GRIN2B

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GRIN2B
Protein GRIN2B PDB 1S11.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGRIN2B, GluN2B, MRD6, NMDAR2B, NR2B, hNR3, EIEE27, glutamate ionotropic receptor NMDA type subunit 2B, NR3, DEE27
External IDsOMIM: 138252 MGI: 95821 HomoloGene: 646 GeneCards: GRIN2B
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000834

NM_008171
NM_001363750

RefSeq (protein)

NP_000825

NP_032197
NP_001350679

Location (UCSC)Chr 12: 13.44 – 13.98 MbChr 6: 135.71 – 136.17 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Glutamate [NMDA] receptor subunit epsilon-2, also known as N-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a protein that in humans is encoded by the GRIN2B gene.[5]

NMDA receptors[edit]

N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. The NMDA receptor 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 heterotetramers composed of two molecules of the key receptor subunit NMDAR1 (GRIN1) and two drawn from one or more of the four NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D). The NR2 subunit acts as the agonist binding site for glutamate, one of the predominant excitatory neurotransmitter receptors in the mammalian brain.[6]

Function[edit]

NR2B has been associated with age- and visual-experience-dependent plasticity in the neocortex of rats, where an increased NR2B/NR2A ratio correlates directly with the stronger excitatory LTP in young animals. This is thought to contribute to experience-dependent refinement of developing cortical circuits.[7]

Both mice and rats that were engineered to over-express GRIN2B in their brains have increased mental ability. The "Doogie" mouse had double the learning ability on one measure of learning.[8][9]

Ligands[edit]

  • Besonprodil
  • CERC-301, a selective NR2B receptor antagonist
  • Eliprodil
  • Ethanol - apparent induction of dephosphorylation of the NR2B Tyr1472 residue by STEP, leading to reduced receptor function
  • Ifenprodil
  • Evt 101, a selective NR2B receptor antagonist. This compound was tested as a potentially fast-acting antidepressant.[10] In 2011 it was voluntarily withdrawn from a Phase II clinical study in treatment-resistant depression due to an unsatisfactory toxicity profile.[11]
  • Felbamate, an anticonvulsant that is also a positive allosteric modulator for the GABAA receptor
  • Ro-25-6981 (also known as MI-4), a selective NR2B receptor antagonist
  • Traxoprodil, a selective NR2B receptor antagonist
  • Toluene - noncompetitive antagonist

Interactions[edit]

GRIN2B has been shown to interact with:

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000273079 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030209 - 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. ^ Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (May 1992). "Heteromeric NMDA receptors: molecular and functional distinction of subtypes". Science. 256 (5060): 1217–21. Bibcode:1992Sci...256.1217M. doi:10.1126/science.256.5060.1217. PMID 1350383. S2CID 989677.
  6. ^ "Entrez Gene: GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B".
  7. ^ Yoshimura Y, Ohmura T, Komatsu Y (July 2003). "Two forms of synaptic plasticity with distinct dependence on age, experience, and NMDA receptor subtype in rat visual cortex". The Journal of Neuroscience. 23 (16): 6557–66. doi:10.1523/JNEUROSCI.23-16-06557.2003. PMC 6740618. PMID 12878697.
  8. ^ Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Liu G, Tsien JZ (September 1999). "Genetic enhancement of learning and memory in mice". Nature. 401 (6748): 63–9. Bibcode:1999Natur.401...63T. doi:10.1038/43432. PMID 10485705. S2CID 481884.
  9. ^ Wang D, Cui Z, Zeng Q, Kuang H, Wang LP, Tsien JZ, Cao X (October 2009). "Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats". PLOS ONE. 4 (10): e7486. Bibcode:2009PLoSO...4.7486W. doi:10.1371/journal.pone.0007486. PMC 2759522. PMID 19838302.
  10. ^ "The Effects of a Novel NMDA NR2B-Subtype Selective Antagonist, EVT 101, on Brain Function". NCT00526968. ClinicalTrials.gov. 2008-02-14. Retrieved 2010-08-19.
  11. ^ "Phase II study with NR2B sub-type selective NMDA antagonist in treatment-resistant depression voluntarily terminated". evotec.com. 2011-05-18. Retrieved 2015-08-24.
  12. ^ Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M (January 1997). "Competitive binding of alpha-actinin and calmodulin to the NMDA receptor". Nature. 385 (6615): 439–42. Bibcode:1997Natur.385..439W. doi:10.1038/385439a0. PMID 9009191. S2CID 4266742.
  13. ^ a b c Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y (June 2002). "Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses". American Journal of Physiology. Cell Physiology. 282 (6): C1396–403. doi:10.1152/ajpcell.00615.2001. PMID 11997254.
  14. ^ a b c 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". Science. 277 (5331): 1511–5. doi:10.1126/science.277.5331.1511. PMID 9278515.
  15. ^ a b c Sans N, Prybylowski K, Petralia RS, Chang K, Wang YX, Racca C, Vicini S, Wenthold RJ (June 2003). "NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex". Nature Cell Biology. 5 (6): 520–30. doi:10.1038/ncb990. PMID 12738960. S2CID 13444388.
  16. ^ 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): 21697–711. doi:10.1074/jbc.M112339200. PMID 11937501.
  17. ^ Niethammer M, Valtschanoff JG, Kapoor TM, Allison DW, Weinberg RJ, Craig AM, Sheng M (April 1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90". Neuron. 20 (4): 693–707. doi:10.1016/s0896-6273(00)81009-0. PMID 9581762. S2CID 16068361.
  18. ^ Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (September 1995). "Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95". Science. 269 (5231): 1737–40. Bibcode:1995Sci...269.1737K. doi:10.1126/science.7569905. PMID 7569905.
  19. ^ Jo K, Derin R, Li M, Bredt DS (June 1999). "Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex". The Journal of Neuroscience. 19 (11): 4189–99. doi:10.1523/JNEUROSCI.19-11-04189.1999. PMC 6782594. PMID 10341223.
  20. ^ Nakazawa T, Watabe AM, Tezuka T, Yoshida Y, Yokoyama K, Umemori H, Inoue A, Okabe S, Manabe T, Yamamoto T (July 2003). "p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPases, is involved in the N-methyl-d-aspartate receptor signaling". Molecular Biology of the Cell. 14 (7): 2921–34. doi:10.1091/mbc.E02-09-0623. PMC 165687. PMID 12857875.

Further reading[edit]

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