Grm4 glutamate receptor, metabotropic 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Grm4provided by MGI
Official Full Name: glutamate receptor, metabotropic 4provided by MGI
Primary source: MGI:MGI:1351341
See related: Ensembl:ENSMUSG00000063239 AllianceGenome:MGI:1351341
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Gprc1d; mGluR4
Summary: Predicted to enable adenylate cyclase inhibiting G protein-coupled glutamate receptor activity; calcium-dependent protein binding activity; and calmodulin binding activity. Involved in presynaptic modulation of chemical synaptic transmission. Acts upstream of or within chemical synaptic transmission and learning. Located in neuron projection. Is active in cerebellar granule cell to Purkinje cell synapse; parallel fiber to Purkinje cell synapse; and presynaptic active zone membrane. Is expressed in central nervous system; dorsal root ganglion; foot; sensory organ; and skeleton. Orthologous to human GRM4 (glutamate metabotropic receptor 4). [provided by Alliance of Genome Resources, Jan 2025]
Expression: Biased expression in cerebellum adult (RPKM 60.6), frontal lobe adult (RPKM 7.3) and 3 other tissues See more
Orthologs: human all
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Genomic context

Location:: 17 A3.3; 17 14.05 cM

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	17	NC_000083.7 (27641361..27732800, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	17	NC_000083.6 (27422387..27513826, complement)

Chromosome 17 - NC_000083.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome.
Title: The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome.
Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4.
Title: Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4.
This immuno-electron microscopic studies suggest that pre-synaptic metabotropic glutamate receptor 4 (mGluR4) in striatal glutamatergic terminals is expressed almost exclusively in cortical boutons to subserve regulatory influences upon a large contingent of corticostriatal terminals that preferentially target putative "indirect" pathway striatal projection neurons in mice.
Title: mGluR4-containing corticostriatal terminals: synaptic interactions with direct and indirect pathway neurons in mice.
Study assessed the actions of the first mGlur4-selective orthosteric agonist, LSP4-2022, in several tests reflecting positive, negative, and cognitive symptoms of schizophrenia; results suggest that the interplay between mGlu4 and GABAB receptors may become the basis for a novel therapy for schizophrenic patients with predomination of positive symptoms
Title: Involvement of GABAB Receptor Signaling in Antipsychotic-like Action of the Novel Orthosteric Agonist of the mGlu4 Receptor, LSP4-2022.
Results offer the first evidence that changes in the striatal expression of mGlu4 and mGlu5 receptors occur in acute models of parkinsonisms
Title: Changes in the expression of genes encoding for mGlu4 and mGlu5 receptors and other regulators of the indirect pathway in acute mouse models of drug-induced parkinsonism.
Involvement of multiple taste receptors in umami taste: analysis of gustatory nerve responses in metabotropic glutamate receptor 4 knockout mice
Title: Involvement of multiple taste receptors in umami taste: analysis of gustatory nerve responses in metabotropic glutamate receptor 4 knockout mice.
A functional hetero-complex is formed with mGluR2 and mGluR4 in central nervous system.
Title: Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS.
mGluR4-/- mice show increased long-term potentiation in hippocampal CA1 region and improved maze learning.
Title: Improved spatial learning is associated with increased hippocampal but not prefrontal long-term potentiation in mGluR4 knockout mice.
data support a role for mGluR4 signaling in acquisition of fear learning and memory.
Title: Role of mGluR4 in acquisition of fear learning and memory.
The expression of mGluR4 is down-regulated in the cardiomyocyte differentiation of embryonic stem cells.
Title: [Expression of metabotropic glutamate receptor 4 in cardiomyocytes differentiated from mouse embryonic stem cells in vitro].

Submit: New GeneRIF Correction See all GeneRIFs (19)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (5)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D17Mit30 (e-PCR), detects polymorphism
- UniSTS:128079

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables G protein-coupled receptor activity	ISO Inferred from Sequence Orthology more info
enables G protein-coupled receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables adenylate cyclase inhibiting G protein-coupled glutamate receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium-dependent protein binding	ISO Inferred from Sequence Orthology more info
enables calmodulin binding	ISO Inferred from Sequence Orthology more info
enables glutamate receptor activity	ISO Inferred from Sequence Orthology more info
enables glutamate receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables group III metabotropic glutamate receptor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled glutamate receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within chemical synaptic transmission	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in presynaptic modulation of chemical synaptic transmission	EXP Inferred from Experiment more info	PubMed
involved_in presynaptic modulation of chemical synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in presynaptic modulation of chemical synaptic transmission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cerebellar granule cell to Purkinje cell synapse	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	ISO Inferred from Sequence Orthology more info
located_in dendritic shaft	ISO Inferred from Sequence Orthology more info
is_active_in glutamatergic synapse	EXP Inferred from Experiment more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in neuron projection	IDA Inferred from Direct Assay more info	PubMed
is_active_in parallel fiber to Purkinje cell synapse	EXP Inferred from Experiment more info	PubMed
is_active_in parallel fiber to Purkinje cell synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in parallel fiber to Purkinje cell synapse	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in presynaptic active zone membrane	IDA Inferred from Direct Assay more info	PubMed
located_in presynaptic active zone membrane	ISO Inferred from Sequence Orthology more info
located_in terminal bouton	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: metabotropic glutamate receptor 4

Names: G protein-coupled receptor GRM4; G protein-coupled receptor, family C, group 1, member D

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001013385.2 → NP_001013403.1 metabotropic glutamate receptor 4 isoform 2 precursor

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an exon in the 3' coding region and uses an alternate 3' terminal exon compared to variant 1. The resulting protein (isoform 2) is shorter and has a distinct C-terminus compared to isoform 1.

Source sequence(s)

AC127341, BC080284

Consensus CDS

CCDS28563.1

UniProtKB/Swiss-Prot

Q68EF4, Q80UC2

UniProtKB/TrEMBL

A0A140T8R6

Related

ENSMUSP00000112578.3, ENSMUST00000118489.8

Conserved Domains (4) summary

pfam00003
Location:599 → 812

7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR

pfam01094
Location:77 → 477

ANF_receptor; Receptor family ligand binding region

pfam07562
Location:517 → 564

NCD3G; Nine Cysteines Domain of family 3 GPCR

cl10011
Location:47 → 508

Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
NM_001291045.2 → NP_001277974.1 metabotropic glutamate receptor 4 isoform 1 precursor

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer protein (isoform 1).

Source sequence(s)

AC127341

Consensus CDS

CCDS70775.1

UniProtKB/Swiss-Prot

Q68EF4, Q80UC2

UniProtKB/TrEMBL

G3XA00

Related

ENSMUSP00000113819.2, ENSMUST00000118161.3

Conserved Domains (3) summary

cd15452
Location:586 → 912

7tmC_mGluR4; metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors

pfam07562
Location:516 → 566

NCD3G; Nine Cysteines Domain of family 3 GPCR

cd06376
Location:43 → 508

PBP1_mGluR_groupIII; ligand-binding domain of the group III metabotropic glutamate receptor
NM_001360192.1 → NP_001347121.1 metabotropic glutamate receptor 4 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (3) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC127341

UniProtKB/TrEMBL

A0A338P783

Related

ENSMUSP00000156277.2, ENSMUST00000231416.2

Conserved Domains (3) summary

cd15452
Location:378 → 704

7tmC_mGluR4; metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors

pfam07562
Location:308 → 358

NCD3G; Nine Cysteines Domain of family 3 GPCR

cl10011
Location:1 → 300

Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily
NM_001379317.1 → NP_001366246.1 metabotropic glutamate receptor 4 isoform 3

Status: VALIDATED

Source sequence(s)

AC127341

UniProtKB/TrEMBL

A0A338P783

Conserved Domains (3) summary

cd15452
Location:378 → 704

7tmC_mGluR4; metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors

pfam07562
Location:308 → 358

NCD3G; Nine Cysteines Domain of family 3 GPCR

cl10011
Location:1 → 300

Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000083.7 Reference GRCm39 C57BL/6J

Range

27641361..27732800 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011246475.3 → XP_011244777.1 metabotropic glutamate receptor 4 isoform X1

UniProtKB/Swiss-Prot

Q68EF4, Q80UC2

UniProtKB/TrEMBL

G3XA00

Related

ENSMUSP00000156001.2, ENSMUST00000231290.2

Conserved Domains (3) summary

cd15452
Location:586 → 912

7tmC_mGluR4; metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors

pfam07562
Location:516 → 566

NCD3G; Nine Cysteines Domain of family 3 GPCR

cd06376
Location:43 → 508

PBP1_mGluR_groupIII; ligand-binding domain of the group III metabotropic glutamate receptor
XM_030249828.1 → XP_030105688.1 metabotropic glutamate receptor 4 isoform X2

UniProtKB/TrEMBL

A0A338P783

Conserved Domains (3) summary

cd15452
Location:278 → 604

7tmC_mGluR4; metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors

pfam07562
Location:208 → 258

NCD3G; Nine Cysteines Domain of family 3 GPCR

cl10011
Location:1 → 200

Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily
XM_006524320.4 → XP_006524383.1 metabotropic glutamate receptor 4 isoform X2

UniProtKB/TrEMBL

A0A338P783

Conserved Domains (3) summary

cd15452
Location:278 → 604

7tmC_mGluR4; metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors

pfam07562
Location:208 → 258

NCD3G; Nine Cysteines Domain of family 3 GPCR

cl10011
Location:1 → 200

Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily
XM_006524321.4 → XP_006524384.1 metabotropic glutamate receptor 4 isoform X3

Conserved Domains (1) summary

cd06376
Location:43 → 501

PBP1_mGluR_groupIII; ligand-binding domain of the group III metabotropic glutamate receptor