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FLASH GENE
Symbol ARC contributors: mct/pgu - updated : 16-02-2013
HGNC name activity-regulated cytoskeleton-associated protein
HGNC id 648
Location 8q24.3      Physical location : 143.692.409 - 143.695.833
Synonym name
  • activity-regulated gene 3.1 protein homolog
  • similar to rat growth factor Arc
    • Synonym symbol(s) KIAA0278, ARC/ARG3.1, Arg3.1, MYC, NOL3, NOP
    DNA
    TYPE functioning gene
    STRUCTURE 3.43 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • a SARE (synaptic activity-responsive element) in the promoter essential for synapse-to-nucleus signaling in activated neurons
    • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 2985 45 396 - 2011 22036569
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainlimbic systemhippocampusdentate gyrus  Homo sapiensAdult
    Reproductivemale systemprostate   
    Respiratorylung    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • ARC/ARG3.1 family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text
  • present exclusively in the postsynaptic compartment
    • basic FUNCTION
  • comodulator with FB1 of cell death in brain
  • required for the late-phase of long-term potentiation (LTP) and memory consolidation, and has been implicated in AMPA receptor trafficking
  • required for multiple forms of synaptic plasticity that depend on its endocytic function including homeostatic scaling
  • first target of serum response factor that functions at synapses to mediate plasticity
  • functions as a spectrin-binding protein, forming a complex that may provide a role at sites of transcriptional regulation within the nucleus
  • synaptic protein that promotes the internalization of the AMPA subtype of glutamate receptors
  • PDGF-mediated induction of ARC involved activation of the MAPK/ERK (MEK) pathway
  • effector immediate-early gene rapidly induced by strong neural activity
  • functional rolein memory reconsolidation processes in the mammalian brain
  • required for activity-dependent generation of APP
  • role in postsynaptic trafficking and processing of APP that appears relevant to the pathogenesis of Alzheimer disease
  • potentially functioning to increase gamma-secretase in dendritic trafficking endosomes that process APP
  • critically contributes to weakening synapses by promoting AMPAR endocytosis
  • essential roles both for the late phase of long-term plasticity and for reduction of surface AMPA-Rs in stimulated neurons
  • crucial mediator for actin polymerization functions
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with SH3GL1/endophilin-2, SH3GL3/endophilin-3 and DNM2
  • neuron-specific, postsynaptic protein that interacts with endophilin and dynamin and contributes to an endocytic pathway that accelerates removal of AMPA receptors from excitatory synapses
  • interacting with UBE3A (UBE3A regulates excitatory synapse development by controlling the degradation of ARC)
  • neuronal NOTCH1 signaling is positively regulated by ARC, an activity-induced gene required for synaptic plasticity
  • physically associates with presenilin1 (PSEN1) to regulate gamma-secretase trafficking and confer activity dependence
  • ARC and PSEN1 directly and specifically interact
  • activation of intracellular GRM5 also up-regulates genes involved in synaptic plasticity including activity-regulated cytoskeletal-associated protein (ARC)
    • cell & other
    REGULATION
    induced by specific patterns of synaptic activity
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    ARC expression is maintained at normal or supranormal levels in a brain area impacted by AD, and thus could contribute to APP generation and pathology
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS