GRIN1

GRIN1
Identifiers
Aliases	GRIN1, GluN1, MRD8, NMDA1, NMDAR1, NR1, NMD-R1, glutamate ionotropic receptor NMDA type subunit 1, NDHMSR, NDHMSD, DEE101
External IDs	OMIM: 138249; MGI: 95819; GeneCards: GRIN1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2HQW, 2NR1, 3BYA, 5H8N, 5H8H, 5H8Q, 5H8F, 5I2N, 5I2K, 5KCJ, 5KDT
Gene location (Human)
Chr.	Chromosome 9 (human)
End	137,168,756 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	25,209,199 bp
RNA expression pattern
	Top expressed in
	right hemisphere of cerebellum; ; right frontal lobe; ; anterior cingulate cortex; ; nucleus accumbens; ; prefrontal cortex; ; Brodmann area 9; ; putamen; ; amygdala; ; caudate nucleus; ; Brodmann area 10;
	Top expressed in
	perirhinal cortex; ; entorhinal cortex; ; primary visual cortex; ; superior frontal gyrus; ; CA3 field; ; dentate gyrus of hippocampal formation granule cell; ; cerebellar cortex; ; superior colliculus; ; molecular layer of cerebellar cortex; ; primary motor cortex;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	calcium ion binding; signaling receptor binding; glycine binding; calmodulin binding; protein binding; cation channel activity; extracellularly glutamate-gated ion channel activity; glutamate binding; calcium channel activity; NMDA glutamate receptor activity; ion channel activity; ionotropic glutamate receptor activity; neurotransmitter binding; transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; amyloid-beta binding; glutamate-gated calcium ion channel activity; signaling receptor activity; protein-containing complex binding;
Cellular component	cytoplasm; postsynaptic membrane; membrane; synapse; NMDA selective glutamate receptor complex; neuron projection; synaptic vesicle; dendritic spine; cell surface; endoplasmic reticulum; integral component of membrane; plasma membrane; postsynaptic density; integral component of plasma membrane; excitatory synapse; cell junction; dendrite; synaptic cleft; terminal bouton; postsynaptic density membrane; synaptic membrane; glutamatergic synapse; integral component of postsynaptic density membrane;
Biological process	negative regulation of neuron apoptotic process; pons maturation; synaptic transmission, glutamatergic; regulation of respiratory gaseous exchange; response to amphetamine; regulation of membrane potential; regulation of synapse assembly; learning; positive regulation of excitatory postsynaptic potential; response to ethanol; calcium ion transport; suckling behavior; prepulse inhibition; male mating behavior; regulation of long-term neuronal synaptic plasticity; adult locomotory behavior; regulation of neuron apoptotic process; ion transport; memory; regulation of axonogenesis; neuromuscular process; ionotropic glutamate receptor signaling pathway; excitatory postsynaptic potential; learning or memory; social behavior; regulation of neuronal synaptic plasticity; associative learning; startle response; calcium ion homeostasis; cation transport; cellular calcium ion homeostasis; cation transmembrane transport; respiratory gaseous exchange by respiratory system; regulation of synaptic plasticity; response to morphine; propylene metabolic process; conditioned taste aversion; cerebral cortex development; transport; sensory perception of pain; olfactory learning; regulation of cell communication; visual learning; ephrin receptor signaling pathway; MAPK cascade; regulation of dendrite morphogenesis; ion transmembrane transport; long-term memory; positive regulation of apoptotic process; positive regulation of transcription by RNA polymerase II; positive regulation of GTPase activity; calcium ion transmembrane transport; regulation of ion transmembrane transport; brain development; positive regulation of calcium ion transport into cytosol; calcium-mediated signaling; protein heterotetramerization; calcium ion transmembrane import into cytosol; excitatory chemical synaptic transmission; positive regulation of reactive oxygen species biosynthetic process; protein localization to postsynaptic membrane; cellular response to amyloid-beta; response to glycine; positive regulation of cysteine-type endopeptidase activity; regulation of NMDA receptor activity;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	2902
	14810
	ENSG00000176884
	ENSMUSG00000026959
	Q05586
	P35438
	NM_000832; NM_001185090; NM_001185091; NM_007327; NM_021569
NM_001177656; NM_001177657; NM_008169; NM_001372558; NM_001372559;
	NM_001372560; NM_001372561; NM_001372562
	NP_000823; NP_001172019; NP_001172020; NP_015566; NP_067544
NP_001171127; NP_001171128; NP_032195; NP_001359487; NP_001359488;
	NP_001359489; NP_001359490; NP_001359491
	Wikidata
View/Edit Human	View/Edit Mouse

Glutamate Receptor Ionotropic, [NMDA] subunit zeta-1 is a protein that in humans is encoded by the GRIN1 gene.

Gene

The gene consists of 21 exons and undergoes alternative splicing, producing transcript variants that encode different GluN1 isoforms. Alternative splicing affects both the N-terminal region, through inclusion or exclusion of exon 5, and the C-terminal region. The sequence of exon 5 is identical in vertebrates, and its alternative splicing has been demonstrated in humans, mice and rats.

Structure

The encoded protein, GluN1, is a subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily. These receptors are heteromeric protein complexes whose subunits assemble to form a ligand-gated ion channel.

GluN1 exists as eight splice isoforms:

GluN1-1a
GluN1-1b
GluN1-2a
GluN1-2b
GluN1-3a
GluN1-3b
GluN1-4a
GluN1-4b

GluN1-1a, GluN1-1b, GluN1-2a and GluN1-2b contain the C2 cassette, whereas GluN1-3a, GluN1-3b, GluN1-4a and GluN1-4b contain the alternative C2' cassette.

Function

GluN1 is obligatory for NMDA receptor function and contains the binding site for the co-agonist glycine. NMDA receptors play a key role in synaptic plasticity, which is believed to underlie learning and memory.

Cell-specific factors are thought to regulate the expression of GluN1 isoforms, potentially contributing to the functional diversity of NMDA receptors. GluN1-1a is the most abundantly expressed isoform across the central nervous system (CNS). Activity-dependent alternative splicing of the C-terminal region regulates GluN1 export from the endoplasmic reticulum and delivery of NMDA receptors to synapses. The functional significance of C-terminal splice variants varies across the CNS.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000176884 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026959 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, et al. (May 1992). "Heteromeric NMDA receptors: molecular and functional distinction of subtypes". Science. 256 (5060). New York, N.Y.: 1217–1221. Bibcode:1992Sci...256.1217M. doi:10.1126/science.256.5060.1217. PMID 1350383. S2CID 989677.
↑ "Entrez Gene: GRIN1 glutamate receptor, ionotropic, N-methyl D-aspartate 1".
↑ Sengar AS, Li H, Zhang W, Leung C, Ramani AK, Saw NM, et al. (December 2019). "Control of Long-Term Synaptic Potentiation and Learning by Alternative Splicing of the NMDA Receptor Subunit GluN1". Cell Reports. 29 (13): 4285–4294.e5. doi:10.1016/j.celrep.2019.11.087. PMID 31875540. S2CID 209482250.
↑ Liu H, Wang H, Peterson M, Zhang W, Hou G, Zhang ZW (October 2019). "N-terminal alternative splicing of GluN1 regulates the maturation of excitatory synapses and seizure susceptibility". Proceedings of the National Academy of Sciences of the United States of America. 116 (42): 21207–21212. Bibcode:2019PNAS..11621207L. doi:10.1073/pnas.1905721116. PMC 6800312. PMID 31570583.
↑ 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.
↑ Manta G, Spathis AD, Taraviras S, Kouvelas ED, Mitsacos A (August 2011). "Age and visual experience-dependent expression of NMDAR1 splice variants in rat retina". Neurochemical Research. 36 (8): 1417–1425. doi:10.1007/s11064-011-0467-5. PMID 21499738. S2CID 11853676.
↑ Mu Y, Otsuka T, Horton AC, Scott DB, Ehlers MD (October 2003). "Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptors". Neuron. 40 (3): 581–594. doi:10.1016/s0896-6273(03)00676-7. PMID 14642281.

Lin JW, Wyszynski M, Madhavan R, Sealock R, Kim JU, Sheng M (March 1998). "Yotiao, a novel protein of neuromuscular junction and brain that interacts with specific splice variants of NMDA receptor subunit NR1". The Journal of Neuroscience. 18 (6): 2017–2027. doi:10.1523/JNEUROSCI.18-06-02017.1998. PMC 6792910. PMID 9482789.
Schröder HC, Perovic S, Kavsan V, Ushijima H, Müller WE (1998). "Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death". Neurotoxicology. 19 (4–5): 683–688. PMID 9745929.
Adriani W, Felici A, Sargolini F, Roullet P, Usiello A, Oliverio A, et al. (November 1998). "N-methyl-D-aspartate and dopamine receptor involvement in the modulation of locomotor activity and memory processes". Experimental Brain Research. 123 (1–2): 52–59. doi:10.1007/s002210050544. PMID 9835392. S2CID 8388670.
Dingledine R, Borges K, Bowie D, Traynelis SF (March 1999). "The glutamate receptor ion channels". Pharmacological Reviews. 51 (1): 7–61. doi:10.1016/S0031-6997(24)01394-2. PMID 10049997.
King JE, Eugenin EA, Buckner CM, Berman JW (April 2006). "HIV tat and neurotoxicity". Microbes and Infection. 8 (5): 1347–1357. doi:10.1016/j.micinf.2005.11.014. PMID 16697675.
Zimmer M, Fink TM, Franke Y, Lichter P, Spiess J (July 1995). "Cloning and structure of the gene encoding the human N-methyl-D-aspartate receptor (NMDAR1)". Gene. 159 (2): 219–223. doi:10.1016/0378-1119(95)00044-7. PMID 7622053.
Karp SJ, Masu M, Eki T, Ozawa K, Nakanishi S (February 1993). "Molecular cloning and chromosomal localization of the key subunit of the human N-methyl-D-aspartate receptor". The Journal of Biological Chemistry. 268 (5): 3728–3733. doi:10.1016/S0021-9258(18)53754-6. PMID 7679115.
Younkin DP, Tang CM, Hardy M, Reddy UR, Shi QY, Pleasure SJ, et al. (March 1993). "Inducible expression of neuronal glutamate receptor channels in the NT2 human cell line". Proceedings of the National Academy of Sciences of the United States of America. 90 (6): 2174–2178. Bibcode:1993PNAS...90.2174Y. doi:10.1073/pnas.90.6.2174. PMC 46048. PMID 7681588.
Planells-Cases R, Sun W, Ferrer-Montiel AV, Montal M (June 1993). "Molecular cloning, functional expression, and pharmacological characterization of an N-methyl-D-aspartate receptor subunit from human brain". Proceedings of the National Academy of Sciences of the United States of America. 90 (11): 5057–5061. Bibcode:1993PNAS...90.5057P. doi:10.1073/pnas.90.11.5057. PMC 46653. PMID 7685113.
Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (March 1995). "Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity". Annals of Neurology. 37 (3): 373–380. doi:10.1002/ana.410370314. PMID 7695237. S2CID 24405132.
Foldes RL, Rampersad V, Kamboj RK (September 1994). "Cloning and sequence analysis of additional splice variants encoding human N-methyl-D-aspartate receptor (hNR1) subunits". Gene. 147 (2): 303–304. doi:10.1016/0378-1119(94)90089-2. PMID 7926821.
Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY (March 1994). "Changing subunit composition of heteromeric NMDA receptors during development of rat cortex". Nature. 368 (6467): 144–147. Bibcode:1994Natur.368..144S. doi:10.1038/368144a0. PMID 8139656. S2CID 4332025.
Tingley WG, Roche KW, Thompson AK, Huganir RL (July 1993). "Regulation of NMDA receptor phosphorylation by alternative splicing of the C-terminal domain". Nature. 364 (6432): 70–73. Bibcode:1993Natur.364...70T. doi:10.1038/364070a0. PMID 8316301. S2CID 4322831.
Foldes RL, Rampersad V, Kamboj RK (September 1993). "Cloning and sequence analysis of cDNAs encoding human hippocampus N-methyl-D-aspartate receptor subunits: evidence for alternative RNA splicing". Gene. 131 (2): 293–298. doi:10.1016/0378-1119(93)90309-Q. PMID 8406025.
Collins C, Duff C, Duncan AM, Planells-Cases R, Sun W, Norremolle A, et al. (July 1993). "Mapping of the human NMDA receptor subunit (NMDAR1) and the proposed NMDA receptor glutamate-binding subunit (NMDARA1) to chromosomes 9q34.3 and chromosome 8, respectively". Genomics. 17 (1): 237–239. doi:10.1006/geno.1993.1311. PMID 8406459.
Lannuzel A, Lledo PM, Lamghitnia HO, Vincent JD, Tardieu M (November 1995). "HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i increase, alter [Ca2+]i homeostasis and induce neurotoxicity in human embryonic neurons". The European Journal of Neuroscience. 7 (11): 2285–2293. doi:10.1111/j.1460-9568.1995.tb00649.x. PMID 8563977. S2CID 27201873.
Corasaniti MT, Melino G, Navarra M, Garaci E, Finazzi-Agrò A, Nisticò G (September 1995). "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. 4 (3): 315–321. doi:10.1016/1055-8330(95)90021-7. PMID 8581564.
Ehlers MD, Zhang S, Bernhadt JP, Huganir RL (March 1996). "Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit". Cell. 84 (5): 745–755. doi:10.1016/S0092-8674(00)81052-1. PMID 8625412. S2CID 1376853.
Pittaluga A, Pattarini R, Severi P, Raiteri M (May 1996). "Human brain N-methyl-D-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120". AIDS. 10 (5). London, England: 463–468. doi:10.1097/00002030-199605000-00003. PMID 8724036. S2CID 1669986.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000176884 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026959 – 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.

[Monyer_1992-5] 1 2 Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, et al. (May 1992). "Heteromeric NMDA receptors: molecular and functional distinction of subtypes". Science. 256 (5060). New York, N.Y.: 1217–1221. Bibcode:1992Sci...256.1217M. doi:10.1126/science.256.5060.1217. PMID 1350383. S2CID 989677.

[entrez-6] "Entrez Gene: GRIN1 glutamate receptor, ionotropic, N-methyl D-aspartate 1".

[7] Sengar AS, Li H, Zhang W, Leung C, Ramani AK, Saw NM, et al. (December 2019). "Control of Long-Term Synaptic Potentiation and Learning by Alternative Splicing of the NMDA Receptor Subunit GluN1". Cell Reports. 29 (13): 4285–4294.e5. doi:10.1016/j.celrep.2019.11.087. PMID 31875540. S2CID 209482250.

[8] Liu H, Wang H, Peterson M, Zhang W, Hou G, Zhang ZW (October 2019). "N-terminal alternative splicing of GluN1 regulates the maturation of excitatory synapses and seizure susceptibility". Proceedings of the National Academy of Sciences of the United States of America. 116 (42): 21207–21212. Bibcode:2019PNAS..11621207L. doi:10.1073/pnas.1905721116. PMC 6800312. PMID 31570583.

[9] 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.

[10] Manta G, Spathis AD, Taraviras S, Kouvelas ED, Mitsacos A (August 2011). "Age and visual experience-dependent expression of NMDAR1 splice variants in rat retina". Neurochemical Research. 36 (8): 1417–1425. doi:10.1007/s11064-011-0467-5. PMID 21499738. S2CID 11853676.

[Mu_2003-11] Mu Y, Otsuka T, Horton AC, Scott DB, Ehlers MD (October 2003). "Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptors". Neuron. 40 (3): 581–594. doi:10.1016/s0896-6273(03)00676-7. PMID 14642281.

GRIN1

Gene

Structure

Function

See also

References

Further reading