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FLASH GENE
Symbol FIS1 contributors: mct/pgu - updated : 16-09-2011
HGNC name fission 1 (mitochondrial outer membrane) homolog (S. cerevisiae)
HGNC id 21689
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • cytosolic domain forms a six-helix bundle, in which the central four helices consist of two tandem tetratricopeptide repeat (TPR)-like motifs
  • mono polymer dimer
    HOMOLOGY
    interspecies homolog to murine Fis1 (94.7pc)
    homolog to rattus Fis1 (95.4pc)
    Homologene
    FAMILY
  • FIS1 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,peroxisome
    text
  • anchored at the outer membrane by a C-terminal transmembrane domain
  • MFF and FIS1 are both tail anchored in the mitochondrial outer membrane
  • basic FUNCTION
  • may regulates mitochondrial fission and perinuclear clustering by interacting with DNM1L
  • anchors fission complexes onto the mitochondrial outer membrane
  • fragmentation followed by the release of cytochrome c and apoptosis, suggesting that regulation of the fission may be involved in apoptotic mechanisms
  • limiting factor in mitochondrial fission, the number of FIS1 molecules on the mitochondrial surface determines fission frequency
  • mediating peroxisomal fission
  • DNM1L, and FIS1 are two key players of mitochondrial fission
  • oligomerization of FIS1 in the mitochondrial outer membrane plays a role in mitochondrial fission, potentially through participating in fission factor recruitment
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the mitochondrial fission machinery
  • FIS1-BCAP31 complex (ARCosome) spanning the mitochondria-ER interface serves as a platform to activate the initiator procaspase-8, and thereby bridges two critical organelles for apoptosis signalling
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with the dynamin-like protein DNM1L
  • FIS1 plays important roles in peroxisome division and maintenance of peroxisome morphology in mammalian cells, possibly in a concerted manner with PEX11B and DNM1L
  • targeting of FIS1 to peroxisomes and mitochondria are independent events and support a direct, PEX19-dependent targeting of peroxisomal tail-anchored proteins (
  • DNM1L and possibly other proteins are thought to interact with the FIS1 TPR region during the fission process (
  • FIS1 degradation by PARK7 signalling in the regulation of oxidative stress-induced neuronal cell death supplies a novel mechanism of PARK7 in neuronal protection
  • cell & other
  • can bind to multiple amino acids sequences via its TPR-like motifs
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    defects in mitochondrial fission also disrupt mitochondrial distribution in neurons and result in defective synaptic transmission
    constitutional        
    loss of mitochondrial fission results in neonatal lethality with microcephaly, developmental delay, and metabolic aberrations
    constitutional     --over  
    found in Huntington disease patients relative to the controls
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • TPR-like motifs might be potential therapeutic target
  • ANIMAL & CELL MODELS