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FLASH GENE
Symbol GRIN1 contributors: mct - updated : 21-10-2018
HGNC name glutamate receptor, ionotropic, N-methyl D-aspartate 1
HGNC id 4584
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four transmembrane segments (4TM)
  • a long extracellular domain
  • twofold symmetry axis running through the entire molecule composed of an N terminal domain (ATD), a ligand-binding domain (LBD), and a transmembrane domain (TMD)
  • critical role of the single AA within the GRIN1 M4 domain in the surface delivery of functional NMDA receptors
  • conjugated GlycoP , PhosphoP
    mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Grin1
    homolog to C.elegans F07f6.6
    Homologene
    FAMILY
  • ligand-gated ionic channels family
  • glutamate-regulated superfamily of ion channels
  • CATEGORY receptor membrane , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text post-synaptic membrane
    basic FUNCTION
  • playing a central role in verbal memory and cognitive function
  • playing a key role in the plasticity of synapses
  • and in excitatory neurostransmission
  • ligand-gated ion channel (Ca2+) transporting, when bound to glutamate and Mg2+ released
  • playing a central role in the striatum, in long potentiation memory, motor learning and cognitive function
  • playinga role in controlling T cell activation
  • activates multiple kinases and changes the phosphorylation of many postsynaptic proteins organized in signaling networks
  • its activation induces postnatal Müller glia-derived retinal cell progenitor proliferation and transcription factor CREB phosphorylation (activation induces postnatal Müller glia-derived retinal cell progenitor proliferation and transcription factor CREB phosphorylation)
  • by tethering Galpha with mu-opioid receptor (OPM1), GRIN1 stabilizes the receptor within the lipid rafts and potentiates the receptor signaling in the neurite outgrowth processes
  • main component of functional N-methyl-d-aspartic acid receptors that are involved in the glucocorticoid-induced neuronal damage
  • activity of the GRIN1/GRIN2D NMDA receptor is controlled distinctively by the endogenous neurotransmitter L-glutamate
  • role in controlling the intrinsic excitability of primary sensory neurons possibly via Ca(2+)-activated slow conductance K(+) (SK) channels
  • primary motor cortex NMDA receptors are necessary for activity-dependent synaptic strengthening and associative learning
  • Schwann cell signaling receptor for protein ligands and a major regulator of Schwann cell physiology, which may be particularly important in peripheral nervous system (PNS) injury
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS nervous system
    text small molecule transport
    PATHWAY
    metabolism
    signaling neurotransmission
  • glutamate signaling pathway, excitatory neurotransmission
  • GRIN1/PRKCG signaling pathway may participate in the development of bone cancer pain
  • a component
  • GRIN2A, GRIN2B, GRIN2C, GRIN2D
  • N-methyl D-aspartate receptor 1, zeta 1 subunit glutamate receptor
  • heterodimers of an epsilon subunit and a zeta subunit
  • dimer of GRIN1-GRIN2B heterodimers with the twofold symmetry axis running through the entire molecule composed of an amino terminal domain (ATD), a ligand-binding domain (LBD), and a transmembrane domain (TMD)
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • magnesium Mg2+ blocking the NMDA receptor in the depolarized postsynaptic membrane
  • protein
  • GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRINA
  • interacting with RALA (GRIN1 activation stimulates RALA, which binds and translocates widespread RALBP1 to synapses)
  • interacting with importin alpha (importin alpha is tethered at the postsynaptic density by binding to the NLS present in NR1-1a)
  • NRF1 co-regulates oxidative enzymes that generate energy and neurochemicals that consume energy related to glutamatergic neurotransmission, such as KIF17, GRIN1, and GRIN2B, thereby ensuring that energy production matches energy utilization at the molecular and cellular levels
  • FMR1 is required for translation downstream of GRIN1 stimulation and MOV10 is the key specificity factor in this process
  • FMR1 and MOV10 have an important regulatory role in GRIN1 mediated translation at the synapse
  • cell & other
    REGULATION
    activated by selectively activated by the artificial glutamate analog N-methyl D-aspartate
    Other regulated by C terminal phosphorylation by PKC
    activated in ischaemia
    ASSOCIATED DISORDERS
    corresponding disease(s) MRD8 , DEE101
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    significantly increased in male patients with AD
    constitutional     --low  
    decreased in postmortem brain from people with schizophrenia
    Susceptibility
  • to schizophrenia
  • to infantile spasms responsive to to adrenocorticotropic hormone
  • Variant & Polymorphism other
  • polymorphism G1001C asssociated to allele T4197C and T5988C of GRIN2B increasing the risk of schizophrenia
  • in homozygous carriers of the CTA haplotype was higher responsive to adrenocorticotropic hormone than that in heterozygous carriers and non-carriers
  • Candidate gene torsion dystonia
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyacquired 
    a potential therapeutic target for preventing white matter damage in a variety of diseases
    obesity  
    dorsal vagal complex GRIN2A, GRIN1 can a potential therapeutic target for obesity
    diabete  
    dorsal vagal complex GRIN2A, GRIN1 can a potential therapeutic target for diabetes
    ANIMAL & CELL MODELS
  • CA1-specific Nmdar 1 knockout mice
  • GluN1 hypomorph mice exhibit wide-ranging behavioral alterations