Recombinant Human Spastin (SPAST), partial

Function

Involved in lipid metabolism by regulating the size and distribution of lipid droplets

Subcellular Location

Cytoplasm; Endosome; Nucleus membrane; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome

Disease Association

Spastic paraplegia 4, autosomal dominant (SPG4) : A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. The short isoforms may predominate in brain and spinal cord

Subunit

Homohexamer (PubMed:17389232, PubMed:22637577). Mostly monomeric, but assembles into hexameric structure for short periods of time. Oligomerization seems to be a prerequisite for catalytic activity (PubMed:17389232, PubMed:22637577). Binding to ATP in a cleft between two adjacent subunits stabilizes the homohexameric form (PubMed:17389232, PubMed:22637577). Binds to microtubules at least in part via the alpha-tubulin and beta-tubulin tails (PubMed:15269182, PubMed:15716377, PubMed:23272056). The hexamer adopts a ring conformation through which microtubules pass prior to being severed (PubMed:17389232, PubMed:22637577). Does not interact strongly with tubulin heterodimers (PubMed:15269182, PubMed:15716377, PubMed:23272056). Interacts (via MIT domain) with CHMP1B; the interaction is direct (PubMed:15537668, PubMed:18997780). Interacts with SSNA1 (PubMed:15269182, PubMed:25390646). Interacts with ATL1 (PubMed:16339213, PubMed:16815977). Interacts with RTN1 (PubMed:16602018). Interacts with ZFYVE27 (PubMed:16826525, PubMed:23969831). Isoform 1 but not isoform 3 interacts with RTN2 (PubMed:22232211). Interacts with REEP1 (PubMed:20200447). Interacts (via MIT domain) with IST1 (PubMed:23897888, PubMed:26040712)

• Hazan J. et al. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. — Nat. Genet. (1999)
• Kikuno R. et al. Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. — DNA Res. (1999)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Errico A. et al. Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics. — Hum. Mol. Genet. (2002)
• Ciccarelli F.D. et al. The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia. — Genomics (2003)
• Beetz C. et al. Identification of nuclear localisation sequences in spastin (SPG4) using a novel Tetra-GFP reporter system. — Biochem. Biophys. Res. Commun. (2004)
• Errico A. et al. Spastin interacts with the centrosomal protein NA14, and is enriched in the spindle pole, the midbody and the distal axon. — Hum. Mol. Genet. (2004)