ID  A2VDN5;
PN  Spastin;
GN  SPAST;
OS  9913;
SL  Nucleus Position: SL-0198;
SL  Comments: Membrane {ECO:0000255|HAMAP-Rule:MF_03021}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_03021}. Endoplasmic reticulum {ECO:0000255|HAMAP-Rule:MF_03021}. Midbody {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm, cytoskeleton {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm, perinuclear region {ECO:0000255|HAMAP-Rule:MF_03021}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm, cytoskeleton, spindle {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm {ECO:0000255|HAMAP- Rule:MF_03021}. Cell projection, axon {ECO:0000250|UniProtKB:Q9UBP0}. Note=Forms an intramembrane hairpin-like structure in the membrane. Localization to the centrosome is independent of microtubules. Localizes to the midbody of dividing cells, and this requires CHMP1B. Enriched in the distal axons and branches of postmitotic neurons. Localizes to endoplasmic reticulum tubular network. Mainly nuclear in interphase cells and becomes associated with the centrosomes, spindle microtubules, midzone and finally the midbody during cell division (By similarity). {ECO:0000250|UniProtKB:Q9UBP0, ECO:0000255|HAMAP- Rule:MF_03021}.
DR  UNIPROT: A2VDN5;
DR  Pfam: PF00004;
DR  Pfam: PF17862;
DR  Pfam: PF09336;
DR  PROSITE: PS00674;
DE  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. {ECO:0000255|HAMAP- Rule:MF_03021}.
DE  Disease: Note=Defects in SPAST are the cause of bovine spinal dysmyelination (BSD), a neurodegenerative disorder characterized by pathological changes of the myelin sheaths in the spinal cord. Defects appear immediately at birth and include lateral recumbency with slight to moderate opisthotonos, body tremor, and spastic extension of the limbs. General muscle atrophy due to denervation occurs to variable degrees and is most obvious in the hind limbs. BSD is a longstanding problem in the American Brown Swiss (ABS) breed and in several European cattle breeds upgraded with ABS. The morphological cause of the phenotype is bilateral symmetrical hypo- and demyelination of axons in the cervical and thoracic segments of the spinal cord. The disease is caused by variants affecting the gene represented in this entry. {ECO:0000269|PubMed:19714378}.
DE  Reference Proteome: Yes;
GO  GO:0030424;
GO  GO:1904115;
GO  GO:0005813;
GO  GO:0005829;
GO  GO:0005783;
GO  GO:0005768;
GO  GO:0016021;
GO  GO:0005874;
GO  GO:0015630;
GO  GO:0030496;
GO  GO:0031965;
GO  GO:0005654;
GO  GO:0005634;
GO  GO:0048471;
GO  GO:0000922;
GO  GO:0043014;
GO  GO:0005524;
GO  GO:0016887;
GO  GO:0048487;
GO  GO:0016853;
GO  GO:0008017;
GO  GO:0008568;
GO  GO:0008089;
GO  GO:0019896;
GO  GO:0007409;
GO  GO:0032506;
GO  GO:0006888;
GO  GO:0010458;
GO  GO:0090148;
GO  GO:0008152;
GO  GO:0001578;
GO  GO:0051013;
GO  GO:0000281;
GO  GO:0051228;
GO  GO:0031468;
GO  GO:0032467;
GO  GO:0031117;
GO  GO:0034214;
GO  GO:0051260;
TP  Membrane Topology: Peripheral; Source: UniProt - Sequence Analysis {ECO:0000255|HAMAP-Rule:MF_03021};
SQ  MNSPGGRGKKKGSGGPSSPVPPRPPPPCQARSRPAPKPAPPPQSPHKRNLYYFSYPLFLGFALLRLVAFHLGLLFVWLCQ
SQ  RFSRALMAAKRSSGAAPASASPPAPVPGGEAERVRAFHKQAFEYISVALRIDEDEKVGQKDQAVEWYKKGIEELEKGIAV
SQ  VVTGQGEQCERARRLQAKMMTNLVMAKDRLQLLEKLQPSLQFSKSQTDVYNDSTNLTCRNGHLQSESGAVPKRKDPLTHA
SQ  SNSLPRSKTVMKTGPTGLSGHHRAPSCSGLSMVSGVRQGPGSAAATHKSTPKTNRTNKPSTPTTAARKKKDLKNFRNVDS
SQ  NLANLIMNEIVDNGTAVKFDDIAGQELAKQALQEIVILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAESNAT
SQ  FFNISAASLTSKYVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIEFDGVQSAGDDRVLV
SQ  MGATNRPQELDEAVLRRFTKRVYVSLPNEETRLLLLKNLLCKQGSPLTQKELAQLARMTNGYSGSDLTALAKDAALGPIR
SQ  ELKPEQVKNMSASEMRNIRLSDFTESLKKIKRSVSPQTLEAYIRWNKDFGDTTV
//