ID   NMDE4_HUMAN             Reviewed;        1336 AA.
AC   O15399;
DT   29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 2.
DT   27-MAR-2024, entry version 198.
DE   RecName: Full=Glutamate receptor ionotropic, NMDA 2D;
DE            Short=GluN2D;
DE   AltName: Full=EB11;
DE   AltName: Full=Glutamate [NMDA] receptor subunit epsilon-4;
DE   AltName: Full=N-methyl D-aspartate receptor subtype 2D;
DE            Short=NMDAR2D;
DE            Short=NR2D;
DE   Flags: Precursor;
GN   Name=GRIN2D; Synonyms=GluN2D, NMDAR2D;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RC   TISSUE=Fetal brain;
RX   PubMed=9489750; DOI=10.1046/j.1471-4159.1998.70031269.x;
RA   Hess S.D., Daggett L.P., Deal C., Lu C.-C., Johnson E.C., Velicelebi G.;
RT   "Functional characterization of human N-methyl-D-aspartate subtype 1A/2D
RT   receptors.";
RL   J. Neurochem. 70:1269-1279(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [3]
RP   FUNCTION, INVOLVEMENT IN DEE46, VARIANT DEE46 ILE-667, AND CHARACTERIZATION
RP   OF VARIANT DEE46 ILE-667.
RX   PubMed=27616483; DOI=10.1016/j.ajhg.2016.07.013;
RA   Li D., Yuan H., Ortiz-Gonzalez X.R., Marsh E.D., Tian L., McCormick E.M.,
RA   Kosobucki G.J., Chen W., Schulien A.J., Chiavacci R., Tankovic A.,
RA   Naase C., Brueckner F., von Stuelpnagel-Steinbeis C., Hu C., Kusumoto H.,
RA   Hedrich U.B., Elsen G., Hoertnagel K., Aizenman E., Lemke J.R.,
RA   Hakonarson H., Traynelis S.F., Falk M.J.;
RT   "GRIN2D recurrent de novo dominant mutation causes a severe epileptic
RT   encephalopathy treatable with NMDA receptor channel blockers.";
RL   Am. J. Hum. Genet. 99:802-816(2016).
RN   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX   PubMed=26875626; DOI=10.1016/j.neuron.2016.01.016;
RA   Hackos D.H., Lupardus P.J., Grand T., Chen Y., Wang T.M., Reynen P.,
RA   Gustafson A., Wallweber H.J., Volgraf M., Sellers B.D., Schwarz J.B.,
RA   Paoletti P., Sheng M., Zhou Q., Hanson J.E.;
RT   "Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct
RT   Modes of Action and Impacts on Circuit Function.";
RL   Neuron 89:983-999(2016).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF MET-845.
RX   PubMed=28126851; DOI=10.1124/mol.116.106781;
RA   Chen W., Tankovic A., Burger P.B., Kusumoto H., Traynelis S.F., Yuan H.;
RT   "Functional evaluation of a de novo GRIN2A mutation identified in a patient
RT   with profound global developmental delay and refractory epilepsy.";
RL   Mol. Pharmacol. 91:317-330(2017).
RN   [6]
RP   FUNCTION, AND MUTAGENESIS OF PRO-580.
RX   PubMed=28095420; DOI=10.1371/journal.pgen.1006536;
RA   Ogden K.K., Chen W., Swanger S.A., McDaniel M.J., Fan L.Z., Hu C.,
RA   Tankovic A., Kusumoto H., Kosobucki G.J., Schulien A.J., Su Z., Pecha J.,
RA   Bhattacharya S., Petrovski S., Cohen A.E., Aizenman E., Traynelis S.F.,
RA   Yuan H.;
RT   "Molecular mechanism of disease-associated mutations in the pre-M1 helix of
RT   NMDA receptors and potential rescue pharmacology.";
RL   PLoS Genet. 13:E1006536-E1006536(2017).
RN   [7]
RP   VARIANTS [LARGE SCALE ANALYSIS] SER-140; ARG-286 AND GLY-527.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [8]
RP   VARIANTS VAL-466; LEU-592; VAL-733; HIS-872; ILE-883; VAL-922; THR-926;
RP   PRO-982 AND SER-1317.
RX   PubMed=22833210; DOI=10.1038/tp.2011.52;
RG   S2D team;
RA   Tarabeux J., Kebir O., Gauthier J., Hamdan F.F., Xiong L., Piton A.,
RA   Spiegelman D., Henrion E., Millet B., Fathalli F., Joober R.,
RA   Rapoport J.L., DeLisi L.E., Fombonne E., Mottron L., Forget-Dubois N.,
RA   Boivin M., Michaud J.L., Drapeau P., Lafreniere R.G., Rouleau G.A.,
RA   Krebs M.O.;
RT   "Rare mutations in N-methyl-D-aspartate glutamate receptors in autism
RT   spectrum disorders and schizophrenia.";
RL   Transl. Psychiatry 1:E55-E55(2011).
CC   -!- FUNCTION: Component of NMDA receptor complexes that function as
CC       heterotetrameric, ligand-gated ion channels with high calcium
CC       permeability and voltage-dependent sensitivity to magnesium. Channel
CC       activation requires binding of the neurotransmitter glutamate to the
CC       epsilon subunit, glycine binding to the zeta subunit, plus membrane
CC       depolarization to eliminate channel inhibition by Mg(2+)
CC       (PubMed:9489750, PubMed:27616483, PubMed:26875626, PubMed:28126851).
CC       Sensitivity to glutamate and channel kinetics depend on the subunit
CC       composition (PubMed:9489750). {ECO:0000269|PubMed:26875626,
CC       ECO:0000269|PubMed:27616483, ECO:0000269|PubMed:28095420,
CC       ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:9489750}.
CC   -!- SUBUNIT: Heterotetramer. Forms heterotetrameric channels composed of
CC       two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B,
CC       GRIN2C or GRIN2D) (in vitro) (PubMed:9489750, PubMed:26875626,
CC       PubMed:28126851). In vivo, the subunit composition may depend on the
CC       expression levels of the different subunits (Probable). Interacts with
CC       PDZ domains of PATJ and DLG4 (By similarity). {ECO:0000250,
CC       ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:28126851,
CC       ECO:0000269|PubMed:9489750, ECO:0000305}.
CC   -!- INTERACTION:
CC       O15399; Q62936: Dlg3; Xeno; NbExp=2; IntAct=EBI-1754030, EBI-349596;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26875626,
CC       ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:9489750}; Multi-pass
CC       membrane protein. Postsynaptic cell membrane; Multi-pass membrane
CC       protein.
CC   -!- DOMAIN: A hydrophobic region that gives rise to the prediction of a
CC       transmembrane span does not cross the membrane, but is part of a
CC       discontinuously helical region that dips into the membrane and is
CC       probably part of the pore and of the selectivity filter.
CC       {ECO:0000250|UniProtKB:Q00960}.
CC   -!- DISEASE: Developmental and epileptic encephalopathy 46 (DEE46)
CC       [MIM:617162]: A form of epileptic encephalopathy, a heterogeneous group
CC       of severe early-onset epilepsies characterized by refractory seizures,
CC       neurodevelopmental impairment, and poor prognosis. Development is
CC       normal prior to seizure onset, after which cognitive and motor delays
CC       become apparent. {ECO:0000269|PubMed:27616483}. Note=The disease is
CC       caused by variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC       family. NR2D/GRIN2D subfamily. {ECO:0000305}.
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DR   EMBL; U77783; AAC15910.1; -; mRNA.
DR   EMBL; AC008403; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC011527; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS12719.1; -.
DR   RefSeq; NP_000827.2; NM_000836.2.
DR   RefSeq; XP_011525174.1; XM_011526872.1.
DR   PDB; 7YFF; EM; 3.60 A; B/D=1-879.
DR   PDB; 7YFL; EM; 3.90 A; B/D=1-879.
DR   PDB; 7YFM; EM; 5.10 A; B/D=1-879.
DR   PDB; 7YFO; EM; 6.40 A; B/D=1-879.
DR   PDB; 7YFR; EM; 5.10 A; B/D=1-879.
DR   PDB; 8E96; EM; 3.38 A; B/D=28-879.
DR   PDBsum; 7YFF; -.
DR   PDBsum; 7YFL; -.
DR   PDBsum; 7YFM; -.
DR   PDBsum; 7YFO; -.
DR   PDBsum; 7YFR; -.
DR   PDBsum; 8E96; -.
DR   AlphaFoldDB; O15399; -.
DR   EMDB; EMD-27957; -.
DR   EMDB; EMD-33788; -.
DR   EMDB; EMD-33792; -.
DR   EMDB; EMD-33793; -.
DR   EMDB; EMD-33795; -.
DR   EMDB; EMD-33798; -.
DR   SMR; O15399; -.
DR   BioGRID; 109163; 7.
DR   ComplexPortal; CPX-289; NMDA receptor complex, GluN1-GluN2D.
DR   IntAct; O15399; 6.
DR   MINT; O15399; -.
DR   STRING; 9606.ENSP00000263269; -.
DR   BindingDB; O15399; -.
DR   ChEMBL; CHEMBL2591; -.
DR   DrugBank; DB00659; Acamprosate.
DR   DrugBank; DB06151; Acetylcysteine.
DR   DrugBank; DB01238; Aripiprazole.
DR   DrugBank; DB00289; Atomoxetine.
DR   DrugBank; DB00647; Dextropropoxyphene.
DR   DrugBank; DB00843; Donepezil.
DR   DrugBank; DB00228; Enflurane.
DR   DrugBank; DB11823; Esketamine.
DR   DrugBank; DB13146; Fluciclovine (18F).
DR   DrugBank; DB06741; Gavestinel.
DR   DrugBank; DB00142; Glutamic acid.
DR   DrugBank; DB00874; Guaifenesin.
DR   DrugBank; DB06738; Ketobemidone.
DR   DrugBank; DB09409; Magnesium acetate tetrahydrate.
DR   DrugBank; DB09481; Magnesium carbonate.
DR   DrugBank; DB01043; Memantine.
DR   DrugBank; DB00454; Meperidine.
DR   DrugBank; DB00333; Methadone.
DR   DrugBank; DB04896; Milnacipran.
DR   DrugBank; DB01173; Orphenadrine.
DR   DrugBank; DB00312; Pentobarbital.
DR   DrugBank; DB01174; Phenobarbital.
DR   DrugBank; DB01708; Prasterone.
DR   DrugBank; DB00418; Secobarbital.
DR   DrugBank; DB01520; Tenocyclidine.
DR   DrugBank; DB00193; Tramadol.
DR   DrugCentral; O15399; -.
DR   GlyCosmos; O15399; 7 sites, No reported glycans.
DR   GlyGen; O15399; 7 sites.
DR   iPTMnet; O15399; -.
DR   PhosphoSitePlus; O15399; -.
DR   BioMuta; GRIN2D; -.
DR   EPD; O15399; -.
DR   jPOST; O15399; -.
DR   MassIVE; O15399; -.
DR   PaxDb; 9606-ENSP00000263269; -.
DR   PeptideAtlas; O15399; -.
DR   ProteomicsDB; 48638; -.
DR   Antibodypedia; 31709; 237 antibodies from 29 providers.
DR   DNASU; 2906; -.
DR   Ensembl; ENST00000263269.4; ENSP00000263269.2; ENSG00000105464.4.
DR   GeneID; 2906; -.
DR   KEGG; hsa:2906; -.
DR   MANE-Select; ENST00000263269.4; ENSP00000263269.2; NM_000836.4; NP_000827.2.
DR   UCSC; uc002pjc.4; human.
DR   AGR; HGNC:4588; -.
DR   CTD; 2906; -.
DR   DisGeNET; 2906; -.
DR   GeneCards; GRIN2D; -.
DR   GeneReviews; GRIN2D; -.
DR   HGNC; HGNC:4588; GRIN2D.
DR   HPA; ENSG00000105464; Tissue enhanced (brain).
DR   MalaCards; GRIN2D; -.
DR   MIM; 602717; gene.
DR   MIM; 617162; phenotype.
DR   neXtProt; NX_O15399; -.
DR   OpenTargets; ENSG00000105464; -.
DR   Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR   PharmGKB; PA28982; -.
DR   VEuPathDB; HostDB:ENSG00000105464; -.
DR   eggNOG; KOG1053; Eukaryota.
DR   GeneTree; ENSGT00940000159109; -.
DR   HOGENOM; CLU_002039_3_1_1; -.
DR   InParanoid; O15399; -.
DR   OMA; DRWRRPK; -.
DR   OrthoDB; 1034721at2759; -.
DR   PhylomeDB; O15399; -.
DR   TreeFam; TF314731; -.
DR   PathwayCommons; O15399; -.
DR   Reactome; R-HSA-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR   Reactome; R-HSA-442982; Ras activation upon Ca2+ influx through NMDA receptor.
DR   Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR   Reactome; R-HSA-8849932; Synaptic adhesion-like molecules.
DR   Reactome; R-HSA-9609736; Assembly and cell surface presentation of NMDA receptors.
DR   Reactome; R-HSA-9617324; Negative regulation of NMDA receptor-mediated neuronal transmission.
DR   Reactome; R-HSA-9620244; Long-term potentiation.
DR   SignaLink; O15399; -.
DR   SIGNOR; O15399; -.
DR   BioGRID-ORCS; 2906; 17 hits in 1167 CRISPR screens.
DR   ChiTaRS; GRIN2D; human.
DR   GeneWiki; GRIN2D; -.
DR   GenomeRNAi; 2906; -.
DR   Pharos; O15399; Tclin.
DR   PRO; PR:O15399; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; O15399; Protein.
DR   Bgee; ENSG00000105464; Expressed in cingulate cortex and 93 other cell types or tissues.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR   GO; GO:0017146; C:NMDA selective glutamate receptor complex; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR   GO; GO:0045211; C:postsynaptic membrane; NAS:ComplexPortal.
DR   GO; GO:0048787; C:presynaptic active zone membrane; IEA:Ensembl.
DR   GO; GO:0016595; F:glutamate binding; IEA:Ensembl.
DR   GO; GO:0022849; F:glutamate-gated calcium ion channel activity; IDA:UniProtKB.
DR   GO; GO:0004970; F:glutamate-gated receptor activity; IDA:UniProtKB.
DR   GO; GO:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IEA:Ensembl.
DR   GO; GO:0004972; F:NMDA glutamate receptor activity; IDA:UniProtKB.
DR   GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR   GO; GO:0022843; F:voltage-gated monoatomic cation channel activity; IEA:Ensembl.
DR   GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR   GO; GO:0007420; P:brain development; NAS:ARUK-UCL.
DR   GO; GO:0097553; P:calcium ion transmembrane import into cytosol; IDA:UniProtKB.
DR   GO; GO:1905232; P:cellular response to L-glutamate; IEA:Ensembl.
DR   GO; GO:0098976; P:excitatory chemical synaptic transmission; NAS:ARUK-UCL.
DR   GO; GO:0060079; P:excitatory postsynaptic potential; IBA:GO_Central.
DR   GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISO:ComplexPortal.
DR   GO; GO:0060291; P:long-term synaptic potentiation; IBA:GO_Central.
DR   GO; GO:0098655; P:monoatomic cation transmembrane transport; ISO:ComplexPortal.
DR   GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISO:ComplexPortal.
DR   GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISO:ComplexPortal.
DR   GO; GO:1904062; P:regulation of monoatomic cation transmembrane transport; ISO:ComplexPortal.
DR   GO; GO:0048168; P:regulation of neuronal synaptic plasticity; NAS:ComplexPortal.
DR   GO; GO:0051930; P:regulation of sensory perception of pain; IEA:Ensembl.
DR   GO; GO:0048167; P:regulation of synaptic plasticity; NAS:ARUK-UCL.
DR   GO; GO:0001964; P:startle response; IEA:Ensembl.
DR   GO; GO:0035249; P:synaptic transmission, glutamatergic; IBA:GO_Central.
DR   CDD; cd06378; PBP1_iGluR_NMDA_NR2; 1.
DR   CDD; cd13718; PBP2_iGluR_NMDA_Nr2; 1.
DR   Gene3D; 3.40.50.2300; -; 2.
DR   Gene3D; 3.40.190.10; Periplasmic binding protein-like II; 2.
DR   InterPro; IPR001828; ANF_lig-bd_rcpt.
DR   InterPro; IPR019594; Glu/Gly-bd.
DR   InterPro; IPR001508; Iono_Glu_rcpt_met.
DR   InterPro; IPR015683; Ionotropic_Glu_rcpt.
DR   InterPro; IPR001320; Iontro_rcpt_C.
DR   InterPro; IPR028082; Peripla_BP_I.
DR   InterPro; IPR001638; Solute-binding_3/MltF_N.
DR   PANTHER; PTHR18966:SF385; GLUTAMATE RECEPTOR IONOTROPIC, NMDA 2D; 1.
DR   PANTHER; PTHR18966; IONOTROPIC GLUTAMATE RECEPTOR; 1.
DR   Pfam; PF01094; ANF_receptor; 1.
DR   Pfam; PF00060; Lig_chan; 1.
DR   Pfam; PF10613; Lig_chan-Glu_bd; 1.
DR   Pfam; PF00497; SBP_bac_3; 1.
DR   PRINTS; PR00177; NMDARECEPTOR.
DR   SMART; SM00918; Lig_chan-Glu_bd; 1.
DR   SMART; SM00079; PBPe; 1.
DR   SUPFAM; SSF53822; Periplasmic binding protein-like I; 1.
DR   SUPFAM; SSF53850; Periplasmic binding protein-like II; 1.
DR   Genevisible; O15399; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium; Cell membrane; Disease variant; Disulfide bond;
KW   Epilepsy; Glycoprotein; Ion channel; Ion transport;
KW   Ligand-gated ion channel; Magnesium; Membrane; Methylation; Phosphoprotein;
KW   Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW   Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   CHAIN           28..1336
FT                   /note="Glutamate receptor ionotropic, NMDA 2D"
FT                   /id="PRO_0000011583"
FT   TOPO_DOM        28..584
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   TRANSMEM        585..603
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   TOPO_DOM        604..630
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   INTRAMEM        631..650
FT                   /note="Discontinuously helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   TOPO_DOM        651..657
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   TRANSMEM        658..673
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   TOPO_DOM        674..844
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   TRANSMEM        845..864
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   TOPO_DOM        865..1336
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   REGION          631..650
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   REGION          900..934
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          981..1123
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1225..1336
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           1334..1336
FT                   /note="PDZ-binding"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        902..932
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1021..1038
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1093..1108
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1225..1256
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         539..541
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:Q00959"
FT   BINDING         541
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   BINDING         546
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   BINDING         717..718
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:Q00959"
FT   BINDING         759
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:Q00960"
FT   SITE            642
FT                   /note="Functional determinant of NMDA receptors"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1316
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q03391"
FT   MOD_RES         1326
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q03391"
FT   CARBOHYD        92
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        352
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        366
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        384
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        467
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        569
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        715
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        104..348
FT                   /evidence="ECO:0000250|UniProtKB:Q00959"
FT   DISULFID        455..483
FT                   /evidence="ECO:0000250|UniProtKB:Q00959"
FT   DISULFID        462..484
FT                   /evidence="ECO:0000250|UniProtKB:Q00959"
FT   DISULFID        773..828
FT                   /evidence="ECO:0000250|UniProtKB:Q00959"
FT   VARIANT         140
FT                   /note="P -> S (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035698"
FT   VARIANT         286
FT                   /note="G -> R (in a breast cancer sample; somatic mutation;
FT                   dbSNP:rs1259830926)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035699"
FT   VARIANT         466
FT                   /note="L -> V (found in a patient with schizophrenia;
FT                   uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:22833210"
FT                   /id="VAR_079975"
FT   VARIANT         527
FT                   /note="E -> G (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035700"
FT   VARIANT         592
FT                   /note="M -> L (found in a patient with autism spectrum
FT                   disorder; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:22833210"
FT                   /id="VAR_079976"
FT   VARIANT         667
FT                   /note="V -> I (in DEE46; gain-of-function mutation that
FT                   potentiates ionotropic glutamate receptor signaling; mutant
FT                   receptors are activated by lower concentrations of
FT                   glutamate and glycine and show slower deactivation after
FT                   agonist removal as well as decreased sensitivity to
FT                   allosteric inhibitors indicating that NMDA glutamate
FT                   receptor activity is changed; dbSNP:rs886040861)"
FT                   /evidence="ECO:0000269|PubMed:27616483"
FT                   /id="VAR_077103"
FT   VARIANT         733
FT                   /note="M -> V (found in a patient with schizophrenia;
FT                   uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:22833210"
FT                   /id="VAR_079977"
FT   VARIANT         872
FT                   /note="R -> H (found in a patient with schizophrenia;
FT                   uncertain significance; dbSNP:rs750543659)"
FT                   /evidence="ECO:0000269|PubMed:22833210"
FT                   /id="VAR_079978"
FT   VARIANT         883
FT                   /note="M -> I (in dbSNP:rs781567305)"
FT                   /evidence="ECO:0000269|PubMed:22833210"
FT                   /id="VAR_079979"
FT   VARIANT         922
FT                   /note="A -> V (found in patients with schizophrenia;
FT                   uncertain significance; dbSNP:rs571334598)"
FT                   /evidence="ECO:0000269|PubMed:22833210"
FT                   /id="VAR_079980"
FT   VARIANT         926
FT                   /note="A -> T (found in a patient with autism spectrum
FT                   disorder; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:22833210"
FT                   /id="VAR_079981"
FT   VARIANT         982
FT                   /note="A -> P (in dbSNP:rs1225338399)"
FT                   /evidence="ECO:0000269|PubMed:22833210"
FT                   /id="VAR_079982"
FT   VARIANT         1317
FT                   /note="G -> S (in dbSNP:rs191119443)"
FT                   /evidence="ECO:0000269|PubMed:22833210"
FT                   /id="VAR_079983"
FT   MUTAGEN         580
FT                   /note="P->R: Changed glutamate-gated calcium ion channel
FT                   activity characterized by increased glutamate and glycine
FT                   potency."
FT                   /evidence="ECO:0000269|PubMed:28095420"
FT   MUTAGEN         845
FT                   /note="M->V: Increased glutamate and glycine agonist
FT                   potency."
FT                   /evidence="ECO:0000269|PubMed:28126851"
FT   CONFLICT        924
FT                   /note="R -> G (in Ref. 1; AAC15910)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1005
FT                   /note="P -> A (in Ref. 1; AAC15910)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1097
FT                   /note="R -> C (in Ref. 1; AAC15910)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1130
FT                   /note="E -> D (in Ref. 1; AAC15910)"
FT                   /evidence="ECO:0000305"
FT   STRAND          54..59
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           60..64
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   TURN            65..68
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           69..76
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          87..91
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          94..96
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           99..107
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          115..117
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           127..137
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          141..143
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           168..171
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           174..181
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          186..191
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           197..208
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          216..222
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   TURN            225..227
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           229..236
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          242..247
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   TURN            250..252
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           253..263
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          266..269
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          271..274
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          304..309
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           310..313
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           316..329
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           332..337
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           359..363
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          367..369
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          372..374
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          387..390
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          394..396
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          400..405
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          408..413
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          417..419
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          430..436
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   TURN            440..442
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          443..446
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          451..453
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          483..486
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           487..498
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          502..507
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          510..513
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          515..517
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          520..523
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           524..529
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          534..536
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           544..547
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          550..552
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          556..566
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           634..640
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           656..680
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          692..695
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           696..699
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           701..704
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           718..723
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           727..733
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   TURN            734..736
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           743..750
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          756..758
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           763..766
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          773..781
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   STRAND          784..788
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           800..812
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   TURN            813..819
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           820..823
FT                   /evidence="ECO:0007829|PDB:8E96"
FT   HELIX           849..861
FT                   /evidence="ECO:0007829|PDB:8E96"
SQ   SEQUENCE   1336 AA;  143752 MW;  0DB7559056AE4593 CRC64;
     MRGAGGPRGP RGPAKMLLLL ALACASPFPE EAPGPGGAGG PGGGLGGARP LNVALVFSGP
     AYAAEAARLG PAVAAAVRSP GLDVRPVALV LNGSDPRSLV LQLCDLLSGL RVHGVVFEDD
     SRAPAVAPIL DFLSAQTSLP IVAVHGGAAL VLTPKEKGST FLQLGSSTEQ QLQVIFEVLE
     EYDWTSFVAV TTRAPGHRAF LSYIEVLTDG SLVGWEHRGA LTLDPGAGEA VLSAQLRSVS
     AQIRLLFCAR EEAEPVFRAA EEAGLTGSGY VWFMVGPQLA GGGGSGAPGE PPLLPGGAPL
     PAGLFAVRSA GWRDDLARRV AAGVAVVARG AQALLRDYGF LPELGHDCRA QNRTHRGESL
     HRYFMNITWD NRDYSFNEDG FLVNPSLVVI SLTRDRTWEV VGSWEQQTLR LKYPLWSRYG
     RFLQPVDDTQ HLTVATLEER PFVIVEPADP ISGTCIRDSV PCRSQLNRTH SPPPDAPRPE
     KRCCKGFCID ILKRLAHTIG FSYDLYLVTN GKHGKKIDGV WNGMIGEVFY QRADMAIGSL
     TINEERSEIV DFSVPFVETG ISVMVARSNG TVSPSAFLEP YSPAVWVMMF VMCLTVVAVT
     VFIFEYLSPV GYNRSLATGK RPGGSTFTIG KSIWLLWALV FNNSVPVENP RGTTSKIMVL
     VWAFFAVIFL ASYTANLAAF MIQEEYVDTV SGLSDRKFQR PQEQYPPLKF GTVPNGSTEK
     NIRSNYPDMH SYMVRYNQPR VEEALTQLKA GKLDAFIYDA AVLNYMARKD EGCKLVTIGS
     GKVFATTGYG IALHKGSRWK RPIDLALLQF LGDDEIEMLE RLWLSGICHN DKIEVMSSKL
     DIDNMAGVFY MLLVAMGLSL LVFAWEHLVY WRLRHCLGPT HRMDFLLAFS RGMYSCCSAE
     AAPPPAKPPP PPQPLPSPAY PAPRPAPGPA PFVPRERASV DRWRRTKGAG PPGGAGLADG
     FHRYYGPIEP QGLGLGLGEA RAAPRGAAGR PLSPPAAQPP QKPPPSYFAI VRDKEPAEPP
     AGAFPGFPSP PAPPAAAATA VGPPLCRLAF EDESPPAPAR WPRSDPESQP LLGPGAGGAG
     GTGGAGGGAP AAPPPCRAAP PPCPYLDLEP SPSDSEDSES LGGASLGGLE PWWFADFPYP
     YAERLGPPPG RYWSVDKLGG WRAGSWDYLP PRSGPAAWHC RHCASLELLP PPRHLSCSHD
     GLDGGWWAPP PPPWAAGPLP RRRARCGCPR SHPHRPRASH RTPAAAAPHH HRHRRAAGGW
     DLPPPAPTSR SLEDLSSCPR AAPARRLTGP SRHARRCPHA AHWGPPLPTA SHRRHRGGDL
     GTRRGSAHFS SLESEV
//