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FLASH GENE
Symbol GRM1 contributors: mct - updated : 17-10-2017
HGNC name glutamate receptor, metabotropic 1
HGNC id 4593
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
- - - - - mRNA was observed in two different melanoma cell lines and is overexpressed, compared with melanoma precursor cells, melanocytes 2013 23481697
  • encodes a predicted C-terminal splice variant of 10 additional amino acids
  • play a distinct role in primate glutamatergic signaling
  • 9 - 6757 - 906 - 2014 25158311
    10 - 6839 - 906 . GRM1A and GRM1B variants distribution overlaps in Purkinje cells and the two variants colocalize in their spines . GRM1A, GRM1B show distinct sub-cellular localization when expressed alone in neurons 2014 25158311
    GRM1B
    8 - 6707 - 1194 . GRM1A and GRM1B variants distribution overlaps in Purkinje cells and the two variants colocalize in their spines . GRM1A, GRM1B show distinct sub-cellular localization when expressed alone in neurons 2014 25158311
  • GRM1A
  • a long C-terminal domain (341 amino acids), shown to scaffold with several proteins and contribute to the structure of the post-synaptic density
  • predominant splice variant in Purkinje cells, having a long (C)-terminal domain that interacts with HOMER scaffolding proteins
  • 8 - 6672 - 908 - 2014 25158311
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly Homo sapiens
     brainforebraincerebral cortex   Homo sapiens
     brainhindbraincerebellum highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    NervousPurkinje cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven transmembrane segments (7TM) receptor
  • C-terminal PDZ-binding motif
  • HOMOLOGY
    Homologene
    FAMILY
  • G-protein coupled receptor family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,nucleus
    text
  • recruitment to lipid rafts is enhanced by agonist binding and is supported at least in part by an intact cholesterol recognition/interaction amino acid consensus (CRAC) motif in the receptor
  • basic FUNCTION
  • activating PI turnover and triggering intracellular calcium release
  • important neuronal mediator of postsynaptic signaling that influence synaptic strength, plasticity, and other factors
  • control metaplasticity of spinal learning through a PKC-dependent mechanism
  • with GRM5, plays a role in the early stages of corticogenesis with, however, a different contribution to human cortical developmental events
  • involved in synaptic activities, learning and neuroprotection
  • important role of GRM1 in pain-related amygdala plasticity and evidence for the involvement of HOMER1 proteins in the forebrain in the modulation of pain hypersensitivity
  • plays an important role in cerebellar development and synaptic plasticity
  • can be an oncogene in epithelial cells
  • GRM1, GRM5 play critical functions in forms of activity-dependent synaptic plasticity and synapse remodeling in physiological and pathological states
  • assembly of two covalently linked monomers into dimeric complexes is a prerequisite for metabotropic glutamate receptor 1 (GRM1) function
  • plays an important role in synaptic plasticity and cerebellar development
  • GRM1, GRM5 are key elements in the dynamic regulation of cholinergic synaptic inputs onto neurons of the thalamic reticular nucleus (TRN)
  • novel function of ubiquitination in the regulation of GRM1, as well as its role in mGluR-dependent AMPAR endocytosis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of phosphate receptors
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to homer proteins
  • activating FMR1, TRPC1 and DLG4(activation GRM1-dependent)
  • binding partner of GOPC, through its PSD95/discslarge/ZO1 homology domain (inhibit GRM1-mediated ERK1/2 activation, without an apparent effect, via the C-terminal-truncated receptor)
  • molecular link between GRM1 and FMR1 in the anterior cingulate cortex (ACC), a key region involved in high brain cognitive and executive functions
  • associates with the PDZ protein tamalin (GRASP)
  • interaction with caveolin-1 which controls the rate of constitutive GRM1 internalization
  • 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
  • STIM1 controls neuronal Ca++ signaling, GRM1-dependent synaptic transmission, and cerebellar motor behavior
  • cooperative signaling between GRM1 and GRM5 is in a manner inconsistent with heterodimerization, and thus suggest an interaction between homodimers
  • NRG1 selectively increases GRM1-activated currents by inducing synthesis and trafficking to membrane of functional receptors
  • cell & other
  • linked to inositol phosphate receptors
  • REGULATION
    Other regulation of its localization and function by Homer proteins
    ASSOCIATED DISORDERS
    corresponding disease(s) SCAR13 , SCA44
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    aberrantly expressed in melanomas
    tumoral       gain of function
    through gene fusion and promoter swapping in chondromyxoid fibroma
    Susceptibility to melanoma
    Variant & Polymorphism other increasing the risk of GRM1
    Candidate gene
    Marker
    Therapy target
  • potential therapeutic target for promoting use-dependent plasticity after spinal cord injury
  • ANIMAL & CELL MODELS