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FLASH GENE
Symbol HOMER1 contributors: mct/npt - updated : 23-12-2014
HGNC name homer homolog 1 (Drosophila)
HGNC id 17512
Location 5q14.1      Physical location : 78.669.786 - 78.809.700
Synonym name
  • homer 1, neuralized binding protein
  • homer, neuronal immediate early gene, 1
  • Synonym symbol(s) SYN47, HOMER1A, HOMER1B, HOMER1C, Vesl-1, HOMER
    DNA
    TYPE functioning gene
    STRUCTURE 140.01 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    Map pter - D5S1977 - D5S1962 - ARSB - HOMER1 - THBS4 - D5S620 - D5S2029 - D5S627 - D5S626 - HAPLN1 - D5S459 - D5S428 - cen
    Physical map
    OTP 5q13.3 orthopedia homolog (Drosophila) TBCA 5q13.3 tubulin-specific chaperone A ACTBP2 5q14.1 actin, beta pseudogene 2 AP3B1 5q12-q13.2 adaptor-related protein complex 3, beta 1 subunit SCAMP1 5q13.3-q14.1 secretory carrier membrane protein 1 LHFPL2 5q13.3 lipoma HMGIC fusion partner-like 2 ARSB 5q13 arylsulfatase B DMGDH 5q12.2-q12.3 arylsulfatase B BHMT2 5q13 betaine-homocysteine methyltransferase 2 BHMT 5q13.1-q15 betaine-homocysteine methyltransferase JMY 5q14.1 junction-mediating and regulatory protein HOMER1 5q25 homer homolog 1 (Drosophila) LOC133748 5q14.1 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) FLJ38499 5q14.1 hypothetical protein FLJ38499 CMYA5 5q14.1 cardiomyopathy associated 5 LOC391802 5 similar to 60S ribosomal protein L10 (QM protein homolog) LOC345778 5q14.1 similar to hypothetical protein THBS4 5q13 thrombospondin 4 C5orf12 5 chromosome 5 open reading frame 12 LOC391803 5 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC134478 5q14.1 similar to cytoplasmic beta-actin NYD-TSP1 5q14.1 testis-specific protein NYD-TSP1 LOC391804 5 similar to hypothetical protein LOC391805 5 hypothetical gene supported by NM_004269 LOC153817 5q14.1 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP) ZFYVE16 5p15.2-q14.3 zinc finger, FYVE domain containing 16 LOC167555 5q14.1 similar to AASA9217 LOC340120 5q14.1 similar to RIKEN cDNA 6430502M16 gene LOC389306 5 LOC389306 DBIL1 5pter-p15.32 diazepam binding inhibitor-like 1 DHFR 5q13.2 dihydrofolate reductase MSH3 5q11-q12 mutS homolog 3 (E. coli) RASGRF2 5q13 Ras protein-specific guanine nucleotide-releasing factor 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 4228 39 354 in the brain 2012 22749857
  • also called HOMER1A or Vesl1s
  • exons 1-5, regulating trafficking and surface expression at metabotropic Glu receptors
  • a long 3-prime UTR with multiple destabilizing repeat sequences typical of immediate early genes, whereas the subsequently identified Homer family members have a short 3-prime UTR without the repeats
  • associated with global GRM5 distribution
  • activity-induced protein believed to participate in synaptic remodeling/plasticity responses to temporal lobe seizure and learning
  • 10 - 1166 39 354 constitutive,low expression in dentritic spines, expressed at high levels in cortex, hippocampus, and cerebellum, with moderate expression in heart and kidney and weaker expression in liver 2012 22749857
  • also called HOMER1B
  • exons 1-10, inhibiting surface expression of metabotropic Glu receptors
  • coexpression with HOMER1C induced dendritic expression of GRM5
  • HOMER1B/C might promote neuronal apoptosis via the BAX/BCL2 dependent pathway during neuroinflammation in CNS
  • long form, that reduced cell surface expression by retaining GRM in the endoplasmic reticulum
  • - - - - 366 expressed at high levels in hippocampus, striatum, and cortex 2012 22749857
  • also called HOMER1C
  • an insertion of 12 amino acids between the conserved N terminus and the CC domain
  • coexpression with HOMER1B induced dendritic expression of GRM5
  • may play an important role in the mechanisms of neuronal death in the striatum
  • HOMER1B/C might promote neuronal apoptosis via the BAX/BCL2 dependent pathway during neuroinflammation in CNS
  • 6 - 3922 - 224 - 2012 22749857
    also called HOMER1E
    - - 641 - 180 - 2012 22749857
  • also called HOMER1F
  • short HOMER isoforms lacking the coiled-coil domain and thus acting in a dominant negative manner by binding to HOMER ligands displacing them from the HOMER scaffold
  • 6 - 3923 - 177 - 2012 22749857
  • also called HOMER1H
  • short HOMER isoforms lacking the coiled-coil domain and thus acting in a dominant negative manner by binding to HOMER ligands displacing them from the HOMER scaffold
  • short HOMER proteins act in a dominant negative manner to prevent retention in subcellular compartments
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinethyroid   highly
    Nervousbraindiencephalonhypothalamus  
     brainbasal nucleistriatum  
     brainlimbic systemhippocampus highly
     brainforebrain  highly Homo sapiens
    Reproductivefemale systemplacenta  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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