GRIN2A (glutamate ionotropic receptor NMDA type subunit 2A)[1], ook bekend als LKS, EPND, FESD, NR2A, GluN2A, NMDAR2A, is een proteïne dat bij mensen wordt gecodeerd door het GRIN2A-gen.[2] Met 1464 aminozuren is de normale, proteïne-isovorme GluN2A-subeenheid groot. De korte GluN2A isovormen die specifiek zijn voor primaten worden gevormd door alternatieve splicing en bevatten 1281 aminozuren.[3][4]
Het eiwit dat door dit gen wordt gecodeerd is een subeenheid van de N-methyl-D-aspartaatreceptoren, die heteroisomere eiwitcomplexen zijn met meerdere subeenheden voor het vormen van een ionotrope receptor. Deze subeenheden spelen een sleutelrol in de synaptische plasticiteit, waarvan wordt aangenomen dat ze ten grondslag liggen aan het geheugen en het leren.
↑(en) Kalsi G, Whiting P, Bourdelles BL, Callen D, Barnard EA, Gurling H (February 1998). Localization of the human NMDAR2D receptor subunit gene (GRIN2D) to 19q13.1-qter, the NMDAR2A subunit gene to 16p13.2 (GRIN2A), and the NMDAR2C subunit gene (GRIN2C) to 17q24-q25 using somatic cell hybrid and radiation hybrid mapping panels. Genomics47 (3): 423–425. PMID9480759. DOI: 10.1006/geno.1997.5132.
↑(en) Warming H, Pegasiou CM, Pitera AP, Kariis H, Houghton SD, Kurbatskaya K, Ahmed A, Grundy P, Vajramani G, Bulters D, Altafaj X, Deinhardt K, Vargas-Caballero M (July 2019). A primate-specific short GluN2A-NMDA receptor isoform is expressed in the human brain. Molecular Brain12 (1): 64. PMID31272478. PMC6610962. DOI: 10.1186/s13041-019-0485-9.
↑(en) Herbrechter R, Hube N, Buchholz R, Reiner A (July 2021). Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data. Cellular and Molecular Life Sciences78 (14): 5605–5630. PMID34100982. PMC8257547. DOI: 10.1007/s00018-021-03865-z.
↑(en) Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, Tenesa A, Kusel VI, Sheehan P, Eaaswarkhanth M, Yearout D, Samii A, Roberts JW, Agarwal P, Bordelon Y, Park Y, Wang L, Gao J, Vance JM, Kendler KS, Bacanu SA, Scott WK, Ritz B, Nutt J, Factor SA, Zabetian CP, Payami H (August 2011). Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee. PLOS Genetics7 (8): e1002237. PMID21876681. PMC3158052. DOI: 10.1371/journal.pgen.1002237.
↑(en) Yamada-Fowler N, Fredrikson M, Söderkvist P (June 2014). Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population. PLOS ONE9 (6): e99294. PMID24915238. PMC4051678. DOI: 10.1371/journal.pone.0099294.
↑(en) Venkateswaran S, Myers KA, Smith AC, Beaulieu CL, Schwartzentruber JA, Majewski J, Bulman D, Boycott KM, Dyment DA (July 2014). Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation. Epilepsia55 (7): e75–e79. PMID24903190. DOI: 10.1111/epi.12663.
↑(en) Yuan H, Low CM, Moody OA, Jenkins A, Traynelis SF (July 2015). Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases. Molecular Pharmacology88 (1): 203–217. PMID25904555. PMC4468639. DOI: 10.1124/mol.115.097998.
↑(en) Gardoni F, Mauceri D, Fiorentini C, Bellone C, Missale C, Cattabeni F, Di Luca M (November 2003). CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction. The Journal of Biological Chemistry278 (45): 44745–44752. PMID12933808. DOI: 10.1074/jbc.M303576200.
↑ ab(en) Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Südhof TC (September 1997). Binding of neuroligins to PSD-95. Science277 (5331): 1511–1515. PMID9278515. DOI: 10.1126/science.277.5331.1511.
↑ ab(en) Lim IA, Hall DD, Hell JW (June 2002). Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102. The Journal of Biological Chemistry277 (24): 21697–21711. PMID11937501. DOI: 10.1074/jbc.M112339200.
↑ ab(en) Hou XY, Zhang GY, Yan JZ, Chen M, Liu Y (November 2002). Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia. Brain Research955 (1–2): 123–132. PMID12419528. DOI: 10.1016/s0006-8993(02)03376-0.
↑(en) Satoh K, Yanai H, Senda T, Kohu K, Nakamura T, Okumura N, Matsumine A, Kobayashi S, Toyoshima K, Akiyama T (June 1997). DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95. Genes to Cells2 (6): 415–424. PMID9286858. DOI: 10.1046/j.1365-2443.1997.1310329.x.
↑(en) Sans N, Petralia RS, Wang YX, Blahos J, Hell JW, Wenthold RJ (February 2000). A developmental change in NMDA receptor-associated proteins at hippocampal synapses. The Journal of Neuroscience20 (3): 1260–1271. PMID10648730. PMC6774158. DOI: 10.1523/JNEUROSCI.20-03-01260.2000.
↑ ab(en) Ma J, Zhang GY (September 2003). Lithium reduced N-methyl-D-aspartate receptor subunit 2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 in rat hippocampus following cerebral ischemia. Neuroscience Letters348 (3): 185–189. PMID12932824. DOI: 10.1016/s0304-3940(03)00784-5.
↑(en) Tezuka T, Umemori H, Akiyama T, Nakanishi S, Yamamoto T (January 1999). PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A. Proceedings of the National Academy of Sciences of the United States of America96 (2): 435–440. PMID9892651. PMC15154. DOI: 10.1073/pnas.96.2.435.
↑ ab(en) Takagi N, Cheung HH, Bissoon N, Teves L, Wallace MC, Gurd JW (August 1999). The effect of transient global ischemia on the interaction of Src and Fyn with the N-methyl-D-aspartate receptor and postsynaptic densities: possible involvement of Src homology 2 domains. Journal of Cerebral Blood Flow and Metabolism19 (8): 880–888. PMID10458595. DOI: 10.1097/00004647-199908000-00007.
↑(en) Seabold GK, Burette A, Lim IA, Weinberg RJ, Hell JW (April 2003). Interaction of the tyrosine kinase Pyk2 with the N-methyl-D-aspartate receptor complex via the Src homology 3 domains of PSD-95 and SAP102. The Journal of Biological Chemistry278 (17): 15040–15048. PMID12576483. DOI: 10.1074/jbc.M212825200.
↑(en) Liu Y, Zhang G, Gao C, Hou X (August 2001). NMDA receptor activation results in tyrosine phosphorylation of NMDA receptor subunit 2A(NR2A) and interaction of Pyk2 and Src with NR2A after transient cerebral ischemia and reperfusion. Brain Research909 (1–2): 51–58. PMID11478920. DOI: 10.1016/s0006-8993(01)02619-1.