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Gene and Protein Information ![]() |
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Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 3 | 1 | 938 | 9q34.3 | GRIN1 | glutamate ionotropic receptor NMDA type subunit 1 | |
Mouse | 3 | 1 | 938 | 2 17.14 cM | Grin1 | glutamate receptor, ionotropic, NMDA1 (zeta 1) | |
Rat | 3 | 1 | 938 | 3p13 | Grin1 | glutamate ionotropic receptor NMDA type subunit 1 |
Previous and Unofficial Names ![]() |
NMDAR1 | GluRzeta1 | NMDA-R1 | glutamate receptor, ionotropic, NMDA1 (zeta 1) | glutamate receptor |
Database Links ![]() |
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Alphafold | Q05586 (Hs), P35438 (Mm), P35439 (Rn) |
ChEMBL Target | CHEMBL2015 (Hs), CHEMBL3885583 (Mm), CHEMBL330 (Rn) |
DrugBank Target | Q05586 (Hs), Q05586 (Hs) |
Ensembl Gene | ENSG00000176884 (Hs), ENSMUSG00000026959 (Mm), ENSRNOG00000011726 (Rn) |
Entrez Gene | 2902 (Hs), 14810 (Mm), 24408 (Rn) |
Human Protein Atlas | ENSG00000176884 (Hs) |
KEGG Gene | hsa:2902 (Hs), mmu:14810 (Mm), rno:24408 (Rn) |
OMIM | 138249 (Hs) |
Orphanet | ORPHA282786 (Hs) |
Pharos | Q05586 (Hs) |
RefSeq Nucleotide | NM_007327 (Hs), NM_008169 (Mm), NM_017010 (Rn) |
RefSeq Protein | NP_015566 (Hs), NP_032195 (Mm), NP_058706 (Rn) |
UniProtKB | Q05586 (Hs), P35438 (Mm), P35439 (Rn) |
Wikipedia | GRIN1 (Hs) |
Selected 3D Structures ![]() |
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Natural/Endogenous Ligands ![]() |
D-aspartic acid |
D-serine |
glycine |
L-aspartic acid |
L-glutamic acid |
Download all structure-activity data for this target as a CSV file
Agonists | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
GV196771A has two binding sites on rat GluN1 subunits expressed in HEK293 cells. The low affinity site has a Ki value of 121-153 nM depending on the splice variant tested [2]. |
Immunopharmacology Comments |
Autoantibodies that target GluN1 cause anti-NMDA receptor encephalitis [8,11,14]. Approximately 50% of cases occur in the presence ovarian teratoma. The condition can manifest postviral infection [12], but many cases are idiopathic [7]. Anti-NMDA receptor encephalitis has been identified in a non-human mammal [13], and fulminant disease can be induced in a mouse model by active immunisation with conformationally stabilised, native-like NMDA holoreceptors (GluN1-GluN2B tetramers embedded in liposomes) [4]. |
Clinically-Relevant Mutations and Pathophysiology ![]() |
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1. Chazot PL, Reiss C, Chopra B, Stephenson FA. (1998) [3H]MDL 105,519 binds with equal high affinity to both assembled and unassembled NR1 subunits of the NMDA receptor. Eur J Pharmacol, 353 (1): 137-40. [PMID:9721050]
2. Chopra B, Chazot PL, Stephenson FA. (2000) Characterization of the binding of two novel glycine site antagonists to cloned NMDA receptors: evidence for two pharmacological classes of antagonists. Br J Pharmacol, 130 (1): 65-72. [PMID:10780999]
3. Deur C, Agrawal AK, Baum H, Booth J, Bove S, Brieland J, Bunker A, Connolly C, Cornicelli J, Dumin J et al.. (2007) N-(6,7-dichloro-2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-N-alkylsulfonamides as peripherally restricted N-methyl-D-aspartate receptor antagonists for the treatment of pain. Bioorg Med Chem Lett, 17 (16): 4599-603. [PMID:17562362]
4. Jones BE, Tovar KR, Goehring A, Jalali-Yazdi F, Okada NJ, Gouaux E, Westbrook GL. (2019) Autoimmune receptor encephalitis in mice induced by active immunization with conformationally stabilized holoreceptors. Sci Transl Med, 11 (500). DOI: 10.1126/scitranslmed.aaw0044 [PMID:31292262]
5. Karakas E, Furukawa H. (2014) Crystal structure of a heterotetrameric NMDA receptor ion channel. Science, 344 (6187): 992-7. [PMID:24876489]
6. Karakas E, Simorowski N, Furukawa H. (2011) Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors. Nature, 475 (7355): 249-53. [PMID:21677647]
7. Kayser MS, Dalmau J. (2016) Anti-NMDA receptor encephalitis, autoimmunity, and psychosis. Schizophr Res, 176 (1): 36-40. [PMID:25458857]
8. Kelleher E, Barry H, Cotter DR, Corvin A, Murphy KC. (2020) Autoantibodies and Psychosis. Curr Top Behav Neurosci, 44: 85-123. [PMID:31292938]
9. Kulagowski JJ, Baker R, Curtis NR, Leeson PD, Mawer IM, Moseley AM, Ridgill MP, Rowley M, Stansfield I, Foster AC et al.. (1994) 3'-(Arylmethyl)- and 3'-(aryloxy)-3-phenyl-4-hydroxyquinolin-2(1H)-ones: orally active antagonists of the glycine site on the NMDA receptor. J Med Chem, 37 (10): 1402-5. [PMID:8182696]
10. Leeson PD, Carling RW, Moore KW, Moseley AM, Smith JD, Stevenson G, Chan T, Baker R, Foster AC, Grimwood S et al.. (1992) 4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor. J Med Chem, 35 (11): 1954-68. [PMID:1534584]
11. Newman MP, Blum S, Wong RC, Scott JG, Prain K, Wilson RJ, Gillis D. (2016) Autoimmune encephalitis. Intern Med J, 46 (2): 148-57. [PMID:26899887]
12. Prüss H. (2017) Postviral autoimmune encephalitis: manifestations in children and adults. Curr Opin Neurol, 30 (3): 327-333. [PMID:28234798]
13. Prüss H, Leubner J, Wenke NK, Czirják GÁ, Szentiks CA, Greenwood AD. (2015) Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut. Sci Rep, 5: 12805. [PMID:26313569]
14. Venkatesan A, Adatia K. (2017) Anti-NMDA-Receptor Encephalitis: From Bench to Clinic. ACS Chem Neurosci, 8 (12): 2586-2595. [PMID:29077387]
Bettler B, Collingridge GL, Dingledine R, Heinemann SF, Hollmann M, Lerma J, Lodge D, Mayer M, Mishina M, Mulle C, Nakanishi S, Olsen R, Peineau S, Peters JA, Seeburg P, Spedding M, Watkins JC. Ionotropic glutamate receptors in GtoPdb v.2023.1. IUPHAR/BPS Guide to Pharmacology CITE. 2023; 2023(1). Available from: https://doi.org/10.2218/gtopdb/F75/2023.1.