Metabotropic glutamate receptor 7

GRM7
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3MQ4, 5C5C
Identifiers
Aliases	GRM7, GLUR7, GPRC1G, MGLU7, MGLUR7, PPP1R87, glutamate metabotropic receptor 7, NEDSHBA
External IDs	OMIM: 604101 MGI: 1351344 HomoloGene: 20233 GeneCards: GRM7
Gene location (Human)
Chr.	Chromosome 3 (human)[1]
End	7,741,533 bp[1]
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)[2]
End	111,544,191 bp[2]
RNA expression pattern
	Top expressed in
	endothelial cell; ; middle temporal gyrus; ; Region I of hippocampus proper; ; Brodmann area 23; ; entorhinal cortex; ; sperm; ; orbitofrontal cortex; ; dorsolateral prefrontal cortex; ; Brodmann area 9; ; superior frontal gyrus;
	Top expressed in
	medial dorsal nucleus; ; superior colliculus; ; mammillary body; ; olfactory tubercle; ; medial geniculate nucleus; ; piriform cortex; ; subiculum; ; ventromedial nucleus; ; substantia nigra; ; nucleus accumbens;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	glutamate receptor activity; calcium ion binding; PDZ domain binding; serine binding; G protein-coupled receptor activity; group III metabotropic glutamate receptor activity; adenylate cyclase inhibitor activity; signal transducer activity; glutamate binding; calcium channel regulator activity;
Cellular component	integral component of membrane; postsynaptic membrane; membrane; receptor complex; plasma membrane; integral component of plasma membrane; dendritic shaft; presynaptic active zone; axon; dendrite; cell cortex; asymmetric synapse; presynaptic membrane;
Biological process	negative regulation of glutamate secretion; response to stimulus; sensory perception of sound; behavioral fear response; adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway; signal transduction; regulation of cyclase activity; regulation of synaptic transmission, glutamatergic; chemical synaptic transmission; G protein-coupled receptor signaling pathway; adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; G protein-coupled glutamate receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	2917
	108073
	ENSG00000196277
	ENSMUSG00000056755
	Q14831
	Q68ED2
	NM_000844; NM_181874; NM_181875
	NM_177328; NM_001346640; NM_177970
	NP_000835; NP_870989
	NP_001333569; NP_796302
	Wikidata
View/Edit Human	View/Edit Mouse

Metabotropic glutamate receptor 7 is a protein that in humans is encoded by the GRM7 gene.[5][6][7]

Function

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternative splice variants of GRM8 have been described but their full-length nature has not been determined.[7]

Glutamate has lower affinity for mGluR7 than the other metabotropic glutamate receptors and it has been suggested that mGluR7 may have a regulatory role to dampen the effects of excessive glutamate levels.[8]

Ligands

Agonists

AMN082: allosteric agonist;[9][10] induces rapid internalization;[11] non-glutamatergic binding component[10]

LSP2-9166: mixed agonist at mGluR₄ and mGluR₇

Antagonists

MMPIP: allosteric antagonist/inverse agonist[12]
XAP044

Negative allosteric modulators

ADX71743[13]

Interactions

Metabotropic glutamate receptor 7 has been shown to interact with PICK1.[14]

Clinical

Mutations in both copies have been associated with developmental and epileptic encephalopathy, microcephaly, hypomyelination and cerebral atrophy.[15]

References

GRCh38: Ensembl release 89: ENSG00000196277 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000056755 - 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.
Okamoto N, Hori S, Akazawa C, Hayashi Y, Shigemoto R, Mizuno N, Nakanishi S (January 1994). "Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction". The Journal of Biological Chemistry. 269 (2): 1231–1236. doi:10.1016/S0021-9258(17)42247-2. PMID 8288585.
Makoff A, Pilling C, Harrington K, Emson P (August 1996). "Human metabotropic glutamate receptor type 7: molecular cloning and mRNA distribution in the CNS". Brain Research. Molecular Brain Research. 40 (1): 165–170. doi:10.1016/0169-328X(96)00110-6. PMID 8840028.
"Entrez Gene: GRM7 glutamate receptor, metabotropic 7".
Fisher NM, Seto M, Lindsley CW, Niswender CM (2018). "Metabotropic Glutamate Receptor 7: A New Therapeutic Target in Neurodevelopmental Disorders". Frontiers in Molecular Neuroscience. 11: 387. doi:10.3389/fnmol.2018.00387. PMC 6206046. PMID 30405350.
Li X, Gardner EL, Xi ZX (March 2008). "The metabotropic glutamate receptor 7 (mGluR7) allosteric agonist AMN082 modulates nucleus accumbens GABA and glutamate, but not dopamine, in rats". Neuropharmacology. 54 (3): 542–551. doi:10.1016/j.neuropharm.2007.11.005. PMC 2410088. PMID 18155073.
Palucha A, Klak K, Branski P, van der Putten H, Flor PJ, Pilc A (November 2007). "Activation of the mGlu7 receptor elicits antidepressant-like effects in mice". Psychopharmacology. 194 (4): 555–562. doi:10.1007/s00213-007-0856-2. PMID 17622518. S2CID 22011436.
Pelkey KA, Yuan X, Lavezzari G, Roche KW, McBain CJ (January 2007). "mGluR7 undergoes rapid internalization in response to activation by the allosteric agonist AMN082". Neuropharmacology. 52 (1): 108–117. doi:10.1016/j.neuropharm.2006.07.020. PMID 16914173. S2CID 23372757.
Suzuki G, Tsukamoto N, Fushiki H, Kawagishi A, Nakamura M, Kurihara H, et al. (October 2007). "In vitro pharmacological characterization of novel isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists". The Journal of Pharmacology and Experimental Therapeutics. 323 (1): 147–156. doi:10.1124/jpet.107.124701. PMID 17609420. S2CID 10402176.
Kalinichev M, Rouillier M, Girard F, Royer-Urios I, Bournique B, Finn T, et al. (March 2013). "ADX71743, a potent and selective negative allosteric modulator of metabotropic glutamate receptor 7: in vitro and in vivo characterization". The Journal of Pharmacology and Experimental Therapeutics. 344 (3): 624–636. doi:10.1124/jpet.112.200915. PMID 23257312. S2CID 5774001.
Dev KK, Nakajima Y, Kitano J, Braithwaite SP, Henley JM, Nakanishi S (October 2000). "PICK1 interacts with and regulates PKC phosphorylation of mGLUR7". The Journal of Neuroscience. 20 (19): 7252–7257. doi:10.1523/JNEUROSCI.20-19-07252.2000. PMC 6772771. PMID 11007882.
Marafi D, Mitani T, Isikay S, Hertecant J, Almannai M, Manickam K, et al. (May 2020). "Biallelic GRM7 variants cause epilepsy, microcephaly, and cerebral atrophy". Annals of Clinical and Translational Neurology. 7 (5): 610–627. doi:10.1002/acn3.51003. PMC 7261753. PMID 32286009.

Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC (January 1996). "Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q". Genomics. 31 (2): 230–233. doi:10.1006/geno.1996.0036. PMID 8824806.
Flor PJ, Van Der Putten H, Rüegg D, Lukic S, Leonhardt T, Bence M, et al. (February 1997). "A novel splice variant of a metabotropic glutamate receptor, human mGluR7b". Neuropharmacology. 36 (2): 153–159. doi:10.1016/S0028-3908(96)00176-1. PMID 9144652. S2CID 27492811.
Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR, et al. (January 1998). "Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells". Brain Research. Molecular Brain Research. 53 (1–2): 88–97. doi:10.1016/S0169-328X(97)00277-5. PMID 9473604.
Nakajima Y, Yamamoto T, Nakayama T, Nakanishi S (September 1999). "A relationship between protein kinase C phosphorylation and calmodulin binding to the metabotropic glutamate receptor subtype 7". The Journal of Biological Chemistry. 274 (39): 27573–27577. doi:10.1074/jbc.274.39.27573. PMID 10488094.
O'Connor V, El Far O, Bofill-Cardona E, Nanoff C, Freissmuth M, Karschin A, et al. (November 1999). "Calmodulin dependence of presynaptic metabotropic glutamate receptor signaling". Science. 286 (5442): 1180–1184. doi:10.1126/science.286.5442.1180. hdl:11858/00-001M-0000-0012-FB4D-F. PMID 10550060.
Barbon A, Ferraboli S, Barlati S (2000). "Assignment of the human metabotropic glutamate receptor gene GRM7 to chromosome 3p26.1-->p25.2 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 88 (3–4): 288. doi:10.1159/000015541. PMID 10828612. S2CID 202654909.
Dev KK, Nakajima Y, Kitano J, Braithwaite SP, Henley JM, Nakanishi S (October 2000). "PICK1 interacts with and regulates PKC phosphorylation of mGLUR7". The Journal of Neuroscience. 20 (19): 7252–7257. doi:10.1523/JNEUROSCI.20-19-07252.2000. PMC 6772771. PMID 11007882.
Bolonna AA, Kerwin RW, Munro J, Arranz MJ, Makoff AJ (January 2001). "Polymorphisms in the genes for mGluR types 7 and 8: association studies with schizophrenia". Schizophrenia Research. 47 (1): 99–103. doi:10.1016/S0920-9964(99)00235-2. PMID 11163549. S2CID 40047571.
Hirbec H, Perestenko O, Nishimune A, Meyer G, Nakanishi S, Henley JM, Dev KK (May 2002). "The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs". The Journal of Biological Chemistry. 277 (18): 15221–15224. doi:10.1074/jbc.C200112200. PMID 11891216.
Enz R (March 2002). "The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7". FEBS Letters. 514 (2–3): 184–188. doi:10.1016/S0014-5793(02)02361-X. PMID 11943148. S2CID 44474808.
Saugstad JA, Yang S, Pohl J, Hall RA, Conn PJ (March 2002). "Interaction between metabotropic glutamate receptor 7 and alpha tubulin". Journal of Neurochemistry. 80 (6): 980–988. doi:10.1046/j.0022-3042.2002.00778.x. PMC 2925652. PMID 11953448.
Schulz HL, Stohr H, Weber BH (June 2002). "Characterization of three novel isoforms of the metabotrobic glutamate receptor 7 (GRM7)". Neuroscience Letters. 326 (1): 37–40. doi:10.1016/S0304-3940(02)00306-3. PMID 12052533. S2CID 32389200.
Kobayashi Y, Akiyoshi J, Kanehisa M, Ichioka S, Tanaka Y, Tsuru J, et al. (February 2007). "Lack of polymorphism in genes encoding mGluR 7, mGluR 8, GABA(A) receptor alfa-6 subunit and nociceptin/orphanin FQ receptor and panic disorder". Psychiatric Genetics. 17 (1): 9. doi:10.1097/YPG.0b013e32801118bc. PMID 17167337.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000196277 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000056755 - 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.

[pmid8288585-5] Okamoto N, Hori S, Akazawa C, Hayashi Y, Shigemoto R, Mizuno N, Nakanishi S (January 1994). "Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction". The Journal of Biological Chemistry. 269 (2): 1231–1236. doi:10.1016/S0021-9258(17)42247-2. PMID 8288585.

[pmid8840028-6] Makoff A, Pilling C, Harrington K, Emson P (August 1996). "Human metabotropic glutamate receptor type 7: molecular cloning and mRNA distribution in the CNS". Brain Research. Molecular Brain Research. 40 (1): 165–170. doi:10.1016/0169-328X(96)00110-6. PMID 8840028.

[entrez-7] "Entrez Gene: GRM7 glutamate receptor, metabotropic 7".

[pmid30405350-8] Fisher NM, Seto M, Lindsley CW, Niswender CM (2018). "Metabotropic Glutamate Receptor 7: A New Therapeutic Target in Neurodevelopmental Disorders". Frontiers in Molecular Neuroscience. 11: 387. doi:10.3389/fnmol.2018.00387. PMC 6206046. PMID 30405350.

[9] Li X, Gardner EL, Xi ZX (March 2008). "The metabotropic glutamate receptor 7 (mGluR7) allosteric agonist AMN082 modulates nucleus accumbens GABA and glutamate, but not dopamine, in rats". Neuropharmacology. 54 (3): 542–551. doi:10.1016/j.neuropharm.2007.11.005. PMC 2410088. PMID 18155073.

[pmid17622518-10] Palucha A, Klak K, Branski P, van der Putten H, Flor PJ, Pilc A (November 2007). "Activation of the mGlu7 receptor elicits antidepressant-like effects in mice". Psychopharmacology. 194 (4): 555–562. doi:10.1007/s00213-007-0856-2. PMID 17622518. S2CID 22011436.

[11] Pelkey KA, Yuan X, Lavezzari G, Roche KW, McBain CJ (January 2007). "mGluR7 undergoes rapid internalization in response to activation by the allosteric agonist AMN082". Neuropharmacology. 52 (1): 108–117. doi:10.1016/j.neuropharm.2006.07.020. PMID 16914173. S2CID 23372757.

[12] Suzuki G, Tsukamoto N, Fushiki H, Kawagishi A, Nakamura M, Kurihara H, et al. (October 2007). "In vitro pharmacological characterization of novel isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists". The Journal of Pharmacology and Experimental Therapeutics. 323 (1): 147–156. doi:10.1124/jpet.107.124701. PMID 17609420. S2CID 10402176.

[pmid23257312-13] Kalinichev M, Rouillier M, Girard F, Royer-Urios I, Bournique B, Finn T, et al. (March 2013). "ADX71743, a potent and selective negative allosteric modulator of metabotropic glutamate receptor 7: in vitro and in vivo characterization". The Journal of Pharmacology and Experimental Therapeutics. 344 (3): 624–636. doi:10.1124/jpet.112.200915. PMID 23257312. S2CID 5774001.

[pmid11007882-14] Dev KK, Nakajima Y, Kitano J, Braithwaite SP, Henley JM, Nakanishi S (October 2000). "PICK1 interacts with and regulates PKC phosphorylation of mGLUR7". The Journal of Neuroscience. 20 (19): 7252–7257. doi:10.1523/JNEUROSCI.20-19-07252.2000. PMC 6772771. PMID 11007882.

[Marafi2020-15] Marafi D, Mitani T, Isikay S, Hertecant J, Almannai M, Manickam K, et al. (May 2020). "Biallelic GRM7 variants cause epilepsy, microcephaly, and cerebral atrophy". Annals of Clinical and Translational Neurology. 7 (5): 610–627. doi:10.1002/acn3.51003. PMC 7261753. PMID 32286009.