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

Gene ID: 2912, updated on 11-Apr-2024

Summary

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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
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Genomic context

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See GRM2 in Genome Data Viewer
Location:
3p21.2
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (51707068..51718613)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (51738578..51751605)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (51741084..51752629)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene RAD54 like 2 Neighboring gene uncharacterized LOC124906237 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14416 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:51712641-51713399 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14417 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:51721007-51721622 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:51724855-51725678 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:51725679-51726501 Neighboring gene testis expressed 264, ER-phagy receptor Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:51737956-51738824 Neighboring gene RNA, 5S ribosomal pseudogene 132 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:51750466-51751323 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:51776905-51777405 Neighboring gene uncharacterized LOC105377087 Neighboring gene NANOG hESC enhancer GRCh37_chr3:51835876-51836627 Neighboring gene IQ motif containing F6 Neighboring gene IQ motif containing F4, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state. Cao AM, et al. Nat Commun, 2021 Sep 14. PMID 34521824, Free PMC Article
  2. DNA methylation changes in genes involved in inflammation and depression in fibromyalgia: a pilot study. Gerra MC, et al. Scand J Pain, 2021 Apr 27. PMID 34387961
  3. G-protein activation by a metabotropic glutamate receptor. Seven AB, et al. Nature, 2021 Jul. PMID 34194039, Free PMC Article
  4. Conformational rearrangement during activation of a metabotropic glutamate receptor. Liauw BW, et al. Nat Chem Biol, 2021 Mar. PMID 33398167, Free PMC Article
  5. Unstructured loop is essential for the activation of mGluR2. Singh DR, et al. Biochem Biophys Res Commun, 2020 Jan 15. PMID 31706572

See all (61) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Heterodimerization of Chemoreceptors TAS1R3 and mGlu2 in Human Blood Leukocytes.
    Title: Heterodimerization of Chemoreceptors TAS1R3 and mGlu(2) in Human Blood Leukocytes.
  2. The crosstalk between 5-HT2AR and mGluR2 in schizophrenia.
    Title: The crosstalk between 5-HT(2A)R and mGluR2 in schizophrenia.
  3. G-protein activation by a metabotropic glutamate receptor.
    Title: G-protein activation by a metabotropic glutamate receptor.
  4. Structures of Gi-bound metabotropic glutamate receptors mGlu2 and mGlu4.
    Title: Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4.
  5. Structures of human mGlu2 and mGlu7 homo- and heterodimers.
    Title: Structures of human mGlu2 and mGlu7 homo- and heterodimers.
  6. 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.
  7. 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.
  8. Conformational rearrangement during activation of a metabotropic glutamate receptor.
    Title: Conformational rearrangement during activation of a metabotropic glutamate receptor.
  9. 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.
  10. data suggests that glutamatergic activity through GRM2 in cerebral cortex may differ with gender and suicide ideation.
    Title: Changes in levels of cortical metabotropic glutamate 2 receptors with gender and suicide but not psychiatric diagnoses.
Submit: New GeneRIF Correction See all GeneRIFs (45)

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)

Genotypes

Pathways from PubChem

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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

Homology

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 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 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)

  1. 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

  2. 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

  3. 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

  1. 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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    51707068..51718613
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. XM_047448047.1 → XP_047304003.1  metabotropic glutamate receptor 2 isoform X2

  4. 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

  5. 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

  6. XM_047448051.1 → XP_047304007.1  metabotropic glutamate receptor 2 isoform X4

  7. XM_047448048.1 → XP_047304004.1  metabotropic glutamate receptor 2 isoform X4

  8. XM_047448049.1 → XP_047304005.1  metabotropic glutamate receptor 2 isoform X4

  9. XM_047448050.1 → XP_047304006.1  metabotropic glutamate receptor 2 isoform X4

  10. 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

  11. 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

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    51738578..51751605
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054346368.1 → XP_054202343.1  metabotropic glutamate receptor 2 isoform X2

  2. XM_054346369.1 → XP_054202344.1  metabotropic glutamate receptor 2 isoform X3

  3. XM_054346367.1 → XP_054202342.1  metabotropic glutamate receptor 2 isoform X1

    UniProtKB/Swiss-Prot
    B0M0K7, Q14416, Q14CU5, Q52MC6, Q9H3N6

  4. XM_054346375.1 → XP_054202350.1  metabotropic glutamate receptor 2 isoform X5

  5. XM_054346377.1 → XP_054202352.1  metabotropic glutamate receptor 2 isoform X7

    UniProtKB/TrEMBL
    H7BXL3

  6. XM_054346374.1 → XP_054202349.1  metabotropic glutamate receptor 2 isoform X4

  7. XM_054346371.1 → XP_054202346.1  metabotropic glutamate receptor 2 isoform X4

  8. XM_054346372.1 → XP_054202347.1  metabotropic glutamate receptor 2 isoform X4

  9. XM_054346373.1 → XP_054202348.1  metabotropic glutamate receptor 2 isoform X4

  10. XM_054346370.1 → XP_054202345.1  metabotropic glutamate receptor 2 isoform X4

  11. XM_054346376.1 → XP_054202351.1  metabotropic glutamate receptor 2 isoform X6

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q14416.2 GenPept UniProtKB/Swiss-Prot:Q14416

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