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FLASH GENE
Symbol FBXO32 contributors: mct - updated : 25-10-2014
HGNC name F-box only protein 32
HGNC id 16731
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumcardiac  
Muscularstriatumskeletal  
cells
SystemCellPubmedSpeciesStageRna symbol
Muscularmyocyte
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 40AA F-box motif
  • a nuclear localization signal
  • a PDZ binding domain
  • a RING zinc finger domain
  • two functional nuclear localization signals (NLS)
  • HOMOLOGY
    intraspecies homolog to FBXO25
    Homologene
    FAMILY F-box protein family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • nucleocytoplasmic shuttling of FBXO32 represents a novel mechanism for targeting its substrates and its cytosolic partners in muscle atrophy
  • basic FUNCTION
  • phosphorylating dependent ubiquination
  • mitotic regulator, inhibiting the anaphase promoting complex (cyclosome APC) and preventing mitotic exit in cytostatic factor (CSF) arrested eggs
  • functions as an F-box protein for ubiquitination of myogenin
  • increase in FBXO32 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy
  • major atrophy-related E3 ubiquitin ligase that functions as a negative regulator of cardiac hypertrophy
  • muscle-specific E3 ligase, targeting MYOD1 for degradation through the ubiquitin-proteasome-mediated system
  • FBXO32 and TRIM63 are two E3 ubiquitin ligases that are important regulators of ubiquitin-mediated protein degradation in skeletal muscle
  • promotes cardiomyocyte health through mediating the interplay between ubiquitin/proteasome system (UPS) and autophagy/lysosome system and its alteration promotes development of cardiomyopathies
  • CELLULAR PROCESS cell cycle, division, mitosis
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • putative component of a E3 ubiquitin protein ligase complex (SCF) with SKP1, CUL1, RBX1 bringing ubiquitin conjugating enzymes to substrates recruited by F-box
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with calcineurin A and alpha-actinin-2 at the Z-disc of cardiomyocytes (decreases levels of calcineurin A and promotes its ubiquitination, leading to inhibition of cardiac hypertrophy in response to pathologic stimuli)
  • interacting with EIF3F (highly conserved C-terminal domain is implicated for FBXO32-directed polyubiquitination and proteasomal degradation)
  • rapid suppression of MYOD1 by FBXO32 seems to be a major event leading to skeletal muscle wasting
  • MYOG interacted with FBXO32 (FBXO32 activated polyubiquitination of MYOG)
  • not only associates with myosin heavy and light chain, but it also ubiquitinates these sarcomeric proteins 1)
  • is the predominant E3 ligase through which MSTN manifests skeletal muscle wasting 1)
  • putatively interacts with sarcomeric proteins, transcriptional factors, metabolic enzymes, components of translation, and spliceosome formation
  • desmin and vimentin, two components of the intermediate filament in muscle, directly interacted with and were degraded by FBXO32 in response to MSTN
  • EIF3F is a target of the E3 ubiquitin ligase FBXO32 for proteasome-mediated breakdown under atrophic conditions
  • CHMP2B is a target of FBXO32-mediated degradation
  • cell & other
    REGULATION
    activated by myostatin
    Other enhanced,markedly increased in patients with atrophying muscles
    regulation of the stability of FBXO32 partially by MAPK14 signaling
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    epigenetically silenced in ovarian cancer cell lines with disrupted TGFB1/SMAD4 signaling, and its methylation status predicts survival in patients with ovarian cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • induced in fasted mice
  • mice lacking atrogin-1 failed to degrade Chmp2b, resulting in autophagy impairment, intracellular protein aggregate accumulation, unfolded protein response activation, and subsequent cardiomyocyte apoptosis, all of which increased progressively with age