Protein: Spastin (EC 5.6.1.1) (Spastic paraplegia 4 protein) (Q9UBP0)
Organism: Homo sapiens (Human)
Function: ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated. 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. Severing activity is not dependent on tubulin acetylation or detyrosination. 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. Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex. Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling. Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing. Probably plays a role in axon growth and the formation of axonal branches.
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, ECO:0000269|PubMed:25390646}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15891913, ECO:0000269|PubMed:25390646}. 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:15147984, ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15537668}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15147984, ECO:0000269|PubMed:15269182, 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}. Cell projection, axon {ECO:0000269|PubMed:15269182}. 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). Mainly nuclear in interphase cells and becomes associated with the centrosomes, spindle microtubules, midzone and finally the midbody during cell division (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}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:25390646}. 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}.
Interaction partners:
- Charged multivesicular body protein 1b
- IST1 homolog
- Atlastin-1
- Receptor expression-enhancing protein 1
- Atlastin-2
- Atlastin-3
- Protrudin
- Spatacsin
- Magnesium transporter NIPA1
- Reticulon-1
Sequence:
MNSPGGRGKKKGSGGASNPVPPRPPPPCLAPAPPAAGPAPPPESPHKRNLYYFSYPLFVGFALLRLVAFHLGLLFVWLCQRFSRALMAAKRSSGAAPAPASASAPAPVPGGEAERVRVFHKQAFEYISIALRIDEDEKAGQKEQAVEWYKKGIEELEKGIAVIVTGQGEQCERARRLQAKMMTNLVMAKDRLQLLEKMQPVLPFSKSQTDVYNDSTNLACRNGHLQSESGAVPKRKDPLTHTSNSLPRSKTVMKTGSAGLSGHHRAPSYSGLSMVSGVKQGSGPAPTTHKGTPKTNRTNKPSTPTTATRKKKDLKNFRNVDSNLANLIMNEIVDNGTAVKFDDIAGQDLAKQALQEIVILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAESNATFFNISAASLTSKYVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIEFDGVQSAGDDRVLVMGATNRPQELDEAVLRRFIKRVYVSLPNEETRLLLLKNLLCKQGSPLTQKELAQLARMTDGYSGSDLTALAKDAALGPIRELKPEQVKNMSASEMRNIRLSDFTESLKKIKRSVSPQTLEAYIRWNKDFGDTTV