GRIN2A

Glutamate receptor, ionotropic, N-methyl D-aspartate 2A
PDB rendering based on 2a5s.
Available structures PDB 2a5s, 2a5t
Identifiers
Symbols	GRIN2A; NMDAR2A; NR2A
External IDs	OMIM: 138253 MGI: 95820 HomoloGene: 645 GeneCards: GRIN2A Gene
Gene Ontology Molecular function • receptor activity • N-methyl-D-aspartate selective glutamate receptor activity • transporter activity • extracellular-glutamate-gated ion channel activity • calcium channel activity • protein binding • zinc ion binding • glutamate binding • protein kinase binding • voltage-gated cation channel activity • protein complex binding • glutamate receptor binding • neurotransmitter binding • metal ion binding • cell adhesion molecule binding • ATPase binding Cellular component • plasma membrane • integral to plasma membrane • postsynaptic density • flotillin complex • N-methyl-D-aspartate selective glutamate receptor complex • synaptosome • cell junction • outer membrane-bounded periplasmic space • presynaptic membrane • neuron projection • terminal button • dendritic spine • synapse • postsynaptic membrane Biological process • regulation of action potential • startle response • response to amphetamine • transport • ion transport • glutamate signaling pathway • synaptic transmission • learning or memory • learning • memory • protein localization • visual learning • response to light stimulus • response to wounding • response to carbohydrate stimulus • positive regulation of cell death • response to organic cyclic compound • spinal cord development • hippocampus development • cerebral cortex development • neurogenesis • sleep • directional locomotion • ionotropic glutamate receptor signaling pathway • negative regulation of protein catabolic process • response to cocaine • dopamine metabolic process • serotonin metabolic process • response to drug • positive regulation of apoptosis • response to ethanol • regulation of synaptic plasticity • regulation of long-term neuronal synaptic plasticity • rhythmic process • response to calcium ion • response to methylmercury • response to other organism • regulation of sensory perception of pain • regulation of excitatory postsynaptic membrane potential • response to ammonium ion • response to fungicide • cellular response to amino acid stimulus • cellular response to magnesium ion • cellular response to manganese ion • cellular response to zinc ion • cellular response to dsRNA • cellular response to growth factor stimulus • cellular response to lipid • cellular response to protein stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2903	14811
Ensembl	ENSG00000183454	ENSMUSG00000059003
UniProt	Q12879	P35436
RefSeq (mRNA)	NM_000833.3	NM_008170.2
RefSeq (protein)	NP_000824.1	NP_032196.2
Location (UCSC)	Chr 16: 9.85 – 10.28 Mb	Chr 16: 9.58 – 10 Mb
PubMed search	[1]	[2]

Glutamate [NMDA] receptor subunit epsilon-1 is a protein that in humans is encoded by the GRIN2A gene.^[1]

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).^[2]

Interactions

GRIN2A has been shown to interact with FYN,^[3][4][5][6] DLG4,^{[5][7][8][9][10]} DLG3,^[7][10] DLG1,^[11] Src,^[3][6] PTK2B^[12][13] and Interleukin 16.^[14]

See also

• Glutamate receptor
• NMDA receptor

References

1. ^ Kalsi G, Whiting P, Bourdelles BL, Callen D, Barnard EA, Gurling H (Apr 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): 423–5. doi:10.1006/geno.1997.5132. PMID 9480759. 
2. ^ "Entrez Gene: GRIN2A glutamate receptor, ionotropic, N-methyl D-aspartate 2A". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2903. 
3. ^ ^{a b} Ma, Juan; Zhang Guang-Yi (Sep. 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". Neurosci. Lett. (Ireland) 348 (3): 185–9. doi:10.1016/S0304-3940(03)00784-5. ISSN 0304-3940. PMID 12932824. 
4. ^ Tezuka, T; Umemori H, Akiyama T, Nakanishi S, Yamamoto T (Jan. 1999). "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (2): 435–40. doi:10.1073/pnas.96.2.435. ISSN 0027-8424. PMC 15154. PMID 9892651. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15154. 
5. ^ ^{a b} Hou, Xiao-Yu; Zhang Guang-Yi, Yan Jing-Zhi, Chen Min, Liu Yong (Nov. 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 Res. (Netherlands) 955 (1-2): 123–32. doi:10.1016/S0006-8993(02)03376-0. ISSN 0006-8993. PMID 12419528. 
6. ^ ^{a b} Takagi, N; Cheung H H, Bissoon N, Teves L, Wallace M C, Gurd J W (Aug. 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". J. Cereb. Blood Flow Metab. (UNITED STATES) 19 (8): 880–8. doi:10.1097/00004647-199908000-00007. ISSN 0271-678X. PMID 10458595. 
7. ^ ^{a b} Irie, M; Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl T W, Südhof T C (Sep. 1997). "Binding of neuroligins to PSD-95". Science (UNITED STATES) 277 (5331): 1511–5. doi:10.1126/science.277.5331.1511. ISSN 0036-8075. PMID 9278515. 
8. ^ Satoh, K; Yanai H, Senda T, Kohu K, Nakamura T, Okumura N, Matsumine A, Kobayashi S, Toyoshima K, Akiyama T (Jun. 1997). "DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95". Genes Cells (ENGLAND) 2 (6): 415–24. doi:10.1046/j.1365-2443.1997.1310329.x. ISSN 1356-9597. PMID 9286858. 
9. ^ Sans, N; Petralia R S, Wang Y X, Blahos J, Hell J W, Wenthold R J (Feb. 2000). "A developmental change in NMDA receptor-associated proteins at hippocampal synapses". J. Neurosci. (UNITED STATES) 20 (3): 1260–71. PMID 10648730. 
10. ^ ^{a b} Lim, Indra Adi; Hall Duane D, Hell Johannes W (Jun. 2002). "Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102". J. Biol. Chem. (United States) 277 (24): 21697–711. doi:10.1074/jbc.M112339200. ISSN 0021-9258. PMID 11937501. 
11. ^ Gardoni, Fabrizio; Mauceri Daniela, Fiorentini Chiara, Bellone Camilla, Missale Cristina, Cattabeni Flaminio, Di Luca Monica (Nov. 2003). "CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction". J. Biol. Chem. (United States) 278 (45): 44745–52. doi:10.1074/jbc.M303576200. ISSN 0021-9258. PMID 12933808. 
12. ^ Seabold, Gail K; Burette Alain, Lim Indra A, Weinberg Richard J, Hell Johannes W (Apr. 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". J. Biol. Chem. (United States) 278 (17): 15040–8. doi:10.1074/jbc.M212825200. ISSN 0021-9258. PMID 12576483. 
13. ^ Liu, Y; Zhang G, Gao C, Hou X (Aug. 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 Res. (Netherlands) 909 (1-2): 51–8. doi:10.1016/S0006-8993(01)02619-1. ISSN 0006-8993. PMID 11478920. 
14. ^ Kurschner, C; Yuzaki M (Sep. 1999). "Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein". J. Neurosci. (UNITED STATES) 19 (18): 7770–80. PMID 10479680. 

Further reading

• Schröder HC, Perovic S, Kavsan V, et al. (1998). "Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death.". Neurotoxicology 19 (4-5): 683–8. PMID 9745929. 
• King JE, Eugenin EA, Buckner CM, Berman JW (2006). "HIV tat and neurotoxicity.". Microbes Infect. 8 (5): 1347–57. doi:10.1016/j.micinf.2005.11.014. PMID 16697675. 
• Monyer H, Sprengel R, Schoepfer R, et al. (1992). "Heteromeric NMDA receptors: molecular and functional distinction of subtypes.". Science 256 (5060): 1217–21. doi:10.1126/science.256.5060.1217. PMID 1350383. 
• Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (1995). "Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95.". Science 269 (5231): 1737–40. doi:10.1126/science.7569905. PMID 7569905. 
• Magnuson DS, Knudsen BE, Geiger JD, et al. (1995). "Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity.". Ann. Neurol. 37 (3): 373–80. doi:10.1002/ana.410370314. PMID 7695237. 
• Sakimura K, Kutsuwada T, Ito I, et al. (1995). "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon 1 subunit.". Nature 373 (6510): 151–5. doi:10.1038/373151a0. PMID 7816096. 
• Foldes RL, Adams SL, Fantaske RP, Kamboj RK (1994). "Human N-methyl-D-aspartate receptor modulatory subunit hNR2A: cloning and sequencing of the cDNA and primary structure of the protein.". Biochim. Biophys. Acta 1223 (1): 155–9. doi:10.1016/0167-4889(94)90086-8. PMID 8061049. 
• Sheng M, Cummings J, Roldan LA, et al. (1994). "Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.". Nature 368 (6467): 144–7. doi:10.1038/368144a0. PMID 8139656. 
• Roche KW, Raymond LA, Blackstone C, Huganir RL (1994). "Transmembrane topology of the glutamate receptor subunit GluR6.". J. Biol. Chem. 269 (16): 11679–82. PMID 8163463. 
• Takano H, Onodera O, Tanaka H, et al. (1994). "Chromosomal localization of the epsilon 1, epsilon 3 and zeta 1 subunit genes of the human NMDA receptor channel.". Biochem. Biophys. Res. Commun. 197 (2): 922–6. doi:10.1006/bbrc.1993.2567. PMID 8267632. 
• Lannuzel A, Lledo PM, Lamghitnia HO, et al. (1996). "HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i increase, alter [Ca2+]i homeostasis and induce neurotoxicity in human embryonic neurons.". Eur. J. Neurosci. 7 (11): 2285–93. doi:10.1111/j.1460-9568.1995.tb00649.x. PMID 8563977. 
• Corasaniti MT, Melino G, Navarra M, et al. (1996). "Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is prevented by NMDA receptor antagonists and inhibitors of nitric oxide and cyclooxygenase.". Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration 4 (3): 315–21. PMID 8581564. 
• Niethammer M, Kim E, Sheng M (1996). "Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases.". J. Neurosci. 16 (7): 2157–63. PMID 8601796. 
• Pittaluga A, Pattarini R, Severi P, Raiteri M (1996). "Human brain N-methyl-D-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120.". AIDS 10 (5): 463–8. doi:10.1097/00002030-199605000-00003. PMID 8724036. 
• Hess SD, Daggett LP, Crona J, et al. (1996). "Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors.". J. Pharmacol. Exp. Ther. 278 (2): 808–16. PMID 8768735. 
• Wu P, Price P, Du B, et al. (1996). "Direct cytotoxicity of HIV-1 envelope protein gp120 on human NT neurons.". Neuroreport 7 (5): 1045–9. doi:10.1097/00001756-199604100-00018. PMID 8804048. 
• Bennett BA, Rusyniak DE, Hollingsworth CK (1996). "HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures.". Brain Res. 705 (1-2): 168–76. doi:10.1016/0006-8993(95)01166-8. PMID 8821747. 
• Toggas SM, Masliah E, Mucke L (1996). "Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine.". Brain Res. 706 (2): 303–7. doi:10.1016/0006-8993(95)01197-8. PMID 8822372. 
• Dreyer EB, Lipton SA (1996). "The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid.". Eur. J. Neurosci. 7 (12): 2502–7. doi:10.1111/j.1460-9568.1995.tb01048.x. PMID 8845955. 
• Raber J, Toggas SM, Lee S, et al. (1997). "Central nervous system expression of HIV-1 Gp120 activates the hypothalamic-pituitary-adrenal axis: evidence for involvement of NMDA receptors and nitric oxide synthase.". Virology 226 (2): 362–73. doi:10.1006/viro.1996.0664. PMID 8955056. 

Ionotropic glutamates

Ligand-gated only	AMPA (1, 2, 3, 4) · Kainate (1, 2, 3, 4, 5)
Voltage- and ligand-gated	NMDA (1, 2A, 2B, 2C, 2D, 3A, 3B, L1A, L1B)
‘Orphan’	GluD (δ1, δ2)

ATP-gated channels

Purinergic receptors

P2X (1, 2, 3, 4, 5, 6, 7)

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)