NMDE1_HUMAN
ID NMDE1_HUMAN Reviewed; 1464 AA.
AC Q12879; O00669; Q17RZ6;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Glutamate receptor ionotropic, NMDA 2A;
DE Short=GluN2A;
DE AltName: Full=Glutamate [NMDA] receptor subunit epsilon-1;
DE AltName: Full=N-methyl D-aspartate receptor subtype 2A;
DE Short=NMDAR2A {ECO:0000303|PubMed:8768735};
DE Short=NR2A;
DE Short=hNR2A {ECO:0000303|PubMed:8061049};
DE Flags: Precursor;
GN Name=GRIN2A; Synonyms=NMDAR2A;
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] (ISOFORM 1), AND VARIANT GLU-270.
RX PubMed=8061049; DOI=10.1016/0167-4889(94)90086-8;
RA Foldes R.L., Adams S.L., Fantaske R.P., Kamboj R.K.;
RT "Human N-methyl-D-aspartate receptor modulatory subunit hNR2A: cloning and
RT sequencing of the cDNA and primary structure of the protein.";
RL Biochim. Biophys. Acta 1223:155-159(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP SUBUNIT.
RC TISSUE=Cerebellum;
RX PubMed=8768735;
RA Hess S.D., Daggett L.P., Crona J., Deal C., Lu C.-C., Urrutia A.,
RA Chavez-Noriega L., Ellis S.B., Johnson E.C., Velicelebi G.;
RT "Cloning and functional characterization of human heteromeric N-methyl-D-
RT aspartate receptors.";
RL J. Pharmacol. Exp. Ther. 278:808-816(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5] {ECO:0007744|PDB:5I2K, ECO:0007744|PDB:5I2N, ECO:0007744|PDB:5KDT}
RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF 401-539 AND 566-800 IN COMPLEX
RP WITH GLUTAMATE AND GRIN1, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND
RP DISULFIDE BONDS.
RX PubMed=26919761; DOI=10.1021/acs.jmedchem.5b02010;
RA Volgraf M., Sellers B.D., Jiang Y., Wu G., Ly C.Q., Villemure E.,
RA Pastor R.M., Yuen P.W., Lu A., Luo X., Liu M., Zhang S., Sun L., Fu Y.,
RA Lupardus P.J., Wallweber H.J., Liederer B.M., Deshmukh G., Plise E.,
RA Tay S., Reynen P., Herrington J., Gustafson A., Liu Y., Dirksen A.,
RA Dietz M.G., Liu Y., Wang T.M., Hanson J.E., Hackos D., Scearce-Levie K.,
RA Schwarz J.B.;
RT "Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators
RT (PAMs): Tuning Deactivation Kinetics via Structure-Based Design.";
RL J. Med. Chem. 59:2760-2779(2016).
RN [6] {ECO:0007744|PDB:5H8F, ECO:0007744|PDB:5H8H, ECO:0007744|PDB:5H8N, ECO:0007744|PDB:5H8Q, ECO:0007744|PDB:5KCJ}
RP X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 401-539 AND 566-800 IN COMPLEX
RP WITH GLUTAMATE AND GRIN1, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP DISULFIDE BONDS.
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 [7] {ECO:0007744|PDB:5TP9, ECO:0007744|PDB:5TPA}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 401-539 AND 566-800 IN COMPLEX
RP WITH GRIN1 AND GLUTAMATE, SUBCELLULAR LOCATION, SUBUNIT, FUNCTION, AND
RP DISULFIDE BONDS.
RX PubMed=28105280; DOI=10.1021/acsmedchemlett.6b00388;
RA Villemure E., Volgraf M., Jiang Y., Wu G., Ly C.Q., Yuen P.W., Lu A.,
RA Luo X., Liu M., Zhang S., Lupardus P.J., Wallweber H.J., Liederer B.M.,
RA Deshmukh G., Plise E., Tay S., Wang T.M., Hanson J.E., Hackos D.H.,
RA Scearce-Levie K., Schwarz J.B., Sellers B.D.;
RT "GluN2A-Selective Pyridopyrimidinone Series of NMDAR Positive Allosteric
RT Modulators with an Improved in Vivo Profile.";
RL ACS Med. Chem. Lett. 8:84-89(2017).
RN [8]
RP CHROMOSOMAL TRANSLOCATION, VARIANT FESD LYS-615, AND CHARACTERIZATION OF
RP VARIANT FESD LYS-615.
RX PubMed=20890276; DOI=10.1038/ng.677;
RA Endele S., Rosenberger G., Geider K., Popp B., Tamer C., Stefanova I.,
RA Milh M., Kortum F., Fritsch A., Pientka F.K., Hellenbroich Y.,
RA Kalscheuer V.M., Kohlhase J., Moog U., Rappold G., Rauch A., Ropers H.H.,
RA von Spiczak S., Tonnies H., Villeneuve N., Villard L., Zabel B., Zenker M.,
RA Laube B., Reis A., Wieczorek D., Van Maldergem L., Kutsche K.;
RT "Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA
RT receptors cause variable neurodevelopmental phenotypes.";
RL Nat. Genet. 42:1021-1026(2010).
RN [9]
RP PROBABLE INVOLVEMENT IN MELANOMA, AND VARIANTS LEU-57; ILE-183; ASN-252;
RP PHE-278; LYS-371; LYS-373; GLU-449; SER-459; ARG-595; PHE-598; ILE-653;
RP GLU-712; TRP-740; GLU-889; LYS-920; PHE-929; LYS-962; LYS-1073; LEU-1074;
RP ASN-1153; LYS-1175; GLY-1276; LYS-1285; TRP-1318; LEU-1366; ASN-1421;
RP LEU-1425; LYS-1426 AND CYS-1462.
RX PubMed=21499247; DOI=10.1038/ng.810;
RA Wei X., Walia V., Lin J.C., Teer J.K., Prickett T.D., Gartner J., Davis S.,
RA Stemke-Hale K., Davies M.A., Gershenwald J.E., Robinson W., Robinson S.,
RA Rosenberg S.A., Samuels Y.;
RT "Exome sequencing identifies GRIN2A as frequently mutated in melanoma.";
RL Nat. Genet. 43:442-446(2011).
RN [10]
RP VARIANTS ILE-143; ASN-189; SER-336; MET-452; SER-576; MET-852; VAL-922;
RP ASN-937; THR-968; MET-998; ALA-1064; SER-1229 AND GLY-1276.
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).
RN [11]
RP VARIANTS FESD ARG-552 AND VAL-649.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [12]
RP VARIANTS FESD SER-184; SER-295; ARG-483; TRP-504; HIS-518; THR-548;
RP VAL-652; ASN-669; THR-694; THR-716; ASN-731; ASN-933 AND ASN-1251, VARIANT
RP GLY-1276, AND CHARACTERIZATION OF VARIANTS FESD HIS-518 AND VAL-652.
RX PubMed=23933820; DOI=10.1038/ng.2726;
RA Lesca G., Rudolf G., Bruneau N., Lozovaya N., Labalme A., Boutry-Kryza N.,
RA Salmi M., Tsintsadze T., Addis L., Motte J., Wright S., Tsintsadze V.,
RA Michel A., Doummar D., Lascelles K., Strug L., Waters P., de Bellescize J.,
RA Vrielynck P., de Saint Martin A., Ville D., Ryvlin P., Arzimanoglou A.,
RA Hirsch E., Vincent A., Pal D., Burnashev N., Sanlaville D., Szepetowski P.;
RT "GRIN2A mutations in acquired epileptic aphasia and related childhood focal
RT epilepsies and encephalopathies with speech and language dysfunction.";
RL Nat. Genet. 45:1061-1066(2013).
RN [13]
RP VARIANTS FESD ARG-79; TYR-231; VAL-243; VAL-290; TRP-370; ARG-436; SER-547
RP DEL; SER-699; VAL-705; LYS-714; THR-727; LEU-734; GLU-772; THR-814; PHE-904
RP AND SER-976, VARIANT ILE-183, AND CHARACTERIZATION OF VARIANT FESD VAL-243.
RX PubMed=23933819; DOI=10.1038/ng.2728;
RA Lemke J.R., Lal D., Reinthaler E.M., Steiner I., Nothnagel M., Alber M.,
RA Geider K., Laube B., Schwake M., Finsterwalder K., Franke A.,
RA Schilhabel M., Jahn J.A., Muhle H., Boor R., Van Paesschen W.,
RA Caraballo R., Fejerman N., Weckhuysen S., De Jonghe P., Larsen J.,
RA Moller R.S., Hjalgrim H., Addis L., Tang S., Hughes E., Pal D.K., Veri K.,
RA Vaher U., Talvik T., Dimova P., Guerrero Lopez R., Serratosa J.M.,
RA Linnankivi T., Lehesjoki A.E., Ruf S., Wolff M., Buerki S., Wohlrab G.,
RA Kroell J., Datta A.N., Fiedler B., Kurlemann G., Kluger G., Hahn A.,
RA Haberlandt D.E., Kutzer C., Sperner J., Becker F., Weber Y.G., Feucht M.,
RA Steinbock H., Neophythou B., Ronen G.M., Gruber-Sedlmayr U., Geldner J.,
RA Harvey R.J., Hoffmann P., Herms S., Altmuller J., Toliat M.R., Thiele H.,
RA Nurnberg P., Wilhelm C., Stephani U., Helbig I., Lerche H., Zimprich F.,
RA Neubauer B.A., Biskup S., von Spiczak S.;
RT "Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic
RT spikes.";
RL Nat. Genet. 45:1067-1072(2013).
RN [14]
RP VARIANT FESD MET-531, AND CHARACTERIZATION OF VARIANT FESD MET-531.
RX PubMed=23933818; DOI=10.1038/ng.2727;
RA Carvill G.L., Regan B.M., Yendle S.C., O'Roak B.J., Lozovaya N.,
RA Bruneau N., Burnashev N., Khan A., Cook J., Geraghty E., Sadleir L.G.,
RA Turner S.J., Tsai M.H., Webster R., Ouvrier R., Damiano J.A.,
RA Berkovic S.F., Shendure J., Hildebrand M.S., Szepetowski P., Scheffer I.E.,
RA Mefford H.C.;
RT "GRIN2A mutations cause epilepsy-aphasia spectrum disorders.";
RL Nat. Genet. 45:1073-1076(2013).
RN [15]
RP PROBABLE INVOLVEMENT IN MELANOMA, AND VARIANTS PHE-349; ALA-762; GLU-889;
RP LEU-1132 AND SER-1133.
RX PubMed=24455489; DOI=10.3389/fonc.2013.00333;
RA D'mello S.A., Flanagan J.U., Green T.N., Leung E.Y., Askarian-Amiri M.E.,
RA Joseph W.R., McCrystal M.R., Isaacs R.J., Shaw J.H., Furneaux C.E.,
RA During M.J., Finlay G.J., Baguley B.C., Kalev-Zylinska M.L.;
RT "Evidence that GRIN2A mutations in melanoma correlate with decreased
RT survival.";
RL Front. Oncol. 3:333-333(2014).
RN [16]
RP VARIANT FESD VAL-817.
RX PubMed=24903190; DOI=10.1111/epi.12663;
RG FORGE Canada Consortium;
RA Venkateswaran S., Myers K.A., Smith A.C., Beaulieu C.L.,
RA Schwartzentruber J.A., Majewski J., Bulman D., Boycott K.M., Dyment D.A.;
RT "Whole-exome sequencing in an individual with severe global developmental
RT delay and intractable epilepsy identifies a novel, de novo GRIN2A
RT mutation.";
RL Epilepsia 55:E75-E79(2014).
RN [17]
RP VARIANT FESD MET-812, AND CHARACTERIZATION OF VARIANT FESD MET-812.
RX PubMed=24504326; DOI=10.1038/ncomms4251;
RA Yuan H., Hansen K.B., Zhang J., Pierson T.M., Markello T.C., Fajardo K.V.,
RA Holloman C.M., Golas G., Adams D.R., Boerkoel C.F., Gahl W.A.,
RA Traynelis S.F.;
RT "Functional analysis of a de novo GRIN2A missense mutation associated with
RT early-onset epileptic encephalopathy.";
RL Nat. Commun. 5:3251-3251(2014).
RN [18]
RP VARIANT ASN-884.
RX PubMed=26637798; DOI=10.1016/j.neuron.2015.11.009;
RA D'Gama A.M., Pochareddy S., Li M., Jamuar S.S., Reiff R.E., Lam A.T.,
RA Sestan N., Walsh C.A.;
RT "Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates
RT Multiple Genetic Mechanisms.";
RL Neuron 88:910-917(2015).
RN [19]
RP VARIANTS FESD ALA-506 AND GLY-685, CHARACTERIZATION OF VARIANT FESD
RP ARG-436; ARG-483; TRP-504; ALA-506; HIS-518; MET-531; ASN-669; GLY-685;
RP THR-694; SER-699; VAL-705; LYS-714; THR-716; THR-727; ASN-731; LEU-734;
RP GLU-772, AND CHARACTERIZATION OF VARIANT MET-452.
RX PubMed=27839871; DOI=10.1016/j.ajhg.2016.10.002;
RA Swanger S.A., Chen W., Wells G., Burger P.B., Tankovic A., Bhattacharya S.,
RA Strong K.L., Hu C., Kusumoto H., Zhang J., Adams D.R., Millichap J.J.,
RA Petrovski S., Traynelis S.F., Yuan H.;
RT "Mechanistic insight into NMDA receptor dysregulation by rare variants in
RT the GluN2A and GluN2B agonist binding domains.";
RL Am. J. Hum. Genet. 99:1261-1280(2016).
RN [20]
RP VARIANTS ASP-380; SER-989 AND GLY-1276, AND VARIANT FESD ASP-716.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
RN [21]
RP CHARACTERIZATION OF VARIANT FESD VAL-817.
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 [22]
RP VARIANT FESD ASN-731, AND CHARACTERIZATION OF VARIANT FESD ASN-731.
RX PubMed=28182669; DOI=10.1371/journal.pone.0170818;
RA Gao K., Tankovic A., Zhang Y., Kusumoto H., Zhang J., Chen W., XiangWei W.,
RA Shaulsky G.H., Hu C., Traynelis S.F., Yuan H., Jiang Y.;
RT "A de novo loss-of-function GRIN2A mutation associated with childhood focal
RT epilepsy and acquired epileptic aphasia.";
RL PLoS ONE 12:E0170818-E0170818(2017).
RN [23]
RP CHARACTERIZATION OF VARIANTS FESD THR-548 AND ARG-552, AND MUTAGENESIS OF
RP PRO-552.
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).
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:8768735, PubMed:26919761, PubMed:26875626, PubMed:28105280).
CC Sensitivity to glutamate and channel kinetics depend on the subunit
CC composition; channels containing GRIN1 and GRIN2A have lower
CC sensitivity to glutamate and faster deactivation kinetics than channels
CC formed by GRIN1 and GRIN2B (PubMed:26919761, PubMed:26875626).
CC Contributes to the slow phase of excitatory postsynaptic current, long-
CC term synaptic potentiation, and learning (By similarity).
CC {ECO:0000250|UniProtKB:P35436, ECO:0000250|UniProtKB:Q00959,
CC ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761,
CC ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:8768735}.
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:8768735, PubMed:26919761,
CC PubMed:26875626, PubMed:28105280). Can also form heterotetrameric
CC channels that contain at least one zeta subunit (GRIN1), at least one
CC epsilon subunit, plus GRIN3A or GRIN3B. In vivo, the subunit
CC composition may depend on the expression levels of the different
CC subunits. Found in a complex with GRIN1, GRIN3A and PPP2CB (By
CC similarity). Found in a complex with GRIN1 and GRIN3B (By similarity).
CC Interacts with AIP1 (By similarity). Interacts with HIP1 and NETO1.
CC Interacts with SNX27 (via PDZ domain); the interaction is required for
CC recycling to the plasma membrane when endocytosed and prevent
CC degradation in lysosomes (By similarity). Interacts with PDZ domains of
CC PATJ and DLG4. Interacts with LRFN2 (By similarity). Interacts with
CC RPH3A and DLG4; this ternary complex regulates NMDA receptor
CC composition at postsynaptic membranes (By similarity). Interacts with
CC SORCS2 (By similarity). Interacts with ARC; preventing ARC
CC oligomerization (By similarity). {ECO:0000250|UniProtKB:P35436,
CC ECO:0000250|UniProtKB:Q00959, ECO:0000269|PubMed:26875626,
CC ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28105280,
CC ECO:0000269|PubMed:8768735}.
CC -!- INTERACTION:
CC Q12879; P78352: DLG4; NbExp=6; IntAct=EBI-7249937, EBI-80389;
CC Q12879; Q07954: LRP1; NbExp=2; IntAct=EBI-7249937, EBI-1046087;
CC Q12879; Q62936: Dlg3; Xeno; NbExp=5; IntAct=EBI-7249937, EBI-349596;
CC Q12879; P31016: Dlg4; Xeno; NbExp=2; IntAct=EBI-7249937, EBI-375655;
CC Q12879-1; Q05586-1: GRIN1; NbExp=2; IntAct=EBI-27070593, EBI-27070564;
CC -!- SUBCELLULAR LOCATION: Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:Q00959}. Cell membrane
CC {ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761,
CC ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:8768735}; Multi-pass
CC membrane protein {ECO:0000305}. Synapse {ECO:0000250|UniProtKB:P35436}.
CC Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q00959}; Multi-pass
CC membrane protein {ECO:0000305}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:P35436}. Note=Expression at the dendrite cell
CC membrane and at synapses is regulated by SORCS2 and the retromer
CC complex. {ECO:0000250|UniProtKB:P35436}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q12879-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q12879-2; Sequence=VSP_044300;
CC -!- DOMAIN: Contains an N-terminal domain, a ligand-binding domain and a
CC transmembrane domain. Agonist binding to the extracellular ligand-
CC binding domains triggers channel gating.
CC {ECO:0000250|UniProtKB:Q00959}.
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:B7ZSK1}.
CC -!- DISEASE: Epilepsy, focal, with speech disorder and with or without
CC impaired intellectual development (FESD) [MIM:245570]: An autosomal
CC dominant, highly variable neurologic disorder. Features range from
CC severe early-onset seizures associated with delayed psychomotor
CC development, persistent speech difficulties, and intellectual
CC disability to a more benign entity characterized by childhood onset of
CC mild or asymptomatic seizures associated with transient speech
CC difficulties followed by remission of seizures in adolescence and
CC normal psychomotor development. The disorder encompasses several
CC clinical entities, including Landau-Kleffner syndrome, epileptic
CC encephalopathy with continuous spike and wave during slow-wave sleep,
CC autosomal dominant rolandic epilepsy, intellectual disability and
CC speech dyspraxia, and benign epilepsy with centrotemporal spikes.
CC {ECO:0000269|PubMed:20890276, ECO:0000269|PubMed:23033978,
CC ECO:0000269|PubMed:23933818, ECO:0000269|PubMed:23933819,
CC ECO:0000269|PubMed:23933820, ECO:0000269|PubMed:24504326,
CC ECO:0000269|PubMed:24903190, ECO:0000269|PubMed:27839871,
CC ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28095420,
CC ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:28182669}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=A chromosomal aberration involving GRIN2A has been found
CC in a family with epilepsy and neurodevelopmental defects. Translocation
CC t(16;17)(p13.2;q11.2).
CC -!- DISEASE: Note=GRIN2A somatic mutations have been frequently found in
CC cutaneous malignant melanoma, suggesting that the glutamate signaling
CC pathway may play a role in the pathogenesis of melanoma.
CC {ECO:0000269|PubMed:21499247, ECO:0000269|PubMed:24455489}.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. NR2A/GRIN2A subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; U09002; AAB60343.1; -; mRNA.
DR EMBL; U90277; AAB49992.1; -; mRNA.
DR EMBL; AC006531; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007218; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022168; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026423; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133565; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117131; AAI17132.1; -; mRNA.
DR EMBL; BC143273; AAI43274.1; -; mRNA.
DR CCDS; CCDS10539.1; -. [Q12879-1]
DR CCDS; CCDS45407.1; -. [Q12879-2]
DR PIR; S47555; S47555.
DR RefSeq; NP_000824.1; NM_000833.4. [Q12879-1]
DR RefSeq; NP_001127879.1; NM_001134407.2. [Q12879-1]
DR RefSeq; NP_001127880.1; NM_001134408.2. [Q12879-2]
DR RefSeq; XP_011520763.1; XM_011522461.2. [Q12879-2]
DR PDB; 3NFL; X-ray; 1.91 A; E/F/G/H=1449-1464.
DR PDB; 5H8F; X-ray; 1.81 A; A=401-539, A=661-802.
DR PDB; 5H8H; X-ray; 2.23 A; A=401-539, A=661-802.
DR PDB; 5H8N; X-ray; 2.50 A; A=401-539, A=661-802.
DR PDB; 5H8Q; X-ray; 1.90 A; A=401-539, A=661-802.
DR PDB; 5I2K; X-ray; 2.86 A; A=401-539, A=661-802.
DR PDB; 5I2N; X-ray; 2.12 A; A=401-539, A=661-802.
DR PDB; 5KCJ; X-ray; 2.09 A; A=401-539, A=661-802.
DR PDB; 5KDT; X-ray; 2.44 A; A=401-539, A=661-802.
DR PDB; 5TP9; X-ray; 2.40 A; A=401-539, A=661-802.
DR PDB; 5TPA; X-ray; 2.48 A; A=401-539, A=661-802.
DR PDB; 6IRA; EM; 4.50 A; B/D=1-842.
DR PDB; 6IRF; EM; 5.10 A; B/D=1-841.
DR PDB; 6IRG; EM; 5.50 A; B/D=1-841.
DR PDB; 6IRH; EM; 7.80 A; B/D=1-841.
DR PDB; 7EOQ; EM; 4.10 A; A/C=1-842.
DR PDB; 7EOR; EM; 4.00 A; A/C=1-842.
DR PDB; 7EOS; EM; 3.90 A; A/C=1-842.
DR PDB; 7EOT; EM; 3.80 A; A/C=1-842.
DR PDB; 7EOU; EM; 4.30 A; A/C=1-842.
DR PDB; 7EU7; EM; 3.50 A; B/D=1-841.
DR PDBsum; 3NFL; -.
DR PDBsum; 5H8F; -.
DR PDBsum; 5H8H; -.
DR PDBsum; 5H8N; -.
DR PDBsum; 5H8Q; -.
DR PDBsum; 5I2K; -.
DR PDBsum; 5I2N; -.
DR PDBsum; 5KCJ; -.
DR PDBsum; 5KDT; -.
DR PDBsum; 5TP9; -.
DR PDBsum; 5TPA; -.
DR PDBsum; 6IRA; -.
DR PDBsum; 6IRF; -.
DR PDBsum; 6IRG; -.
DR PDBsum; 6IRH; -.
DR PDBsum; 7EOQ; -.
DR PDBsum; 7EOR; -.
DR PDBsum; 7EOS; -.
DR PDBsum; 7EOT; -.
DR PDBsum; 7EOU; -.
DR PDBsum; 7EU7; -.
DR AlphaFoldDB; Q12879; -.
DR SMR; Q12879; -.
DR BioGRID; 109160; 64.
DR ComplexPortal; CPX-2202; NMDA receptor complex, GluN1-GluN2A.
DR ComplexPortal; CPX-294; NMDA receptor complex, GluN1-GluN2A-GluN2B.
DR CORUM; Q12879; -.
DR DIP; DIP-40798N; -.
DR IntAct; Q12879; 7.
DR MINT; Q12879; -.
DR STRING; 9606.ENSP00000379818; -.
DR BindingDB; Q12879; -.
DR ChEMBL; CHEMBL1972; -.
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; DB00949; Felbamate.
DR DrugBank; DB13146; Fluciclovine (18F).
DR DrugBank; DB06741; Gavestinel.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB00874; Guaifenesin.
DR DrugBank; DB01159; Halothane.
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; DB00312; Pentobarbital.
DR DrugBank; DB01174; Phenobarbital.
DR DrugBank; DB01708; Prasterone.
DR DrugBank; DB00418; Secobarbital.
DR DrugBank; DB01520; Tenocyclidine.
DR DrugBank; DB00193; Tramadol.
DR DrugCentral; Q12879; -.
DR GuidetoPHARMACOLOGY; 456; -.
DR TCDB; 1.A.10.1.20; the glutamate-gated ion channel (gic) family of neurotransmitter receptors.
DR GlyGen; Q12879; 8 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q12879; -.
DR PhosphoSitePlus; Q12879; -.
DR BioMuta; GRIN2A; -.
DR DMDM; 14285603; -.
DR EPD; Q12879; -.
DR MassIVE; Q12879; -.
DR PaxDb; Q12879; -.
DR PeptideAtlas; Q12879; -.
DR PRIDE; Q12879; -.
DR ProteomicsDB; 58998; -. [Q12879-1]
DR ProteomicsDB; 61175; -.
DR ABCD; Q12879; 2 sequenced antibodies.
DR Antibodypedia; 1402; 778 antibodies from 41 providers.
DR DNASU; 2903; -.
DR Ensembl; ENST00000330684.4; ENSP00000332549.3; ENSG00000183454.18. [Q12879-1]
DR Ensembl; ENST00000396573.6; ENSP00000379818.2; ENSG00000183454.18. [Q12879-1]
DR Ensembl; ENST00000562109.5; ENSP00000454998.1; ENSG00000183454.18. [Q12879-2]
DR GeneID; 2903; -.
DR KEGG; hsa:2903; -.
DR MANE-Select; ENST00000330684.4; ENSP00000332549.3; NM_001134407.3; NP_001127879.1.
DR UCSC; uc002czr.5; human. [Q12879-1]
DR CTD; 2903; -.
DR DisGeNET; 2903; -.
DR GeneCards; GRIN2A; -.
DR GeneReviews; GRIN2A; -.
DR HGNC; HGNC:4585; GRIN2A.
DR HPA; ENSG00000183454; Tissue enriched (brain).
DR MalaCards; GRIN2A; -.
DR MIM; 138253; gene.
DR MIM; 245570; phenotype.
DR neXtProt; NX_Q12879; -.
DR OpenTargets; ENSG00000183454; -.
DR Orphanet; 725; Continuous spikes and waves during sleep.
DR Orphanet; 289266; Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation.
DR Orphanet; 98818; Landau-Kleffner syndrome.
DR Orphanet; 1945; Rolandic epilepsy.
DR Orphanet; 163721; Rolandic epilepsy-speech dyspraxia syndrome.
DR PharmGKB; PA28979; -.
DR VEuPathDB; HostDB:ENSG00000183454; -.
DR eggNOG; KOG1053; Eukaryota.
DR GeneTree; ENSGT00940000156222; -.
DR HOGENOM; CLU_002598_0_0_1; -.
DR InParanoid; Q12879; -.
DR OMA; FPDAYQD; -.
DR OrthoDB; 188544at2759; -.
DR PhylomeDB; Q12879; -.
DR TreeFam; TF314731; -.
DR PathwayCommons; Q12879; -.
DR Reactome; R-HSA-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR Reactome; R-HSA-8849932; Synaptic adhesion-like molecules.
DR Reactome; R-HSA-9022699; MECP2 regulates neuronal receptors and channels.
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; Q12879; -.
DR SIGNOR; Q12879; -.
DR BioGRID-ORCS; 2903; 8 hits in 1068 CRISPR screens.
DR ChiTaRS; GRIN2A; human.
DR EvolutionaryTrace; Q12879; -.
DR GeneWiki; GRIN2A; -.
DR GenomeRNAi; 2903; -.
DR Pharos; Q12879; Tclin.
DR PRO; PR:Q12879; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q12879; protein.
DR Bgee; ENSG00000183454; Expressed in Brodmann (1909) area 23 and 139 other tissues.
DR ExpressionAtlas; Q12879; baseline and differential.
DR Genevisible; Q12879; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; ISS:ARUK-UCL.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic 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; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IC:ComplexPortal.
DR GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl.
DR GO; GO:0097060; C:synaptic membrane; ISS:ARUK-UCL.
DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR GO; GO:0001540; F:amyloid-beta binding; TAS:ARUK-UCL.
DR GO; GO:0022849; F:glutamate-gated calcium ion channel activity; IDA:UniProtKB.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0004972; F:NMDA glutamate receptor activity; ISS:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; TAS:ARUK-UCL.
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:0098655; P:cation transmembrane transport; IC:ComplexPortal.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0033058; P:directional locomotion; IEA:Ensembl.
DR GO; GO:0042417; P:dopamine metabolic process; 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:0007215; P:glutamate receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0007611; P:learning or memory; TAS:ProtInc.
DR GO; GO:0060291; P:long-term synaptic potentiation; IBA:GO_Central.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0022008; P:neurogenesis; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IC:ComplexPortal.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IC:ComplexPortal.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:1903539; P:protein localization to postsynaptic membrane; IEA:Ensembl.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; IC:ComplexPortal.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IC:ComplexPortal.
DR GO; GO:0048167; P:regulation of synaptic plasticity; NAS:ARUK-UCL.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IDA:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0042428; P:serotonin metabolic process; IEA:Ensembl.
DR GO; GO:0030431; P:sleep; IEA:Ensembl.
DR GO; GO:0001964; P:startle response; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR IDEAL; IID00664; -.
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; IPR018884; NMDAR2_C.
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 Pfam; PF10565; NMDAR2_C; 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 3D-structure; Alternative splicing; Calcium; Cell membrane;
KW Cell projection; Chromosomal rearrangement; Cytoplasmic vesicle;
KW Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Magnesium; Membrane;
KW Metal-binding; Phosphoprotein; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Transport; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1464
FT /note="Glutamate receptor ionotropic, NMDA 2A"
FT /id="PRO_0000011573"
FT TOPO_DOM 23..555
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TRANSMEM 556..576
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TOPO_DOM 577..600
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT INTRAMEM 601..620
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TOPO_DOM 621..625
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TRANSMEM 626..645
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TOPO_DOM 646..816
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TRANSMEM 817..837
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TOPO_DOM 838..1464
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT REGION 599..620
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT REGION 997..1083
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1335..1372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1462..1464
FT /note="PDZ-binding"
FT /evidence="ECO:0000305"
FT COMPBIAS 1019..1036
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1037..1083
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1353..1372
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 266
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 282
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 511..513
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|PubMed:26875626,
FT ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28105280,
FT ECO:0007744|PDB:5H8F, ECO:0007744|PDB:5H8H,
FT ECO:0007744|PDB:5H8N, ECO:0007744|PDB:5H8Q,
FT ECO:0007744|PDB:5I2K, ECO:0007744|PDB:5I2N,
FT ECO:0007744|PDB:5KCJ, ECO:0007744|PDB:5KDT,
FT ECO:0007744|PDB:5TP9, ECO:0007744|PDB:5TPA"
FT BINDING 518
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|PubMed:26875626,
FT ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28105280,
FT ECO:0007744|PDB:5H8F, ECO:0007744|PDB:5H8H,
FT ECO:0007744|PDB:5H8N, ECO:0007744|PDB:5H8Q,
FT ECO:0007744|PDB:5I2K, ECO:0007744|PDB:5I2N,
FT ECO:0007744|PDB:5KCJ, ECO:0007744|PDB:5KDT,
FT ECO:0007744|PDB:5TP9, ECO:0007744|PDB:5TPA"
FT BINDING 689..690
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 730..731
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT SITE 614
FT /note="Functional determinant of NMDA receptors"
FT /evidence="ECO:0000250"
FT MOD_RES 882
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35436"
FT MOD_RES 890
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35436"
FT MOD_RES 929
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35436"
FT MOD_RES 1025
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT MOD_RES 1059
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35436"
FT MOD_RES 1062
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT MOD_RES 1198
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT MOD_RES 1291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 443
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 444
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 541
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 687
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..320
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 429..455
FT /evidence="ECO:0000269|PubMed:26875626,
FT ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28105280,
FT ECO:0007744|PDB:5H8F, ECO:0007744|PDB:5H8H,
FT ECO:0007744|PDB:5H8N, ECO:0007744|PDB:5H8Q,
FT ECO:0007744|PDB:5I2K, ECO:0007744|PDB:5I2N,
FT ECO:0007744|PDB:5KCJ, ECO:0007744|PDB:5KDT,
FT ECO:0007744|PDB:5TP9, ECO:0007744|PDB:5TPA"
FT DISULFID 436..456
FT /evidence="ECO:0000269|PubMed:26875626,
FT ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28105280,
FT ECO:0007744|PDB:5H8F, ECO:0007744|PDB:5H8H,
FT ECO:0007744|PDB:5H8N, ECO:0007744|PDB:5H8Q,
FT ECO:0007744|PDB:5I2K, ECO:0007744|PDB:5I2N,
FT ECO:0007744|PDB:5KCJ, ECO:0007744|PDB:5KDT,
FT ECO:0007744|PDB:5TP9, ECO:0007744|PDB:5TPA"
FT DISULFID 745..800
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT VAR_SEQ 1259..1464
FT /note="NPATGEQVYQQDWAQNNALQLQKNKLRISRQHSYDNIVDKPRELDLSRPSRS
FT ISLKDRERLLEGNFYGSLFSVPSSKLSGKKSSLFPQGLEDSKRSKSLLPDHTSDNPFLH
FT SHRDDQRLVIGRCPSDPYKHSLPSQAVNDSYLRSSLRSTASYCSRDSRGHNDVYISEHV
FT MPYAANKNNMYSTPRVLNSCSNRRVYKKMPSIESDV -> MTNAWLLGDAPRTLTNTRC
FT HPRR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044300"
FT VARIANT 57
FT /note="P -> L (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067725"
FT VARIANT 79
FT /note="P -> R (in FESD; dbSNP:rs1250662891)"
FT /evidence="ECO:0000269|PubMed:23933819"
FT /id="VAR_070345"
FT VARIANT 143
FT /note="T -> I (found in a patient with autism spectrum
FT disorder; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079929"
FT VARIANT 183
FT /note="F -> I (found in a cutaneous malignant melanoma
FT sample; somatic mutation; also found in a patient with
FT benign epilepsy with centrotemporal spike;
FT dbSNP:rs587780353)"
FT /evidence="ECO:0000269|PubMed:21499247,
FT ECO:0000269|PubMed:23933819"
FT /id="VAR_067726"
FT VARIANT 184
FT /note="I -> S (in FESD; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23933820"
FT /id="VAR_070346"
FT VARIANT 189
FT /note="T -> N (found in a patient with schizophrenia;
FT unknown pathological significance; dbSNP:rs1377082706)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079930"
FT VARIANT 231
FT /note="C -> Y (in FESD; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23933819"
FT /id="VAR_070347"
FT VARIANT 243
FT /note="A -> V (in FESD; results in reduced high-affinity
FT zinc mediated inhibition)"
FT /evidence="ECO:0000269|PubMed:23933819"
FT /id="VAR_070348"
FT VARIANT 252
FT /note="D -> N (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs868215122)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067727"
FT VARIANT 270
FT /note="K -> E"
FT /evidence="ECO:0000269|PubMed:8061049"
FT /id="VAR_010938"
FT VARIANT 278
FT /note="S -> F (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs148531310)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067728"
FT VARIANT 290
FT /note="A -> V (in FESD; dbSNP:rs199528312)"
FT /evidence="ECO:0000269|PubMed:23933819"
FT /id="VAR_070349"
FT VARIANT 295
FT /note="G -> S (in FESD; unknown pathological significance;
FT dbSNP:rs568484876)"
FT /evidence="ECO:0000269|PubMed:23933820"
FT /id="VAR_070350"
FT VARIANT 336
FT /note="P -> S (in dbSNP:rs148511104)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079931"
FT VARIANT 349
FT /note="S -> F (found in a cutaneous malignant melanoma
FT sample)"
FT /evidence="ECO:0000269|PubMed:24455489"
FT /id="VAR_071624"
FT VARIANT 370
FT /note="R -> W (in FESD; dbSNP:rs761168789)"
FT /evidence="ECO:0000269|PubMed:23933819"
FT /id="VAR_070351"
FT VARIANT 371
FT /note="E -> K (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs149344082)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067729"
FT VARIANT 373
FT /note="E -> K (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067730"
FT VARIANT 380
FT /note="N -> D (found in a patient with neonatal onset
FT epileptic encephalopathy; unknown pathological
FT significance; dbSNP:rs1057519551)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078109"
FT VARIANT 436
FT /note="C -> R (in FESD; decreased protein abundance; loss
FT of localization to the cell membrane; changed glutamate-
FT gated calcium ion channel activity characterized by
FT increased glutamate potency and decreased glycine potency;
FT dbSNP:rs1555496111)"
FT /evidence="ECO:0000269|PubMed:23933819,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070352"
FT VARIANT 449
FT /note="G -> E (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs139033056)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067731"
FT VARIANT 452
FT /note="V -> M (no effect on localization to the cell
FT membrane; changed glutamate-gated calcium ion channel
FT activity characterized by increased glutamate potency;
FT dbSNP:rs145956175)"
FT /evidence="ECO:0000269|PubMed:22833210,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_079932"
FT VARIANT 459
FT /note="F -> S (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067732"
FT VARIANT 483
FT /note="G -> R (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; changed
FT glutamate-gated calcium ion channel activity characterized
FT by decreased glutamate potency)"
FT /evidence="ECO:0000269|PubMed:23933820,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070353"
FT VARIANT 504
FT /note="R -> W (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; no significant
FT effect on calcium ion transmembrane import into cytosol;
FT dbSNP:rs1360906241)"
FT /evidence="ECO:0000269|PubMed:23933820,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070354"
FT VARIANT 506
FT /note="V -> A (in FESD; no effect on localization to the
FT cell membrane; changed glutamate-gated calcium ion channel
FT activity characterized by increased glutamate potency;
FT dbSNP:rs796052543)"
FT /evidence="ECO:0000269|PubMed:27839871"
FT /id="VAR_079933"
FT VARIANT 518
FT /note="R -> H (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; changed
FT glutamate-gated calcium ion channel activity characterized
FT by affected receptor kinetics; dbSNP:rs397518470)"
FT /evidence="ECO:0000269|PubMed:23933820,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070355"
FT VARIANT 531
FT /note="T -> M (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; changed
FT glutamate-gated calcium ion channel activity characterized
FT by affected receptor kinetics; dbSNP:rs397518468)"
FT /evidence="ECO:0000269|PubMed:23933818,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070356"
FT VARIANT 547
FT /note="Missing (in FESD)"
FT /evidence="ECO:0000269|PubMed:23933819"
FT /id="VAR_070357"
FT VARIANT 548
FT /note="A -> T (in FESD; no effect on localization to the
FT cell membrane; loss of glutamate-gated calcium ion channel
FT activity)"
FT /evidence="ECO:0000269|PubMed:23933820,
FT ECO:0000269|PubMed:28095420"
FT /id="VAR_070358"
FT VARIANT 552
FT /note="P -> R (in FESD; no effect on localization to the
FT cell membrane; changed glutamate-gated calcium ion channel
FT activity characterized by increased glutamate and glycine
FT potency with delay in rise time and slower deactivation
FT time course; dbSNP:rs397518450)"
FT /evidence="ECO:0000269|PubMed:23033978,
FT ECO:0000269|PubMed:28095420"
FT /id="VAR_069382"
FT VARIANT 576
FT /note="F -> S"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079934"
FT VARIANT 595
FT /note="H -> R (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs551688681)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067733"
FT VARIANT 598
FT /note="S -> F (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067734"
FT VARIANT 615
FT /note="N -> K (in FESD; the mutant receptor has decreased
FT calcium permeability; shows a dominant-negative effect;
FT dbSNP:rs397518447)"
FT /evidence="ECO:0000269|PubMed:20890276"
FT /id="VAR_065899"
FT VARIANT 649
FT /note="L -> V (in FESD; dbSNP:rs397514557)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069383"
FT VARIANT 652
FT /note="F -> V (in FESD; affects receptor kinetics;
FT dbSNP:rs397518471)"
FT /evidence="ECO:0000269|PubMed:23933820"
FT /id="VAR_070359"
FT VARIANT 653
FT /note="M -> I (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067735"
FT VARIANT 669
FT /note="K -> N (in FESD; no effect on localization to the
FT cell membrane; changed glutamate-gated calcium ion channel
FT activity characterized by increased glutamate and glycine
FT potency)"
FT /evidence="ECO:0000269|PubMed:23933820,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070360"
FT VARIANT 685
FT /note="V -> G (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; changed
FT glutamate-gated calcium ion channel activity characterized
FT by decreased glutamate potency; dbSNP:rs796052548)"
FT /evidence="ECO:0000269|PubMed:27839871"
FT /id="VAR_079935"
FT VARIANT 694
FT /note="I -> T (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; changed
FT glutamate-gated calcium ion channel activity characterized
FT by decreased glutamate potency and decreased open
FT probability)"
FT /evidence="ECO:0000269|PubMed:23933820,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070361"
FT VARIANT 699
FT /note="P -> S (in FESD; no effect on localization to the
FT cell membrane; changed glutamate-gated calcium ion channel
FT activity characterized by increased glutamate potency and
FT decreased open probability; dbSNP:rs1555491648)"
FT /evidence="ECO:0000269|PubMed:23933819,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070362"
FT VARIANT 705
FT /note="M -> V (in FESD; decreased localization to the cell
FT membrane; changed glutamate-gated calcium ion channel
FT activity characterized by decreased glutamate potency and
FT decreased open probability)"
FT /evidence="ECO:0000269|PubMed:23933819,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070363"
FT VARIANT 712
FT /note="G -> E (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs143031592)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067736"
FT VARIANT 714
FT /note="E -> K (in FESD; decreased protein abundance; no
FT effect on localization to the cell membrane; no significant
FT effect on calcium ion transmembrane import into cytosol)"
FT /evidence="ECO:0000269|PubMed:23933819,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070364"
FT VARIANT 716
FT /note="A -> D (in FESD; unknown pathological significance;
FT dbSNP:rs1057519552)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078110"
FT VARIANT 716
FT /note="A -> T (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; changed
FT glutamate-gated calcium ion channel activity characterized
FT by decreased glutamate potency; dbSNP:rs762659685)"
FT /evidence="ECO:0000269|PubMed:23933820,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070365"
FT VARIANT 727
FT /note="A -> T (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; changed
FT glutamate-gated calcium ion channel activity characterized
FT by decreased glutamate potency and decreased open
FT probability; dbSNP:rs1555488144)"
FT /evidence="ECO:0000269|PubMed:23933819,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070366"
FT VARIANT 731
FT /note="D -> N (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; decreased
FT glutamate-gated calcium ion channel activity characterized
FT by drastically decreased glutamate agonist potency,
FT decreased glycine agonist potency, reduced amplitude of
FT current response, shortened synaptic-like response time
FT course, decreased channel open probability and enhanced
FT sensitivity to negative allosteric modulators;
FT dbSNP:rs796052549)"
FT /evidence="ECO:0000269|PubMed:23933820,
FT ECO:0000269|PubMed:27839871, ECO:0000269|PubMed:28182669"
FT /id="VAR_070367"
FT VARIANT 734
FT /note="V -> L (in FESD; no effect on localization to the
FT cell membrane; changed glutamate-gated calcium ion channel
FT activity characterized by decreased glutamate potency)"
FT /evidence="ECO:0000269|PubMed:23933819,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070368"
FT VARIANT 740
FT /note="G -> W (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067737"
FT VARIANT 762
FT /note="G -> A (found in a cutaneous malignant melanoma
FT sample)"
FT /evidence="ECO:0000269|PubMed:24455489"
FT /id="VAR_071625"
FT VARIANT 772
FT /note="K -> E (in FESD; decreased protein abundance;
FT decreased localization to the cell membrane; changed
FT glutamate-gated calcium ion channel activity characterized
FT by decreased glutamate potency and decreased open
FT probability)"
FT /evidence="ECO:0000269|PubMed:23933819,
FT ECO:0000269|PubMed:27839871"
FT /id="VAR_070369"
FT VARIANT 812
FT /note="L -> M (in FESD; increase in receptor response to
FT agonists; decrease in the actions of endogenous negative
FT modulators; increase in channel open probability; prolonged
FT deactivation time course)"
FT /evidence="ECO:0000269|PubMed:24504326"
FT /id="VAR_072750"
FT VARIANT 814
FT /note="I -> T (in FESD; unknown pathological significance;
FT dbSNP:rs780654733)"
FT /evidence="ECO:0000269|PubMed:23933819"
FT /id="VAR_070370"
FT VARIANT 817
FT /note="M -> V (in FESD; gain-of-function characterized by
FT enhanced agonist potency, reduced sensitivity to endogenous
FT negative inhibitors, prolonged synaptic-like response time
FT course, increased single-channel mean open time and
FT increased channel open probability; dbSNP:rs796052551)"
FT /evidence="ECO:0000269|PubMed:24903190,
FT ECO:0000269|PubMed:28126851"
FT /id="VAR_071626"
FT VARIANT 852
FT /note="V -> M (in dbSNP:rs150316865)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079936"
FT VARIANT 884
FT /note="D -> N (found in a patient with autism; unknown
FT pathological significance; dbSNP:rs777684328)"
FT /evidence="ECO:0000269|PubMed:26637798"
FT /id="VAR_078690"
FT VARIANT 889
FT /note="G -> E (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247,
FT ECO:0000269|PubMed:24455489"
FT /id="VAR_067738"
FT VARIANT 904
FT /note="I -> F (in FESD; dbSNP:rs1555482933)"
FT /evidence="ECO:0000269|PubMed:23933819"
FT /id="VAR_070371"
FT VARIANT 920
FT /note="R -> K (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067739"
FT VARIANT 922
FT /note="A -> V (in dbSNP:rs200037904)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079937"
FT VARIANT 929
FT /note="S -> F (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs767268773)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067740"
FT VARIANT 933
FT /note="D -> N (in FESD; unknown pathological significance;
FT dbSNP:rs933322445)"
FT /evidence="ECO:0000269|PubMed:23933820"
FT /id="VAR_070372"
FT VARIANT 937
FT /note="D -> N (in dbSNP:rs769602505)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079938"
FT VARIANT 962
FT /note="E -> K (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs765370528)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067741"
FT VARIANT 968
FT /note="A -> T (probable disease-associated variant found in
FT a patient with schizophrenia)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079939"
FT VARIANT 976
FT /note="N -> S (in FESD; dbSNP:rs886039239)"
FT /evidence="ECO:0000269|PubMed:23933819"
FT /id="VAR_070373"
FT VARIANT 989
FT /note="N -> S (found in a patient with neonatal onset
FT epileptic encephalopathy; unknown pathological
FT significance; dbSNP:rs531782747)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078111"
FT VARIANT 998
FT /note="V -> M (found in a patient with schizophrenia;
FT unknown pathological significance; dbSNP:rs1258974659)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079940"
FT VARIANT 1064
FT /note="T -> A (in dbSNP:rs138809301)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079941"
FT VARIANT 1073
FT /note="E -> K (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067742"
FT VARIANT 1074
FT /note="P -> L (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs867432846)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067743"
FT VARIANT 1132
FT /note="P -> L (found in a cutaneous malignant melanoma
FT sample)"
FT /evidence="ECO:0000269|PubMed:24455489"
FT /id="VAR_071627"
FT VARIANT 1133
FT /note="P -> S (found in a cutaneous malignant melanoma
FT sample)"
FT /evidence="ECO:0000269|PubMed:24455489"
FT /id="VAR_071628"
FT VARIANT 1153
FT /note="D -> N (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs267604687)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067744"
FT VARIANT 1175
FT /note="E -> K (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs867464241)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067745"
FT VARIANT 1229
FT /note="T -> S (found in a patient with schizophrenia;
FT unknown pathological significance; dbSNP:rs747136651)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079942"
FT VARIANT 1251
FT /note="D -> N (in FESD)"
FT /evidence="ECO:0000269|PubMed:23933820"
FT /id="VAR_070374"
FT VARIANT 1276
FT /note="A -> G (found in a patient with continuous spike-
FT wave discharges during slow-wave sleep; also found in a
FT patient with drug-resistant focal epilepsy; also found in a
FT cutaneous malignant melanoma sample as somatic mutation;
FT unknown pathological significance; dbSNP:rs145063086)"
FT /evidence="ECO:0000269|PubMed:21499247,
FT ECO:0000269|PubMed:22833210, ECO:0000269|PubMed:23933820,
FT ECO:0000269|PubMed:27864847"
FT /id="VAR_067746"
FT VARIANT 1285
FT /note="R -> K (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs367543132)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067747"
FT VARIANT 1318
FT /note="R -> W (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs774419037)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067748"
FT VARIANT 1366
FT /note="P -> L (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067749"
FT VARIANT 1421
FT /note="D -> N (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067750"
FT VARIANT 1425
FT /note="S -> L (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs976259560)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067751"
FT VARIANT 1426
FT /note="E -> K (found in a cutaneous malignant melanoma
FT sample; somatic mutation; dbSNP:rs138415164)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067752"
FT VARIANT 1462
FT /note="S -> C (found in a cutaneous malignant melanoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067753"
FT MUTAGEN 552
FT /note="P->A: Changed glutamate-gated calcium ion channel
FT activity characterized by increased desensitization."
FT /evidence="ECO:0000269|PubMed:28095420"
FT MUTAGEN 552
FT /note="P->G: Changed glutamate-gated calcium ion channel
FT activity characterized by accelerated response activation
FT time and increased desensitization."
FT /evidence="ECO:0000269|PubMed:28095420"
FT MUTAGEN 552
FT /note="P->I: Changed glutamate-gated calcium ion channel
FT activity characterized by increased desensitization."
FT /evidence="ECO:0000269|PubMed:28095420"
FT MUTAGEN 552
FT /note="P->K: Changed glutamate-gated calcium ion channel
FT activity characterized by increased glutamate and glycine
FT potency with delay in rise time and slower deactivation
FT time course."
FT /evidence="ECO:0000269|PubMed:28095420"
FT MUTAGEN 552
FT /note="P->L: No effect on localization to the cell
FT membrane. Changed glutamate-gated calcium ion channel
FT activity characterized by increased desensitization."
FT /evidence="ECO:0000269|PubMed:28095420"
FT MUTAGEN 552
FT /note="P->Q: No effect on localization to the cell
FT membrane. Changed glutamate-gated calcium ion channel
FT activity characterized by decreased response amplitude and
FT changed desensitization without effect on response rise
FT time or deactivation time course."
FT /evidence="ECO:0000269|PubMed:28095420"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 48..54
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 79..91
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 108..120
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 151..164
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 180..192
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 215..219
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 224..230
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 233..244
FT /evidence="ECO:0007829|PDB:7EU7"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 277..280
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 283..286
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 288..309
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 335..339
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 362..366
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 372..377
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 405..410
FT /evidence="ECO:0007829|PDB:5H8F"
FT TURN 414..416
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 417..421
FT /evidence="ECO:0007829|PDB:5H8F"
FT TURN 424..426
FT /evidence="ECO:0007829|PDB:5KCJ"
FT STRAND 434..442
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 449..458
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 459..471
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 474..479
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 482..485
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 487..489
FT /evidence="ECO:0007829|PDB:5I2K"
FT STRAND 492..494
FT /evidence="ECO:0007829|PDB:5I2K"
FT HELIX 495..501
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 506..508
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 516..519
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 522..524
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 528..538
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 556..577
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 600..613
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 625..654
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 668..671
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 673..675
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 676..678
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 682..684
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 686..688
FT /evidence="ECO:0007829|PDB:5I2K"
FT HELIX 689..697
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 699..705
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 706..708
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 713..721
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 726..731
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 732..740
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 743..745
FT /evidence="ECO:0007829|PDB:5I2N"
FT STRAND 747..750
FT /evidence="ECO:0007829|PDB:5H8F"
FT TURN 751..753
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 756..761
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 764..766
FT /evidence="ECO:0007829|PDB:5I2K"
FT HELIX 772..784
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 787..795
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 799..802
FT /evidence="ECO:0007829|PDB:7EU7"
FT TURN 814..817
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 818..840
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 1461..1464
FT /evidence="ECO:0007829|PDB:3NFL"
SQ SEQUENCE 1464 AA; 165283 MW; AF5EDD599EC0B1E3 CRC64;
MGRVGYWTLL VLPALLVWRG PAPSAAAEKG PPALNIAVML GHSHDVTERE LRTLWGPEQA
AGLPLDVNVV ALLMNRTDPK SLITHVCDLM SGARIHGLVF GDDTDQEAVA QMLDFISSHT
FVPILGIHGG ASMIMADKDP TSTFFQFGAS IQQQATVMLK IMQDYDWHVF SLVTTIFPGY
REFISFVKTT VDNSFVGWDM QNVITLDTSF EDAKTQVQLK KIHSSVILLY CSKDEAVLIL
SEARSLGLTG YDFFWIVPSL VSGNTELIPK EFPSGLISVS YDDWDYSLEA RVRDGIGILT
TAASSMLEKF SYIPEAKASC YGQMERPEVP MHTLHPFMVN VTWDGKDLSF TEEGYQVHPR
LVVIVLNKDR EWEKVGKWEN HTLSLRHAVW PRYKSFSDCE PDDNHLSIVT LEEAPFVIVE
DIDPLTETCV RNTVPCRKFV KINNSTNEGM NVKKCCKGFC IDILKKLSRT VKFTYDLYLV
TNGKHGKKVN NVWNGMIGEV VYQRAVMAVG SLTINEERSE VVDFSVPFVE TGISVMVSRS
NGTVSPSAFL EPFSASVWVM MFVMLLIVSA IAVFVFEYFS PVGYNRNLAK GKAPHGPSFT
IGKAIWLLWG LVFNNSVPVQ NPKGTTSKIM VSVWAFFAVI FLASYTANLA AFMIQEEFVD
QVTGLSDKKF QRPHDYSPPF RFGTVPNGST ERNIRNNYPY MHQYMTKFNQ KGVEDALVSL
KTGKLDAFIY DAAVLNYKAG RDEGCKLVTI GSGYIFATTG YGIALQKGSP WKRQIDLALL
QFVGDGEMEE LETLWLTGIC HNEKNEVMSS QLDIDNMAGV FYMLAAAMAL SLITFIWEHL
FYWKLRFCFT GVCSDRPGLL FSISRGIYSC IHGVHIEEKK KSPDFNLTGS QSNMLKLLRS
AKNISSMSNM NSSRMDSPKR AADFIQRGSL IMDMVSDKGN LMYSDNRSFQ GKESIFGDNM
NELQTFVANR QKDNLNNYVF QGQHPLTLNE SNPNTVEVAV STESKANSRP RQLWKKSVDS
IRQDSLSQNP VSQRDEATAE NRTHSLKSPR YLPEEMAHSD ISETSNRATC HREPDNSKNH
KTKDNFKRSV ASKYPKDCSE VERTYLKTKS SSPRDKIYTI DGEKEPGFHL DPPQFVENVT
LPENVDFPDP YQDPSENFRK GDSTLPMNRN PLHNEEGLSN NDQYKLYSKH FTLKDKGSPH
SETSERYRQN STHCRSCLSN MPTYSGHFTM RSPFKCDACL RMGNLYDIDE DQMLQETGNP
ATGEQVYQQD WAQNNALQLQ KNKLRISRQH SYDNIVDKPR ELDLSRPSRS ISLKDRERLL
EGNFYGSLFS VPSSKLSGKK SSLFPQGLED SKRSKSLLPD HTSDNPFLHS HRDDQRLVIG
RCPSDPYKHS LPSQAVNDSY LRSSLRSTAS YCSRDSRGHN DVYISEHVMP YAANKNNMYS
TPRVLNSCSN RRVYKKMPSI ESDV
