Metabotropic glutamate receptor 7

Glutamate receptor, metabotropic 7

PDB rendering based on 2e4z.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
3MQ4

Identifiers

Symbols

GRM7 ; GLUR7; GPRC1G; MGLU7; MGLUR7; PPP1R87

External IDs

OMIM: 604101 MGI: 1351344 HomoloGene: 20233 IUPHAR: 295 ChEMBL: 3777 GeneCards: GRM7 Gene

Gene ontology
Molecular function	• group III metabotropic glutamate receptor activity • voltage-gated calcium channel activity • calcium channel regulator activity • calcium ion binding • glutamate receptor activity • adenylate cyclase inhibitor activity • glutamate binding • PDZ domain binding • serine binding
Cellular component	• plasma membrane • integral component of plasma membrane • cell cortex • integral component of membrane • axon • dendrite • asymmetric synapse • presynaptic membrane • dendritic shaft • receptor complex • postsynaptic membrane • presynaptic active zone
Biological process	• conditioned taste aversion • behavioral fear response • negative regulation of adenylate cyclase activity • adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway • synaptic transmission • sensory perception of sound • sensory perception of smell • short-term memory • negative regulation of glutamate secretion • transmission of nerve impulse • adult behavior • negative regulation of cAMP biosynthetic process • regulation of cyclase activity • regulation of synaptic transmission, glutamatergic • calcium ion transmembrane transport
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 3:
6.77 – 7.74 Mb

Chr 6:
110.65 – 111.57 Mb

PubMed search

Metabotropic glutamate receptor 7 is a protein that in humans is encoded by the GRM7 gene.^[1]^[2]^[3]

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.^[3]

Ligands

Agonists

AMN082: allosteric agonist;^[4]^[5] induces rapid internalization;^[6] non-glutamatergic binding component^[5]

Antagonists

MMPIP: allosteric antagonist/inverse agonist^[7]

Negative allosteric modulator

ADX-71743^[8]

Interactions

Metabotropic glutamate receptor 7 has been shown to interact with PICK1.^[9]

References

↑ Okamoto N, Hori S, Akazawa C, Hayashi Y, Shigemoto R, Mizuno N, Nakanishi S (February 1994). "Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction". J Biol Chem 269 (2): 1231–6. PMID 8288585.
↑ Makoff A, Pilling C, Harrington K, Emson P (January 1997). "Human metabotropic glutamate receptor type 7: molecular cloning and mRNA distribution in the CNS". Brain Res Mol Brain Res 40 (1): 165–70. doi:10.1016/0169-328X(96)00110-6. PMID 8840028.
1 2 "Entrez Gene: GRM7 glutamate receptor, metabotropic 7".
↑ Li X, Gardner EL, Xi ZX (2008). "The Metabotropic Glutamate Receptor 7 (mGluR7) Allosteric Agonist AMN082 Modulates Nucleus Accumbens GABA and Glutamate, but not Dopamine, in Rats". Neuropharmacology 54 (3): 542–51. doi:10.1016/j.neuropharm.2007.11.005. PMC 2410088. PMID 18155073.
1 2 Palucha A, Klak K, Branski P, van der Putten H, Flor PJ, Pilc A (2007). "Activation of the mGlu7 receptor elicits antidepressant-like effects in mice". Psychopharmacology (Berl.) 194 (4): 555–62. doi:10.1007/s00213-007-0856-2. PMID 17622518.
↑ Pelkey KA, Yuan X, Lavezzari G, Roche KW, McBain CJ (2007). "mGluR7 undergoes rapid internalization in response to activation by the allosteric agonist AMN082". Neuropharmacology 52 (1): 108–17. doi:10.1016/j.neuropharm.2006.07.020. PMID 16914173.
↑ Suzuki G, Tsukamoto N, Fushiki H, Kawagishi A, Nakamura M, Kurihara H, Mitsuya M, Ohkubo M, Ohta H (2007). "In vitro pharmacological characterization of novel isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists". J. Pharmacol. Exp. Ther. 323 (1): 147–56. doi:10.1124/jpet.107.124701. PMID 17609420.
↑ Kalinichev M, Rouillier M, Girard F, et al. (2013). "ADX71743, a potent and selective negative allosteric modulator of metabotropic glutamate receptor 7: in vitro and in vivo characterization". J. Pharmacol. Exp. Ther. 344 (3): 624–36. doi:10.1124/jpet.112.200915. PMID 23257312.
↑ Dev KK, Nakajima Y, Kitano J, Braithwaite SP, Henley JM, Nakanishi S (October 2000). "PICK1 interacts with and regulates PKC phosphorylation of mGLUR7". J. Neurosci. 20 (19): 7252–7. PMID 11007882.

Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC (1997). "Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q". Genomics 31 (2): 230–3. doi:10.1006/geno.1996.0036. PMID 8824806.
Flor PJ, Van Der Putten H, Rüegg D, Lukic S, Leonhardt T, Bence M, Sansig G, Knöpfel T, Kuhn R (1997). "A novel splice variant of a metabotropic glutamate receptor, human mGluR7b". Neuropharmacology 36 (2): 153–9. doi:10.1016/S0028-3908(96)00176-1. PMID 9144652.
Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR, Johnson BG, Schoepp DD, Belagaje RM (1998). "Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells". Brain Res. Mol. Brain Res. 53 (1–2): 88–97. doi:10.1016/S0169-328X(97)00277-5. PMID 9473604.
Nakajima Y, Yamamoto T, Nakayama T, Nakanishi S (1999). "A relationship between protein kinase C phosphorylation and calmodulin binding to the metabotropic glutamate receptor subtype 7". J. Biol. Chem. 274 (39): 27573–7. doi:10.1074/jbc.274.39.27573. PMID 10488094.
O'Connor V, El Far O, Bofill-Cardona E, Nanoff C, Freissmuth M, Karschin A, Airas JM, Betz H, Boehm S (1999). "Calmodulin dependence of presynaptic metabotropic glutamate receptor signaling". Science 286 (5442): 1180–4. doi:10.1126/science.286.5442.1180. 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". Cytogenet. Cell Genet. 88 (3–4): 288. doi:10.1159/000015541. PMID 10828612.
Dev KK, Nakajima Y, Kitano J, Braithwaite SP, Henley JM, Nakanishi S (2001). "PICK1 interacts with and regulates PKC phosphorylation of mGLUR7". J. Neurosci. 20 (19): 7252–7. PMID 11007882.
Bolonna AA, Kerwin RW, Munro J, Arranz MJ, Makoff AJ (2001). "Polymorphisms in the genes for mGluR types 7 and 8: association studies with schizophrenia". Schizophr. Res. 47 (1): 99–103. doi:10.1016/S0920-9964(99)00235-2. PMID 11163549.
Hirbec H, Perestenko O, Nishimune A, Meyer G, Nakanishi S, Henley JM, Dev KK (2002). "The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs". J. Biol. Chem. 277 (18): 15221–4. doi:10.1074/jbc.C200112200. PMID 11891216.
Enz R (2002). "The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7". FEBS Lett. 514 (2–3): 184–8. doi:10.1016/S0014-5793(02)02361-X. PMID 11943148.
Saugstad JA, Yang S, Pohl J, Hall RA, Conn PJ (2002). "Interaction between metabotropic glutamate receptor 7 and alpha tubulin". J. Neurochem. 80 (6): 980–8. doi:10.1046/j.0022-3042.2002.00778.x. PMC 2925652. PMID 11953448.
Schulz HL, Stohr H, Weber BH (2002). "Characterization of three novel isoforms of the metabotrobic glutamate receptor 7 (GRM7)". Neurosci. Lett. 326 (1): 37–40. doi:10.1016/S0304-3940(02)00306-3. PMID 12052533.
Kobayashi Y, Akiyoshi J, Kanehisa M, Ichioka S, Tanaka Y, Tsuru J, Hanada H, Kodama K, Isogawa K, Tsutsumi T (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". Psychiatr. Genet. 17 (1): 9. doi:10.1097/YPG.0b013e32801118bc. PMID 17167337.

PDB gallery

2e4z: Crystal structure of the ligand-binding region of the group III metabotropic glutamate receptor

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

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

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