GRM3 glutamate metabotropic receptor 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRM3provided by HGNC
Official Full Name: glutamate metabotropic receptor 3provided by HGNC
Primary source: HGNC:HGNC:4595
See related: Ensembl:ENSG00000198822 MIM:601115; AllianceGenome:HGNC:4595
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GLUR3; mGlu3; GPRC1C; MGLUR3
Summary: 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. [provided by RefSeq, Jul 2008]
Expression: Restricted expression toward brain (RPKM 15.9) See more
Orthologs: mouse all
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Genomic context

Location:: 7q21.11-q21.12

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (86643909..86864879)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (87893808..88114781)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (86273225..86494195)

Chromosome 7 - NC_000007.14 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Inhibition of metabotropic glutamate receptor III facilitates sensitization to alkylating chemotherapeutics in glioblastoma.
Title: Inhibition of metabotropic glutamate receptor III facilitates sensitization to alkylating chemotherapeutics in glioblastoma.
Internalization of AMPA-type Glutamate Receptor in the MIN6 Pancreatic beta-cell Line.
Title: Internalization of AMPA-type Glutamate Receptor in the MIN6 Pancreatic β-cell Line.
Spatial transcriptomics identifies spatially dysregulated expression of GRM3 and USP47 in amyotrophic lateral sclerosis.
Title: Spatial transcriptomics identifies spatially dysregulated expression of GRM3 and USP47 in amyotrophic lateral sclerosis.
Circ_0079593 facilitates proliferation, metastasis, glucose metabolism and inhibits apoptosis in melanoma by regulating the miR-516b/GRM3 axis.
Title: Circ_0079593 facilitates proliferation, metastasis, glucose metabolism and inhibits apoptosis in melanoma by regulating the miR-516b/GRM3 axis.
We identified multiple novel associations of genetic variants in GRM3, GRM4, and GRM5 with the risk and the survival of renal cell carcinoma (RCC). These relationships were supported by gene expression profiles obtained using bioinformatics analysis. Specifically, the expression of GRM4 and GRM5 showed an increasing trend in RCC tissues, compared to that in normal tissue, whereas GRM3 was downregulated in RCC.
Title: Clinical significance of glutamate metabotropic receptors in renal cell carcinoma risk and survival.
this study demonstrates that metastasized cells are less migratory due in part to the post-metastatic downregulation of S100A4 and GRM3. Targeting S100A4 and GRM3 may help prevent bone metastasis.
Title: Reduction in Migratory Phenotype in a Metastasized Breast Cancer Cell Line via Downregulation of S100A4 and GRM3.
strong interaction between glutamate and Cl(-) ions allows the mGlu3 receptor to sense and efficiently react to sub-micromolar concentrations of glutamate, making it the most sensitive member of mGluR family
Title: Chloride ions stabilize the glutamate-induced active state of the metabotropic glutamate receptor 3.
Tumor-associated GRM3 variants disrupted trafficking of melanosomes, causing their aggregation in the cell body in a cAMP-dependent manner.
Title: Melanoma-associated GRM3 variants dysregulate melanosome trafficking and cAMP signaling.
experiments indicate that mGlu3Delta4 may negatively modulate mGlu3, and thereby impact on the roles of GRM3/mGlu3 in schizophrenia and as a therapeutic target
Title: A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding.
Our findings support the GWAS-implicated link between GRM3 genetic variation and schizophrenia risk as well as the notion that alleles conferring this risk may be population specific.
Title: Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk.

Submit: New GeneRIF Correction See all GeneRIFs (72)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	The gene expression of GRM3 is significantly upregulated in both clade B and clade C Tat treated SK-N-MC neuroblastoma cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-105153 (e-PCR)
- UniSTS:169217

GRM3 (e-PCR)
- UniSTS:503583

D7S644 (e-PCR), detects polymorphism
- UniSTS:15655

D7S753 (e-PCR)
- UniSTS:20778

GDB:1318509 (e-PCR)
- UniSTS:5421

WI-18027 (e-PCR)
- UniSTS:15935

RH78374 (e-PCR)
- UniSTS:80707

G19925 (e-PCR)
- UniSTS:24905

A002C17 (e-PCR)
- UniSTS:24906

Grm3 (e-PCR), detects polymorphism
- UniSTS:506954

RH94155 (e-PCR)
- UniSTS:87889

G59764 (e-PCR)
- UniSTS:137058

RH93070 (e-PCR)
- UniSTS:85870

Grm3 (e-PCR), detects polymorphism
- UniSTS:495991

D7S1965 (e-PCR)
- UniSTS:22912

G17125 (e-PCR)
- UniSTS:24466

D7S644 (e-PCR), detects polymorphism
- UniSTS:39592

GDB:1318302 (e-PCR)
- UniSTS:55031

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein-coupled receptor activity	TAS Traceable Author Statement more info	PubMed
enables calcium channel regulator activity	IEA Inferred from Electronic Annotation more info
enables glutamate receptor activity	TAS Traceable Author Statement more info	PubMed
enables group II metabotropic glutamate receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables scaffold protein binding	ISS Inferred from Sequence or Structural Similarity more info

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	IEA Inferred from Electronic Annotation more info
involved_in cellular response to stress	IEA Inferred from Electronic Annotation more info
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of adenylate cyclase activity	TAS Traceable Author Statement more info	PubMed
involved_in postsynaptic modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in astrocyte projection	ISS Inferred from Sequence or Structural Similarity more info
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in presynaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: metabotropic glutamate receptor 3

Names: glutamate receptor, metabotropic 3

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_000840.3 → NP_000831.2 metabotropic glutamate receptor 3 isoform 1 precursor

See identical proteins and their annotated locations for NP_000831.2

Status: REVIEWED

Source sequence(s)

AC002081, AC004829, BC041407, X77748

Consensus CDS

CCDS5600.1

UniProtKB/Swiss-Prot

Q14832, Q2PNZ6, Q75MV4, Q75N17, Q86YG6, Q8TBH9

UniProtKB/TrEMBL

A4D1D0, A8K5U1

Related

ENSP00000355316.2, ENST00000361669.7

Conserved Domains (4) summary

cd06375
Location:37 → 494

PBP1_mGluR_groupII; Ligand binding domain of the group II metabotropic glutamate receptor

pfam00003
Location:588 → 825

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

pfam01094
Location:67 → 469

ANF_receptor; Receptor family ligand binding region

pfam07562
Location:506 → 554

NCD3G; Nine Cysteines Domain of family 3 GPCR
NM_001363522.2 → NP_001350451.1 metabotropic glutamate receptor 3 isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AC002081, BC041407, DC374499, DQ315361

Consensus CDS

CCDS87515.1

Related

ENSP00000398767.1, ENST00000439827.1

Conserved Domains (1) summary

cd06375
Location:33 → 441

PBP1_mGluR_groupII; ligand binding domain of the group II metabotropic glutamate receptor

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

86643909..86864879

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047420268.1 → XP_047276224.1 metabotropic glutamate receptor 3 isoform X2

UniProtKB/Swiss-Prot

Q14832, Q2PNZ6, Q75MV4, Q75N17, Q86YG6, Q8TBH9

UniProtKB/TrEMBL

A4D1D0
XM_017012073.3 → XP_016867562.1 metabotropic glutamate receptor 3 isoform X1