GRIN2A

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GRIN2A
Protein GRIN2A PDB 2a5s.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGRIN2A, EPND, FESD, GluN2A, LKS, NMDAR2A, NR2A, glutamate ionotropic receptor NMDA type subunit 2A
External IDsOMIM: 138253 MGI: 95820 HomoloGene: 645 GeneCards: GRIN2A
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000833
NM_001134407
NM_001134408

NM_008170

RefSeq (protein)

NP_000824
NP_001127879
NP_001127880

NP_032196

Location (UCSC)Chr 16: 9.75 – 10.18 MbChr 16: 9.39 – 9.81 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Glutamate [NMDA] receptor subunit epsilon-1 is a protein that in humans is encoded by the GRIN2A gene.[5] The canonical GluN2A subunit isoform encompasses 1464 amino acids. Alternative splicing can generate a primate-specific GluN2A-short isoform (1281 amino acids).[6][7]

Function[edit]

N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heteromers composed of the key receptor subunit NMDAR1 (GRIN1) and 1 or more of the 4 NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D).[8]

Associations[edit]

Variants of the gene are associated with the protective effect of coffee on Parkinson's disease.[9][10]

Mutations in GRIN2A are associated to refractory epilepsy.[11]

Whole exome/genome sequencing has led to the discovery of an association between mutations in GRIN2A and a wide variety of neurological diseases, including epilepsy, intellectual disability, autism spectrum disorders, developmental delay, and schizophrenia.[12]

Interactions[edit]

GRIN2A has been shown to interact with:

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000183454 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000059003 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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". Genomics. 47 (3): 423–425. doi:10.1006/geno.1997.5132. PMID 9480759.
  6. ^ Warming H, Pegasiou CM, Pitera AP, Kariis H, Houghton SD, Kurbatskaya K, et al. (July 2019). "A primate-specific short GluN2A-NMDA receptor isoform is expressed in the human brain". Molecular Brain. 12 (1): 64. doi:10.1186/s13041-019-0485-9. PMC 6610962. PMID 31272478.
  7. ^ 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 Sciences. 78 (14): 5605–5630. doi:10.1007/s00018-021-03865-z. PMC 8257547. PMID 34100982.
  8. ^ "Entrez Gene: GRIN2A glutamate receptor, ionotropic, N-methyl D-aspartate 2A".
  9. ^ Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, et al. (August 2011). "Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee". PLOS Genetics. 7 (8): e1002237. doi:10.1371/journal.pgen.1002237. PMC 3158052. PMID 21876681.
  10. ^ Yamada-Fowler N, Fredrikson M, Söderkvist P (June 2014). "Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population". PLOS ONE. 9 (6): e99294. Bibcode:2014PLoSO...999294Y. doi:10.1371/journal.pone.0099294. PMC 4051678. PMID 24915238.
  11. ^ Venkateswaran S, Myers KA, Smith AC, Beaulieu CL, Schwartzentruber JA, Majewski J, et al. (July 2014). "Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation". Epilepsia. 55 (7): e75–e79. doi:10.1111/epi.12663. PMID 24903190. S2CID 205116246.
  12. ^ Yuan H, Low CM, Moody OA, Jenkins A, Traynelis SF (July 2015). "Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases". Molecular Pharmacology. 88 (1): 203–217. doi:10.1124/mol.115.097998. PMC 4468639. PMID 25904555.
  13. ^ 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 Chemistry. 278 (45): 44745–44752. doi:10.1074/jbc.M303576200. PMID 12933808.
  14. ^ a b Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, et al. (September 1997). "Binding of neuroligins to PSD-95". Science. 277 (5331): 1511–1515. doi:10.1126/science.277.5331.1511. PMID 9278515.
  15. ^ a b 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 Chemistry. 277 (24): 21697–21711. doi:10.1074/jbc.M112339200. PMID 11937501.
  16. ^ a b 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 Research. 955 (1–2): 123–132. doi:10.1016/s0006-8993(02)03376-0. PMID 12419528. S2CID 85751.
  17. ^ Satoh K, Yanai H, Senda T, Kohu K, Nakamura T, Okumura N, et al. (June 1997). "DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95". Genes to Cells. 2 (6): 415–424. doi:10.1046/j.1365-2443.1997.1310329.x. PMID 9286858. S2CID 8934092.
  18. ^ 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 Neuroscience. 20 (3): 1260–1271. doi:10.1523/JNEUROSCI.20-03-01260.2000. PMC 6774158. PMID 10648730.
  19. ^ a b 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 Letters. 348 (3): 185–189. doi:10.1016/s0304-3940(03)00784-5. PMID 12932824. S2CID 40684016.
  20. ^ 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 America. 96 (2): 435–440. Bibcode:1999PNAS...96..435T. doi:10.1073/pnas.96.2.435. PMC 15154. PMID 9892651.
  21. ^ a b 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 Metabolism. 19 (8): 880–888. doi:10.1097/00004647-199908000-00007. PMID 10458595.
  22. ^ Kurschner C, Yuzaki M (September 1999). "Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein". The Journal of Neuroscience. 19 (18): 7770–7780. doi:10.1523/JNEUROSCI.19-18-07770.1999. PMC 6782450. PMID 10479680.
  23. ^ 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 Chemistry. 278 (17): 15040–15048. doi:10.1074/jbc.M212825200. PMID 12576483.
  24. ^ 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 Research. 909 (1–2): 51–58. doi:10.1016/s0006-8993(01)02619-1. PMID 11478920. S2CID 21062909.

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.