SPAST_DROME
ID SPAST_DROME Reviewed; 758 AA.
AC Q8I0P1; Q8IMX5; Q8T066;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Spastin {ECO:0000255|HAMAP-Rule:MF_03021};
DE EC=5.6.1.1 {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15823537, ECO:0000269|PubMed:18202664};
DE AltName: Full=D-Spastin;
DE AltName: Full=Dm-Spastin;
DE AltName: Full=Dspastin {ECO:0000303|PubMed:25875445};
GN Name=spas {ECO:0000255|HAMAP-Rule:MF_03021}; ORFNames=CG5977;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Testis;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION, AND DEVELOPMENTAL STAGE.
RX PubMed=12908108; DOI=10.1007/s00427-003-0340-x;
RA Kammermeier L., Spring J., Stierwald M., Burgunder J.-M., Reichert H.;
RT "Identification of the Drosophila melanogaster homolog of the human spastin
RT gene.";
RL Dev. Genes Evol. 213:412-415(2003).
RN [6]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=15242610; DOI=10.1016/j.cub.2004.06.058;
RA Trotta N., Orso G., Rossetto M.G., Daga A., Broadie K.;
RT "The hereditary spastic paraplegia gene, spastin, regulates microtubule
RT stability to modulate synaptic structure and function.";
RL Curr. Biol. 14:1135-1147(2004).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=15562320; DOI=10.1371/journal.pbio.0020429;
RA Sherwood N.T., Sun Q., Xue M., Zhang B., Zinn K.;
RT "Drosophila spastin regulates synaptic microtubule networks and is required
RT for normal motor function.";
RL PLoS Biol. 2:E429-E429(2004).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MICROTUBULES, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF SER-503; LYS-529; GLU-583 AND ASP-697.
RX PubMed=15823537; DOI=10.1016/j.cub.2005.02.029;
RA Roll-Mecak A., Vale R.D.;
RT "The Drosophila homologue of the hereditary spastic paraplegia protein,
RT spastin, severs and disassembles microtubules.";
RL Curr. Biol. 15:650-655(2005).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-529.
RX PubMed=16276413; DOI=10.1172/jci24694;
RA Orso G., Martinuzzi A., Rossetto M.G., Sartori E., Feany M., Daga A.;
RT "Disease-related phenotypes in a Drosophila model of hereditary spastic
RT paraplegia are ameliorated by treatment with vinblastine.";
RL J. Clin. Invest. 115:3026-3034(2005).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17452528; DOI=10.1083/jcb.200612011;
RA Zhang D., Rogers G.C., Buster D.W., Sharp D.J.;
RT "Three microtubule severing enzymes contribute to the 'Pacman-flux'
RT machinery that moves chromosomes.";
RL J. Cell Biol. 177:231-242(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-439, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [12]
RP FUNCTION, AND INTERACTION WITH ATL.
RX PubMed=19341724; DOI=10.1016/j.ydbio.2009.03.019;
RA Lee M., Paik S.K., Lee M.-J., Kim Y.-J., Kim S., Nahm M., Oh S.-J.,
RA Kim H.-M., Yim J., Lee C.J., Bae Y.C., Lee S.;
RT "Drosophila Atlastin regulates the stability of muscle microtubules and is
RT required for synapse development.";
RL Dev. Biol. 330:250-262(2009).
RN [13]
RP FUNCTION.
RX PubMed=23122959; DOI=10.1016/j.celrep.2012.09.032;
RA Stone M.C., Rao K., Gheres K.W., Kim S., Tao J., La Rochelle C.,
RA Folker C.T., Sherwood N.T., Rolls M.M.;
RT "Normal spastin gene dosage is specifically required for axon
RT regeneration.";
RL Cell Rep. 2:1340-1350(2012).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-529.
RX PubMed=25875445; DOI=10.1371/journal.pgen.1005149;
RA Papadopoulos C., Orso G., Mancuso G., Herholz M., Gumeni S., Tadepalle N.,
RA Juengst C., Tzschichholz A., Schauss A., Hoening S., Trifunovic A.,
RA Daga A., Rugarli E.I.;
RT "Spastin binds to lipid droplets and affects lipid metabolism.";
RL PLoS Genet. 11:E1005149-E1005149(2015).
RN [15]
RP DISRUPTION PHENOTYPE.
RX PubMed=26744324; DOI=10.1093/hmg/ddv632;
RA Julien C., Lissouba A., Madabattula S., Fardghassemi Y., Rosenfelt C.,
RA Androschuk A., Strautman J., Wong C., Bysice A., O'sullivan J.,
RA Rouleau G.A., Drapeau P., Parker J.A., Bolduc F.V.;
RT "Conserved pharmacological rescue of hereditary spastic paraplegia-related
RT phenotypes across model organisms.";
RL Hum. Mol. Genet. 25:1088-1099(2016).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 463-758, FUNCTION, CATALYTIC
RP ACTIVITY, HOMOHEXAMERIZATION, INTERACTION WITH MICROTUBULES, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LEU-465; ILE-469; ASP-471; GLU-472; ILE-473;
RP VAL-474; GLY-511; LYS-555; TYR-556; VAL-557; GLY-558; ASP-559; GLY-560;
RP GLU-561; LYS-562; GLU-583; SER-589; ARG-591; GLU-595; HIS-596; GLU-597;
RP ALA-598; ARG-601; PRO-631; GLN-632; GLU-633; ARG-704 AND TYR-753.
RX PubMed=18202664; DOI=10.1038/nature06482;
RA Roll-Mecak A., Vale R.D.;
RT "Structural basis of microtubule severing by the hereditary spastic
RT paraplegia protein spastin.";
RL Nature 451:363-367(2008).
CC -!- FUNCTION: ATP-dependent microtubule severing protein. Stimulates
CC microtubule minus-end depolymerization and poleward microtubule flux in
CC the mitotic spindle (PubMed:15242610, PubMed:15562320, PubMed:15823537,
CC PubMed:16276413, PubMed:17452528, PubMed:25875445, PubMed:18202664,
CC PubMed:19341724). Regulates microtubule stability in the neuromuscular
CC junction synapse (PubMed:15242610, PubMed:15562320, PubMed:19341724).
CC Involved in lipid metabolism by regulating the size and distribution of
CC lipid droplets (PubMed:25875445). Involved in axon regeneration by
CC regulating microtubule severing (PubMed:23122959). {ECO:0000255|HAMAP-
CC Rule:MF_03021, ECO:0000269|PubMed:15242610,
CC ECO:0000269|PubMed:15562320, ECO:0000269|PubMed:15823537,
CC ECO:0000269|PubMed:16276413, ECO:0000269|PubMed:17452528,
CC ECO:0000269|PubMed:18202664, ECO:0000269|PubMed:19341724,
CC ECO:0000269|PubMed:23122959, ECO:0000269|PubMed:25875445}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=n ATP + n H2O + a microtubule = n ADP + n phosphate + (n+1)
CC alpha/beta tubulin heterodimers.; EC=5.6.1.1;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03021,
CC ECO:0000269|PubMed:15823537, ECO:0000269|PubMed:18202664};
CC -!- SUBUNIT: Homohexamer. The homohexamer is stabilized by ATP-binding. The
CC homohexamer may adopt a ring conformation through which microtubules
CC pass prior to being severed (PubMed:18202664). Interacts with
CC microtubules (PubMed:15823537, PubMed:18202664). Interacts with atl;
CC may be involved in microtubule dynamics (PubMed:19341724).
CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15823537,
CC ECO:0000269|PubMed:18202664, ECO:0000269|PubMed:19341724}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255|HAMAP-Rule:MF_03021};
CC Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_03021}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:17452528}.
CC Cytoplasm, cytoskeleton {ECO:0000255|HAMAP-Rule:MF_03021,
CC ECO:0000269|PubMed:15562320, ECO:0000269|PubMed:15823537,
CC ECO:0000269|PubMed:17452528, ECO:0000269|PubMed:18202664}. Chromosome
CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:17452528}. Lipid
CC droplet {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:25875445}.
CC Note=Forms a intramembrane hairpin-like structure in the membrane (By
CC similarity). Colocalizes with cellular microtubule arrays. Localizes to
CC chromosomes from prometaphase/metaphase to anaphase, and this requires
CC microtubules (PubMed:17452528). Localizes to discrete punctate
CC cytoplasmic foci which may correspond to secretory vesicles
CC (PubMed:15823537). {ECO:0000255|HAMAP-Rule:MF_03021,
CC ECO:0000269|PubMed:15823537, ECO:0000269|PubMed:17452528}.
CC -!- DEVELOPMENTAL STAGE: Maternally expressed in early embryogenesis with
CC high expression until blastoderm. At the cell formation stage, strongly
CC expressed near the basal part of the cell layer underlying the surface.
CC During germband extension and stomodeal plate formation, expressed in
CC the ventral head and trunk ectoderm, as well as in cells near the
CC cephalic furrow and in the invaginating hindgut and midgut primordia.
CC After germband retraction and delamination of neuroblasts at stage 13,
CC expressed in subsets of cells in all neuromeres of the CNS including
CC those of the supraesophageal and subesophageal ganglia. In later
CC embryonic stages expressed in cell clusters throughout the
CC supraesophageal ganglion, with pronounced expression also seen in the
CC subesophageal ganglion. In the ventral nerve cord (VNC), expressed in
CC two broad longitudinal stripes located laterally, and weakly expressed
CC in some midline cells. Also expressed in some sensory head organs of
CC the peripheral nervous system (PNS), most probably the Bolwigs organs
CC and/or the dorsal organs. Expressed in the developing larval
CC neuromusculature, muscles and neuronal axons. Enriched in neuromuscular
CC junctions throughout the muscles of the body wall. Enriched in punctate
CC domains of synaptic boutons and excluded from interbouton axonal
CC connections. Colocalizes with the synaptic vesicle pools.
CC {ECO:0000269|PubMed:12908108, ECO:0000269|PubMed:15242610}.
CC -!- DISRUPTION PHENOTYPE: Loss of protein expression throughout the embryo
CC leads to pupal lethality. Loss of protein expression specifically in
CC the nervous system causes synaptic undergrowth and a reduction in total
CC synaptic area. Neuromuscular junction boutons are smaller and more
CC numerous. Microtubule stability appears to be enhanced within neuronal
CC axons and at neuromuscular junctions and synaptic currents are
CC increased. Older flies exhibit numerous vacuoles in the neuropil and
CC cortex. Adult coordination and locomotory behavior are compromised and
CC lifespan is reduced. RNAi-mediated knockdown results in climbing
CC defects, which can be rescued following exposure to the drugs methylene
CC blue, phenazine, or N-acetyl-L-cysteine (PubMed:26744324). RNAi-
CC mediated knockdown results in increased oxidative stress, which can be
CC rescued following exposure to the drug methylene blue
CC (PubMed:26744324). {ECO:0000269|PubMed:15242610,
CC ECO:0000269|PubMed:15562320, ECO:0000269|PubMed:16276413,
CC ECO:0000269|PubMed:26744324}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. Spastin subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03021}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL39667.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AE014297; AAF56223.3; -; Genomic_DNA.
DR EMBL; AE014297; AAN13975.2; -; Genomic_DNA.
DR EMBL; AY069522; AAL39667.1; ALT_INIT; mRNA.
DR EMBL; BT001254; AAN71010.1; -; mRNA.
DR EMBL; BT001351; AAN71106.1; -; mRNA.
DR EMBL; BT044258; ACH92323.1; -; mRNA.
DR RefSeq; NP_001303438.1; NM_001316509.1.
DR RefSeq; NP_651206.3; NM_142949.4.
DR RefSeq; NP_732941.2; NM_170115.3.
DR PDB; 3B9P; X-ray; 2.70 A; A=463-758.
DR PDB; 6NYV; X-ray; 2.42 A; B=445-758.
DR PDB; 6NYW; X-ray; 2.19 A; B=445-758.
DR PDB; 6P10; X-ray; 2.30 A; B=445-758.
DR PDB; 6P11; X-ray; 2.15 A; B=445-758.
DR PDB; 6P12; X-ray; 1.94 A; B=445-758.
DR PDB; 6P13; X-ray; 2.10 A; B=445-758.
DR PDB; 6P14; X-ray; 1.93 A; A=445-758.
DR PDBsum; 3B9P; -.
DR PDBsum; 6NYV; -.
DR PDBsum; 6NYW; -.
DR PDBsum; 6P10; -.
DR PDBsum; 6P11; -.
DR PDBsum; 6P12; -.
DR PDBsum; 6P13; -.
DR PDBsum; 6P14; -.
DR AlphaFoldDB; Q8I0P1; -.
DR SMR; Q8I0P1; -.
DR BioGRID; 67781; 6.
DR DIP; DIP-59834N; -.
DR IntAct; Q8I0P1; 2.
DR STRING; 7227.FBpp0083918; -.
DR iPTMnet; Q8I0P1; -.
DR PaxDb; Q8I0P1; -.
DR PRIDE; Q8I0P1; -.
DR DNASU; 42846; -.
DR EnsemblMetazoa; FBtr0084533; FBpp0083918; FBgn0039141.
DR EnsemblMetazoa; FBtr0084534; FBpp0083919; FBgn0039141.
DR GeneID; 42846; -.
DR KEGG; dme:Dmel_CG5977; -.
DR UCSC; CG5977-RA; d. melanogaster.
DR CTD; 42846; -.
DR FlyBase; FBgn0039141; spas.
DR VEuPathDB; VectorBase:FBgn0039141; -.
DR eggNOG; KOG0740; Eukaryota.
DR GeneTree; ENSGT00940000156258; -.
DR InParanoid; Q8I0P1; -.
DR OMA; GMTNEPM; -.
DR PhylomeDB; Q8I0P1; -.
DR BRENDA; 5.6.1.1; 1994.
DR Reactome; R-DME-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR BioGRID-ORCS; 42846; 0 hits in 1 CRISPR screen.
DR EvolutionaryTrace; Q8I0P1; -.
DR GenomeRNAi; 42846; -.
DR PRO; PR:Q8I0P1; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039141; Expressed in adult abdomen and 42 other tissues.
DR ExpressionAtlas; Q8I0P1; baseline and differential.
DR Genevisible; Q8I0P1; DM.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-UniRule.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:UniProtKB.
DR GO; GO:0031594; C:neuromuscular junction; IDA:FlyBase.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-UniRule.
DR GO; GO:0043195; C:terminal bouton; IDA:FlyBase.
DR GO; GO:0043014; F:alpha-tubulin binding; NAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; IDA:FlyBase.
DR GO; GO:0008568; F:microtubule severing ATPase activity; IDA:FlyBase.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:UniProtKB-UniRule.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0035099; P:hemocyte migration; IMP:FlyBase.
DR GO; GO:0007626; P:locomotory behavior; IMP:FlyBase.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:FlyBase.
DR GO; GO:0051013; P:microtubule severing; IDA:FlyBase.
DR GO; GO:0007079; P:mitotic chromosome movement towards spindle pole; IEA:UniProtKB-UniRule.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IMP:FlyBase.
DR GO; GO:0000022; P:mitotic spindle elongation; IEA:UniProtKB-UniRule.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; IDA:FlyBase.
DR GO; GO:1900074; P:negative regulation of neuromuscular synaptic transmission; IMP:FlyBase.
DR GO; GO:0045886; P:negative regulation of synaptic assembly at neuromuscular junction; IMP:FlyBase.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0048691; P:positive regulation of axon extension involved in regeneration; IGI:FlyBase.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IMP:FlyBase.
DR GO; GO:0045834; P:positive regulation of lipid metabolic process; IMP:FlyBase.
DR GO; GO:0031117; P:positive regulation of microtubule depolymerization; IDA:UniProtKB.
DR GO; GO:1900075; P:positive regulation of neuromuscular synaptic transmission; IMP:FlyBase.
DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; IMP:FlyBase.
DR GO; GO:0034214; P:protein hexamerization; IEA:UniProtKB-UniRule.
DR GO; GO:2000331; P:regulation of terminal button organization; IMP:FlyBase.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_03021; Spastin; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR007330; MIT_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR017179; Spastin.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00745; MIT; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell cycle; Cell division; Chromosome;
KW Cytoplasm; Cytoskeleton; Developmental protein; Differentiation; Isomerase;
KW Lipid droplet; Membrane; Microtubule; Mitosis; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..758
FT /note="Spastin"
FT /id="PRO_0000367144"
FT TOPO_DOM 1..121
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT INTRAMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT TOPO_DOM 143..758
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT DOMAIN 233..308
FT /note="MIT"
FT /evidence="ECO:0000255"
FT REGION 1..210
FT /note="Required for localization to punctate cytoplasmic
FT foci"
FT REGION 1..159
FT /note="Interaction with atl"
FT /evidence="ECO:0000269|PubMed:19341724"
FT REGION 1..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 169..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..758
FT /note="Sufficient for interaction with microtubules and
FT microtubule severing"
FT /evidence="ECO:0000269|PubMed:15823537,
FT ECO:0000269|PubMed:18202664"
FT REGION 353..454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 443..455
FT /note="Required for interaction with microtubules"
FT /evidence="ECO:0000269|PubMed:18202664"
FT COMPBIAS 1..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 60..103
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..201
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..375
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 386..411
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 421..454
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 523..530
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT MOD_RES 439
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 465
FT /note="L->A: Strongly impairs microtubule severing and
FT weakly impairs ATPase activity; when associated with A-471
FT and A-472."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 465
FT /note="L->F: Strongly impairs microtubule severing and
FT weakly impairs ATPase activity."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 469
FT /note="I->A: Strongly impairs microtubule severing and
FT ATPase activity but does not affect interaction with
FT microtubules; when associated with A-473 and A-474."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 471
FT /note="D->A: Strongly impairs microtubule severing and
FT weakly impairs ATPase activity; when associated with A-465
FT and A-472."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 472
FT /note="E->A: Strongly impairs microtubule severing and
FT weakly impairs ATPase activity; when associated with A-465
FT and A-471."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 473
FT /note="I->A: Strongly impairs microtubule severing and
FT ATPase activity but does not affect interaction with
FT microtubules; when associated with A-469 and A-474."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 474
FT /note="V->A: Strongly impairs microtubule severing and
FT ATPase activity but does not affect interaction with
FT microtubules; when associated with A-469 and A-473."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 503
FT /note="S->C: Impairs microtubule severing and ATPase
FT activity."
FT /evidence="ECO:0000269|PubMed:15823537"
FT MUTAGEN 511
FT /note="G->R: Abrogates microtubule severing and strongly
FT impairs ATPase activity."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 529
FT /note="K->R: Abrogates microtubule severing and ATPase
FT activity. Induces accumulation of hyperstable microtubules
FT at the neuromuscular junction presynpatic terminal and
FT reduces synaptic area. Reduces adult lifespan and impairs
FT climbing activity."
FT /evidence="ECO:0000269|PubMed:15823537,
FT ECO:0000269|PubMed:16276413, ECO:0000269|PubMed:25875445"
FT MUTAGEN 555
FT /note="K->A: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 556
FT /note="Y->A: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 557
FT /note="V->A: Abrogates microtubule severing and impairs
FT ATPase activity."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 558
FT /note="G->A,V: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 559
FT /note="D->A,R: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 560
FT /note="G->A: Impairs microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 560
FT /note="G->V: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 561
FT /note="E->A,R: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 562
FT /note="K->A,R: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 583
FT /note="E->A: Abrogates microtubule severing and ATPase
FT activity."
FT /evidence="ECO:0000269|PubMed:15823537,
FT ECO:0000269|PubMed:18202664"
FT MUTAGEN 583
FT /note="E->Q: Impairs interaction with microtubules and
FT promotes hexamerization."
FT /evidence="ECO:0000269|PubMed:15823537,
FT ECO:0000269|PubMed:18202664"
FT MUTAGEN 589
FT /note="S->Y: Impairs microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 591
FT /note="R->A,E: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 595
FT /note="E->A: Impairs microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 595
FT /note="E->R: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 596
FT /note="H->A: Impairs microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 596
FT /note="H->D: Abrogates microtubule severing and impairs
FT ATPase activity."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 596
FT /note="H->Y: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 597
FT /note="E->K: Impairs microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 598
FT /note="A->L: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 601
FT /note="R->E: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 601
FT /note="R->L: Abrogates microtubule severing and strongly
FT impairs ATPase activity."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 631
FT /note="P->L: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 632
FT /note="Q->A: Strongly impairs microtubule severing and
FT weakly impairs ATPase activity."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 633
FT /note="E->A: Weakly impairs microtubule severing and ATPase
FT activity."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 633
FT /note="E->R: Impairs microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 697
FT /note="D->N: Weakly impairs microtubule severing and
FT strongly impairs ATPase activity."
FT /evidence="ECO:0000269|PubMed:15823537"
FT MUTAGEN 704
FT /note="R->Q: Abrogates microtubule severing."
FT /evidence="ECO:0000269|PubMed:18202664"
FT MUTAGEN 753
FT /note="Y->A: Strongly impairs microtubule severing and
FT ATPase activity."
FT /evidence="ECO:0000269|PubMed:18202664"
FT CONFLICT 665
FT /note="Q -> E (in Ref. 3; AAN71010/AAN71106)"
FT /evidence="ECO:0000305"
FT HELIX 464..470
FT /evidence="ECO:0007829|PDB:6P14"
FT TURN 471..473
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 489..498
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 500..504
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 511..513
FT /evidence="ECO:0007829|PDB:6P14"
FT STRAND 517..528
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 529..540
FT /evidence="ECO:0007829|PDB:6P14"
FT STRAND 543..547
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 549..552
FT /evidence="ECO:0007829|PDB:6P12"
FT STRAND 553..556
FT /evidence="ECO:0007829|PDB:3B9P"
FT HELIX 563..573
FT /evidence="ECO:0007829|PDB:6P14"
FT STRAND 576..581
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 584..586
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 602..610
FT /evidence="ECO:0007829|PDB:6P14"
FT STRAND 622..629
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 631..633
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 636..641
FT /evidence="ECO:0007829|PDB:6P14"
FT STRAND 644..647
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 653..665
FT /evidence="ECO:0007829|PDB:6P14"
FT TURN 666..668
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 673..681
FT /evidence="ECO:0007829|PDB:6P14"
FT TURN 682..685
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 688..699
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 701..704
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 708..713
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 716..718
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 724..733
FT /evidence="ECO:0007829|PDB:6P14"
FT HELIX 740..753
FT /evidence="ECO:0007829|PDB:6P14"
SQ SEQUENCE 758 AA; 82749 MW; 406D075DCBD2A9CD CRC64;
MVRTKNQSSS SSASSSSTKS PIKSSSGAGS SGGGLGGRQS THRSSSASNV AAVVAGGSSA
AGGGSSSNRR SPGSSPDGDD DTTTTDDLTP TTCSPRSGHH HSYGGYSSSV HKQNLYVVSF
PIIFLFNVLR SLIYQLFCIF RYLYGASTKV IYRPHRRDCN IEIVVQNSSK EQQQSLNHPS
ELNREGDGQE QQLSNQPQRF RPIQPLEMAA NRPGGGYSPG PGDPLLAKQK HHHRRAFEYI
SKALKIDEEN EGHKELAIEL YRKGIKELED GIAVDCWSGR GDVWDRAQRL HDKMQTNLSM
ARDRLHFLAL REQDLQMQRL SLKEKQKEEA QSKPQKTREP MLAGMTNEPM KLRVRSSGYG
PKATTSAQPT ASGRKLTIGS KRPVNLAVAN KSQTLPRNLG SKTSVGAVQR QPAKTAATPP
AVRRQFSSGR NTPPQRSRTP INNNGPSGSG ASTPVVSVKG VEQKLVQLIL DEIVEGGAKV
EWTDIAGQDV AKQALQEMVI LPSVRPELFT GLRAPAKGLL LFGPPGNGKT LLARAVATEC
SATFLNISAA SLTSKYVGDG EKLVRALFAV ARHMQPSIIF IDEVDSLLSE RSSSEHEASR
RLKTEFLVEF DGLPGNPDGD RIVVLAATNR PQELDEAALR RFTKRVYVSL PDEQTRELLL
NRLLQKQGSP LDTEALRRLA KITDGYSGSD LTALAKDAAL EPIRELNVEQ VKCLDISAMR
AITEQDFHSS LKRIRRSVAP QSLNSYEKWS QDYGDITI
