GRM2 glutamate metabotropic receptor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRM2provided by HGNC
Official Full Name: glutamate metabotropic receptor 2provided by HGNC
Primary source: HGNC:HGNC:4594
See related: Ensembl:ENSG00000164082 MIM:604099; AllianceGenome:HGNC:4594
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: GLUR2; mGlu2; GPRC1B; MGLUR2
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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]
Expression: Biased expression in testis (RPKM 2.8), brain (RPKM 2.2) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (51707068..51718613)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (51738578..51751605)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (51741084..51752629)

Chromosome 3 - NC_000003.12 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 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?

Exploring the activation mechanism of metabotropic glutamate receptor 2.
Title: Exploring the activation mechanism of metabotropic glutamate receptor 2.
Heterodimerization of Chemoreceptors TAS1R3 and mGlu2 in Human Blood Leukocytes.
Title: Heterodimerization of Chemoreceptors TAS1R3 and mGlu(2) in Human Blood Leukocytes.
The crosstalk between 5-HT2AR and mGluR2 in schizophrenia.
Title: The crosstalk between 5-HT(2A)R and mGluR2 in schizophrenia.
G-protein activation by a metabotropic glutamate receptor.
Title: G-protein activation by a metabotropic glutamate receptor.
Structures of Gi-bound metabotropic glutamate receptors mGlu2 and mGlu4.
Title: Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4.
Structures of human mGlu2 and mGlu7 homo- and heterodimers.
Title: Structures of human mGlu2 and mGlu7 homo- and heterodimers.
DNA methylation changes in genes involved in inflammation and depression in fibromyalgia: a pilot study.
Title: DNA methylation changes in genes involved in inflammation and depression in fibromyalgia: a pilot study.
Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state.
Title: Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state.
Conformational rearrangement during activation of a metabotropic glutamate receptor.
Title: Conformational rearrangement during activation of a metabotropic glutamate receptor.
This study investigates the role of unstructured loop (or "BC loop") in Glutamate induced conformation of mGluR2 and its activation. mGluR2 without BC loop does not respond to Glutamate.
Title: Unstructured loop is essential for the activation of mGluR2.

Submit: New GeneRIF Correction See all GeneRIFs (46)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-20087 (e-PCR)
- UniSTS:7224

RH66405 (e-PCR)
- UniSTS:12870

GRM2 (e-PCR)
- UniSTS:264045

SHGC-77001 (e-PCR)
- UniSTS:4979

A002C19 (e-PCR)
- UniSTS:17038

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 protein binding	IPI Inferred from Physical Interaction more info	PubMed
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 behavioral response to nicotine	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 glutamate secretion	IEA Inferred from Electronic Annotation more info
involved_in intracellular glutamate homeostasis	IEA Inferred from Electronic Annotation more info
involved_in long-term synaptic depression	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of adenylate cyclase activity	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in presynaptic modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in regulation of dopamine secretion	IEA Inferred from Electronic Annotation more info
involved_in regulation of glutamate secretion	IEA Inferred from Electronic Annotation more info
involved_in regulation of response to drug	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to cocaine	IEA Inferred from Electronic Annotation 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 dendrite	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 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 2

Names: glutamate receptor homolog; glutamate receptor, metabotropic 2

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_000839.5 → NP_000830.2 metabotropic glutamate receptor 2 isoform a precursor

See identical proteins and their annotated locations for NP_000830.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AC099050, AK315816, BC041447, DA528713

Consensus CDS

CCDS2834.1

UniProtKB/Swiss-Prot

B0M0K7, Q14416, Q14CU5, Q52MC6, Q9H3N6

UniProtKB/TrEMBL

A8K1R9, B0AZM5

Related

ENSP00000378492.3, ENST00000395052.8

Conserved Domains (4) summary

cd06375
Location:30 → 480

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

pfam00003
Location:579 → 816

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

pfam01094
Location:60 → 456

ANF_receptor; Receptor family ligand binding region

pfam07562
Location:498 → 545

NCD3G; Nine Cysteines Domain of family 3 GPCR
NM_001349116.2 → NP_001336045.1 metabotropic glutamate receptor 2 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (c) is shorter at the N-terminus compared to isoform a.

Source sequence(s)

AC099050

UniProtKB/TrEMBL

Q86YG3

Conserved Domains (4) summary

pfam07562
Location:120 → 168

NCD3G; Nine Cysteines Domain of family 3 GPCR

cd14964
Location:189 → 213

7tm_GPCRs; TM helix 1 [structural motif]

cl10011
Location:1 → 102

Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

cl28897
Location:188 → 441

7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily
NM_001349117.2 → NP_001336046.1 metabotropic glutamate receptor 2 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate internal exon compared to variant 1. The resulting isoform (d) has a shorter and distinct N-terminus compared to isoform a.

Source sequence(s)

AC099050, AK313056, BC041447, DA528713

UniProtKB/TrEMBL

Q86YG3

Conserved Domains (4) summary

pfam07562
Location:99 → 149

NCD3G; Nine Cysteines Domain of family 3 GPCR

cd14964
Location:169 → 194

7tm_GPCRs; TM helix 1 [structural motif]

cl10011
Location:29 → 83

Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily

cl28897
Location:169 → 422

7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily

RNA

NR_146059.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two alternate exons compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.

Source sequence(s)

AC099050, BC041447, DA528713

Related

ENST00000475478.5

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_000003.12 Reference GRCh38.p14 Primary Assembly

Range

51707068..51718613

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011533636.2 → XP_011531938.1 metabotropic glutamate receptor 2 isoform X3

Conserved Domains (3) summary

pfam00003
Location:397 → 634

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

pfam07562
Location:316 → 363

NCD3G; Nine Cysteines Domain of family 3 GPCR

cl10011
Location:30 → 298

Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
XM_017006271.2 → XP_016861760.1 metabotropic glutamate receptor 2 isoform X1

UniProtKB/Swiss-Prot

B0M0K7, Q14416, Q14CU5, Q52MC6, Q9H3N6

UniProtKB/TrEMBL

A8K1R9, B0AZM5

Conserved Domains (4) summary

cd06375
Location:30 → 480

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

pfam00003
Location:579 → 816

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

pfam01094
Location:60 → 456

ANF_receptor; Receptor family ligand binding region

pfam07562
Location:498 → 545

NCD3G; Nine Cysteines Domain of family 3 GPCR
XM_047448047.1 → XP_047304003.1 metabotropic glutamate receptor 2 isoform X2
XM_011533642.2 → XP_011531944.1 metabotropic glutamate receptor 2 isoform X5

Conserved Domains (2) summary

cd06375
Location:30 → 470

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

pfam01094
Location:60 → 456

ANF_receptor; Receptor family ligand binding region
XM_024453490.2 → XP_024309258.1 metabotropic glutamate receptor 2 isoform X7

UniProtKB/TrEMBL

H7BXL3

Related

ENSP00000296479.5, ENST00000296479.9

Conserved Domains (1) summary

cl10011
Location:30 → 429

Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
XM_047448051.1 → XP_047304007.1 metabotropic glutamate receptor 2 isoform X4
XM_047448048.1 → XP_047304004.1 metabotropic glutamate receptor 2 isoform X4
XM_047448049.1 → XP_047304005.1 metabotropic glutamate receptor 2 isoform X4
XM_047448050.1 → XP_047304006.1 metabotropic glutamate receptor 2 isoform X4
XM_011533637.2 → XP_011531939.1 metabotropic glutamate receptor 2 isoform X4

See identical proteins and their annotated locations for XP_011531939.1

Conserved Domains (4) summary

pfam00003
Location:385 → 622

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

pfam01094
Location:1 → 262

ANF_receptor; Receptor family ligand binding region

pfam07562
Location:304 → 351

NCD3G; Nine Cysteines Domain of family 3 GPCR

cl10011
Location:1 → 286

Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
XM_011533643.2 → XP_011531945.1 metabotropic glutamate receptor 2 isoform X6

Conserved Domains (2) summary

pfam00003
Location:147 → 384

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

pfam07562
Location:69 → 113

NCD3G; Nine Cysteines Domain of family 3 GPCR

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

51738578..51751605

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054346368.1 → XP_054202343.1 metabotropic glutamate receptor 2 isoform X2
XM_054346369.1 → XP_054202344.1 metabotropic glutamate receptor 2 isoform X3
XM_054346367.1 → XP_054202342.1 metabotropic glutamate receptor 2 isoform X1

UniProtKB/Swiss-Prot

B0M0K7, Q14416, Q14CU5, Q52MC6, Q9H3N6
XM_054346375.1 → XP_054202350.1 metabotropic glutamate receptor 2 isoform X5
XM_054346377.1 → XP_054202352.1 metabotropic glutamate receptor 2 isoform X7

UniProtKB/TrEMBL

H7BXL3
XM_054346374.1 → XP_054202349.1 metabotropic glutamate receptor 2 isoform X4
XM_054346371.1 → XP_054202346.1 metabotropic glutamate receptor 2 isoform X4
XM_054346372.1 → XP_054202347.1 metabotropic glutamate receptor 2 isoform X4
XM_054346373.1 → XP_054202348.1 metabotropic glutamate receptor 2 isoform X4
XM_054346370.1 → XP_054202345.1 metabotropic glutamate receptor 2 isoform X4
XM_054346376.1 → XP_054202351.1 metabotropic glutamate receptor 2 isoform X6