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FLASH GENE
Symbol GRM5 contributors: mct/pgu - updated : 11-01-2015
HGNC name glutamate receptor, metabotropic 5
HGNC id 4597
Location 11q14.3      Physical location : 88.237.744 - 88.796.816
Synonym symbol(s) MGLUR5, GPRC1E, MGLUR5A, MGLUR5B, mGlu5
DNA
TYPE functioning gene
STRUCTURE 559.07 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
RAB38 11q14 RAB38, member RAS oncogene family CTSC 11q21 cathepsin C LOC390230 11 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) GRM5 11q13-q13.4 glutamate receptor, metabotropic 5 TYR 11q14.3 tyrosinase (oculocutaneous albinism IA) NOX4 11q14.2-q21 NADPH oxidase 4 PSMAL/GC LOC390231 11 similar to tripartite motif-containing 43 LOC390232 11 similar to surface glycoprotein, Ig superfamily member LOC120126 11q14.3 similar to autoantigen NOR-90 LOC390233 11 similar to tripartite motif-containing 43 RNF18 11p11.12-q12 ring finger protein 18 LOC387798 11 hypothetical gene supported by NM_024114 LOC387799 11 similar to RING finger protein 18 (Testis-specific ring-finger protein) LOC390234 11 similar to RIKEN cDNA 0610012A05 LOC387800 11 similar to tripartite motif-containing 43
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 splicing 7855 - 1212 - 1994 7908515
variant a
9 splicing 7927 - 1180 at low level, in whole brain, cerebellum, cerebral cortex and hippocampus 1994 7908515
  • variant b
  • has a C-terminal 267 amino acid shorter than that of GLUR5A
  • increased sensitivity to protein kinase C (PKC)-mediated desensitization, relative to GLUR5A
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainforebraincerebral cortex highly Homo sapiens
     brainbasal nucleistriatum   Homo sapiensAdult
    Reproductivemale systemtestis   
    Respiratorylung    
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text during prenatal human cortical development
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven transmembrane segments (7TM) receptor
  • the PPXXF motif binds HOMER1, HOMER2 and HOMER3
  • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
  • G protein coupled receptor 3 family
  • CATEGORY regulatory , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • glutamate receptor group I, activating phosphatidylinositol turnover and triggering intracellular calcium release
  • important neuronal mediator of postsynaptic signaling that influence synaptic strength, plasticity, and other factors
  • plays a pivotal role as a modulator of synaptic plasticity, ion channel activity and excitotoxicity
  • group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C
  • plays a role in pain and addiction
  • critical to the function of neural circuits that are required for inhibitory learning mechanisms, suggesting that targeting metabotropic receptors may be useful in treating psychiatric disorders in which aversive memories are inappropriately retained
  • important for synaptic transmission and synaptic plasticity
  • involved in multiple physiological functions and is a target for treatment of various CNS disorders, including schizophrenia
  • with GRM1, plays a role in the early stages of corticogenesis with, however, a different contribution to human cortical developmental events
  • is a GPCR that plays a crucial role in circuit formation in the brain and also in various forms of synaptic plasticity including learning and memory
  • likely does not get degraded and recycles back to the cell membrane after constitutive endocytosis
  • constitutively endocytosed GRM5 goes to the recycling compartment subsequent to internalization while very little or no receptors enter the lysosomal compartment
  • stress induces a cognitive deficit that is likely mediated by GRM5/HOMER1 signaling in the hippocampus
  • GRM1, GRM5 play critical functions in forms of activity-dependent synaptic plasticity and synapse remodeling in physiological and pathological states
  • GRM1, GRM5 are key elements in the dynamic regulation of cholinergic synaptic inputs onto neurons of the thalamic reticular nucleus (TRN)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of phosphate receptors
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to HOMER proteins
  • interacting with SLC9A3R2
  • interacting with CALM1 (for GRM5, the rapid Ca2+-dependent regulation of CALM1 binding mediates receptor expression at synapses and will likely regulate GRM5-dependent processes)
  • interacts with NCDN (NCDN increases the cell surface localization of the receptor, and positively regulates GRM5 signaling)
  • bind to the PDZ domain of the scaffold protein SLC9A3R2
  • interacting with ADBRK1 (ADBRK1 mediates phosphorylation-independent GRM5 desensitization and internalization in neurons)
  • GRM5 protein expression is physiologically regulated via its interaction with GOPC
  • role of SHANK3 in regulating metabotropic glutamate receptor 5 (GRM5) expression and signaling at synapses
  • activation of intracellular GRM5 also up-regulates genes involved in synaptic plasticity including activity-regulated cytoskeletal-associated protein (ARC)
  • cooperative signaling between GRM1 and GRM5 is in a manner inconsistent with heterodimerization, and thus suggest an interaction between homodimers
  • cell & other
  • linked to inositol phosphate receptors
  • REGULATION
    activated by glutamate (glutamate activation of intracellular GRM5 serves an important role in the regulation of nuclear Ca(2+), transcriptional activation, and gene expression necessary for physiological processes such as synaptic plasticity)
    Other regulated by Homer proteins by acting as adapters and facilitating coupling to effectors such as the inositol triphosphate receptor
    PKC phosphorylation of serine 901 (S901)inhibits CALM1 binding and decreases GRM5 surface expression
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to amyotrophic lateral sclerosis
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Mice lacking metabotropic glutamate receptors 5 (mGluR5) exhibit reduced glutamatergic function and behavioral abnormalities, including deficits in prepulse inhibition (PPI) of the startle response that may be relevant to schizophrenia
  • dysregulation of Fmrp-Grm5 signaling pathway, accompanied with a downregulation of Gabrb3 expression, may contribute to the 'autistic-like' features observed in En2 mice