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FLASH GENE
Symbol GRM2 contributors: mct/npt - updated : 11-02-2013
HGNC name glutamate receptor, metabotropic 2
HGNC id 4594
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven transmembrane segments (7TM) receptor
    • conjugated GlycoP
    mono polymer heteromer
    HOMOLOGY
    Homologene
    FAMILY
  • G protein coupled receptor superfamily
  • G-protein coupled receptor 3 family
    • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • metabotropic glutamate receptor, goup II, linked to the inhibition of cAMP cascade
  • involved in glutamate homeostasis as well as in glial proliferation
  • may participate in mediating the survival of neurons in the face of selective neuronal dysfunction and degeneration in Alzheimer disease
  • is resistant to agonist-induced homologous desensitization
  • functional plasticity of GRM2 in regulating spinal excitatory and inhibitory synaptic input in neuropathic pain
  • GRM2, and GRM3, are inhibitory autoreceptors that negatively modulate the adenylate cyclase signaling cascade
  • within the hippocampus, GRM2 is believed to play a key role in the induction of long-term depression (LTD) at mossy fiber-CA3 synapses
  • plays an important role on the presynaptic control of glutamate release, and negative allosteric modulators (NAMs) acting on GRM2/GRM3 are under assessment for their potential as antidepressants, neurogenics and cognitive enhancers
  • GRM2 and HTR2A form a functional heteromeric complex through which hallucinogenic drugs cross-signal to the Gi-coupled receptor
  • monomeric, couples to G proteins upon direct activation by a positive allosteric modulator
  • dimeric GRM2 activates G protein upon glutamate binding, suggesting that dimerization is required for glutamate induced activation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with HTR2A (complex that may be involved in the altered cortical processes of schizophrenia)
  • HTR2A/GRM2 complex is necessary for the neuropsychological responses induced by hallucinogens 8)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • heteromeric complex between the HTR2A and GRM2, integrates ligand input, modulating signaling output and behavioral changes
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in amyotrophic lateral sclerosis spinal cord
    constitutional     --low  
    in brain from untreated schizophrenic subjects
    constitutional     --over  
    in pyramidal neurons in the hippocampus of Alzheimer disease and often co-localizes with neurofibrillary pathology
    constitutional     --over  
    in schizophrenia, significantly higher levels of GRM2 mRNA in the prefrontal white matter
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    psychiatrybipolar disorder 
    GRM2/GRM3 antagonists are promising targets for the discovery of novel antidepressants
    psychiatryschizophrenia 
    complex HTR2A/GRM2 is a promising new target for the treatment of psychosis
    ANIMAL & CELL MODELS