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
Organism
Humans
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 channel activity / calcium ion binding / calmodulin binding / extracellular-glutamate-gated ion channel activity / glutamate binding / glycine binding / neurotransmitter binding / NMDA glutamate receptor activity / voltage-gated cation channel activity
Processes
activation of MAPKK activity / adult locomotory behavior / axon guidance / calcium ion homeostasis / calcium ion transmembrane transport / cation transport / cellular calcium ion homeostasis / cellular response to manganese ion / cerebral cortex development / conditioned taste aversion / ephrin receptor signaling pathway / epidermal growth factor receptor signaling pathway / excitatory postsynaptic potential / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / innate immune response / insulin receptor signaling pathway / ion transmembrane transport / ionotropic glutamate receptor signaling pathway / long-term memory / male mating behavior / MAPK cascade / negative regulation of neuron apoptotic process / neurotrophin TRK receptor signaling pathway / olfactory learning / pons maturation / positive regulation of apoptotic process / positive regulation of excitatory postsynaptic potential / positive regulation of transcription from RNA polymerase II promoter / prepulse inhibition / propylene metabolic process / protein tetramerization / Ras protein signal transduction / regulation of axonogenesis / regulation of dendrite morphogenesis / regulation of long-term neuronal synaptic plasticity / regulation of membrane potential / regulation of respiratory gaseous exchange / regulation of synapse assembly / respiratory gaseous exchange / response to amphetamine / response to calcium ion / response to ethanol / response to fungicide / response to morphine / rhythmic process / sensory perception of pain / small GTPase mediated signal transduction / social behavior / suckling behavior / synaptic transmission / synaptic transmission, glutamatergic / vascular endothelial growth factor receptor signaling pathway / visual learning
Components
cell junction / cell surface / dendrite / dendrite membrane / dendritic branch / dendritic spine / endoplasmic reticulum / excitatory synapse / integral component of plasma membrane / neuron projection / neuronal cell body / neuronal postsynaptic density / NMDA selective glutamate receptor complex / plasma membrane / postsynaptic density / postsynaptic membrane / synapse / synaptic cleft / synaptic vesicle / terminal bouton
General Function
Voltage-gated cation channel activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors (By similarity).
Pfam Domain Function
Transmembrane Regions
560-580 637-657 813-833
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
GenAtlas IDGRIN1
HGNC IDHGNC:4584
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. [PubMed:8406025]
  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. [PubMed:7679115]
  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. [PubMed:7685113]
  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. [PubMed:7622053]
  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. [PubMed:9231706]
  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. [PubMed:15164053]
  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. [PubMed:7926821]
  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. [PubMed:7681588]
  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. [PubMed:8316301]
  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. [PubMed:14732708]
  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. [PubMed:18849881]
  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. [PubMed:10201407]
  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. [PubMed:21376300]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01173OrphenadrineapprovedyesantagonistDetails
DB03929D-Serineapproved, experimentalunknownDetails
DB00142Glutamic Acidapproved, nutraceuticalunknownDetails
DB04620CycloleucineexperimentalunknownDetails
DB05824CNS-5161investigationalunknownDetails
DB01931Dcka, 5,7-Dichlorokynurenic AcidexperimentalunknownDetails
DB00454MeperidineapprovedunknownantagonistDetails
DB08838Agmatineexperimental, investigationalyesantagonistDetails
DB06151Acetylcysteineapproved, investigationalunknownactivatorDetails
DB01043Memantineapproved, investigationalunknownbinderDetails
DB08954Ifenprodilapproved, investigational, withdrawnyesantagonistDetails
DB00659Acamprosateapproved, investigationalyesantagonistDetails
DB06741GavestinelinvestigationalunknownantagonistDetails
DB09481Magnesium carbonateapproved, investigationalunknownblockerDetails
DB09409Magnesium acetate tetrahydrateapprovedunknownligandDetails
DB13146Fluciclovine (18F)approvednoinhibitorDetails
DB04896Milnacipranapproved, investigationalunknowninhibitorDetails
DB00289AtomoxetineapprovedunknownblockerDetails
DB00312Pentobarbitalapproved, investigational, vet_approvedunknownantagonistDetails
DB00418Secobarbitalapproved, vet_approvedunknownantagonistDetails
DB00996Gabapentinapproved, investigationalunknowninhibitorDetails
DB01174Phenobarbitalapproved, investigationalunknownantagonistDetails
DB01708Prasteroneapproved, investigational, nutraceuticalunknownagonistDetails
DB06738KetobemidoneexperimentalunknownantagonistDetails