UniProt functional annotation for Q9UBP0



	UniProt functional annotation for Q9UBP0

UniProt code: Q9UBP0.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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}.

Function: [Isoform 1]: Involved in lipid metabolism by regulating the size and distribution of lipid droplets. {ECO:0000269|PubMed:25875445}.

Catalytic activity: Reaction=n ATP + n H(2)O + a microtubule = n ADP + n phosphate + (n+1) alpha/beta tubulin heterodimers.; EC=5.6.1.1; Evidence={ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:16219033, ECO:0000269|PubMed:16815977, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:18410514, ECO:0000269|PubMed:22637577};

Activity regulation: Allosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers (PubMed:22637577). Microtubule binding promotes cooperative interactions among spastin subunits (PubMed:22637577). ATP-bound enzyme interacts strongly and cooperatively with microtubules; this interaction stimulates ATP hydrolysis (PubMed:23745751). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23745751}.

Biophysicochemical properties: Kinetic parameters: KM=0.45 mM for ATP {ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:22637577}; Vmax=1.2 nmol/min/ug enzyme {ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:22637577}; Note=Kinetic parameters shown are for full-length enzyme. N- terminally truncated spastin (residues 228-616), which has been shown to exhibit full severing activity, shows a basal ATP turnover rate of 0.78 sec(-1) in the absence of microtubules, a KM of 0.16 mM for ATP, and the ATP turnover rate is extrapolated to 3.83 sec(-1) in the presence of microtubules. ATPase activity shows non-Michaelis-Menten kinetics in the presence of microtubules, but is close to non- cooperative behavior in their absence (PubMed:22637577). {ECO:0000269|PubMed:22637577};

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). 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). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15537668, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:16339213, ECO:0000269|PubMed:16602018, ECO:0000269|PubMed:16815977, ECO:0000269|PubMed:16826525, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:18997780, ECO:0000269|PubMed:20200447, ECO:0000269|PubMed:22232211, ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23272056, ECO:0000269|PubMed:23897888, ECO:0000269|PubMed:23969831, ECO:0000269|PubMed:26040712}.

Subcellular location: Membrane {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:19000169}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000305|PubMed:20200447}. Endoplasmic reticulum {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:16602018}. Midbody {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:18997780, ECO:0000269|PubMed:21310966}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15891913}. Cytoplasm, cytoskeleton {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:18410514, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20200447}. Cytoplasm, perinuclear region {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15537668}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15147984, ECO:0000269|PubMed:16026783}. Cytoplasm, cytoskeleton, spindle {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15269182}. Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:16026783, ECO:0000269|PubMed:20200447}. Note=Forms an intramembrane hairpin-like structure in the membrane (PubMed:20200447). Localization to the centrosome is independent of microtubules (PubMed:15891913). Localizes to the midbody of dividing cells, and this requires CHMP1B (PubMed:18997780). Enriched in the distal axons and branches of postmitotic neurons (PubMed:15269182). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15891913, ECO:0000269|PubMed:18997780, ECO:0000305|PubMed:20200447}.

Subcellular location: [Isoform 1]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:23969831}; Peripheral membrane protein {ECO:0000305|PubMed:20200447}. Nucleus membrane {ECO:0000269|PubMed:26040712}. Lipid droplet {ECO:0000269|PubMed:25875445}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20200447}. Endosome {ECO:0000269|PubMed:23897888}. Note=Forms an intramembrane hairpin-like structure in the membrane (PubMed:20200447). Recruited to nuclear membrane by IST1 during late anaphase (PubMed:26040712). Localizes to endoplasmic reticulum tubular network (PubMed:23969831). {ECO:0000269|PubMed:23969831, ECO:0000269|PubMed:26040712, ECO:0000305|PubMed:20200447}.

Subcellular location: [Isoform 3]: Cytoplasm {ECO:0000269|PubMed:20200447, ECO:0000269|PubMed:23969831}. Endosome {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:23897888}. Nucleus membrane {ECO:0000269|PubMed:16026783, ECO:0000269|PubMed:26040712}. Note=Constitutes the main endosomal form (PubMed:19000169). Recruited to nuclear membrane by IST1 during late anaphase (PubMed:26040712). {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:26040712}.

Tissue specificity: Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. The short isoforms may predominate in brain and spinal cord. {ECO:0000269|PubMed:10610178}.

Developmental stage: Expressed in fetal brain, heart, kidney, liver, lung, skeletal muscle, spleen and thymus. {ECO:0000269|PubMed:10610178}.

Disease: Spastic paraplegia 4, autosomal dominant (SPG4) [MIM:182601]: 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. {ECO:0000269|PubMed:10610178, ECO:0000269|PubMed:10699187, ECO:0000269|PubMed:11015453, ECO:0000269|PubMed:11039577, ECO:0000269|PubMed:11087788, ECO:0000269|PubMed:11309678, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:11843700, ECO:0000269|PubMed:11985387, ECO:0000269|PubMed:12124993, ECO:0000269|PubMed:12161613, ECO:0000269|PubMed:12163196, ECO:0000269|PubMed:12202986, ECO:0000269|PubMed:12460147, ECO:0000269|PubMed:12552568, ECO:0000269|PubMed:12939659, ECO:0000269|PubMed:14732620, ECO:0000269|PubMed:15159500, ECO:0000269|PubMed:15210521, ECO:0000269|PubMed:15248095, ECO:0000269|PubMed:15326248, ECO:0000269|PubMed:15482961, ECO:0000269|PubMed:15667412, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:15891913, ECO:0000269|PubMed:16339213, ECO:0000269|PubMed:16682546, ECO:0000269|PubMed:16684598, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:17594340, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20214791, ECO:0000269|PubMed:20550563, ECO:0000269|PubMed:20562464, ECO:0000269|PubMed:20718791, ECO:0000269|PubMed:20932283, ECO:0000269|PubMed:21546041, ECO:0000269|PubMed:22960362, ECO:0000269|PubMed:23279441, ECO:0000269|PubMed:24824479, ECO:0000269|PubMed:25045380, ECO:0000269|PubMed:25421405, ECO:0000269|PubMed:28572275}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 3]: Produced by alternative promoter usage. May also be produced by alternative initiation at Met-87 of isoform 1. Major isoform. {ECO:0000305}.

Miscellaneous: [Isoform 4]: Produced by alternative promoter usage and alternative splicing. May also be produced by alternative initiation at Met-87 of isoform 2. {ECO:0000305}.

Similarity: Belongs to the AAA ATPase family. Spastin subfamily. {ECO:0000255|HAMAP-Rule:MF_03021}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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}.



Function:		[Isoform 1]: Involved in lipid metabolism by regulating the size and distribution of lipid droplets. {ECO:0000269\|PubMed:25875445}.


Catalytic activity:		Reaction=n ATP + n H(2)O + a microtubule = n ADP + n phosphate + (n+1) alpha/beta tubulin heterodimers.; EC=5.6.1.1; Evidence={ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:15716377, ECO:0000269\|PubMed:16219033, ECO:0000269\|PubMed:16815977, ECO:0000269\|PubMed:17389232, ECO:0000269\|PubMed:18410514, ECO:0000269\|PubMed:22637577};
Activity regulation:		Allosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers (PubMed:22637577). Microtubule binding promotes cooperative interactions among spastin subunits (PubMed:22637577). ATP-bound enzyme interacts strongly and cooperatively with microtubules; this interaction stimulates ATP hydrolysis (PubMed:23745751). {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:22637577, ECO:0000269\|PubMed:23745751}.
Biophysicochemical properties:		Kinetic parameters: KM=0.45 mM for ATP {ECO:0000269\|PubMed:15716377, ECO:0000269\|PubMed:17389232, ECO:0000269\|PubMed:22637577}; Vmax=1.2 nmol/min/ug enzyme {ECO:0000269\|PubMed:15716377, ECO:0000269\|PubMed:17389232, ECO:0000269\|PubMed:22637577}; Note=Kinetic parameters shown are for full-length enzyme. N- terminally truncated spastin (residues 228-616), which has been shown to exhibit full severing activity, shows a basal ATP turnover rate of 0.78 sec(-1) in the absence of microtubules, a KM of 0.16 mM for ATP, and the ATP turnover rate is extrapolated to 3.83 sec(-1) in the presence of microtubules. ATPase activity shows non-Michaelis-Menten kinetics in the presence of microtubules, but is close to non- cooperative behavior in their absence (PubMed:22637577). {ECO:0000269\|PubMed:22637577};
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). 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). {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:15269182, ECO:0000269\|PubMed:15537668, ECO:0000269\|PubMed:15716377, ECO:0000269\|PubMed:16339213, ECO:0000269\|PubMed:16602018, ECO:0000269\|PubMed:16815977, ECO:0000269\|PubMed:16826525, ECO:0000269\|PubMed:17389232, ECO:0000269\|PubMed:18997780, ECO:0000269\|PubMed:20200447, ECO:0000269\|PubMed:22232211, ECO:0000269\|PubMed:22637577, ECO:0000269\|PubMed:23272056, ECO:0000269\|PubMed:23897888, ECO:0000269\|PubMed:23969831, ECO:0000269\|PubMed:26040712}.
Subcellular location:		Membrane {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:19000169}; Peripheral membrane protein {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000305\|PubMed:20200447}. Endoplasmic reticulum {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:16602018}. Midbody {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:18997780, ECO:0000269\|PubMed:21310966}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:15891913}. Cytoplasm, cytoskeleton {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:15716377, ECO:0000269\|PubMed:17389232, ECO:0000269\|PubMed:18410514, ECO:0000269\|PubMed:19000169, ECO:0000269\|PubMed:20200447}. Cytoplasm, perinuclear region {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:11809724, ECO:0000269\|PubMed:15269182, ECO:0000269\|PubMed:15537668}. Nucleus {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:15147984, ECO:0000269\|PubMed:16026783}. Cytoplasm, cytoskeleton, spindle {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:15269182}. Cytoplasm {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:16026783, ECO:0000269\|PubMed:20200447}. Note=Forms an intramembrane hairpin-like structure in the membrane (PubMed:20200447). Localization to the centrosome is independent of microtubules (PubMed:15891913). Localizes to the midbody of dividing cells, and this requires CHMP1B (PubMed:18997780). Enriched in the distal axons and branches of postmitotic neurons (PubMed:15269182). {ECO:0000255\|HAMAP-Rule:MF_03021, ECO:0000269\|PubMed:15269182, ECO:0000269\|PubMed:15891913, ECO:0000269\|PubMed:18997780, ECO:0000305\|PubMed:20200447}.
Subcellular location:		[Isoform 1]: Endoplasmic reticulum membrane {ECO:0000269\|PubMed:19000169, ECO:0000269\|PubMed:23969831}; Peripheral membrane protein {ECO:0000305\|PubMed:20200447}. Nucleus membrane {ECO:0000269\|PubMed:26040712}. Lipid droplet {ECO:0000269\|PubMed:25875445}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:19000169, ECO:0000269\|PubMed:20200447}. Endosome {ECO:0000269\|PubMed:23897888}. Note=Forms an intramembrane hairpin-like structure in the membrane (PubMed:20200447). Recruited to nuclear membrane by IST1 during late anaphase (PubMed:26040712). Localizes to endoplasmic reticulum tubular network (PubMed:23969831). {ECO:0000269\|PubMed:23969831, ECO:0000269\|PubMed:26040712, ECO:0000305\|PubMed:20200447}.
Subcellular location:		[Isoform 3]: Cytoplasm {ECO:0000269\|PubMed:20200447, ECO:0000269\|PubMed:23969831}. Endosome {ECO:0000269\|PubMed:19000169, ECO:0000269\|PubMed:23897888}. Nucleus membrane {ECO:0000269\|PubMed:16026783, ECO:0000269\|PubMed:26040712}. Note=Constitutes the main endosomal form (PubMed:19000169). Recruited to nuclear membrane by IST1 during late anaphase (PubMed:26040712). {ECO:0000269\|PubMed:19000169, ECO:0000269\|PubMed:26040712}.
Tissue specificity:		Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. The short isoforms may predominate in brain and spinal cord. {ECO:0000269\|PubMed:10610178}.
Developmental stage:		Expressed in fetal brain, heart, kidney, liver, lung, skeletal muscle, spleen and thymus. {ECO:0000269\|PubMed:10610178}.
Disease:		Spastic paraplegia 4, autosomal dominant (SPG4) [MIM:182601]: 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. {ECO:0000269\|PubMed:10610178, ECO:0000269\|PubMed:10699187, ECO:0000269\|PubMed:11015453, ECO:0000269\|PubMed:11039577, ECO:0000269\|PubMed:11087788, ECO:0000269\|PubMed:11309678, ECO:0000269\|PubMed:11809724, ECO:0000269\|PubMed:11843700, ECO:0000269\|PubMed:11985387, ECO:0000269\|PubMed:12124993, ECO:0000269\|PubMed:12161613, ECO:0000269\|PubMed:12163196, ECO:0000269\|PubMed:12202986, ECO:0000269\|PubMed:12460147, ECO:0000269\|PubMed:12552568, ECO:0000269\|PubMed:12939659, ECO:0000269\|PubMed:14732620, ECO:0000269\|PubMed:15159500, ECO:0000269\|PubMed:15210521, ECO:0000269\|PubMed:15248095, ECO:0000269\|PubMed:15326248, ECO:0000269\|PubMed:15482961, ECO:0000269\|PubMed:15667412, ECO:0000269\|PubMed:15716377, ECO:0000269\|PubMed:15891913, ECO:0000269\|PubMed:16339213, ECO:0000269\|PubMed:16682546, ECO:0000269\|PubMed:16684598, ECO:0000269\|PubMed:17389232, ECO:0000269\|PubMed:17594340, ECO:0000269\|PubMed:19000169, ECO:0000269\|PubMed:20214791, ECO:0000269\|PubMed:20550563, ECO:0000269\|PubMed:20562464, ECO:0000269\|PubMed:20718791, ECO:0000269\|PubMed:20932283, ECO:0000269\|PubMed:21546041, ECO:0000269\|PubMed:22960362, ECO:0000269\|PubMed:23279441, ECO:0000269\|PubMed:24824479, ECO:0000269\|PubMed:25045380, ECO:0000269\|PubMed:25421405, ECO:0000269\|PubMed:28572275}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 3]: Produced by alternative promoter usage. May also be produced by alternative initiation at Met-87 of isoform 1. Major isoform. {ECO:0000305}.
Miscellaneous:		[Isoform 4]: Produced by alternative promoter usage and alternative splicing. May also be produced by alternative initiation at Met-87 of isoform 2. {ECO:0000305}.
Similarity:		Belongs to the AAA ATPase family. Spastin subfamily. {ECO:0000255\|HAMAP-Rule:MF_03021}.