Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SPAST contributors: mct/npt/pgu/shn - updated : 27-08-2013
HGNC name spastin
HGNC id 11233
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
 mouthtongue  highly
Endocrinethyroid   highly
Nervousspinal cord   predominantly
Respiratoryrespiratory tractlarynx  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
Nervousperipherous   
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousneuron
NervousPurkinje cell
Nervouspyramidal cell
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal, pregnancy
Text tissue, highly in brain
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