======= SPAST ======= == Gene Information == * **Official Symbol**: SPAST * **Official Name**: spastin * **Aliases and Previous Symbols**: N/A * **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6683|6683]] * **UniProt**: [[https://www.uniprot.org/uniprot/Q9UBP0|Q9UBP0]] * **Interactions**: [[https://thebiogrid.org/search.php?search=SPAST&organism=9606|BioGRID]] * **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SPAST|Open PubMed]] * **OMIM**: [[https://omim.org/entry/604277|Open OMIM]] == Function Summary == * **Entrez Summary**: This gene encodes a member of the AAA (ATPases associated with a variety of cellular activities) protein family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. The encoded ATPase may be involved in the assembly or function of nuclear protein complexes. Two transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described but their full length sequences have not been determined. Mutations associated with this gene cause the most frequent form of autosomal dominant spastic paraplegia 4. [provided by RefSeq, Jul 2008]. * **UniProt Summary**: ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, PubMed:20530212, PubMed:22637577, PubMed:26875866). Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Severing activity is not dependent on tubulin acetylation or detyrosination (PubMed:26875866). Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex (PubMed:19000169, PubMed:21310966, PubMed:26040712). Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex (PubMed:21310966). Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling (PubMed:23897888). Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing (PubMed:23897888). Probably plays a role in axon growth and the formation of axonal branches (PubMed:15716377). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:16219033, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20530212, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23897888, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:26875866}. |AAA| |MIT| |mitotic spindle disassembly| |spindle disassembly| |positive regulation of microtubule depolymerization| |microtubule-severing ATPase activity| |microtubule severing| |axonal transport of mitochondrion| |membrane fission| |protein hexamerization| |exit from mitosis| |isomerase activity| |nuclear envelope reassembly| |positive regulation of protein depolymerization| |establishment of mitochondrion localization, microtubule-mediated| |mitochondrion transport along microtubule| |establishment of mitochondrion localization| |regulation of microtubule depolymerization| |positive regulation of microtubule polymerization or depolymerization| |cytokinetic process| |positive regulation of protein complex disassembly| |beta-tubulin binding| |positive regulation of cytokinesis| |alpha-tubulin binding| |anterograde axonal transport| |mitochondrion localization| |nuclear envelope organization| |cytoplasmic microtubule organization| |axonal transport| |axon cytoplasm| |organelle disassembly| |axo-dendritic transport| |mitotic cytokinesis| |mitotic spindle organization| |organelle transport along microtubule| |regulation of microtubule polymerization or depolymerization| |lipid droplet| |regulation of protein depolymerization| |positive regulation of cell division| |regulation of cytokinesis| |microtubule bundle formation| |cytoskeleton-dependent cytokinesis| |cytokinesis| |microtubule cytoskeleton organization involved in mitosis| |regulation of protein complex disassembly| |spindle| |nucleus organization| |mitotic nuclear division| |microtubule cytoskeleton| |spindle organization| |transport along microtubule| |midbody| |regulation of cell division| |cytoskeleton-dependent intracellular transport| |microtubule-based transport| |regulation of microtubule cytoskeleton organization| |positive regulation of supramolecular fiber organization| |endoplasmic reticulum to Golgi vesicle-mediated transport| |positive regulation of cytoskeleton organization| |regulation of microtubule-based process| |ATPase activity| |microtubule binding| |nuclear membrane| |cytoplasmic vesicle| |protein-containing complex binding| |mitotic cell cycle phase transition| |endosome| |microtubule-based movement| |cell cycle phase transition| |nuclear division| |positive regulation of cell cycle process| |organelle fission| |microtubule| |protein homooligomerization| |regulation of supramolecular fiber organization| |establishment of organelle localization| |axonogenesis| |Golgi vesicle transport| |positive regulation of cell cycle| |cellular component disassembly| |axon development| |endomembrane system organization| |cell morphogenesis involved in neuron differentiation| |supramolecular fiber organization| |microtubule cytoskeleton organization| |neuron projection morphogenesis| |plasma membrane bounded cell projection morphogenesis| |cell projection morphogenesis| |centrosome| |cell division| |cell part morphogenesis| |protein complex oligomerization| |regulation of cytoskeleton organization| |cell morphogenesis involved in differentiation| |organelle localization| |mitotic cell cycle process| |positive regulation of organelle organization| |neuron projection development| |microtubule-based process| |mitotic cell cycle| |perinuclear region of cytoplasm| |cell morphogenesis| |regulation of cell cycle process| |neuron development| |cellular component morphogenesis| |membrane organization| |endoplasmic reticulum membrane| |cell cycle process| |endoplasmic reticulum| |neuron differentiation| |cytoskeleton organization| |plasma membrane bounded cell projection organization| |cell projection organization| |regulation of cell cycle| |positive regulation of cellular component organization| |regulation of organelle organization| |cell cycle| |ATP binding| |intracellular transport| |generation of neurons| |movement of cell or subcellular component| |protein-containing complex assembly| |neurogenesis| |cell development| |establishment of localization in cell| |protein-containing complex subunit organization| |vesicle-mediated transport| \\ === CRISPR Data === ^Screen^Score^ |[[:results:exp82|Torin1 0.08μM R02 exp82]]|-1.87| |[[:results:exp85|UM0129480 7μM R02 exp85]]|1.71| |[[:results:exp37|Wortmannin 0.5μM R00 exp37]]|2.01| No correlation found to any other genes in chemogenomics. Global Fraction of Cell Lines Where Essential: 0/739 ^Tissue^Fraction Of Cell Lines Where Essential^ |1290807.0|0/1| |909776.0|0/1| |bile duct|0/28| |blood|0/28| |bone|0/26| |breast|0/33| |central nervous system|0/56| |cervix|0/4| |colorectal|0/17| |esophagus|0/13| |fibroblast|0/1| |gastric|0/16| |kidney|0/21| |liver|0/20| |lung|0/75| |lymphocyte|0/16| |ovary|0/26| |pancreas|0/24| |peripheral nervous system|0/16| |plasma cell|0/15| |prostate|0/1| |skin|0/24| |soft tissue|0/9| |thyroid|0/2| |upper aerodigestive|0/22| |urinary tract|0/29| |uterus|0/5| == Essentiality in NALM6 == * **Essentiality Rank**: 3820 * **Expression level (log2 read counts)**: 5.81 {{:chemogenomics:nalm6 dist.png?nolink |}}