My NCBISign In

Display Settings:

Format

Send to:

Choose Destination

    GRM1 glutamate receptor, metabotropic 1 [ Homo sapiens ]

    Gene ID: 2911, updated on 19-May-2012
    Help top of page

    Summary

    Official Symbol
    GRM1provided by HGNC
    Official Full Name
    glutamate receptor, metabotropic 1provided by HGNC
    Primary source
    HGNC:4593
    See related
    Ensembl:ENSG00000152822; HPRD:05129; MIM:604473; Vega:OTTHUMG00000015752
    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
    GRM1A; mGlu1; GPRC1A; MGLUR1; MGLUR1A
    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. The canonical alpha isoform of the metabotropic glutamate receptor 1 gene is a disulfide-linked homodimer whose activity is mediated by a G-protein-coupled phosphatidylinositol-calcium second messenger system. Alternative splicing results in multiple transcript variants encoding distinct isoforms; some of which may have distinct functions. [provided by RefSeq, Jul 2008]
    Help top of page

    Genomic context

    Location :
    6q24
    Sequence :
    Chromosome: 6; NC_000006.11 (146348782..146758731)
    See GRM1 in Epigenomics, MapViewer

    Chromosome 6 - NC_000006.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100507557 Neighboring gene F-box protein 30 Neighboring gene SNF2 histone linker PHD RING helicase, E3 ubiquitin protein ligase Neighboring gene FUN14 domain containing 2 pseudogene 3 Neighboring gene RAB32, member RAS oncogene family Neighboring gene androglobin Neighboring gene chromosome 15 open reading frame 29 pseudogene

    Help top of page

    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
    Helptop of page

    Bibliography

    Related articles in PubMed

    1. Clustered coding variants in the glutamate receptor complexes of individuals with schizophrenia and bipolar disorder. Frank RA, et al. PLoS One, 2011 Apr 29. PMID 21559497.
    2. Disruption of metabotropic glutamate receptor signalling is a major defect at cerebellar parallel fibre-Purkinje cell synapses in staggerer mutant mice. Mitsumura K, et al. J Physiol, 2011 Jul 1. PMID 21558162.
    3. Potential therapeutic interventions for fragile X syndrome. Levenga J, et al. Trends Mol Med, 2010 Nov. PMID 20864408.
    4. Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol. Giegling I, et al. Pharmacogenet Genomics, 2011 Apr. PMID 20859245.
    5. Elucidation of a novel extracellular calcium-binding site on metabotropic glutamate receptor 1{alpha} (mGluR1{alpha}) that controls receptor activation. Jiang Y, et al. J Biol Chem, 2010 Oct 22. PMID 20705606.

    See all (68) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Disruption of mGluR1 signaling at parallel fiber-Purkinje cell synapses is a major synaptic defect in homozygous staggerer mice, correlating with spinocerebellar ataxia (SCA) type 1 pathology in the extreme mouse model.
      Title: Disruption of metabotropic glutamate receptor signalling is a major defect at cerebellar parallel fibre-Purkinje cell synapses in staggerer mutant mice.
    2. analysis of clustered coding variants in the glutamate receptor complexes of individuals with schizophrenia and bipolar disorder
      Title: Clustered coding variants in the glutamate receptor complexes of individuals with schizophrenia and bipolar disorder.
    3. Data reveal that Pyk2 couples the activation mGluRs to the ERK1/2 mitogen-activated protein kinase pathway even though it attenuates mGluR1-dependent G protein signaling.
      Title: Pyk2 uncouples metabotropic glutamate receptor G protein signaling but facilitates ERK1/2 activation.
    4. Studies indicate that FXS has been linked to altered group I metabotropic glutamate receptor (mGluR)-dependent, and potential targeted therapeutic strategies developed to specifically correct disturbances in the excitatory mGluR.
      Title: Potential therapeutic interventions for fragile X syndrome.
    5. Elucidation of a novel extracellular calcium-binding site on metabotropic glutamate receptor 1{alpha} (mGluR1{alpha}) that controls receptor activation.
      Title: Elucidation of a novel extracellular calcium-binding site on metabotropic glutamate receptor 1{alpha} (mGluR1{alpha}) that controls receptor activation.
    6. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol.
    7. These findings show a differential expression pattern of mGluR1a and mGluR5, suggesting a role for both receptors in the early stages of corticogenesis with, however, a different contribution to human cortical developmental events.
      Title: Differential distribution of group I metabotropic glutamate receptors in developing human cortex.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    9. Absence of mutations in a relatively small cohort of patients appears to suggest that mutations in GRM1 are not frequent in cerebellar ataxias.
      Title: The metabotropic glutamate receptor 1, GRM1: evaluation as a candidate gene for inherited forms of cerebellar ataxia.
    10. Taken together, these results showed that, in addition to the MAPK pathway previously reported being a downstream target of stimulated Grm1, AKT2 is another downstream target in Grm1 mediated melanocyte transformation.
      Title: AKT2 is a downstream target of metabotropic glutamate receptor 1 (Grm1).
    Submit: New GeneRIF Correction See all (35)
    Help top of page

    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Help top of page

    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat upregulates N-methyl-D-aspartate receptor function by activating metabotropic glutamate receptor 1 in human brain noradrenergic neurons PubMed

    Go to the HIV-1, Human Protein Interaction Database

    Help top of page

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q13255 P30542 ADORA1    HPRD  PubMed  
    Q13255 P25098 ADRBK1    HPRD  PubMed  
    Q13255 P52799 EFNB2    HPRD  PubMed  
    Q13255 P04406 GAPDH    HPRD  PubMed  
    Q13255 Q5JY77 GPRASP1    HPRD  PubMed  
    Q13255 Q7Z6J2 GRASP    HPRD  PubMed  
    Q13255 Q13255 GRM1    HPRD  PubMed  
    Q13255 Q86YM7 HOMER1    HPRD  PubMed  
    Q13255 Q9NSB8 HOMER2    HPRD  PubMed  
    Q13255 Q14643 ITPR1    HPRD  PubMed  
    Q13255 P17252 PRKCA    HPRD  PubMed  
    Q13255 P07437 TUBB    HPRD  PubMed  
    BioGRID:109168 BioGRID:106646 ADORA1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109168 BioGRID:109168 GRM1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:109168 BioGRID:113071 TRPC1    BioGRID  PubMed Affinity Capture-Western 
    Help top of page

    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Calcium signaling pathway, organism-specific biosystem (from KEGG)
      Calcium signaling pathway, organism-specific biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
    • Calcium signaling pathway, conserved biosystem (from KEGG)
      Calcium signaling pathway, conserved biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
    • Class C/3 (Metabotropic glutamate/pheromone receptors), organism-specific biosystem (from REACTOME)
      Class C/3 (Metabotropic glutamate/pheromone receptors), organism-specific biosystemThe class C G-protein-coupled receptors are a class of G-protein coupled receptors that include the metabotropic glutamate receptors and several additional receptors (Bräuner-Osborne H et al, 2007)....
    • GPCR ligand binding, organism-specific biosystem (from REACTOME)
      GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
    • GPCRs, Class C Metabotropic glutamate, pheromone, organism-specific biosystem (from WikiPathways)
      GPCRs, Class C Metabotropic glutamate, pheromone, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.cmbi.kun.nl/7tm/. The groupings are based on the GPCR phylogenetic tree available from the GPCRDB and the training sets used ...
    • GPCRs, Other, organism-specific biosystem (from WikiPathways)
      GPCRs, Other, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.cmbi.kun.nl/7tm/. The groupings are based on the GPCR phylogenetic tree available from the GPCRDB and the training sets used ...
    • Gap junction, organism-specific biosystem (from KEGG)
      Gap junction, organism-specific biosystemGap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels'...
    • Gap junction, conserved biosystem (from KEGG)
      Gap junction, conserved biosystemGap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels'...
    • Glutamatergic synapse, organism-specific biosystem (from KEGG)
      Glutamatergic synapse, organism-specific biosystemGlutamate is the major excitatory neurotransmitter in the mammalian central nervous system(CNS). Glutamate is packaged into synaptic vesicles in the presynaptic terminal. Once released into the synap...
    • Glutamatergic synapse, conserved biosystem (from KEGG)
      Glutamatergic synapse, conserved biosystemGlutamate is the major excitatory neurotransmitter in the mammalian central nervous system(CNS). Glutamate is packaged into synaptic vesicles in the presynaptic terminal. Once released into the synap...
    • Huntington's disease, organism-specific biosystem (from KEGG)
      Huntington's disease, organism-specific biosystemHuntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality...
    • Huntington's disease, conserved biosystem (from KEGG)
      Huntington's disease, conserved biosystemHuntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality...
    • Hypothetical Network for Drug Addiction, organism-specific biosystem (from WikiPathways)
      Hypothetical Network for Drug Addiction, organism-specific biosystemAdapted from figure 2 in [http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0040002 Li et al.].
    • Long-term depression, organism-specific biosystem (from KEGG)
      Long-term depression, organism-specific biosystemCerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and...
    • Long-term depression, conserved biosystem (from KEGG)
      Long-term depression, conserved biosystemCerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and...
    • Long-term potentiation, organism-specific biosystem (from KEGG)
      Long-term potentiation, organism-specific biosystemHippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippo...
    • Long-term potentiation, conserved biosystem (from KEGG)
      Long-term potentiation, conserved biosystemHippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippo...
    • Neuroactive ligand-receptor interaction, organism-specific biosystem (from KEGG)
      Neuroactive ligand-receptor interaction, organism-specific biosystem
      Neuroactive ligand-receptor interaction
    • Neuroactive ligand-receptor interaction, conserved biosystem (from KEGG)
      Neuroactive ligand-receptor interaction, conserved biosystem
      Neuroactive ligand-receptor interaction
    • Retrograde endocannabinoid signaling, organism-specific biosystem (from KEGG)
      Retrograde endocannabinoid signaling, organism-specific biosystemEndogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The family of endocannabinoids includes at least five derivatives of arachidonic...
    • Retrograde endocannabinoid signaling, conserved biosystem (from KEGG)
      Retrograde endocannabinoid signaling, conserved biosystemEndogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The family of endocannabinoids includes at least five derivatives of arachidonic...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    G-protein coupled receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    estrogen receptor binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    glutamate receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    signal transducer activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    G-protein coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    activation of MAPK activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    activation of MAPKK activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    calcium-mediated signaling IEA
    Inferred from Electronic Annotation
    more info
    		  
    cellular response to electrical stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    locomotory behavior IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of sensory perception of pain IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of synaptic transmission, glutamatergic IEA
    Inferred from Electronic Annotation
    more info
    		  
    synaptic transmission IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    axon IEA
    Inferred from Electronic Annotation
    more info
    		  
    dendritic spine IEA
    Inferred from Electronic Annotation
    more info
    		  
    integral to plasma membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    microsome IEA
    Inferred from Electronic Annotation
    more info
    		  
    nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    postsynaptic density IEA
    Inferred from Electronic Annotation
    more info
    		  
    presynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    Help top of page

    General protein information

    Preferred Names
    metabotropic glutamate receptor 1
    Names
    metabotropic glutamate receptor 1
    Help top of page

    NCBI Reference Sequences (RefSeq)

    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.

    Genomic

    1. NG_012839.1 RefSeqGene

      Range
      5001..414950
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000838.3 → NP_000829.2  metabotropic glutamate receptor 1 isoform alpha precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (alpha).
      Source sequence(s)
      AB208837, AK308550, L76627
      Consensus CDS
      CCDS5209.1
      UniProtKB/Swiss-Prot
      Q13255
      UniProtKB/TrEMBL
      Q59HC2
      Related
      ENSP00000354896, ENST00000361719
      Conserved Domains (5) summary
      cd06374
      Location:36 – 510
      Blast Score: 2427
      PBP1_mGluR_groupI; Ligand binding domain of the group I metabotropic glutamate receptor
      pfam10606
      Location:1144 – 1194
      Blast Score: 149
      GluR_Homer-bdg; Homer-binding domain of metabotropic glutamate receptor
      pfam07562
      Location:521 – 571
      Blast Score: 209
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      pfam00003
      Location:617 – 838
      Blast Score: 685
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:77 – 485
      Blast Score: 628
      ANF_receptor; Receptor family ligand binding region

    2. NM_001114329.1 → NP_001107801.1  metabotropic glutamate receptor 1 isoform beta precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes the shorter isoform (beta). Isoform beta has a different subcellular distribution than isoform alpha and may be functionally distinct due to differential G-protein coupling of its novel C-terminal sequence.
      Source sequence(s)
      AB208837, AK308550, L76631
      Consensus CDS
      CCDS47497.1
      UniProtKB/Swiss-Prot
      Q13255
      UniProtKB/TrEMBL
      Q59HC2
      Related
      ENSP00000376119, ENST00000392299
      Conserved Domains (4) summary
      cd06374
      Location:36 – 510
      Blast Score: 2426
      PBP1_mGluR_groupI; Ligand binding domain of the group I metabotropic glutamate receptor
      pfam07562
      Location:521 – 571
      Blast Score: 205
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      pfam00003
      Location:617 – 838
      Blast Score: 657
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:77 – 485
      Blast Score: 622
      ANF_receptor; Receptor family ligand binding region

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000006.11 Reference GRCh37.p5 Primary Assembly

      Range
      146348782..146758731
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000138.1 Alternate HuRef

      Range
      143912005..144322102
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Help top of page

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL031769.1 None
    genomic AL035698.12 CAI22468.1
      CAI22469.1
    genomic AL096867.15 CAI20335.1
      CAI20336.1
    genomic AL592423.8 CAH71181.1
      CAH71182.1
    genomic CH471051.2 EAW47834.1
      EAW47835.1
    mRNA AB208837.1 BAD92074.1
    mRNA AK308550.1 None
    mRNA BC136280.1 AAI36281.1
    mRNA BC143777.1 None
    mRNA BC143779.1 None
    mRNA L76627.1 AAB05337.1
    mRNA L76631.1 AAB05338.1
    mRNA U31215.1 AAA87843.1
    mRNA U31216.1 AAA87844.1
    other-genetic BC111844.2 AAI11845.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13255.3 GenPept UniProtKB/Swiss-Prot:Q13255
    Q59HC2 GenPept UniProtKB/TrEMBL:Q59HC2
    Help top of page

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Links

      Links to other resources

      General information

      Related sites

      Feedback

      Subscription

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...