Metabotropic glutamate receptor 4

Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the GRM4 gene.^[5][6][7]

GRM4
Identifiers
Aliases	GRM4, GPRC1D, MGLUR4, mGlu4, glutamate metabotropic receptor 4
External IDs	OMIM: 604100; MGI: 1351341; HomoloGene: 20230; GeneCards: GRM4; OMA:GRM4 - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p21.31 Start 34,018,643 bp[1] End 34,155,622 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 A3.3 Start 27,641,361 bp[2] End 27,740,377 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in paraflocculus of cerebellum right hemisphere of cerebellum cerebellar vermis nucleus accumbens putamen caudate nucleus Brodmann area 10 middle frontal gyrus islet of Langerhans quadriceps femoris muscle Top expressed in cerebellar cortex cerebellar vermis lobe of cerebellum zygote secondary oocyte medial dorsal nucleus primary oocyte medial geniculate nucleus olfactory tubercle nucleus of stria terminalis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function glutamate receptor activity G protein-coupled receptor activity signal transducer activity Cellular component integral component of membrane plasma membrane integral component of plasma membrane intracellular anatomical structure presynaptic membrane cytoplasmic vesicle membrane Biological process regulation of neuron apoptotic process adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway neurotransmitter secretion positive regulation of MAPK cascade signal transduction chemical synaptic transmission regulation of synaptic transmission, glutamatergic G protein-coupled receptor signaling pathway G protein-coupled glutamate receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2914 268934 Ensembl ENSG00000124493 ENSMUSG00000063239 UniProt Q14833 Q68EF4 RefSeq (mRNA) NM_000841 NM_001256809 NM_001256810 NM_001256811 NM_001256812 NM_001256813 NM_001256814 NM_001282847 NM_001013385 NM_001291045 NM_001360192 NM_001379317 RefSeq (protein) NP_000832 NP_001243738 NP_001243740 NP_001243741 NP_001243742 NP_001269776 NP_001013403 NP_001277974 NP_001347121 Location (UCSC) Chr 6: 34.02 – 34.16 Mb Chr 17: 27.64 – 27.74 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Together with GRM6, GRM7 and GRM8 it belongs to group III of the metabotropic glutamate receptor family. Group III receptors are linked to the inhibition of the cyclic AMP cascade.^[7] Activation of GRM4 has potential therapeutic benefits in the treatment of parkinson's disease. Splice variant "taste-GRM4" is involved in the perception of umami taste.^[8]

Ligands

Orthosteric

• Cinnabarinic acid, a tryptophan metabolite^[9]
• LSP1-2111: agonist^[10]
• LSP4-2022: agonist^[11]
• LSP2-9166: mixed agonist at mGluR₄ and mGluR₇

Positive allosteric modulators (PAMs)

• ADX88178
• Foliglurax (PXT-002331, DT-1687)
• Tricyclic thiazolopyrazole derivative 22a: EC₅₀ = 9 nM, E_max = 120%^[12]
• ML-128: EC₅₀ = 240 nM, E_max = 182%^[13][14]
• Valiglurax (AP-472) (VU0652957)^[15]
• VU-0418506^[16][17]
• VU-001171: EC₅₀ = 650 nM, E_max = 141%, 36-fold shift^[18]
• VU0155041: subtype-selective PAM, intrinsic allosteric agonist activity, robust in-vivo activity^[19]
• VU0364770
• PHCCC: PAM of mGluR4, negative allosteric modulator of mGluR1,^[20] direct agonist at mGluR6^[21]
• TC-N 22A