Glutamate receptor ionotropic, NMDA 1

Details

Name
Glutamate receptor ionotropic, NMDA 1
Synonyms
  • GluN1
  • Glutamate [NMDA] receptor subunit zeta-1
  • N-methyl-D-aspartate receptor subunit NR1
  • NMD-R1
  • NMDAR1
Gene Name
GRIN1
UniProtKB Entry
Q05586Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0000727|Glutamate receptor ionotropic, NMDA 1
MSTMRLLTLALLFSCSVARAACDPKIVNIGAVLSTRKHEQMFREAVNQANKRHGSWKIQL
NATSVTHKPNAIQMALSVCEDLISSQVYAILVSHPPTPNDHFTPTPVSYTAGFYRIPVLG
LTTRMSIYSDKSIHLSFLRTVPPYSHQSSVWFEMMRVYSWNHIILLVSDDHEGRAAQKRL
ETLLEERESKAEKVLQFDPGTKNVTALLMEAKELEARVIILSASEDDAATVYRAAAMLNM
TGSGYVWLVGEREISGNALRYAPDGILGLQLINGKNESAHISDAVGVVAQAVHELLEKEN
ITDPPRGCVGNTNIWKTGPLFKRVLMSSKYADGVTGRVEFNEDGDRKFANYSIMNLQNRK
LVQVGIYNGTHVIPNDRKIIWPGGETEKPRGYQMSTRLKIVTIHQEPFVYVKPTLSDGTC
KEEFTVNGDPVKKVICTGPNDTSPGSPRHTVPQCCYGFCIDLLIKLARTMNFTYEVHLVA
DGKFGTQERVNNSNKKEWNGMMGELLSGQADMIVAPLTINNERAQYIEFSKPFKYQGLTI
LVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVMLYLLDRFSPFGRFKVNSEEEEEDA
LTLSSAMWFSWGVLLNSGIGEGAPRSFSARILGMVWAGFAMIIVASYTANLAAFLVLDRP
EERITGINDPRLRNPSDKFIYATVKQSSVDIYFRRQVELSTMYRHMEKHNYESAAEAIQA
VRDNKLHAFIWDSAVLEFEASQKCDLVTTGELFFRSGFGIGMRKDSPWKQNVSLSILKSH
ENGFMEDLDKTWVRYQECDSRSNAPATLTFENMAGVFMLVAGGIVAGIFLIFIEIAYKRH
KDARRKQMQLAFAAVNVWRKNLQDRKSGRAEPDPKKKATFRAITSTLASSFKRRRSSKDT
STGGGRGALQNQKDTVLPRRAIEREEGQLQLCSRHRES
Number of residues
938
Molecular Weight
105371.945
Theoretical pI
9.2
GO Classification
Functions
calcium ion binding / calmodulin binding / glutamate binding / glycine binding / NMDA glutamate receptor activity
Processes
calcium ion homeostasis / excitatory postsynaptic potential / ionotropic glutamate receptor signaling pathway / positive regulation of excitatory postsynaptic potential / propylene metabolic process / regulation of membrane potential / response to ethanol / visual learning
Components
cell surface / dendrite / dendritic spine / excitatory synapse / neuron projection / NMDA selective glutamate receptor complex / plasma membrane / postsynaptic density / postsynaptic membrane / synapse / synaptic cleft / synaptic vesicle / terminal bouton
General Function
Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:26919761, PubMed:28105280, PubMed:28126851, PubMed:7685113). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:26919761)
Specific Function
amyloid-beta binding
Pfam Domain Function
Signal Regions
1-18
Transmembrane Regions
560-580 631-647 813-833
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0016071|Glutamate receptor ionotropic, NMDA 1 (GRIN1)
ATGAGCACCATGCGCCTGCTGACGCTCGCCCTGCTGTTCTCCTGCTCCGTCGCCCGTGCC
GCGTGCGACCCCAAGATCGTCAACATTGGCGCGGTGCTGAGCACGCGGAAGCACGAGCAG
ATGTTCCGCGAGGCCGTGAACCAGGCCAACAAGCGGCACGGCTCCTGGAAGATTCAGCTC
AATGCCACCTCCGTCACGCACAAGCCCAACGCCATCCAGATGGCTCTGTCGGTGTGCGAG
GACCTCATCTCCAGCCAGGTCTACGCCATCCTAGTTAGCCATCCACCTACCCCCAACGAC
CACTTCACTCCCACCCCTGTCTCCTACACAGCCGGCTTCTACCGCATACCCGTGCTGGGG
CTGACCACCCGCATGTCCATCTACTCGGACAAGAGCATCCACCTGAGCTTCCTGCGCACC
GTGCCGCCCTACTCCCACCAGTCCAGCGTGTGGTTTGAGATGATGCGTGTCTACAGCTGG
AACCACATCATCCTGCTGGTCAGCGACGACCACGAGGGCCGGGCGGCTCAGAAACGCCTG
GAGACGCTGCTGGAGGAGCGTGAGTCCAAGGCAGAGAAGGTGCTGCAGTTTGACCCAGGG
ACCAAGAACGTGACGGCCCTGCTGATGGAGGCGAAAGAGCTGGAGGCCCGGGTCATCATC
CTTTCTGCCAGCGAGGACGATGCTGCCACTGTATACCGCGCAGCCGCGATGCTGAACATG
ACGGGCTCCGGGTACGTGTGGCTGGTCGGCGAGCGCGAGATCTCGGGGAACGCCCTGCGC
TACGCCCCAGACGGCATCCTCGGGCTGCAGCTCATCAACGGCAAGAACGAGTCGGCCCAC
ATCAGCGACGCCGTGGGCGTGGTGGCCCAGGCCGTGCACGAGCTCCTCGAGAAGGAGAAC
ATCACCGACCCGCCGCGGGGCTGCGTGGGCAACACCAACATCTGGAAGACCGGGCCGCTC
TTCAAGAGAGTGCTGATGTCTTCCAAGTATGCGGATGGGGTGACTGGTCGCGTGGAGTTC
AATGAGGATGGGGACCGGAAGTTCGCCAACTACAGCATCATGAACCTGCAGAACCGCAAG
CTGGTGCAAGTGGGCATCTACAATGGCACCCACGTCATCCCTAATGACAGGAAGATCATC
TGGCCAGGCGGAGAGACAGAGAAGCCTCGAGGGTACCAGATGTCCACCAGACTGAAGATT
GTGACGATCCACCAGGAGCCCTTCGTGTACGTCAAGCCCACGCTGAGTGATGGGACATGC
AAGGAGGAGTTCACAGTCAACGGCGACCCAGTCAAGAAGGTGATCTGCACCGGGCCCAAC
GACACGTCGCCGGGCAGCCCCCGCCACACGGTGCCTCAGTGTTGCTACGGCTTTTGCATC
GACCTGCTCATCAAGCTGGCACGGACCATGAACTTCACCTACGAGGTGCACCTGGTGGCA
GATGGCAAGTTCGGCACACAGGAGCGGGTGAACAACAGCAACAAGAAGGAGTGGAATGGG
ATGATGGGCGAGCTGCTCAGCGGGCAGGCAGACATGATCGTGGCGCCGCTAACCATAAAC
AACGAGCGCGCGCAGTACATCGAGTTTTCCAAGCCCTTCAAGTACCAGGGCCTGACTATT
CTGGTCAAGAAGGAGATTCCCCGGAGCACGCTGGACTCGTTCATGCAGCCGTTCCAGAGC
ACACTGTGGCTGCTGGTGGGGCTGTCGGTGCACGTGGTGGCCGTGATGCTGTACCTGCTG
GACCGCTTCAGCCCCTTCGGCCGGTTCAAGGTGAACAGCGAGGAGGAGGAGGAGGACGCA
CTGACCCTGTCCTCGGCCATGTGGTTCTCCTGGGGCGTCCTGCTCAACTCCGGCATCGGG
GAAGGCGCCCCCAGAAGCTTCTCAGCGCGCATCCTGGGCATGGTGTGGGCCGGCTTTGCC
ATGATCATCGTGGCCTCCTACACCGCCAACCTGGCGGCCTTCCTGGTGCTGGACCGGCCG
GAGGAGCGCATCACGGGCATCAACGACCCTCGGCTGAGGAACCCCTCGGACAAGTTTATC
TACGCCACGGTGAAGCAGAGCTCCGTGGATATCTACTTCCGGCGCCAGGTGGAGCTGAGC
ACCATGTACCGGCATATGGAGAAGCACAACTACGAGAGTGCGGCGGAGGCCATCCAGGCC
GTGAGAGACAACAAGCTGCATGCCTTCATCTGGGACTCGGCGGTGCTGGAGTTCGAGGCC
TCGCAGAAGTGCGACCTGGTGACGACTGGAGAGCTGTTTTTCCGCTCGGGCTTCGGCATA
GGCATGCGCAAAGACAGCCCCTGGAAGCAGAACGTCTCCCTGTCCATCCTCAAGTCCCAC
GAGAATGGCTTCATGGAAGACCTGGACAAGACGTGGGTTCGGTATCAGGAATGTGACTCG
CGCAGCAACGCCCCTGCGACCCTTACTTTTGAGAACATGGCCGGGGTCTTCATGCTGGTA
GCTGGGGGCATCGTGGCCGGGATCTTCCTGATTTTCATCGAGATTGCCTACAAGCGGCAC
AAGGATGCTCGCCGGAAGCAGATGCAGCTGGCCTTTGCCGCCGTTAACGTGTGGCGGAAG
AACCTGCAGCAGTACCATCCCACTGATATCACGGGCCCGCTCAACCTCTCAGATCCCTCG
GTCAGCACCGTGGTGTGA
Chromosome Location
9
Locus
9q34.3
External Identifiers
ResourceLink
UniProtKB IDQ05586
UniProtKB Entry NameNMDZ1_HUMAN
GenBank Protein ID219920
GenBank Gene IDD13515
GeneCard IDGRIN1
GenAtlas IDGRIN1
HGNC IDHGNC:4584
PDB ID(s)2HQW, 2NR1, 3BYA, 5H8F, 5H8H, 5H8N, 5H8Q, 5I2K, 5I2N, 5KCJ, 5KDT, 5TP9, 5TPA, 6IRA, 6IRF, 6IRG, 6IRH, 7EOQ, 7EOR, 7EOS, 7EOT, 7EOU, 7EU7, 7EU8, 7YFF, 7YFL, 7YFM, 7YFO, 7YFR, 8E92, 8E93, 8E94, 8E96, 8E97, 8E98, 8E99, 8JIZ, 8JJ0, 8JJ1, 8JJ2, 8UUE
KEGG IDhsa:2902
IUPHAR/Guide To Pharmacology ID455
NCBI Gene ID2902
General References
  1. Foldes RL, Rampersad V, Kamboj RK: Cloning and sequence analysis of cDNAs encoding human hippocampus N-methyl-D-aspartate receptor subunits: evidence for alternative RNA splicing. Gene. 1993 Sep 15;131(2):293-8. [Article]
  2. Karp SJ, Masu M, Eki T, Ozawa K, Nakanishi S: Molecular cloning and chromosomal localization of the key subunit of the human N-methyl-D-aspartate receptor. J Biol Chem. 1993 Feb 15;268(5):3728-33. [Article]
  3. Planells-Cases R, Sun W, Ferrer-Montiel AV, Montal M: Molecular cloning, functional expression, and pharmacological characterization of an N-methyl-D-aspartate receptor subunit from human brain. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5057-61. [Article]
  4. Zimmer M, Fink TM, Franke Y, Lichter P, Spiess J: Cloning and structure of the gene encoding the human N-methyl-D-aspartate receptor (NMDAR1). Gene. 1995 Jul 4;159(2):219-23. [Article]
  5. Nash NR, Heilman CJ, Rees HD, Levey AI: Cloning and localization of exon 5-containing isoforms of the NMDAR1 subunit in human and rat brains. J Neurochem. 1997 Aug;69(2):485-93. [Article]
  6. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
  7. Foldes RL, Rampersad V, Kamboj RK: Cloning and sequence analysis of additional splice variants encoding human N-methyl-D-aspartate receptor (hNR1) subunits. Gene. 1994 Sep 30;147(2):303-4. [Article]
  8. Younkin DP, Tang CM, Hardy M, Reddy UR, Shi QY, Pleasure SJ, Lee VM, Pleasure D: Inducible expression of neuronal glutamate receptor channels in the NT2 human cell line. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2174-8. [Article]
  9. Tingley WG, Roche KW, Thompson AK, Huganir RL: Regulation of NMDA receptor phosphorylation by alternative splicing of the C-terminal domain. Nature. 1993 Jul 1;364(6432):70-3. [Article]
  10. Papadakis M, Hawkins LM, Stephenson FA: Appropriate NR1-NR1 disulfide-linked homodimer formation is requisite for efficient expression of functional, cell surface N-methyl-D-aspartate NR1/NR2 receptors. J Biol Chem. 2004 Apr 9;279(15):14703-12. Epub 2004 Jan 19. [Article]
  11. Roginski RS, Goubaeva F, Mikami M, Fried-Cassorla E, Nair MR, Yang J: GRINL1A colocalizes with N-methyl D-aspartate receptor NR1 subunit and reduces N-methyl D-aspartate toxicity. Neuroreport. 2008 Nov 19;19(17):1721-6. doi: 10.1097/WNR.0b013e328317f05f. [Article]
  12. Opella SJ, Marassi FM, Gesell JJ, Valente AP, Kim Y, Oblatt-Montal M, Montal M: Structures of the M2 channel-lining segments from nicotinic acetylcholine and NMDA receptors by NMR spectroscopy. Nat Struct Biol. 1999 Apr;6(4):374-9. [Article]
  13. Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, Spiegelman D, Dobrzeniecka S, Piton A, Tomitori H, Daoud H, Massicotte C, Henrion E, Diallo O, Shekarabi M, Marineau C, Shevell M, Maranda B, Mitchell G, Nadeau A, D'Anjou G, Vanasse M, Srour M, Lafreniere RG, Drapeau P, Lacaille JC, Kim E, Lee JR, Igarashi K, Huganir RL, Rouleau GA, Michaud JL: Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet. 2011 Mar 11;88(3):306-16. doi: 10.1016/j.ajhg.2011.02.001. Epub 2011 Mar 3. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Glutamate receptor ionotropic, NMDA 1 (Humans)protein
primary
Glutamate (NMDA) receptor (Humans)protein
NMDA receptor (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
OrphenadrineapprovedyestargetantagonistDetails
D-Serineapproved, experimentalyestargetinhibitorDetails
Glutamic acidapproved, nutraceuticalunknowntargetDetails
CycloleucineexperimentalyestargetinhibitorDetails
CNS-5161investigationalunknowntargetDetails
5,7-Dichlorokynurenic acidexperimentalyestargetinhibitorDetails
MeperidineapprovedunknowntargetantagonistDetails
AgmatineexperimentalyestargetantagonistDetails
Acetylcysteineapproved, investigationalunknowntargetactivatorDetails
Memantineapproved, investigationalunknowntargetbinderDetails
Ifenprodilinvestigational, withdrawnyestargetantagonistDetails
D-Aspartic AcidexperimentalyestargetagonistDetails
Aspartic acidapproved, nutraceuticalyestargetagonistDetails
FG-9041experimentalyestargetinhibitorDetails
PhencyclidineillicityestargetinhibitorDetails
Kynurenic AcidinvestigationalyestargetinhibitorDetails
EliprodilinvestigationalyestargetinhibitorDetails
CycloserineapprovedyestargetinhibitorDetails
Spermineexperimental, nutraceuticalyestargetinhibitorDetails
Enfluraneapproved, investigational, vet_approvedunknowntargetantagonistDetails
Acamprosateapproved, investigationalyestargetantagonistDetails
GavestinelinvestigationalunknowntargetantagonistDetails
Magnesium carbonateapproved, investigationalunknowntargetblockerDetails
Magnesium acetate tetrahydrateapprovedunknowntargetligandDetails
Fluciclovine (18F)approvednotargetinhibitorDetails
Memantineapproved, investigationalyestargetantagonistDetails
Aripiprazoleapproved, investigationalunknowntargetligandDetails
MethadoneapprovedyestargetantagonistDetails
Milnacipranapproved, investigationalunknowntargetinhibitorDetails
AtomoxetineapprovedunknowntargetblockerDetails
Pentobarbitalapproved, investigational, vet_approvedunknowntargetantagonistDetails
Secobarbitalapproved, vet_approvedunknowntargetantagonistDetails
Phenobarbitalapproved, investigationalunknowntargetantagonistDetails
Prasteroneapproved, investigational, nutraceuticalunknowntargetagonistDetails
KetobemidoneinvestigationalunknowntargetantagonistDetails
Esketamineapproved, investigationalyestargetantagonistDetails
Guaifenesinapproved, investigational, vet_approvedunknowntargetantagonistDetails
DonepezilapprovedunknowntargetdownregulatorDetails
Tramadolapproved, investigationalyestargetinhibitorDetails
Dextropropoxypheneapproved, illicit, investigational, withdrawnunknowntargetantagonistDetails