Metabotropic glutamate receptor 2

Function

Dimeric G protein-coupled receptor which is activated by the excitatory neurotransmitter L-glutamate. Plays critical roles in modulating synaptic transmission and neuronal excitability. Upon activation by glutamate, inhibits presynaptic calcium channels, reducing further glutamate release and dampening excitatory signaling (By similarity). Mechanistically, ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.

Classification

Family (Pfam)

PF00003 7tm_3, PF01094 ANF_receptor, PF07562 NCD3G

InterPro

ANF_lig-bd_rcpt, GPCR_3, GPCR_3_9-Cys_dom, GPCR_3_9-Cys_sf, GPCR_3_C, GPCR_3_CS, GPCR_3_mGluR2, GPCR_3_mtglu_rcpt, mGluR, Peripla_BP_I

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 31

• 4XAQ X-ray 2.21A
• 4XAS X-ray 2.35A
• 5CNI X-ray 2.69A
• 5CNJ X-ray 2.65A
• 5KZN X-ray 2.80A
• 5KZQ X-ray 2.80A
• 7E9G EM 3.50A
• 7EPA EM 3.60A
• 7EPB EM 3.10A
• 7EPD EM 3.90A
• 7EPE X-ray 2.50A
• 7EPF X-ray 2.70A
• … and 19 more

A predicted model is available from AlphaFold.

Gene Ontology · 24

• GO:0097449 astrocyte projection
• GO:0030424 axon
• GO:0030425 dendrite
• GO:0098978 glutamatergic synapse
• GO:0005886 plasma membrane
• GO:0045211 postsynaptic membrane
• GO:0042734 presynaptic membrane
• GO:0005246 calcium channel regulator activity
• GO:0004930 G protein-coupled receptor activity
• GO:0008066 glutamate receptor activity
• GO:0001641 group II metabotropic glutamate receptor activity
• GO:0097110 scaffold protein binding
• GO:0035095 behavioral response to nicotine
• GO:0007268 chemical synaptic transmission
• GO:0007216 G protein-coupled glutamate receptor signaling pathway
• GO:0014047 glutamate secretion
• GO:0007194 negative regulation of adenylate cyclase activity
• GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0099171 presynaptic modulation of chemical synaptic transmission
• GO:0014059 regulation of dopamine secretion
• GO:0014048 regulation of glutamate secretion
• GO:2001023 regulation of response to drug
• GO:0051966 regulation of synaptic transmission, glutamatergic
• GO:0042220 response to cocaine

Drugs targeting this protein · 5

• POMAGLUMETAD METHIONIL ANHYDROUS agonist
• DECOGLURANT modulator
• JNJ-40411813 positive allosteric modulator
• LY404039 agonist
• LY2979165 agonist

Related proteins · sequence + function similarity

• Metabotropic glutamate receptor 2 1.00
• Metabotropic glutamate receptor 2 1.00
• Metabotropic glutamate receptor 6 0.83
• Metabotropic glutamate receptor 6 0.83
• Metabotropic glutamate receptor 6 0.83
• Metabotropic glutamate receptor 3 0.82
• Metabotropic glutamate receptor 6 0.82
• Metabotropic glutamate receptor 3 0.82
• Metabotropic glutamate receptor 3 0.81
• Metabotropic glutamate receptor 3 0.81
• Metabotropic glutamate receptor 3 0.80
• Glutamate receptor ionotropic, kainate 5 0.77

Co-cited proteins · studied together in the literature

• Metabotropic glutamate receptor 2 2 shared papers
• Glycoprotein 1 shared papers
• 5-hydroxytryptamine receptor 2A 2 shared papers
• 5-hydroxytryptamine receptor 2A 2 shared papers
• Spike glycoprotein 1 shared papers

Literature · 10 cited papers

• Influenza virus uses mGluR2 as an endocytic receptor to enter cells. Nat. Microbiol. · 2024
• Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers. Cell Res. · 2023
• SARS-CoV-2 uses metabotropic glutamate receptor subtype 2 as an internalization factor to infect cells. Cell Discov. · 2021
• Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus. PLoS Pathog. · 2018
• Synthesis and Pharmacological Characterization of C4-(Thiotriazolyl)-substituted-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1R,2S,4R,5R,6R)-2-Amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2812223), a Highly Potent, Functionally Selective mGlu2 Receptor Agonist. J. Med. Chem. · 2015
• Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A.mGlu2) receptor heteromerization and its psychoactive behavioral function. J. Biol. Chem. · 2012
• Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades. Neuropharmacology · 2012
• Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature · 2008
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2. Eur. J. Neurosci. · 1995