NMDE4_HUMAN
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 03-AUG-2022, entry version 189.
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 AlphaFoldDB; O15399; -.
DR SMR; O15399; -.
DR BioGRID; 109163; 6.
DR ComplexPortal; CPX-289; NMDA receptor complex, GluN1-GluN2D.
DR IntAct; O15399; 8.
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; 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 GlyGen; O15399; 7 sites.
DR iPTMnet; O15399; -.
DR PhosphoSitePlus; O15399; -.
DR BioMuta; GRIN2D; -.
DR EPD; O15399; -.
DR jPOST; O15399; -.
DR MassIVE; O15399; -.
DR PaxDb; O15399; -.
DR PeptideAtlas; O15399; -.
DR PRIDE; O15399; -.
DR ProteomicsDB; 48638; -.
DR Antibodypedia; 31709; 186 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 CTD; 2906; -.
DR DisGeNET; 2906; -.
DR GeneCards; GRIN2D; -.
DR HGNC; HGNC:4588; GRIN2D.
DR HPA; ENSG00000105464; Tissue enriched (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; CGCPRSH; -.
DR OrthoDB; 188544at2759; -.
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 1081 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 92 other tissues.
DR Genevisible; O15399; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IC:ComplexPortal.
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:ionotropic glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0042165; F:neurotransmitter binding; IEA:Ensembl.
DR GO; GO:0004972; F:NMDA glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; 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:0098976; P:excitatory chemical synaptic transmission; NAS:ARUK-UCL.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IBA:GO_Central.
DR GO; GO:0060291; P:long-term synaptic potentiation; IBA:GO_Central.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IEA:Ensembl.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; IEA:Ensembl.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IC: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; IEA:Ensembl.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR019594; Glu/Gly-bd.
DR InterPro; IPR001508; Iono_rcpt_met.
DR InterPro; IPR001320; Iontro_rcpt.
DR InterPro; IPR028082; Peripla_BP_I.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00060; Lig_chan; 1.
DR Pfam; PF10613; Lig_chan-Glu_bd; 1.
DR PRINTS; PR00177; NMDARECEPTOR.
DR SMART; SM00918; Lig_chan-Glu_bd; 1.
DR SMART; SM00079; PBPe; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Disease variant; Disulfide bond; Epilepsy;
KW Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel;
KW 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 unknown pathological 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; unknown pathological 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 unknown pathological 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 unknown pathological 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 unknown pathological 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; unknown pathological 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"
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
