Metabotropic glutamate receptor 7

Glutamate receptor, metabotropic 7

PDB rendering based on 2e4z.

Available structures
PDB	2e4z

Identifiers

Symbols

GRM7; FLJ40498; GLUR7; GPRC1G; MGLU7; MGLUR7

External IDs

OMIM: 604101 MGI: 1351344 HomoloGene: 20233 IUPHAR: mGlu₇ GeneCards: GRM7 Gene

Gene Ontology
Molecular function	• group III metabotropic glutamate receptor activity • receptor activity • G-protein coupled receptor 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 to plasma membrane • cell cortex • integral to membrane • axon • dendrite • asymmetric synapse • dendritic shaft • postsynaptic membrane • presynaptic active zone
Biological process	• conditioned taste aversion • behavioral fear response • negative regulation of adenylate cyclase activity • synaptic transmission • sensory perception of sound • sensory perception of smell • short-term memory • negative regulation of glutamate secretion • adult behavior • negative regulation of cAMP biosynthetic process • multicellular organismal response to stress • response to stimulus
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 3:
6.81 – 7.78 Mb

Chr 6:
110.6 – 111.52 Mb

PubMed search

[1]

[2]

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

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]

1 Ligands
- 1.1 Agonists
- 1.2 Antagonists
2 Interactions
3 References
4 External links
5 Further reading

Ligands

Agonists

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

Antagonists

MMPIP: allosteric antagonist/inverse agonist^[7]

Interactions

Metabotropic glutamate receptor 7 has been shown to interact with PICK1.^[8]

References

^ Okamoto N, Hori S, Akazawa C, Hayashi Y, Shigemoto R, Mizuno N, Nakanishi S (Feb 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 (Jan 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.
^ ^a ^b "Entrez Gene: GRM7 glutamate receptor, metabotropic 7". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2917.
^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2410088.
^ ^a ^b 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 et al. (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.
^ Dev, K K; Nakajima Y, Kitano J, Braithwaite S P, Henley J M, Nakanishi S (Oct. 2000). "PICK1 interacts with and regulates PKC phosphorylation of mGLUR7". J. Neurosci. (UNITED STATES) 20 (19): 7252–7. PMID 11007882.

External links

"Metabotropic Glutamate Receptors: mGlu₇". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2280.

Scherer SW, Duvoisin RM, Kuhn R et al. (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 et al. (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 et al. (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 et al. (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 et al. (2001). "PICK1 interacts with and regulates PKC phosphorylation of mGLUR7". J. Neurosci. 20 (19): 7252–7. PMID 11007882.
Bolonna AA, Kerwin RW, Munro J et al. (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 et al. (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 et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2925652.
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.
Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Kobayashi Y, Akiyoshi J, Kanehisa M et al. (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

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

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

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, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)

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

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)