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FLASH GENE
Symbol HOMER1 contributors: mct/npt - updated : 23-12-2014
HGNC name homer homolog 1 (Drosophila)
HGNC id 17512
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminus Ena/vasodilator-stimulated phosphoprotein homology 1 (EVH-1) domain that contains a PDZ domain capable of binding to HOMER ligands such as cell surface receptors, other scaffolding proteins and enzymes involved in cell signaling cascades
  • a WAS homology domain (WH1),variant EVASP
  • a C terminal coiled-coil region,mediating self-multimerization
  • mono polymer monomer , oligo
    HOMOLOGY
    interspecies homolog to murine Ania3
    Homologene
    FAMILY
  • Homer protein family
  • CATEGORY adaptor , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    text HOMER1B in ER and Golgi
    basic FUNCTION
  • clustering and linking metabotropic glutamate receptors group I with the inositol triphosphate receptors regulator of GRMs signaling
  • "adapter" that also modifies signaling properties of its target protein and modulating the function of its target protein RyR1 and excitation-contraction coupling in skeletal myotubes
  • synaptic scaffolding protein having a function crucially involved in pain plasticity and protecting against chronic inflammatory pain
  • can reduce GRM5 coupling to postsynaptic effectors without relying on large changes in the subcellular distribution of the receptor
  • may have a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness (Maret 2007)
  • regulates the activity-induced biphasic changes of post- and pre-synaptic sites (Inoue 2007)
  • brain-coping marker against stressors, and might represent the molecular link between sleep, cognition, and neuropsychiatric disorder
  • activation of HOMER 1 suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness
  • plays a critical role in determining the apoptotic susceptibility to TNFSF10 (Shin 2009)
  • 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
  • accelerate ATP2B1 mediated Ca2+ clearance in hippocampal neurons
  • stress induces a cognitive deficit that is likely mediated by GRM5/HOMER1 signaling in the hippocampus
  • may play an important role in the etiology and pathogenesis of attention deficit hyperactivity disorder (ADHD)
  • postsynaptic density scaffold protein, playing a vital role in maintaining synaptic integrity, regulating intracellular calcium mobilization, and being critical for the regulation of cellular apoptosis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    PATHWAY
    metabolism
    signaling neurotransmission
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HOMER3
  • binding of SHANK3 C terminus to HOMER1 is critical for its expression at synapses, and HOMER1 stabilizes SHANK3 protein
  • ATP2B1 mediated Ca2+ clearance from hippocampal neurons was accelerated in the presence of HOMER proteins
  • regulation of HOMER1 splicing by GNRH1 contributes to gonadotropin gene control
  • role for OPHN1 as an interaction partner of HOMER1B/C in spine endocytic zone (EZ) positioning
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in spinal cord neurons after peripheral inflammation in an NMDA receptor-dependent manner
    constitutional     --over  
    after sleep deprivation and after inflammation, seizure, and psychostimulant or antipsychotic drug use, playing a major role in neuroprotection
    tumoral     --over  
    in intrahepatic cholangiocarcinoma, with a worse prognosis
    Susceptibility to psychotic symptoms in Parkinson disease (PD)
    Variant & Polymorphism other allele A of the rs4704559 marker associated to psychotic symptoms in PD (De Luca 2009)
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    promising therapeutic target for the treatment of chronic inflammatory pain
    neurologyacquired 
    suppression of HOMER1B/C expression potentially protects neurons from glutamate excitotoxicity after injury and might be an effective intervention target in traumatic brain injury
    ANIMAL & CELL MODELS