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FLASH GENE
Symbol SPAST contributors: mct/npt/pgu/shn - updated : 27-08-2013
HGNC name spastin
HGNC id 11233
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal 80 AAs domain required for binding to atlastin
  • a putative nuclear localization signal (NLS) the AAA domain chaperone like adenosine triphosphatases (ATPase associated with diverse cellular activities)
  • two leucine zipper domains
  • a coiled-coil dimerization motif
  • a proline/serine/threonine/glycine-rich domain important for microtubule binding of spastin between AAs 227 and 342 (sometimes called linker), and MTBD, microtubule binding domain, AAs 270–328
  • a three-helix domain from AA 116 to 196 with homology to other enzymes involved in various cellular processes (termed the MIT domain (for “contained within microtubule-interacting and trafficking molecules) , dispensable for ATPase and severing activities
  • C-terminal AAA+ ATPase domain forms a hexamer around a central pore, AAs 342–599 , essential for microtubule severing, from AA 343 to the C terminus (AA 616) , , and the presence of domain iv is necessary and sufficient for the interaction with microtubules
  • mono polymer hexamer
    HOMOLOGY
    interspecies homolog to murine Spg4
    Homologene
    FAMILY
  • AAA ATPase family
  • spastin subfamily
  • CATEGORY chaperone/stress , enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • perinuclear distribution
  • co-localization with microtubule of an ATPase-defective spastin
  • onset expression in microtubule-organizing center (tranfection experiments)
  • localize to the endosomal membrane traffic compartment, suggesting that the long axons of the corticospinal tract may be especially vulnerable to endosomal dysfunction
  • centriolar localization
  • localize prominently to the midbody
  • basic FUNCTION
  • putative chaperone protein involved in the transport of dopamine-containing membranous vesicles and in membrane-microtubule interactions
  • playing a role in cytoskeletal rearrangements and dynamics
  • the transient association to microtubules is regulated through the ATPase activity of the AAA domain
  • playing a role in membrane traffic and in microtubule dynamics an in maintenance of motor neuron function
  • microtubule-severing proteins SPAST and KATNA1 participate differently in the formation of axonal branches
  • may selectively recognize post-translationally modified tubulins (Glu tubulins) that are part of stable microtubules
  • implicated in cytoskeletal rearrangement and dynamics
  • inhibitor of BMP signalling in neuronal and non-neuronal cells
  • microtubule-severing enzyme, critically important for the development of the nervous system, and also for its maintenance throughout adult life
  • is active in the form of homohexameric rings that dynamically assemble and disassemble
  • microtubule severing ATPase that regulates intracellular and axonal transport of vesicles
  • promotes the formation of microtubule networks that are essential for axon growth and branching which are important for neuronal plasticity
  • hexameric ring AAA ATPase that severs microtubules
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text putatively involved in some aspects of microtubule disassembly
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • microtubules via spastin N-terminal region
  • interacting with SSNA1
  • interacting with CHMP1B (interact in a highly specific manner and CHMP1B recruits spastin to the midbody, suggesting that spastin could have a role in cytokinesis)
  • binding partner of SPG3A
  • pulls the C terminus of tubulin through its central pore, generating a mechanical force that destabilizes tubulin
  • tubulin interactions within the microtubule lattice
  • with ATL1 and REEP1, interact within the tubular ER membrane in corticospinal neurons to coordinate ER shaping and microtubule dynamics
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SPG4
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • cells lacking the MT-severing protein spastin had increased tubulation of and defective receptor sorting through endosomal tubular recycling compartments
  • Zebrafish spinal motor axons depleted of spastin has abnormal endosomal tubulation