NMDZ1_HUMAN
ID NMDZ1_HUMAN Reviewed; 938 AA.
AC Q05586; A6NLK7; A6NLR1; C9K0X1; P35437; Q12867; Q12868; Q5VSF3; Q5VSF4;
AC Q5VSF5; Q5VSF6; Q5VSF7; Q5VSF8; Q9UPF8; Q9UPF9;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 243.
DE RecName: Full=Glutamate receptor ionotropic, NMDA 1;
DE Short=GluN1;
DE AltName: Full=Glutamate [NMDA] receptor subunit zeta-1;
DE AltName: Full=N-methyl-D-aspartate receptor subunit NR1;
DE Short=NMD-R1;
DE Flags: Precursor;
GN Name=GRIN1; Synonyms=NMDAR1;
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), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 11-938 (ISOFORM 3), AND NUCLEOTIDE SEQUENCE [MRNA] OF 300-938 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=8406025; DOI=10.1016/0378-1119(93)90309-q;
RA Foldes R.L., Rampersad V., Kamboj R.K.;
RT "Cloning and sequence analysis of cDNAs encoding human hippocampus N-
RT methyl-D-aspartate receptor subunits: evidence for alternative RNA
RT splicing.";
RL Gene 131:293-298(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=7679115; DOI=10.1016/s0021-9258(18)53754-6;
RA Karp S.J., Masu M., Eki T., Ozawa K., Nakanishi S.;
RT "Molecular cloning and chromosomal localization of the key subunit of the
RT human N-methyl-D-aspartate receptor.";
RL J. Biol. Chem. 268:3728-3733(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=7685113; DOI=10.1073/pnas.90.11.5057;
RA Planells-Cases R., Sun W., Ferrer-Montiel A.V., Montal M.;
RT "Molecular cloning, functional expression, and pharmacological
RT characterization of an N-methyl-D-aspartate receptor subunit from human
RT brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5057-5061(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7622053; DOI=10.1016/0378-1119(95)00044-7;
RA Zimmer M., Fink T.M., Franke Y., Lichter P., Spiess J.;
RT "Cloning and structure of the gene encoding the human N-methyl-D-aspartate
RT receptor (NMDAR1).";
RL Gene 159:219-223(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6 AND 7), AND VARIANTS MET-540 AND
RP SER-682.
RX PubMed=9231706; DOI=10.1046/j.1471-4159.1997.69020485.x;
RA Nash N.R., Heilman C.J., Rees H.D., Levey A.I.;
RT "Cloning and localization of exon 5-containing isoforms of the NMDAR1
RT subunit in human and rat brains.";
RL J. Neurochem. 69:485-493(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 332-922 (ISOFORM 4), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 86-259 (ISOFORM 5).
RC TISSUE=Cerebellum, and Hippocampus;
RX PubMed=7926821; DOI=10.1016/0378-1119(94)90089-2;
RA Foldes R.L., Rampersad V., Kamboj R.K.;
RT "Cloning and sequence analysis of additional splice variants encoding human
RT N-methyl-D-aspartate receptor (hNR1) subunits.";
RL Gene 147:303-304(1994).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 364-464 (ISOFORMS 1/2/3).
RX PubMed=7681588; DOI=10.1073/pnas.90.6.2174;
RA Younkin D.P., Tang C.-M., Hardy M., Reddy U.R., Shi Q.-Y., Pleasure S.J.,
RA Lee V.M.-Y., Pleasure D.;
RT "Inducible expression of neuronal glutamate receptor channels in the NT2
RT human cell line.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:2174-2178(1993).
RN [9]
RP PHOSPHORYLATION AT SER-889; SER-890; SER-896 AND SER-897 BY PKC.
RX PubMed=8316301; DOI=10.1038/364070a0;
RA Tingley W.G., Roche K.W., Thompson A.K., Huganir R.L.;
RT "Regulation of NMDA receptor phosphorylation by alternative splicing of the
RT C-terminal domain.";
RL Nature 364:70-73(1993).
RN [10]
RP INTERACTION WITH MYZAP.
RX PubMed=18849881; DOI=10.1097/wnr.0b013e328317f05f;
RA Roginski R.S., Goubaeva F., Mikami M., Fried-Cassorla E., Nair M.R.,
RA Yang J.;
RT "GRINL1A colocalizes with N-methyl D-aspartate receptor NR1 subunit and
RT reduces N-methyl D-aspartate toxicity.";
RL NeuroReport 19:1721-1726(2008).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH GRIN2B AND PRR7, AND INTERACTION WITH
RP PRR7.
RX PubMed=27458189; DOI=10.15252/embj.201593070;
RA Kravchick D.O., Karpova A., Hrdinka M., Lopez-Rojas J., Iacobas S.,
RA Carbonell A.U., Iacobas D.A., Kreutz M.R., Jordan B.A.;
RT "Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates
RT NMDA-mediated excitotoxicity.";
RL EMBO J. 35:1923-1934(2016).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF MET-813.
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 [13]
RP STRUCTURE BY NMR OF 599-621.
RX PubMed=10201407; DOI=10.1038/7610;
RA Opella S.J., Marassi F.M., Gesell J.J., Valente A.P., Kim Y.,
RA Oblatt-Montal M., Montal M.;
RT "Structures of the M2 channel-lining segments from nicotinic acetylcholine
RT and NMDA receptors by NMR spectroscopy.";
RL Nat. Struct. Biol. 6:374-379(1999).
RN [14] {ECO:0007744|PDB:5I2K, ECO:0007744|PDB:5I2N, ECO:0007744|PDB:5KDT}
RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF 394-544 AND 663-800 IN COMPLEXES
RP WITH GRIN2A AND GLYCINE, 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 [15] {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 394-544 AND 663-800 IN COMPLEXES
RP WITH GRIN2A AND GLYCINE, 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 [16] {ECO:0007744|PDB:5TP9, ECO:0007744|PDB:5TPA}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 394-544 AND 663-800 IN COMPLEX
RP WITH GRIN2A AND GLYCINE, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, 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 [17]
RP VARIANTS NDHMSD SER-560 INS AND LYS-662, AND CHARACTERIZATION OF VARIANTS
RP NDHMSD SER-560 INS AND LYS-662.
RX PubMed=21376300; DOI=10.1016/j.ajhg.2011.02.001;
RA Hamdan F.F., Gauthier J., Araki Y., Lin D.T., Yoshizawa Y., Higashi K.,
RA Park A.R., Spiegelman D., Dobrzeniecka S., Piton A., Tomitori H., Daoud H.,
RA Massicotte C., Henrion E., Diallo O., Shekarabi M., Marineau C.,
RA Shevell M., Maranda B., Mitchell G., Nadeau A., D'Anjou G., Vanasse M.,
RA Srour M., Lafreniere R.G., Drapeau P., Lacaille J.C., Kim E., Lee J.R.,
RA Igarashi K., Huganir R.L., Rouleau G.A., Michaud J.L.;
RT "Excess of de novo deleterious mutations in genes associated with
RT glutamatergic systems in nonsyndromic intellectual disability.";
RL Am. J. Hum. Genet. 88:306-316(2011).
RN [18]
RP VARIANTS GLN-306; SER-349 AND ALA-419.
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 [19]
RP VARIANT NDHMSD ARG-557.
RX PubMed=25167861; DOI=10.1136/jmedgenet-2014-102554;
RA Redin C., Gerard B., Lauer J., Herenger Y., Muller J., Quartier A.,
RA Masurel-Paulet A., Willems M., Lesca G., El-Chehadeh S., Le Gras S.,
RA Vicaire S., Philipps M., Dumas M., Geoffroy V., Feger C., Haumesser N.,
RA Alembik Y., Barth M., Bonneau D., Colin E., Dollfus H., Doray B.,
RA Delrue M.A., Drouin-Garraud V., Flori E., Fradin M., Francannet C.,
RA Goldenberg A., Lumbroso S., Mathieu-Dramard M., Martin-Coignard D.,
RA Lacombe D., Morin G., Polge A., Sukno S., Thauvin-Robinet C., Thevenon J.,
RA Doco-Fenzy M., Genevieve D., Sarda P., Edery P., Isidor B., Jost B.,
RA Olivier-Faivre L., Mandel J.L., Piton A.;
RT "Efficient strategy for the molecular diagnosis of intellectual disability
RT using targeted high-throughput sequencing.";
RL J. Med. Genet. 51:724-736(2014).
RN [20]
RP VARIANTS NDHMSD GLU-552; ILE-641; LYS-650 AND ARG-815.
RX PubMed=25864721; DOI=10.1111/epi.12987;
RA Ohba C., Shiina M., Tohyama J., Haginoya K., Lerman-Sagie T., Okamoto N.,
RA Blumkin L., Lev D., Mukaida S., Nozaki F., Uematsu M., Onuma A., Kodera H.,
RA Nakashima M., Tsurusaki Y., Miyake N., Tanaka F., Kato M., Ogata K.,
RA Saitsu H., Matsumoto N.;
RT "GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and
RT hyperkinetic and stereotyped movement disorders.";
RL Epilepsia 56:841-848(2015).
RN [21]
RP VARIANTS NDHMSD GLU-552; ARG-557; ARG-618; ARG-620; SER-645; SER-647;
RP ARG-815; VAL-815; LEU-817; ARG-827 AND CYS-844, VARIANTS NDHMSR TRP-217 AND
RP 556-GLN--SER-938 DEL, CHARACTERIZATION OF VARIANTS NDHMSD ARG-557; ARG-618;
RP ARG-620; SER-645; SER-647; ARG-815; LEU-817; ARG-827 AND CYS-844, AND
RP CHARACTERIZATION OF VARIANTS NDHMSR TRP-217 AND 556-GLN--SER-938 DEL.
RX PubMed=27164704; DOI=10.1212/wnl.0000000000002740;
RA Lemke J.R., Geider K., Helbig K.L., Heyne H.O., Schuetz H., Hentschel J.,
RA Courage C., Depienne C., Nava C., Heron D., Moeller R.S., Hjalgrim H.,
RA Lal D., Neubauer B.A., Nuernberg P., Thiele H., Kurlemann G., Arnold G.L.,
RA Bhambhani V., Bartholdi D., Pedurupillay C.R., Misceo D., Frengen E.,
RA Stroemme P., Dlugos D.J., Doherty E.S., Bijlsma E.K., Ruivenkamp C.A.,
RA Hoffer M.J., Goldstein A., Rajan D.S., Narayanan V., Ramsey K., Belnap N.,
RA Schrauwen I., Richholt R., Koeleman B.P., Sa J., Mendonca C.,
RA de Kovel C.G., Weckhuysen S., Hardies K., De Jonghe P., De Meirleir L.,
RA Milh M., Badens C., Lebrun M., Busa T., Francannet C., Piton A., Riesch E.,
RA Biskup S., Vogt H., Dorn T., Helbig I., Michaud J.L., Laube B., Syrbe S.;
RT "Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA
RT receptor encephalopathy.";
RL Neurology 86:2171-2178(2016).
RN [22]
RP VARIANT NDHMSR HIS-227.
RX PubMed=28051072; DOI=10.1038/ejhg.2016.163;
RA Rossi M., Chatron N., Labalme A., Ville D., Carneiro M., Edery P.,
RA des Portes V., Lemke J.R., Sanlaville D., Lesca G.;
RT "Novel homozygous missense variant of GRIN1 in two sibs with intellectual
RT disability and autistic features without epilepsy.";
RL Eur. J. Hum. Genet. 25:376-380(2017).
RN [23]
RP VARIANTS NDHMSD TYR-688 AND ARG-827.
RX PubMed=28389307; DOI=10.1016/j.ejmg.2017.04.001;
RA Zehavi Y., Mandel H., Zehavi A., Rashid M.A., Straussberg R., Jabur B.,
RA Shaag A., Elpeleg O., Spiegel R.;
RT "De novo GRIN1 mutations: An emerging cause of severe early infantile
RT encephalopathy.";
RL Eur. J. Med. Genet. 60:317-320(2017).
RN [24]
RP VARIANT NDHMSD ARG-620, AND CHARACTERIZATION OF VARIANT NDHMSD ARG-620.
RX PubMed=28228639; DOI=10.1038/jhg.2017.19;
RA Chen W., Shieh C., Swanger S.A., Tankovic A., Au M., McGuire M.,
RA Tagliati M., Graham J.M., Madan-Khetarpal S., Traynelis S.F., Yuan H.,
RA Pierson T.M.;
RT "GRIN1 mutation associated with intellectual disability alters NMDA
RT receptor trafficking and function.";
RL J. Hum. Genet. 62:589-597(2017).
RN [25]
RP CHARACTERIZATION OF VARIANT NDHMSD GLU-552 AND ARG-557.
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:7685113, PubMed:28126851, PubMed:26919761, PubMed:26875626,
CC PubMed:28105280). Sensitivity to glutamate and channel kinetics depend
CC on the subunit composition (PubMed:26919761).
CC {ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761,
CC ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:28126851,
CC ECO:0000269|PubMed:7685113}.
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:7685113, PubMed:28126851,
CC PubMed:26919761, PubMed:26875626, PubMed:28105280). Can also form
CC heterotetrameric channels that contain at least one zeta subunit
CC (GRIN1), an epsilon subunit, plus GRIN3A or GRIN3B (in vitro). In vivo,
CC the subunit composition may vary in function of the expression levels
CC of the different subunits. Found in a complex with GRIN2A or GRIN2B,
CC GRIN3A and PPP2CB (By similarity). Found in a complex with GRIN2A or
CC GRIN2B and GRIN3B (By similarity). Interacts with SNX27 (via PDZ
CC domain); the interaction is required for recycling to the plasma
CC membrane when endocytosed and prevent degradation in lysosomes (By
CC similarity). Interacts with DLG4 and MPDZ. Interacts with LRFN1 and
CC LRFN2 (By similarity). Interacts with MYZAP (PubMed:18849881). Found in
CC a complex with DLG4 and PRR7 (By similarity). Found in a complex with
CC GRIN2B and PRR7 (PubMed:27458189). Interacts with PRR7; the interaction
CC is reduced following NMDA receptor activity (PubMed:27458189).
CC {ECO:0000250|UniProtKB:P35438, ECO:0000250|UniProtKB:P35439,
CC ECO:0000269|PubMed:18849881, ECO:0000269|PubMed:26875626,
CC ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:27458189,
CC ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:28126851,
CC ECO:0000269|PubMed:7685113}.
CC -!- INTERACTION:
CC Q05586; P05067: APP; NbExp=3; IntAct=EBI-998542, EBI-77613;
CC Q05586; P35637: FUS; NbExp=3; IntAct=EBI-998542, EBI-400434;
CC Q05586-1; Q12879-1: GRIN2A; NbExp=2; IntAct=EBI-27070564, EBI-27070593;
CC Q05586-1; Q13224: GRIN2B; NbExp=2; IntAct=EBI-27070564, EBI-2256942;
CC Q05586-2; Q62936: Dlg3; Xeno; NbExp=3; IntAct=EBI-8286218, EBI-349596;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26875626,
CC ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28105280,
CC ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:7685113}; Multi-pass
CC membrane protein {ECO:0000250}. Postsynaptic cell membrane
CC {ECO:0000250}. Postsynaptic density {ECO:0000250}. Note=Enriched in
CC postsynaptic plasma membrane and postsynaptic densities. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=3; Synonyms=Long, NR1-3;
CC IsoId=Q05586-1; Sequence=Displayed;
CC Name=1; Synonyms=Short, NR1-1;
CC IsoId=Q05586-2; Sequence=VSP_000137, VSP_000138;
CC Name=2; Synonyms=Medium, NR1-2;
CC IsoId=Q05586-3; Sequence=VSP_000139;
CC Name=4;
CC IsoId=Q05586-4; Sequence=VSP_011778, VSP_011779;
CC Name=5;
CC IsoId=Q05586-5; Sequence=VSP_011777;
CC Name=6;
CC IsoId=Q05586-6; Sequence=VSP_011777, VSP_011778, VSP_011779;
CC Name=7;
CC IsoId=Q05586-7; Sequence=VSP_011777, VSP_045464;
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:A0A1L8F5J9}.
CC -!- PTM: NMDA is probably regulated by C-terminal phosphorylation of an
CC isoform of NR1 by PKC. Dephosphorylated on Ser-897 probably by protein
CC phosphatase 2A (PPP2CB). Its phosphorylated state is influenced by the
CC formation of the NMDAR-PPP2CB complex and the NMDAR channel activity.
CC {ECO:0000269|PubMed:8316301}.
CC -!- DISEASE: Neurodevelopmental disorder with or without hyperkinetic
CC movements and seizures, autosomal dominant (NDHMSD) [MIM:614254]: An
CC autosomal dominant neurodevelopmental disorder characterized by severe
CC intellectual disability and developmental delay, absent speech,
CC muscular hypotonia, dyskinesia, and hyperkinetic movements. Cortical
CC blindness, cerebral atrophy, and seizures are present in some patients.
CC {ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:25167861,
CC ECO:0000269|PubMed:25864721, ECO:0000269|PubMed:27164704,
CC ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28228639,
CC ECO:0000269|PubMed:28389307}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neurodevelopmental disorder with or without hyperkinetic
CC movements and seizures, autosomal recessive (NDHMSR) [MIM:617820]: An
CC autosomal recessive neurodevelopmental disorder characterized by severe
CC intellectual disability and psychomotor developmental delay,
CC involuntary and stereotypic movements, spasticity, and inability to
CC walk without support. Intractable seizures manifest in some patients.
CC {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28051072}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. NR1/GRIN1 subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=NMDA receptor entry;
CC URL="https://en.wikipedia.org/wiki/NMDA_receptor";
CC ---------------------------------------------------------------------------
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DR EMBL; L13266; AAB59360.1; -; mRNA.
DR EMBL; L13267; AAA36198.1; -; mRNA.
DR EMBL; L13268; AAB59361.1; -; mRNA.
DR EMBL; D13515; BAA02732.1; -; mRNA.
DR EMBL; L05666; AAA21180.1; -; mRNA.
DR EMBL; AF015730; AAB67723.1; -; mRNA.
DR EMBL; AF015731; AAB67724.1; -; mRNA.
DR EMBL; Z32772; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z32773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z32774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929554; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U08106; AAA62111.1; -; mRNA.
DR EMBL; U08107; AAA62112.1; -; mRNA.
DR EMBL; S57708; AAB25917.1; -; mRNA.
DR CCDS; CCDS43910.1; -. [Q05586-2]
DR CCDS; CCDS55354.1; -. [Q05586-6]
DR CCDS; CCDS55355.1; -. [Q05586-7]
DR CCDS; CCDS7031.1; -. [Q05586-1]
DR CCDS; CCDS7032.1; -. [Q05586-3]
DR PIR; A46612; A46612.
DR PIR; A47551; A47551.
DR RefSeq; NP_000823.4; NM_000832.6. [Q05586-2]
DR RefSeq; NP_001172019.1; NM_001185090.1. [Q05586-6]
DR RefSeq; NP_001172020.1; NM_001185091.1. [Q05586-7]
DR RefSeq; NP_015566.1; NM_007327.3. [Q05586-1]
DR RefSeq; NP_067544.1; NM_021569.3. [Q05586-3]
DR RefSeq; XP_005266128.1; XM_005266071.3. [Q05586-4]
DR RefSeq; XP_005266130.1; XM_005266073.4. [Q05586-5]
DR PDB; 2HQW; X-ray; 1.90 A; B=875-898.
DR PDB; 2NR1; NMR; -; A=599-621.
DR PDB; 3BYA; X-ray; 1.85 A; B=875-898.
DR PDB; 5H8F; X-ray; 1.81 A; B=394-544, B=663-800.
DR PDB; 5H8H; X-ray; 2.23 A; B=394-544, B=663-800.
DR PDB; 5H8N; X-ray; 2.50 A; B=394-544, B=663-800.
DR PDB; 5H8Q; X-ray; 1.90 A; B=394-544, B=663-800.
DR PDB; 5I2K; X-ray; 2.86 A; B=394-544, B=663-800.
DR PDB; 5I2N; X-ray; 2.12 A; B=394-544, B=663-800.
DR PDB; 5KCJ; X-ray; 2.09 A; B=394-544, B=663-800.
DR PDB; 5KDT; X-ray; 2.44 A; B=394-544, B=663-800.
DR PDB; 5TP9; X-ray; 2.40 A; B=394-544, B=663-800.
DR PDB; 5TPA; X-ray; 2.48 A; B=394-544, B=663-800.
DR PDB; 6IRA; EM; 4.50 A; A/C=1-847.
DR PDB; 6IRF; EM; 5.10 A; A/C=1-847.
DR PDB; 6IRG; EM; 5.50 A; A/C=1-847.
DR PDB; 6IRH; EM; 7.80 A; A/C=1-847.
DR PDB; 7EOQ; EM; 4.10 A; B/D=1-847.
DR PDB; 7EOR; EM; 4.00 A; B/D=1-847.
DR PDB; 7EOS; EM; 3.90 A; B/D=1-847.
DR PDB; 7EOT; EM; 3.80 A; B/D=1-847.
DR PDB; 7EOU; EM; 4.30 A; B/D=1-847.
DR PDB; 7EU7; EM; 3.50 A; A/C=1-847.
DR PDB; 7EU8; EM; 4.07 A; A/C=1-847.
DR PDBsum; 2HQW; -.
DR PDBsum; 2NR1; -.
DR PDBsum; 3BYA; -.
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 PDBsum; 7EU8; -.
DR AlphaFoldDB; Q05586; -.
DR SMR; Q05586; -.
DR BioGRID; 109159; 61.
DR ComplexPortal; CPX-2202; NMDA receptor complex, GluN1-GluN2A.
DR ComplexPortal; CPX-285; NMDA receptor complex, GluN1-GluN2B.
DR ComplexPortal; CPX-286; NMDA receptor complex, GluN1-GluN2C.
DR ComplexPortal; CPX-289; NMDA receptor complex, GluN1-GluN2D.
DR ComplexPortal; CPX-294; NMDA receptor complex, GluN1-GluN2A-GluN2B.
DR CORUM; Q05586; -.
DR IntAct; Q05586; 13.
DR MINT; Q05586; -.
DR STRING; 9606.ENSP00000360608; -.
DR BindingDB; Q05586; -.
DR ChEMBL; CHEMBL2015; -.
DR DrugBank; DB01931; 5,7-Dichlorokynurenic acid.
DR DrugBank; DB00659; Acamprosate.
DR DrugBank; DB06151; Acetylcysteine.
DR DrugBank; DB08838; Agmatine.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB00289; Atomoxetine.
DR DrugBank; DB05824; CNS-5161.
DR DrugBank; DB04620; Cycloleucine.
DR DrugBank; DB03929; D-Serine.
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; DB08954; Ifenprodil.
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; DB00193; Tramadol.
DR DrugCentral; Q05586; -.
DR GuidetoPHARMACOLOGY; 455; -.
DR TCDB; 1.A.10.1.20; the glutamate-gated ion channel (gic) family of neurotransmitter receptors.
DR GlyGen; Q05586; 13 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q05586; -.
DR PhosphoSitePlus; Q05586; -.
DR BioMuta; GRIN1; -.
DR DMDM; 548377; -.
DR EPD; Q05586; -.
DR MassIVE; Q05586; -.
DR PaxDb; Q05586; -.
DR PeptideAtlas; Q05586; -.
DR PRIDE; Q05586; -.
DR ProteomicsDB; 58336; -. [Q05586-1]
DR ProteomicsDB; 58337; -. [Q05586-2]
DR ProteomicsDB; 58338; -. [Q05586-3]
DR ProteomicsDB; 58339; -. [Q05586-4]
DR ProteomicsDB; 58340; -. [Q05586-5]
DR ProteomicsDB; 65258; -.
DR ProteomicsDB; 65259; -.
DR ABCD; Q05586; 8 sequenced antibodies.
DR Antibodypedia; 3475; 1291 antibodies from 49 providers.
DR DNASU; 2902; -.
DR Ensembl; ENST00000371546.8; ENSP00000360601.4; ENSG00000176884.16. [Q05586-5]
DR Ensembl; ENST00000371550.8; ENSP00000360605.4; ENSG00000176884.16. [Q05586-3]
DR Ensembl; ENST00000371553.7; ENSP00000360608.3; ENSG00000176884.16. [Q05586-6]
DR Ensembl; ENST00000371559.8; ENSP00000360614.4; ENSG00000176884.16. [Q05586-2]
DR Ensembl; ENST00000371560.4; ENSP00000360615.3; ENSG00000176884.16. [Q05586-7]
DR Ensembl; ENST00000371561.8; ENSP00000360616.3; ENSG00000176884.16. [Q05586-1]
DR GeneID; 2902; -.
DR KEGG; hsa:2902; -.
DR MANE-Select; ENST00000371561.8; ENSP00000360616.3; NM_007327.4; NP_015566.1.
DR UCSC; uc004clk.4; human. [Q05586-1]
DR CTD; 2902; -.
DR DisGeNET; 2902; -.
DR GeneCards; GRIN1; -.
DR GeneReviews; GRIN1; -.
DR HGNC; HGNC:4584; GRIN1.
DR HPA; ENSG00000176884; Tissue enriched (brain).
DR MalaCards; GRIN1; -.
DR MIM; 138249; gene.
DR MIM; 614254; phenotype.
DR MIM; 617820; phenotype.
DR neXtProt; NX_Q05586; -.
DR OpenTargets; ENSG00000176884; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR Orphanet; 208447; Bilateral generalized polymicrogyria.
DR Orphanet; 1934; Early infantile epileptic encephalopathy.
DR PharmGKB; PA28978; -.
DR VEuPathDB; HostDB:ENSG00000176884; -.
DR eggNOG; KOG4440; Eukaryota.
DR GeneTree; ENSGT00940000158016; -.
DR HOGENOM; CLU_007257_2_0_1; -.
DR InParanoid; Q05586; -.
DR OMA; KPEGFMI; -.
DR OrthoDB; 188544at2759; -.
DR PhylomeDB; Q05586; -.
DR TreeFam; TF351405; -.
DR PathwayCommons; Q05586; -.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
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; Q05586; -.
DR SIGNOR; Q05586; -.
DR BioGRID-ORCS; 2902; 8 hits in 1066 CRISPR screens.
DR ChiTaRS; GRIN1; human.
DR EvolutionaryTrace; Q05586; -.
DR GeneWiki; GRIN1; -.
DR GenomeRNAi; 2902; -.
DR Pharos; Q05586; Tclin.
DR PRO; PR:Q05586; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q05586; protein.
DR Bgee; ENSG00000176884; Expressed in right hemisphere of cerebellum and 166 other tissues.
DR ExpressionAtlas; Q05586; baseline and differential.
DR Genevisible; Q05586; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; ISS:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISS:ARUK-UCL.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; ISS:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0060076; C:excitatory synapse; ISS:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
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:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0043083; C:synaptic cleft; ISS:BHF-UCL.
DR GO; GO:0097060; C:synaptic membrane; ISS:ARUK-UCL.
DR GO; GO:0008021; C:synaptic vesicle; ISS:UniProtKB.
DR GO; GO:0043195; C:terminal bouton; ISS:BHF-UCL.
DR GO; GO:0001540; F:amyloid-beta binding; ISS:ARUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0016595; F:glutamate binding; IDA:UniProtKB.
DR GO; GO:0022849; F:glutamate-gated calcium ion channel activity; IDA:UniProtKB.
DR GO; GO:0016594; F:glycine binding; IDA:UniProtKB.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0042165; F:neurotransmitter binding; ISS:BHF-UCL.
DR GO; GO:0004972; F:NMDA glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISS:ARUK-UCL.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; NAS:ARUK-UCL.
DR GO; GO:0055074; P:calcium ion homeostasis; ISS:UniProtKB.
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:0006812; P:cation transport; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0098976; P:excitatory chemical synaptic transmission; NAS:ARUK-UCL.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISS:UniProtKB.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; ISS:ARUK-UCL.
DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; ISS:ARUK-UCL.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:BHF-UCL.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IC:ComplexPortal.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0018964; P:propylene metabolic process; ISS:BHF-UCL.
DR GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; IC:ComplexPortal.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:UniProtKB.
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:0045471; P:response to ethanol; IDA:UniProtKB.
DR GO; GO:1905429; P:response to glycine; IDA:UniProtKB.
DR GO; GO:0008542; P:visual learning; ISS:UniProtKB.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR018882; CaM-bd_C0_NMDA_rcpt_NR1.
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; PF10562; CaM_bdg_C0; 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 3D-structure; Alternative splicing; Calcium; Cell membrane;
KW Disease variant; Disulfide bond; Glycoprotein; Intellectual disability;
KW Ion channel; Ion transport; Ligand-gated ion channel; Magnesium; Membrane;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..938
FT /note="Glutamate receptor ionotropic, NMDA 1"
FT /id="PRO_0000011587"
FT TOPO_DOM 19..559
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P35439"
FT TRANSMEM 560..580
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35439"
FT TOPO_DOM 581..602
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P35439"
FT INTRAMEM 603..624
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:A0A1L8F5J9"
FT TOPO_DOM 625..630
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P35439"
FT TRANSMEM 631..647
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35439"
FT TOPO_DOM 648..812
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P35439"
FT TRANSMEM 813..833
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35439"
FT TOPO_DOM 834..938
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P35439"
FT REGION 603..624
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:A0A1L8F5J9"
FT REGION 889..938
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 917..938
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 516..518
FT /ligand="glycine"
FT /ligand_id="ChEBI:CHEBI:57305"
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 523
FT /ligand="glycine"
FT /ligand_id="ChEBI:CHEBI:57305"
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 688
FT /ligand="glycine"
FT /ligand_id="ChEBI:CHEBI:57305"
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 732
FT /ligand="glycine"
FT /ligand_id="ChEBI:CHEBI:57305"
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 MOD_RES 889
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000305|PubMed:8316301"
FT MOD_RES 890
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000305|PubMed:8316301"
FT MOD_RES 896
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000305|PubMed:8316301"
FT MOD_RES 897
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000305|PubMed:8316301"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 239
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 471
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 674
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 771
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 79..308
FT /evidence="ECO:0000250|UniProtKB:P35439"
FT DISULFID 420..454
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..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 744..798
FT /evidence="ECO:0000269|PubMed:26875626,
FT ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28105280,
FT ECO:0007744|PDB:5H8F, ECO:0007744|PDB:5I2K,
FT ECO:0007744|PDB:5TPA"
FT VAR_SEQ 190
FT /note="K -> KSKKRNYENLDQLSYDNKRGPK (in isoform 5, isoform 6
FT and isoform 7)"
FT /evidence="ECO:0000303|PubMed:7926821,
FT ECO:0000303|PubMed:9231706"
FT /id="VSP_011777"
FT VAR_SEQ 864..938
FT /note="DRKSGRAEPDPKKKATFRAITSTLASSFKRRRSSKDTSTGGGRGALQNQKDT
FT VLPRRAIEREEGQLQLCSRHRES -> QYHPTDITGPLNLSDPSVSTVV (in
FT isoform 7)"
FT /evidence="ECO:0000303|PubMed:9231706"
FT /id="VSP_045464"
FT VAR_SEQ 864..900
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8406025"
FT /id="VSP_000139"
FT VAR_SEQ 864..885
FT /note="DRKSGRAEPDPKKKATFRAITS -> QYHPTDITGPLNLSDPSVSTVV (in
FT isoform 1)"
FT /evidence="ECO:0000303|PubMed:7685113,
FT ECO:0000303|PubMed:8406025"
FT /id="VSP_000137"
FT VAR_SEQ 886..938
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:7685113,
FT ECO:0000303|PubMed:8406025"
FT /id="VSP_000138"
FT VAR_SEQ 901..922
FT /note="STGGGRGALQNQKDTVLPRRAI -> QYHPTDITGPLNLSDPSVSTVV (in
FT isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:7926821,
FT ECO:0000303|PubMed:9231706"
FT /id="VSP_011778"
FT VAR_SEQ 923..938
FT /note="Missing (in isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:7926821,
FT ECO:0000303|PubMed:9231706"
FT /id="VSP_011779"
FT VARIANT 217
FT /note="R -> W (in NDHMSR; changed glutamate-gated calcium
FT ion channel activity; increased inhibition by zinc;
FT dbSNP:rs200777850)"
FT /evidence="ECO:0000269|PubMed:27164704"
FT /id="VAR_079984"
FT VARIANT 227
FT /note="D -> H (in NDHMSR; unknown pathological
FT significance; dbSNP:rs869312865)"
FT /evidence="ECO:0000269|PubMed:28051072"
FT /id="VAR_079985"
FT VARIANT 306
FT /note="R -> Q (found in a patient with schizophrenia;
FT unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079986"
FT VARIANT 349
FT /note="A -> S (in dbSNP:rs148008303)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079987"
FT VARIANT 419
FT /note="T -> A (in dbSNP:rs763133592)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079988"
FT VARIANT 540
FT /note="I -> M (in dbSNP:rs3181457)"
FT /evidence="ECO:0000269|PubMed:9231706"
FT /id="VAR_049187"
FT VARIANT 552
FT /note="D -> E (in NDHMSD; changed localization to the cell
FT membrane; decreased glutamate-gated calcium ion channel
FT activity; dbSNP:rs1554770054)"
FT /evidence="ECO:0000269|PubMed:25864721,
FT ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420"
FT /id="VAR_079989"
FT VARIANT 556..938
FT /note="Missing (in NDHMSR; loss of function in calcium ion
FT transmembrane import into cytosol)"
FT /evidence="ECO:0000269|PubMed:27164704"
FT /id="VAR_079990"
FT VARIANT 557
FT /note="P -> R (in NDHMSD; changed localization to the cell
FT membrane; loss of glutamate-gated calcium ion channel
FT activity; dbSNP:rs878853143)"
FT /evidence="ECO:0000269|PubMed:25167861,
FT ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420"
FT /id="VAR_079991"
FT VARIANT 560
FT /note="S -> SS (in NDHMSD; there is near abolition of the
FT activity of the NMDA receptor in Xenopus oocytes; alters
FT the 3-dimensional structure at the receptor's channel pore
FT entrance)"
FT /evidence="ECO:0000269|PubMed:21376300"
FT /id="VAR_066597"
FT VARIANT 618
FT /note="G -> R (in NDHMSD; loss of function in calcium ion
FT transmembrane import into cytosol)"
FT /evidence="ECO:0000269|PubMed:27164704"
FT /id="VAR_079992"
FT VARIANT 620
FT /note="G -> R (in NDHMSD; decreased localization to the
FT plasma membrane of GRIN1/GRIN2B NMDA receptor complexes;
FT changed glutamate-gated calcium ion channel activity;
FT decreased activation by glutamate and glycine; decreased
FT sensitivity to magnesium block; loss of function in calcium
FT ion transmembrane import into cytosol; dbSNP:rs797045047)"
FT /evidence="ECO:0000269|PubMed:27164704,
FT ECO:0000269|PubMed:28228639"
FT /id="VAR_079993"
FT VARIANT 641
FT /note="M -> I (in NDHMSD; unknown pathological
FT significance; dbSNP:rs1060500046)"
FT /evidence="ECO:0000269|PubMed:25864721"
FT /id="VAR_079994"
FT VARIANT 645
FT /note="A -> S (in NDHMSD; unknown pathological
FT significance; no effect on glutamate-gated calcium ion
FT channel activity)"
FT /evidence="ECO:0000269|PubMed:27164704"
FT /id="VAR_079995"
FT VARIANT 647
FT /note="Y -> S (in NDHMSD; loss of glutamate-gated calcium
FT ion channel activity)"
FT /evidence="ECO:0000269|PubMed:27164704"
FT /id="VAR_079996"
FT VARIANT 650
FT /note="N -> K (in NDHMSD; unknown pathological
FT significance; dbSNP:rs771610568)"
FT /evidence="ECO:0000269|PubMed:25864721"
FT /id="VAR_079997"
FT VARIANT 662
FT /note="E -> K (in NDHMSD; this mutation produces a
FT significant increase in NMDA receptor-induced calcium
FT currents; excessive calcium influx through NMDA receptor
FT could lead to excitotoxic neuronal cell damage;
FT dbSNP:rs387906635)"
FT /evidence="ECO:0000269|PubMed:21376300"
FT /id="VAR_066598"
FT VARIANT 682
FT /note="A -> S (in dbSNP:rs1126448)"
FT /evidence="ECO:0000269|PubMed:9231706"
FT /id="VAR_069057"
FT VARIANT 688
FT /note="S -> Y (in NDHMSD)"
FT /evidence="ECO:0000269|PubMed:28389307"
FT /id="VAR_079998"
FT VARIANT 815
FT /note="G -> R (in NDHMSD; loss of glutamate-gated calcium
FT ion channel activity; dbSNP:rs797044925)"
FT /evidence="ECO:0000269|PubMed:25864721,
FT ECO:0000269|PubMed:27164704"
FT /id="VAR_079999"
FT VARIANT 815
FT /note="G -> V (in NDHMSD)"
FT /evidence="ECO:0000269|PubMed:27164704"
FT /id="VAR_080000"
FT VARIANT 817
FT /note="F -> L (in NDHMSD; decreased glutamate-gated calcium
FT ion channel activity; dbSNP:rs1554770624)"
FT /evidence="ECO:0000269|PubMed:27164704"
FT /id="VAR_080001"
FT VARIANT 827
FT /note="G -> R (in NDHMSD; loss of function in calcium ion
FT transmembrane import into cytosol; dbSNP:rs1451230055)"
FT /evidence="ECO:0000269|PubMed:27164704,
FT ECO:0000269|PubMed:28389307"
FT /id="VAR_080002"
FT VARIANT 844
FT /note="R -> C (in NDHMSD; no effect on glutamate-gated
FT calcium ion channel activity; dbSNP:rs1554770667)"
FT /evidence="ECO:0000269|PubMed:27164704"
FT /id="VAR_080003"
FT MUTAGEN 813
FT /note="M->V: Slight decrease in glycine agonist potency; no
FT effect on glutamate agonist potency."
FT /evidence="ECO:0000269|PubMed:28126851"
FT CONFLICT 389
FT /note="P -> S (in Ref. 8; AAB25917)"
FT /evidence="ECO:0000305"
FT CONFLICT 488
FT /note="E -> K (in Ref. 1; AAB59361)"
FT /evidence="ECO:0000305"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 36..52
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 71..81
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 104..113
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:7EU7"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 134..141
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 171..184
FT /evidence="ECO:0007829|PDB:7EU7"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 192..196
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 205..212
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 225..236
FT /evidence="ECO:0007829|PDB:7EU7"
FT TURN 237..241
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 257..261
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 266..271
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 277..296
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 318..327
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 344..348
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 351..357
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 360..367
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 398..402
FT /evidence="ECO:0007829|PDB:5H8F"
FT TURN 406..408
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 409..413
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:5I2K"
FT STRAND 434..441
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 443..446
FT /evidence="ECO:0007829|PDB:7EU7"
FT STRAND 450..457
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 458..470
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 474..478
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 487..489
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 496..498
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 500..506
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 511..513
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 521..524
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 527..529
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 533..543
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 554..558
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 560..581
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 603..613
FT /evidence="ECO:0007829|PDB:7EU7"
FT TURN 614..616
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 627..656
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 666..668
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 670..673
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 677..679
FT /evidence="ECO:0007829|PDB:5I2N"
FT HELIX 688..695
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 697..699
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 700..707
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 711..713
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 714..722
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 727..732
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 733..742
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 746..758
FT /evidence="ECO:0007829|PDB:5H8F"
FT STRAND 761..763
FT /evidence="ECO:0007829|PDB:5H8Q"
FT HELIX 769..781
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 784..792
FT /evidence="ECO:0007829|PDB:5H8F"
FT HELIX 811..837
FT /evidence="ECO:0007829|PDB:7EU7"
FT TURN 838..840
FT /evidence="ECO:0007829|PDB:7EU7"
FT HELIX 877..892
FT /evidence="ECO:0007829|PDB:3BYA"
SQ SEQUENCE 938 AA; 105373 MW; CDF5402769E530AB CRC64;
MSTMRLLTLA LLFSCSVARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL
NATSVTHKPN AIQMALSVCE DLISSQVYAI LVSHPPTPND HFTPTPVSYT AGFYRIPVLG
LTTRMSIYSD KSIHLSFLRT VPPYSHQSSV WFEMMRVYSW NHIILLVSDD HEGRAAQKRL
ETLLEERESK AEKVLQFDPG TKNVTALLME AKELEARVII LSASEDDAAT VYRAAAMLNM
TGSGYVWLVG EREISGNALR YAPDGILGLQ LINGKNESAH ISDAVGVVAQ AVHELLEKEN
ITDPPRGCVG NTNIWKTGPL FKRVLMSSKY ADGVTGRVEF NEDGDRKFAN YSIMNLQNRK
LVQVGIYNGT HVIPNDRKII WPGGETEKPR GYQMSTRLKI VTIHQEPFVY VKPTLSDGTC
KEEFTVNGDP VKKVICTGPN DTSPGSPRHT VPQCCYGFCI DLLIKLARTM NFTYEVHLVA
DGKFGTQERV NNSNKKEWNG MMGELLSGQA DMIVAPLTIN NERAQYIEFS KPFKYQGLTI
LVKKEIPRST LDSFMQPFQS TLWLLVGLSV HVVAVMLYLL DRFSPFGRFK VNSEEEEEDA
LTLSSAMWFS WGVLLNSGIG EGAPRSFSAR ILGMVWAGFA MIIVASYTAN LAAFLVLDRP
EERITGINDP RLRNPSDKFI YATVKQSSVD IYFRRQVELS TMYRHMEKHN YESAAEAIQA
VRDNKLHAFI WDSAVLEFEA SQKCDLVTTG ELFFRSGFGI GMRKDSPWKQ NVSLSILKSH
ENGFMEDLDK TWVRYQECDS RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH
KDARRKQMQL AFAAVNVWRK NLQDRKSGRA EPDPKKKATF RAITSTLASS FKRRRSSKDT
STGGGRGALQ NQKDTVLPRR AIEREEGQLQ LCSRHRES
