaling receptor complex), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0098827 (endoplasmic reticulum subcompartment), GO:0042175 (nuclear outer membrane-endoplasmic reticulum membrane network), GO:0045211 (postsynaptic membrane), GO:0098797 (plasma membrane protein complex), GO:0098590 (plasma membrane region), GO:1902495 (transmembrane transporter complex), GO:0005783 (endoplasmic reticulum), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0097060 (synaptic membrane), GO:0098878 (neurotransmitter receptor complex), GO:0043231 (intracellular membrane-bounded organelle), GO:0034702 (ion channel complex), GO:0005789 (endoplasmic reticulum membrane), GO:0008328 (ionotropic glutamate receptor complex), GO:0017146 (NMDA selective glutamate receptor complex)