Metabotropic glutamate receptor 5

Function

G protein-coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity.

Classification

Family (Pfam)

PF00003 7tm_3, PF01094 ANF_receptor, PF10606 GluR_Homer-bdg, 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_mGluR5, GPCR_3_mtglu_rcpt, Metabotropic_Glu_rcpt_Homer-bd, mGluR, Peripla_BP_I

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 27

• 3LMK X-ray 2.44A
• 4OO9 X-ray 2.60A
• 5CGC X-ray 3.10A
• 5CGD X-ray 2.60A
• 6FFH X-ray 2.65A
• 6FFI X-ray 2.20A
• 6N4X X-ray 4.00A
• 6N4Y X-ray 3.26A
• 6N50 X-ray 3.75A
• 6N51 EM 4.00A
• 6N52 EM 4.00A
• 7FD8 EM 3.80A
• … and 15 more

A predicted model is available from AlphaFold.

Gene Ontology · 51

• GO:0097449 astrocyte projection
• GO:0005737 cytoplasm
• GO:0030425 dendrite
• GO:0043198 dendritic shaft
• GO:0043197 dendritic spine
• GO:0098978 glutamatergic synapse
• GO:0043025 neuronal cell body
• GO:0005637 nuclear inner membrane
• GO:0005886 plasma membrane
• GO:0098839 postsynaptic density membrane
• GO:0098685 Schaffer collateral - CA1 synapse
• GO:0031687 A2A adenosine receptor binding
• GO:0001640 adenylate cyclase inhibiting G protein-coupled glutamate receptor activity
• GO:0004930 G protein-coupled receptor activity
• GO:0099530 G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential
• GO:0008066 glutamate receptor activity
• GO:0042802 identical protein binding
• GO:0099583 neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration
• GO:0030296 protein tyrosine kinase activator activity
• GO:1990782 protein tyrosine kinase binding
• GO:1904646 cellular response to amyloid-beta
• GO:0007268 chemical synaptic transmission
• GO:0050890 cognition
• GO:1990708 conditioned place preference
• GO:0002029 desensitization of G protein-coupled receptor signaling pathway
• GO:0007216 G protein-coupled glutamate receptor signaling pathway
• GO:0007611 learning or memory
• GO:0061002 negative regulation of dendritic spine morphogenesis
• GO:0090394 negative regulation of excitatory postsynaptic potential
• GO:0035106 operant conditioning
• GO:0007206 phospholipase C-activating G protein-coupled glutamate receptor signaling pathway
• GO:0050850 positive regulation of calcium-mediated signaling
• GO:1900039 positive regulation of cellular response to hypoxia
• GO:0007204 positive regulation of cytosolic calcium ion concentration
• GO:0033603 positive regulation of dopamine secretion
• GO:0048170 positive regulation of long-term neuronal synaptic plasticity
• GO:0043410 positive regulation of MAPK cascade
• GO:2000179 positive regulation of neural precursor cell proliferation
• GO:1904058 positive regulation of sensory perception of pain
• GO:0036228 protein localization to nuclear inner membrane
• GO:0006355 regulation of DNA-templated transcription
• GO:1900452 regulation of long-term synaptic depression
• GO:0051966 regulation of synaptic transmission, glutamatergic
• GO:0001975 response to amphetamine
• GO:0046677 response to antibiotic
• GO:0051412 response to corticosterone
• GO:0045471 response to ethanol
• GO:0043278 response to morphine
• GO:0062036 sensory perception of hot stimulus
• GO:0050808 synapse organization
• GO:0001659 temperature homeostasis

Drugs targeting this protein · 7

• DASOLAMPANEL ETIBUTIL antagonist
• DIPRAGLURANT modulator
• MAVOGLURANT antagonist
• BASIMGLURANT modulator
• RASEGLURANT modulator
• AZD2066 modulator
• STX107 negative allosteric modulator

Related proteins · sequence + function similarity

• Metabotropic glutamate receptor 5 1.00
• Metabotropic glutamate receptor 5 0.99
• Metabotropic glutamate receptor 1 0.97
• Metabotropic glutamate receptor 1 0.97
• Metabotropic glutamate receptor 1 0.97
• Metabotropic glutamate receptor 3 0.91
• Metabotropic glutamate receptor 3 0.91
• Metabotropic glutamate receptor 3 0.90
• Metabotropic glutamate receptor 3 0.90
• Metabotropic glutamate receptor 3 0.90
• Metabotropic glutamate receptor 0.87
• Probable metabotropic glutamate receptor mgl-1 0.83

Co-cited proteins · studied together in the literature

• Metabotropic glutamate receptor 5 2 shared papers
• N-terminal EF-hand calcium-binding protein 2 1 shared papers
• N-terminal EF-hand calcium-binding protein 2 1 shared papers
• Leucine-rich repeat-containing protein 7 1 shared papers
• Calcium/calmodulin-dependent protein kinase type II subunit alpha 1 shared papers
• Voltage-dependent L-type calcium channel subunit beta-2 1 shared papers
• SH3 and multiple ankyrin repeat domains protein 3 1 shared papers
• Calcium/calmodulin-dependent protein kinase type II subunit alpha 1 shared papers
• Glutamate receptor ionotropic, NMDA 2B 1 shared papers

Literature · 6 cited papers

• Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors. J. Neurosci. · 2017
• Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature · 2014
• The association of metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function. J. Neurochem. · 2009
• Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
• Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5. Biochem. Biophys. Res. Commun. · 1994
• A variant of metabotropic glutamate receptor subtype 5: an evolutionally conserved insertion with no termination codon. Biochem. Biophys. Res. Commun. · 1993