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FLASH GENE
Symbol SPART contributors: mct/shn - updated : 22-01-2020
HGNC name spastic paraplegia 20 (Troyer syndrome)
HGNC id 18514
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a MIT domain (contained within microtubule-intreacting and trafficking molecules)
  • an ESP domain
  • mono polymer aggregate
    HOMOLOGY
    interspecies homolog to spastic paraplegia 20, spartin (Troyer syndrome) homolog (human) , Mus musculus
    ortholog to spastic paraplegia 20 (Troyer syndrome), Pan troglodytes
    homolog to spastic paraplegia 20, spartin (Troyer syndrome) homolog (human) , Rattus norvegicus
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • co-localization with microtubules
  • localizes to mitochondria dependending on sequences in the C-terminal region
  • upon EGF stimulation, spartin translocates from the cytoplasm to the plasma membrane and colocalizes with internalized EGF-Alexa
  • exists in a cytosolic pool that can be recruited to endosomes and to lipid droplets
  • localize to the endosomal membrane traffic compartment, suggesting that the long axons of the corticospinal tract may be especially vulnerable to endosomal dysfunction
  • localizes to mitochondria and this localization is dependent on sequences in the C-terminal region (mutant spartin containing the 1110delA mutation has lost mitochondrial localization)
  • colocalizes with IST1 at the midbody, and depletion of IST1 in cells by small interfering RNA significantly decreases the number of cells where spartin is present at midbodies
  • basic FUNCTION
  • involved in microtubule interaction
  • may be involved in endocytosis, vesicle trafficking, or mitogenic activity
  • mono-ubiquitinated and functioning in degradation of the epidermal growth factor receptor (EGFR) involved in the intracellular trafficking of EGFR (Bakowska 2007)
  • involved in the intracellular trafficking of EGFR (Bakowska 2007)
  • inhibitor of BMP signalling in neuronal and non-neuronal cells (Tsang 2009)
  • acts as an adaptor for WWP1 and ITCH (Edwards 2009)
  • involved in diverse cellular functions, which may be of relevance to the complex phenotype seen in Troyer syndrome (Edwards 2009)
  • multifunctional protein and that may have a role in protein folding and turnover both in mitochondria and endoplasmic reticulum (Milewska 2009)
  • a role in the regulation of lipid droplets turnover
  • SPART is involved in many cellular processes and associates with several intracellular organelles, including mitochondria.
  • inhibits bone morphogenetic protein signaling by promoting endocytic degradation of BMP receptor wishful thinking
  • regulates synaptic growth and function
  • regulates both synaptic development and neuronal survival by controlling microtubule stability via the BMP-dFMRP-Futsch pathway
  • there is a critical level of spartin expression which must be maintained for proper cellular functions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule other,
  • associates with the surface of lipid droplets (LDs) and can regulate their size and number (Eastman 2009)
  • protein
  • epidermal growth factor receptor pathway substrate 15, EPS15
  • ubiquitin and the E3 ubiquitin-protein ligases, ITCH and WWP1
  • binds to another lipid droplets (LD) protein, M6PRBP1, and both proteins compete with an additional LD protein, adipophilin/adipocyte differentiation-related protein, for occupancy of LDs (Eastman 2009)
  • PPXY motif with the ubiquitin E3 ligases atrophin-interacting protein 4, AIP4; itchy E3 ubiquitin protein ligase homologue, ITCH and WW domain containing E3 ubiquitin protein ligase 1, WWP1
  • IST1 interaction is important for SPART recruitment to the midbody , suggesting that SPART participates in cytokinesis
  • FK506
  • efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the microtubule interacting and trafficking (MIT) domains of VPS4A, VTA1, and SPART via its C-terminal MIT-interacting motif (MIM)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SPG20
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    hypermethylated in 89p100 of colorectal carcinomas, 78p100 of adenomas and only 1p100 of normal mucosa samples
    tumoral     --low  
    in cancer cells resulted in cytokinesis arrest, which was reversed when SPG20 methylation was inhibited
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • SPG20 promoter hypermethylation as a biomarker suitable for non-invasive detection of colorectal cancer, and a possible mechanism for cytokinesis arrest in colorectal tumorigenesis
  • ANIMAL & CELL MODELS
  • Loss of Spartin in Drosophila induces age-dependent progressive defects resembling hereditary spastic paraplegias, including motor dysfunction and brain neurodegeneration