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

    Gene ID: 2912, updated on 17-Jun-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
    mouse all
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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. Exploring the activation mechanism of metabotropic glutamate receptor 2.
      Title: Exploring the activation mechanism of metabotropic glutamate receptor 2.
    2. Heterodimerization of Chemoreceptors TAS1R3 and mGlu2 in Human Blood Leukocytes.
      Title: Heterodimerization of Chemoreceptors TAS1R3 and mGlu(2) in Human Blood Leukocytes.
    3. The crosstalk between 5-HT2AR and mGluR2 in schizophrenia.
      Title: The crosstalk between 5-HT(2A)R and mGluR2 in schizophrenia.
    4. G-protein activation by a metabotropic glutamate receptor.
      Title: G-protein activation by a metabotropic glutamate receptor.
    5. Structures of Gi-bound metabotropic glutamate receptors mGlu2 and mGlu4.
      Title: Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4.
    6. Structures of human mGlu2 and mGlu7 homo- and heterodimers.
      Title: Structures of human mGlu2 and mGlu7 homo- and heterodimers.
    7. 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.
    8. 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.
    9. Conformational rearrangement during activation of a metabotropic glutamate receptor.
      Title: Conformational rearrangement during activation of a metabotropic glutamate receptor.
    10. 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)

    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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    NEW Try the new Transcript table

    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

      UniProtKB/TrEMBL
      A8K1R9, B0AZM5

    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

      UniProtKB/TrEMBL
      A8K1R9, B0AZM5

    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
      UniProtKB/TrEMBL
      A8K1R9, B0AZM5

    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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