ID SPAST_HUMAN Reviewed; 616 AA. AC Q9UBP0; A7E2A7; Q9UPR9; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 212. DE RecName: Full=Spastin {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000303|PubMed:10610178}; DE EC=5.6.1.1 {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}; DE AltName: Full=Spastic paraplegia 4 protein; GN Name=SPAST {ECO:0000255|HAMAP-Rule:MF_03021, GN ECO:0000312|HGNC:HGNC:11233}; GN Synonyms=ADPSP, FSP2, KIAA1083 {ECO:0000303|PubMed:10470851}, SPG4 GN {ECO:0000255|HAMAP-Rule:MF_03021}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY, RP DEVELOPMENTAL STAGE, AND VARIANTS SPG4 CYS-362; TYR-448 AND CYS-499. RX PubMed=10610178; DOI=10.1038/15472; RA Hazan J., Fonknechten N., Mavel D., Paternotte C., Samson D., RA Artiguenave F., Davoine C.-S., Cruaud C., Durr A., Wincker P., Brottier P., RA Cattolico L., Barbe V., Burgunder J.-M., Prud'homme J.-F., Brice A., RA Fontaine B., Heilig R., Weissenbach J.; RT "Spastin, a new AAA protein, is altered in the most frequent form of RT autosomal dominant spastic paraplegia."; RL Nat. Genet. 23:296-303(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=10470851; DOI=10.1093/dnares/6.3.197; RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIV. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:197-205(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS SPG4 RP ARG-370; CYS-381; LYS-386; ARG-388; VAL-426; TYR-448; LEU-460; CYS-499 AND RP VAL-556. RX PubMed=11809724; DOI=10.1093/hmg/11.2.153; RA Errico A., Ballabio A., Rugarli E.I.; RT "Spastin, the protein mutated in autosomal dominant hereditary spastic RT paraplegia, is involved in microtubule dynamics."; RL Hum. Mol. Genet. 11:153-163(2002). RN [6] RP DOMAIN MIT, AND PROBABLE FUNCTION. RX PubMed=12676568; DOI=10.1016/s0888-7543(03)00011-9; RA Ciccarelli F.D., Proukakis C., Patel H., Cross H., Azam S., Patton M.A., RA Bork P., Crosby A.H.; RT "The identification of a conserved domain in both spartin and spastin, RT mutated in hereditary spastic paraplegia."; RL Genomics 81:437-441(2003). RN [7] RP SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNAL. RX PubMed=15147984; DOI=10.1016/j.bbrc.2004.03.195; RA Beetz C., Brodhun M., Moutzouris K., Kiehntopf M., Berndt A., Lehnert D., RA Deufel T., Bastmeyer M., Schickel J.; RT "Identification of nuclear localisation sequences in spastin (SPG4) using a RT novel Tetra-GFP reporter system."; RL Biochem. Biophys. Res. Commun. 318:1079-1084(2004). RN [8] RP INTERACTION WITH SSNA1 AND MICROTUBULES, AND SUBCELLULAR LOCATION. RX PubMed=15269182; DOI=10.1093/hmg/ddh223; RA Errico A., Claudiani P., D'Addio M., Rugarli E.I.; RT "Spastin interacts with the centrosomal protein NA14, and is enriched in RT the spindle pole, the midbody and the distal axon."; RL Hum. Mol. Genet. 13:2121-2132(2004). RN [9] RP ALTERNATIVE INITIATION, SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNALS, AND RP MUTAGENESIS OF MET-1 AND MET-87. RX PubMed=16026783; DOI=10.1016/j.yexcr.2005.06.009; RA Claudiani P., Riano E., Errico A., Andolfi G., Rugarli E.I.; RT "Spastin subcellular localization is regulated through usage of different RT translation start sites and active export from the nucleus."; RL Exp. Cell Res. 309:358-369(2005). RN [10] RP INTERACTION WITH CHMP1B, AND SUBCELLULAR LOCATION. RX PubMed=15537668; DOI=10.1093/hmg/ddi003; RA Reid E., Connell J.W., Edwards T.L., Duley S., Brown S.E., Sanderson C.M.; RT "The hereditary spastic paraplegia protein spastin interacts with the RT ESCRT-III complex-associated endosomal protein CHMP1B."; RL Hum. Mol. Genet. 14:19-38(2005). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION RP WITH MICROTUBULES, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-388 AND RP GLU-442, AND CHARACTERIZATION OF VARIANTS SPG4 LYS-344; LYS-347; LYS-386; RP ARG-388 AND CYS-499. RX PubMed=15716377; DOI=10.1083/jcb.200409058; RA Evans K.J., Gomes E.R., Reisenweber S.M., Gundersen G.G., Lauring B.P.; RT "Linking axonal degeneration to microtubule remodeling by Spastin-mediated RT microtubule severing."; RL J. Cell Biol. 168:599-606(2005). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, AND ASSOCIATION WITH MICROTUBULES. RX PubMed=16219033; DOI=10.1111/j.1471-4159.2005.03472.x; RA Salinas S., Carazo-Salas R.E., Proukakis C., Cooper J.M., Weston A.E., RA Schiavo G., Warner T.T.; RT "Human spastin has multiple microtubule-related functions."; RL J. Neurochem. 95:1411-1420(2005). RN [13] RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT SPG4 ARG-388. RX PubMed=15891913; DOI=10.1007/s10048-005-0219-2; RA Svenson I.K., Kloos M.T., Jacon A., Gallione C., Horton A.C., RA Pericak-Vance M.A., Ehlers M.D., Marchuk D.A.; RT "Subcellular localization of spastin: implications for the pathogenesis of RT hereditary spastic paraplegia."; RL Neurogenetics 6:135-141(2005). RN [14] RP INTERACTION WITH ZFYVE27. RX PubMed=16826525; DOI=10.1086/504927; RA Mannan A.U., Krawen P., Sauter S.M., Boehm J., Chronowska A., Paulus W., RA Neesen J., Engel W.; RT "ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary RT spastic paraplegia."; RL Am. J. Hum. Genet. 79:351-357(2006). RN [15] RP INTERACTION WITH ATL1, AND CHARACTERIZATION OF VARIANT SPG4 ARG-388. RX PubMed=16339213; DOI=10.1093/hmg/ddi447; RA Sanderson C.M., Connell J.W., Edwards T.L., Bright N.A., Duley S., RA Thompson A., Luzio J.P., Reid E.; RT "Spastin and atlastin, two proteins mutated in autosomal-dominant RT hereditary spastic paraplegia, are binding partners."; RL Hum. Mol. Genet. 15:307-318(2006). RN [16] RP INTERACTION WITH RTN1, AND SUBCELLULAR LOCATION. RX PubMed=16602018; DOI=10.1007/s10048-006-0034-4; RA Mannan A.U., Boehm J., Sauter S.M., Rauber A., Byrne P.C., Neesen J., RA Engel W.; RT "Spastin, the most commonly mutated protein in hereditary spastic RT paraplegia interacts with Reticulon 1 an endoplasmic reticulum protein."; RL Neurogenetics 7:93-103(2006). RN [17] RP CATALYTIC ACTIVITY, INTERACTION WITH ATL1, AND MUTAGENESIS OF GLU-442. RX PubMed=16815977; DOI=10.1073/pnas.0510863103; RA Evans K.J., Keller C., Pavur K., Glasgow K., Conn B., Lauring B.P.; RT "Interaction of two hereditary spastic paraplegia gene products, spastin RT and atlastin, suggests a common pathway for axonal maintenance."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10666-10671(2006). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, RP HOMOHEXAMERIZATION, INTERACTION WITH TUBULIN AND MICROTUBULES, SUBCELLULAR RP LOCATION, MUTAGENESIS OF TYR-415; GLU-442; ARG-451 AND ALA-457, AND RP CHARACTERIZATION OF VARIANT SPG4 TYR-448. RX PubMed=17389232; DOI=10.1083/jcb.200610072; RA White S.R., Evans K.J., Lary J., Cole J.L., Lauring B.P.; RT "Recognition of C-terminal amino acids in tubulin by pore loops in Spastin RT is important for microtubule severing."; RL J. Cell Biol. 176:995-1005(2007). RN [19] RP ALTERNATIVE PROMOTER USAGE, AND CHARACTERIZATION OF VARIANT LEU-44. RX PubMed=18613979; DOI=10.1186/1741-7007-6-31; RA Mancuso G., Rugarli E.I.; RT "A cryptic promoter in the first exon of the SPG4 gene directs the RT synthesis of the 60-kDa spastin isoform."; RL BMC Biol. 6:31-31(2008). RN [20] RP CATALYTIC ACTIVITY, HOMOHEXAMERIZATION, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF GLU-442. RX PubMed=18410514; DOI=10.1111/j.1471-4159.2008.05414.x; RA Pantakani D.V.K., Swapna L.S., Srinivasan N., Mannan A.U.; RT "Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) RT redistribute the wild-type spastin into filamentous microtubule."; RL J. Neurochem. 106:613-624(2008). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268 AND THR-306, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [23] RP FUNCTION, SUBCELLULAR LOCATION (ISOFORMS 1 AND 3), AND CHARACTERIZATION OF RP VARIANT SPG4 ARG-388. RX PubMed=19000169; DOI=10.1111/j.1600-0854.2008.00847.x; RA Connell J.W., Lindon C., Luzio J.P., Reid E.; RT "Spastin couples microtubule severing to membrane traffic in completion of RT cytokinesis and secretion."; RL Traffic 10:42-56(2009). RN [24] RP INTERACTION WITH REEP1, SUBCELLULAR LOCATION (ISOFORMS 1 AND 3), AND RP TOPOLOGY (ISOFORM 1). RX PubMed=20200447; DOI=10.1172/jci40979; RA Park S.H., Zhu P.P., Parker R.L., Blackstone C.; RT "Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 RT coordinate microtubule interactions with the tubular ER network."; RL J. Clin. Invest. 120:1097-1110(2010). RN [25] RP FUNCTION. RX PubMed=20530212; DOI=10.1083/jcb.201001024; RA Lacroix B., van Dijk J., Gold N.D., Guizetti J., Aldrian-Herrada G., RA Rogowski K., Gerlich D.W., Janke C.; RT "Tubulin polyglutamylation stimulates spastin-mediated microtubule RT severing."; RL J. Cell Biol. 189:945-954(2010). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [28] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=21310966; DOI=10.1126/science.1201847; RA Guizetti J., Schermelleh L., Maentler J., Maar S., Poser I., Leonhardt H., RA Mueller-Reichert T., Gerlich D.W.; RT "Cortical constriction during abscission involves helices of ESCRT-III- RT dependent filaments."; RL Science 331:1616-1620(2011). RN [29] RP HOMOHEXAMERIZATION, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, RP KINETIC PARAMETERS, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, COOPERATIVITY, RP AND MUTAGENESIS OF GLU-442. RX PubMed=22637577; DOI=10.1074/jbc.m111.291898; RA Eckert T., Link S., Le D.T., Sobczak J.P., Gieseke A., Richter K., RA Woehlke G.; RT "Subunit Interactions and cooperativity in the microtubule-severing AAA RT ATPase spastin."; RL J. Biol. Chem. 287:26278-26290(2012). RN [30] RP INTERACTION WITH RTN2. RX PubMed=22232211; DOI=10.1172/jci60560; RA Montenegro G., Rebelo A.P., Connell J., Allison R., Babalini C., RA D'Aloia M., Montieri P., Schule R., Ishiura H., Price J., Strickland A., RA Gonzalez M.A., Baumbach-Reardon L., Deconinck T., Huang J., Bernardi G., RA Vance J.M., Rogers M.T., Tsuji S., De Jonghe P., Pericak-Vance M.A., RA Schols L., Orlacchio A., Reid E., Zuchner S.; RT "Mutations in the ER-shaping protein reticulon 2 cause the axon- RT degenerative disorder hereditary spastic paraplegia type 12."; RL J. Clin. Invest. 122:538-544(2012). RN [31] RP INTERACTION WITH MICROTUBULES, OLIGOMERIZATION, AND MUTAGENESIS OF RP 310-LYS--LYS-312 AND GLU-442. RX PubMed=23272056; DOI=10.1371/journal.pone.0050161; RA Eckert T., Le D.T., Link S., Friedmann L., Woehlke G.; RT "Spastin's microtubule-binding properties and comparison to katanin."; RL PLoS ONE 7:E50161-E50161(2012). RN [32] RP ACTIVITY REGULATION, AND MUTAGENESIS OF GLU-442 AND CYS-448. RX PubMed=23745751; DOI=10.1111/febs.12385; RA Wen M., Wang C.; RT "The nucleotide cycle of spastin correlates with its microtubule-binding RT properties."; RL FEBS J. 280:3868-3877(2013). RN [33] RP FUNCTION, SUBCELLULAR LOCATION (ISOFORMS 1 AND 3), AND INTERACTION WITH RP IST1. RX PubMed=23897888; DOI=10.1083/jcb.201211045; RA Allison R., Lumb J.H., Fassier C., Connell J.W., Ten Martin D., RA Seaman M.N., Hazan J., Reid E.; RT "An ESCRT-spastin interaction promotes fission of recycling tubules from RT the endosome."; RL J. Cell Biol. 202:527-543(2013). RN [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245; SER-268 AND SER-597, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [35] RP SUBCELLULAR LOCATION, AND INTERACTION WITH ZFYVE27. RX PubMed=23969831; DOI=10.1073/pnas.1307391110; RA Chang J., Lee S., Blackstone C.; RT "Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and RT regulates network formation."; RL Proc. Natl. Acad. Sci. U.S.A. 110:14954-14959(2013). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [37] RP INTERACTION WITH SSNA1, AND SUBCELLULAR LOCATION. RX PubMed=25390646; DOI=10.1371/journal.pone.0112428; RA Goyal U., Renvoise B., Chang J., Blackstone C.; RT "Spastin-interacting protein NA14/SSNA1 functions in cytokinesis and axon RT development."; RL PLoS ONE 9:e112428-e112428(2014). RN [38] RP FUNCTION, SUBCELLULAR LOCATION (ISOFORMS 1 AND 3), AND INTERACTION WITH RP IST1. RX PubMed=26040712; DOI=10.1038/nature14408; RA Vietri M., Schink K.O., Campsteijn C., Wegner C.S., Schultz S.W., RA Christ L., Thoresen S.B., Brech A., Raiborg C., Stenmark H.; RT "Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear RT envelope sealing."; RL Nature 522:231-235(2015). RN [39] RP FUNCTION (ISOFORM 1), SUBCELLULAR LOCATION (ISOFORM 1), AND MUTAGENESIS OF RP ARG-65 AND 81-ARG--ARG-84. 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 [40] RP FUNCTION. RX PubMed=26875866; DOI=10.1016/j.cell.2016.01.019; RA Valenstein M.L., Roll-Mecak A.; RT "Graded control of microtubule severing by tubulin glutamylation."; RL Cell 164:911-921(2016). RN [41] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 112-196 IN COMPLEX WITH CHMP1B, RP INTERACTION WITH CHMP1B, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-120 RP AND PHE-124. RX PubMed=18997780; DOI=10.1038/nsmb.1512; RA Yang D., Rismanchi N., Renvoise B., Lippincott-Schwartz J., Blackstone C., RA Hurley J.H.; RT "Structural basis for midbody targeting of spastin by the ESCRT-III protein RT CHMP1B."; RL Nat. Struct. Mol. Biol. 15:1278-1286(2008). RN [42] RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 228-616 OF MUTANT GLN-442, AND RP MUTAGENESIS OF GLU-442. RX PubMed=22446388; DOI=10.1016/j.jsb.2012.03.002; RA Taylor J.L., White S.R., Lauring B., Kull F.J.; RT "Crystal structure of the human spastin AAA domain."; RL J. Struct. Biol. 179:133-137(2012). RN [43] RP VARIANT SPG4 GLY-441. RX PubMed=11039577; DOI=10.1038/sj.ejhg.5200528; RA Buerger J., Fonknechten N., Hoeltzenbein M., Neumann L., Bratanoff E., RA Hazan J., Reis A.; RT "Hereditary spastic paraplegia caused by mutations in the SPG4 gene."; RL Eur. J. Hum. Genet. 8:771-776(2000). RN [44] RP VARIANTS SPG4 CYS-362; ARG-370; CYS-381; LYS-386; ARG-388; VAL-426; RP TYR-448; LEU-460; CYS-499; ASN-555 AND VAL-556. RX PubMed=10699187; DOI=10.1093/hmg/9.4.637; RA Fonknechten N., Mavel D., Byrne P., Davoine C.-S., Cruaud C., Bonsch D., RA Samson D., Coutinho P., Hutchinson M., McMonagle P., Burgunder J.-M., RA Tartaglione A., Heinzlef O., Feki I., Deufel T., Parfrey N., Brice A., RA Fontaine B., Prud'homme J.-F., Weissenbach J., Duerr A., Hazan J.; RT "Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia."; RL Hum. Mol. Genet. 9:637-644(2000). RN [45] RP VARIANTS SPG4 GLY-424 AND HIS-584, AND VARIANT LEU-44. RX PubMed=11015453; DOI=10.1136/jmg.37.10.759; RA Lindsey J.C., Lusher M.E., McDermott C.J., White K.D., Reid E., RA Rubinsztein D.C., Bashir R., Hazan J., Shaw P.J., Bushby K.M.D.; RT "Mutation analysis of the spastin gene (SPG4) in patients with hereditary RT spastic paraparesis."; RL J. Med. Genet. 37:759-765(2000). RN [46] RP VARIANTS SPG4 PHE-436 AND ASP-559. RX PubMed=11087788; DOI=10.1212/wnl.55.9.1388; RA Hentati A., Deng H.-X., Zhai H., Chen W., Yang Y., Hung W.-Y., Azim A.C., RA Bohlega S., Tandan R., Warner C., Laing N.G., Cambi F., Mitsumoto H., RA Roos R.P., Boustany R.-M.N., Ben-Hamida M., Hentati F., Siddique T.; RT "Novel mutations in spastin gene and absence of correlation with age at RT onset of symptoms."; RL Neurology 55:1388-1390(2000). RN [47] RP VARIANTS SPG4 CYS-499 AND GLY-562. RX PubMed=11309678; DOI=10.1086/320111; RA Svenson I.K., Ashley-Koch A.E., Gaskell P.C., Riney T.J., Cumming W.J.K., RA Kingston H.M., Hogan E.L., Boustany R.-M.N., Vance J.M., Nance M.A., RA Pericak-Vance M.A., Marchuk D.A.; RT "Identification and expression analysis of spastin gene mutations in RT hereditary spastic paraplegia."; RL Am. J. Hum. Genet. 68:1077-1085(2001). RN [48] RP VARIANT SPG4 VAL-485. RX PubMed=12460147; DOI=10.1034/j.1600-0404.2002.01254.x; RA Namekawa M., Takiyama Y., Sakoe K., Nagaki H., Shimazaki H., Yoshimura M., RA Ikeguchi K., Nakano I., Nishizawa M.; RT "A Japanese SPG4 family with a novel missense mutation of the SPG4 gene: RT intrafamilial variability in age at onset and clinical severity."; RL Acta Neurol. Scand. 106:387-391(2002). RN [49] RP VARIANTS SPG4 LEU-399; VAL-426; LEU-489; ASP-559 AND GLN-562. RX PubMed=11843700; DOI=10.1001/archneur.59.2.281; RA Meijer I.A., Hand C.K., Cossette P., Figlewicz D.A., Rouleau G.A.; RT "Spectrum of SPG4 mutations in a large collection of North American RT families with hereditary spastic paraplegia."; RL Arch. Neurol. 59:281-286(2002). RN [50] RP VARIANTS SPG4 ARG-407; TYR-551 AND ILE-615. RX PubMed=12124993; DOI=10.1002/humu.10105; RA Sauter S.M., Miterski B., Klimpe S., Boensch D., Schoels L., Visbeck A., RA Papke T., Hopf H.C., Engel W., Deufel T., Epplen J.T., Neesen J.; RT "Mutation analysis of the spastin gene (SPG4) in patients in Germany with RT autosomal dominant hereditary spastic paraplegia."; RL Hum. Mutat. 20:127-132(2002). RN [51] RP VARIANTS SPG4 LYS-347; ARG-388 AND CYS-499. RX PubMed=12161613; DOI=10.1136/jmg.39.8.e46; RA Yabe I., Sasaki H., Tashiro K., Matsuura T., Takegami T., Satoh T.; RT "Spastin gene mutation in Japanese with hereditary spastic paraplegia."; RL J. Med. Genet. 39:E46-E46(2002). RN [52] RP VARIANT SPG4 ASP-512. RX PubMed=11985387; DOI=10.1007/pl00007865; RA Patrono C., Casali C., Tessa A., Cricchi F., Fortini D., Carrozzo R., RA Siciliano G., Bertini E., Santorelli F.M.; RT "Missense and splice site mutations in SPG4 suggest loss-of-function in RT dominant spastic paraplegia."; RL J. Neurol. 249:200-205(2002). RN [53] RP VARIANT SPG4 PHE-404 DEL. RX PubMed=12163196; DOI=10.1016/s0022-510x(02)00192-2; RA Proukakis C., Hart P.E., Cornish A., Warner T.T., Crosby A.H.; RT "Three novel spastin (SPG4) mutations in families with autosomal dominant RT hereditary spastic paraplegia."; RL J. Neurol. Sci. 201:65-69(2002). RN [54] RP VARIANT SPG4 LYS-344. RX PubMed=12202986; DOI=10.1007/s100380200068; RA Ki C.S., Lee W.Y., Han do H., Sung D.H., Lee K.B., Lee K.A., Cho S.S., RA Cho S., Hwang H., Sohn K.M., Choi Y.J., Kim J.W.; RT "A novel missense mutation (I344K) in the SPG4gene in a Korean family with RT autosomal-dominant hereditary spastic paraplegia."; RL J. Hum. Genet. 47:473-477(2002). RN [55] RP VARIANT SPG4 LEU-503. RX PubMed=12552568; DOI=10.1002/humu.9108; RA Proukakis C., Auer-Grumbach M., Wagner K., Wilkinson P.A., Reid E., RA Patton M.A., Warner T.T., Crosby A.H.; RT "Screening of patients with hereditary spastic paraplegia reveals seven RT novel mutations in the SPG4 (Spastin) gene."; RL Hum. Mutat. 21:170-170(2003). RN [56] RP VARIANT SPG4 PRO-534. RX PubMed=12939659; DOI=10.1038/sj.ejhg.5201027; RA Molon A., Montagna P., Angelini C., Pegoraro E.; RT "Novel spastin mutations and their expression analysis in two Italian RT families."; RL Eur. J. Hum. Genet. 11:710-713(2003). RN [57] RP VARIANTS SPG4 GLN-378; VAL-390 AND LEU-515 DEL. RX PubMed=14732620; DOI=10.1001/archneur.61.1.49; RA Tang B., Zhao G., Xia K., Pan Q., Luo W., Shen L., Long Z., Dai H., Zi X., RA Jiang H.; RT "Three novel mutations of the spastin gene in Chinese patients with RT hereditary spastic paraplegia."; RL Arch. Neurol. 61:49-55(2004). RN [58] RP VARIANT SPG4 SER-386. RX PubMed=15210521; DOI=10.1001/archneur.61.6.849; RA Orlacchio A., Kawarai T., Totaro A., Errico A., St George-Hyslop P.H., RA Rugarli E.I., Bernardi G.; RT "Hereditary spastic paraplegia: clinical genetic study of 15 families."; RL Arch. Neurol. 61:849-855(2004). RN [59] RP VARIANT SPG4 GLN-490 DEL. RX PubMed=15667412; DOI=10.1111/j.1468-1331.2004.00888.x; RA Nielsen J.E., Johnsen B., Koefoed P., Scheuer K.H., Groenbech-Jensen M., RA Law I., Krabbe K., Noerremoelle A., Eiberg H., Soendergaard H., Dam M., RA Rehfeld J.F., Krarup C., Paulson O.B., Hasholt L., Soerensen S.A.; RT "Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype RT associated with a new SPG4 gene mutation."; RL Eur. J. Neurol. 11:817-824(2004). RN [60] RP VARIANTS SPG4 VAL-470 AND GLY-562, AND VARIANTS LEU-44 AND GLN-45. RX PubMed=15248095; DOI=10.1007/s10048-004-0186-z; RA Svenson I.K., Kloos M.T., Gaskell P.C., Nance M.A., Garbern J.Y., RA Hisanaga S., Pericak-Vance M.A., Ashley-Koch A.E., Marchuk D.A.; RT "Intragenic modifiers of hereditary spastic paraplegia due to spastin gene RT mutations."; RL Neurogenetics 5:157-164(2004). RN [61] RP VARIANTS SPG4 GLY-459 AND CYS-460. RX PubMed=15482961; DOI=10.1016/j.nmd.2004.05.017; RA Falco M., Scuderi C., Musumeci S., Sturnio M., Neri M., Bigoni S., RA Caniatti L., Fichera M.; RT "Two novel mutations in the spastin gene (SPG4) found by DHPLC mutation RT analysis."; RL Neuromuscul. Disord. 14:750-753(2004). RN [62] RP VARIANT SPG4 ILE-614. RX PubMed=15159500; DOI=10.1212/01.wnl.0000125324.32082.d9; RA Orlacchio A., Gaudiello F., Totaro A., Floris R., St George-Hyslop P.H., RA Bernardi G., Kawarai T.; RT "A new SPG4 mutation in a variant form of spastic paraplegia with RT congenital arachnoid cysts."; RL Neurology 62:1875-1878(2004). RN [63] RP VARIANT SPG4 LEU-361, AND VARIANT LEU-44. RX PubMed=15326248; DOI=10.1212/01.wnl.0000135346.63675.3e; RA Chinnery P.F., Keers S.M., Holden M.J., Ramesh V., Dalton A.; RT "Infantile hereditary spastic paraparesis due to codominant mutations in RT the spastin gene."; RL Neurology 63:710-712(2004). RN [64] RP VARIANTS SPG4 VAL-195; VAL-406; GLY-493; HIS-499; TRP-503 AND CYS-607. RX PubMed=16682546; DOI=10.1001/archneur.63.5.750; RA Crippa F., Panzeri C., Martinuzzi A., Arnoldi A., Redaelli F., Tonelli A., RA Baschirotto C., Vazza G., Mostacciuolo M.L., Daga A., Orso G., Profice P., RA Trabacca A., D'Angelo M.G., Comi G.P., Galbiati S., Lamperti C., Bonato S., RA Pandolfo M., Meola G., Musumeci O., Toscano A., Trevisan C.P., Bresolin N., RA Bassi M.T.; RT "Eight novel mutations in SPG4 in a large sample of patients with RT hereditary spastic paraplegia."; RL Arch. Neurol. 63:750-755(2006). RN [65] RP VARIANT SPG4 LEU-435. RX PubMed=16684598; DOI=10.1016/j.nmd.2006.03.009; RA Magariello A., Muglia M., Patitucci A., Mazzei R., Conforti F.L., RA Gabriele A.L., Sprovieri T., Ungaro C., Gambardella A., Mancuso M., RA Siciliano G., Branca D., Aguglia U., de Angelis M.V., Longo K., RA Quattrone A.; RT "Novel spastin (SPG4) mutations in Italian patients with hereditary spastic RT paraplegia."; RL Neuromuscul. Disord. 16:387-390(2006). RN [66] RP VARIANT [LARGE SCALE ANALYSIS] LEU-423. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [67] RP VARIANTS SPG4 THR-364; HIS-380 AND HIS-579, AND VARIANT LEU-44. RX PubMed=17594340; DOI=10.1111/j.1468-1331.2007.01861.x; RA Erichsen A.K., Inderhaug E., Mattingsdal M., Eiklid K., Tallaksen C.M.; RT "Seven novel mutations and four exon deletions in a collection of Norwegian RT patients with SPG4 hereditary spastic paraplegia."; RL Eur. J. Neurol. 14:809-814(2007). RN [68] RP VARIANTS LEU-44 AND GLY-229, AND VARIANTS SPG4 ILE-162; PHE-426 AND RP SER-460. RX PubMed=20214791; DOI=10.1186/1471-2377-10-17; RA Braschinsky M., Tamm R., Beetz C., Sachez-Ferrero E., Raukas E., Luus S.M., RA Gross-Paju K., Boillot C., Canzian F., Metspalu A., Haldre S.; RT "Unique spectrum of SPAST variants in Estonian HSP patients: presence of RT benign missense changes but lack of exonic rearrangements."; RL BMC Neurol. 10:17-17(2010). RN [69] RP VARIANTS SPG4 THR-287 DEL; LEU-293; LEU-328; ARG-378; HIS-380; PRO-391; RP 393-LYS--ALA-396 DEL; THR-409; ARG-410; PRO-436; ASN-441; SER-460; ALA-463; RP PHE-492; GLY-498; ARG-503 INS; GLY-514 AND THR-580. RX PubMed=20932283; DOI=10.1186/1471-2377-10-89; RA Alvarez V., Sanchez-Ferrero E., Beetz C., Diaz M., Alonso B., Corao A.I., RA Gamez J., Esteban J., Gonzalo J.F., Pascual-Pascual S.I., RA Lopez de Munain A., Moris G., Ribacoba R., Marquez C., Rosell J., Marin R., RA Garcia-Barcina M.J., Del Castillo E., Benito C., Coto E.; RT "Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish RT patients with hereditary spastic paraplegia."; RL BMC Neurol. 10:89-89(2010). RN [70] RP VARIANTS SPG4 ILE-162; LYS-356; SER-365; ARG-382; ILE-407; PHE-422; RP ASN-445; SER-460; LEU-482; GLU-512 DEL; VAL-534 AND PRO-562, AND VARIANT RP LEU-44. RX PubMed=20562464; DOI=10.1136/jnnp.2009.201103; RA de Bot S.T., van den Elzen R.T., Mensenkamp A.R., Schelhaas H.J., RA Willemsen M.A., Knoers N.V., Kremer H.P., van de Warrenburg B.P., RA Scheffer H.; RT "Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch RT patients: new clinical aspects and 27 novel mutations."; RL J. Neurol. Neurosurg. Psych. 81:1073-1078(2010). RN [71] RP VARIANTS SPG4 THR-97; ASP-201; SER-314; VAL-360; ALA-464; GLY-498 AND RP ILE-550. RX PubMed=20718791; DOI=10.1111/j.1399-0004.2010.01501.x; RA McCorquodale D.S. III, Ozomaro U., Huang J., Montenegro G., Kushman A., RA Citrigno L., Price J., Speziani F., Pericak-Vance M.A., Zuchner S.; RT "Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic RT paraplegia."; RL Clin. Genet. 79:523-530(2011). RN [72] RP VARIANTS SPG4 LEU-413 AND LYS-454. RX PubMed=20550563; DOI=10.1111/j.1468-1331.2010.03102.x; RA Battini R., Fogli A., Borghetti D., Michelucci A., Perazza S., RA Baldinotti F., Conidi M.E., Ferreri M.I., Simi P., Cioni G.; RT "Clinical and genetic findings in a series of Italian children with pure RT hereditary spastic paraplegia."; RL Eur. J. Neurol. 18:150-157(2011). RN [73] RP VARIANTS SPG4 MET-364; LEU-368; GLU-377 AND SER-450. RX PubMed=21546041; DOI=10.1016/j.jns.2011.03.043; RA Proukakis C., Moore D., Labrum R., Wood N.W., Houlden H.; RT "Detection of novel mutations and review of published data suggests that RT hereditary spastic paraplegia caused by spastin (SPAST) mutations is found RT more often in males."; RL J. Neurol. Sci. 306:62-65(2011). RN [74] RP VARIANTS SPG4 THR-95; 112-GLU--VAL-616 DEL; 135-GLU--VAL-616 DEL; LEU-399; RP ARG-406; THR-409; VAL-426; 431-ARG--VAL-616 DEL; CYS-460; TRP-503; ARG-559 RP AND 562-ARG--VAL-616 DEL. RX PubMed=22960362; DOI=10.1016/j.neulet.2012.08.036; RA Nanetti L., Baratta S., Panzeri M., Tomasello C., Lovati C., Azzollini J., RA Gellera C., Di Bella D., Taroni F., Mariotti C.; RT "Novel and recurrent spastin mutations in a large series of SPG4 Italian RT families."; RL Neurosci. Lett. 528:42-45(2012). RN [75] RP VARIANT SPG4 HIS-309. RX PubMed=23279441; DOI=10.1111/ene.12000; RA Magariello A., Tortorella C., Patitucci A., Tortelli R., Liguori M., RA Mazzei R., Conforti F.L., Citrigno L., Ungaro C., Simone I.L., Muglia M.; RT "First mutation in the nuclear localization signal sequence of spastin RT protein identified in a patient with hereditary spastic paraplegia."; RL Eur. J. Neurol. 20:E22-E23(2013). RN [76] RP VARIANTS SPG4 244-ASN--VAL-616 DEL; PRO-461; GLY-555 AND 581-ARG--VAL-616 RP DEL. RX PubMed=25421405; DOI=10.1186/s12883-014-0216-x; RA Lan M.Y., Chang Y.Y., Yeh T.H., Lai S.C., Liou C.W., Kuo H.C., Wu Y.R., RA Lyu R.K., Hung J.W., Chang Y.C., Lu C.S.; RT "High frequency of SPG4 in Taiwanese families with autosomal dominant RT hereditary spastic paraplegia."; RL BMC Neurol. 14:216-216(2014). RN [77] RP VARIANTS SPG4 44-SER--VAL-616 DEL; 245-SER--VAL-616 DEL; 254-LYS--VAL-616 RP DEL; GLY-372; LEU-399; ARG-451 DEL; ARG-458; HIS-499 AND 581-ARG--VAL-616 RP DEL. RX PubMed=25045380; DOI=10.3988/jcn.2014.10.3.257; RA Kim T.H., Lee J.H., Park Y.E., Shin J.H., Nam T.S., Kim H.S., Jang H.J., RA Semenov A., Kim S.J., Kim D.S.; RT "Mutation analysis of SPAST, ATL1, and REEP1 in Korean Patients with RT Hereditary Spastic Paraplegia."; RL J. Clin. Neurol. 10:257-261(2014). RN [78] RP VARIANTS SPG4 PRO-363; LEU-399; VAL-441 AND ARG-595. RX PubMed=24824479; DOI=10.1016/j.parkreldis.2014.04.021; RA Wei Q.Q., Chen Y., Zheng Z.Z., Chen X., Huang R., Yang Y., Burgunder J., RA Shang H.F.; RT "Spastin mutation screening in Chinese patients with pure hereditary RT spastic paraplegia."; RL Parkinsonism Relat. Disord. 20:845-849(2014). RN [79] RP VARIANTS SPG4 LYS-328; LYS-366; LEU-368; VAL-368; THR-372; TYR-386; RP THR-390; ALA-418; TYR-470; THR-485; MET-498 AND 546-GLY--VAL-616 DEL. RX PubMed=28572275; DOI=10.1136/jnnp-2017-315796; RA Chelban V., Tucci A., Lynch D.S., Polke J.M., Santos L., Jonvik H., RA Groppa S., Wood N.W., Houlden H.; RT "Truncating mutations in SPAST patients are associated with a high rate of RT psychiatric comorbidities in hereditary spastic paraplegia."; RL J. Neurol. Neurosurg. Psych. 88:681-687(2017). CC -!- FUNCTION: ATP-dependent microtubule severing protein that specifically CC recognizes and cuts microtubules that are polyglutamylated CC (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, CC PubMed:20530212, PubMed:22637577, PubMed:26875866). Preferentially CC recognizes and acts on microtubules decorated with short polyglutamate CC tails: severing activity increases as the number of glutamates per CC tubulin rises from one to eight, but decreases beyond this CC glutamylation threshold (PubMed:26875866). Severing activity is not CC dependent on tubulin acetylation or detyrosination (PubMed:26875866). CC Microtubule severing promotes reorganization of cellular microtubule CC arrays and the release of microtubules from the centrosome following CC nucleation. It is critical for the biogenesis and maintenance of CC complex microtubule arrays in axons, spindles and cilia. SPAST is CC involved in abscission step of cytokinesis and nuclear envelope CC reassembly during anaphase in cooperation with the ESCRT-III complex CC (PubMed:19000169, PubMed:21310966, PubMed:26040712). Recruited at the CC midbody, probably by IST1, and participates in membrane fission during CC abscission together with the ESCRT-III complex (PubMed:21310966). CC Recruited to the nuclear membrane by IST1 and mediates microtubule CC severing, promoting nuclear envelope sealing and mitotic spindle CC disassembly during late anaphase (PubMed:26040712). Required for CC membrane traffic from the endoplasmic reticulum (ER) to the Golgi and CC endosome recycling (PubMed:23897888). Recruited by IST1 to endosomes CC and regulates early endosomal tubulation and recycling by mediating CC microtubule severing (PubMed:23897888). Probably plays a role in axon CC growth and the formation of axonal branches (PubMed:15716377). CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:11809724, CC ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:16219033, CC ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:19000169, CC ECO:0000269|PubMed:20530212, ECO:0000269|PubMed:21310966, CC ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23897888, CC ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:26875866}. CC -!- FUNCTION: [Isoform 1]: Involved in lipid metabolism by regulating the CC size and distribution of lipid droplets. {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:15716377, ECO:0000269|PubMed:16219033, CC ECO:0000269|PubMed:16815977, ECO:0000269|PubMed:17389232, CC ECO:0000269|PubMed:18410514, ECO:0000269|PubMed:22637577}; CC -!- ACTIVITY REGULATION: Allosteric enzyme with a cooperative mechanism; at CC least two neighbor subunits influence each other strongly in spastin CC hexamers (PubMed:22637577). Microtubule binding promotes cooperative CC interactions among spastin subunits (PubMed:22637577). ATP-bound enzyme CC interacts strongly and cooperatively with microtubules; this CC interaction stimulates ATP hydrolysis (PubMed:23745751). CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:22637577, CC ECO:0000269|PubMed:23745751}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.45 mM for ATP {ECO:0000269|PubMed:15716377, CC ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:22637577}; CC Vmax=1.2 nmol/min/ug enzyme {ECO:0000269|PubMed:15716377, CC ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:22637577}; CC Note=Kinetic parameters shown are for full-length enzyme. CC N-terminally truncated spastin (residues 228-616), which has been CC shown to exhibit full severing activity, shows a basal ATP turnover CC rate of 0.78 sec(-1) in the absence of microtubules, a KM of 0.16 mM CC for ATP, and the ATP turnover rate is extrapolated to 3.83 sec(-1) in CC the presence of microtubules. ATPase activity shows CC non-Michaelis-Menten kinetics in the presence of microtubules, but is CC close to non-cooperative behavior in their absence (PubMed:22637577). CC {ECO:0000269|PubMed:22637577}; CC -!- SUBUNIT: Homohexamer (PubMed:17389232, PubMed:22637577). Mostly CC monomeric, but assembles into hexameric structure for short periods of CC time. Oligomerization seems to be a prerequisite for catalytic activity CC (PubMed:17389232, PubMed:22637577). Binding to ATP in a cleft between CC two adjacent subunits stabilizes the homohexameric form CC (PubMed:17389232, PubMed:22637577). Binds to microtubules at least in CC part via the alpha-tubulin and beta-tubulin tails (PubMed:15269182, CC PubMed:15716377, PubMed:23272056). The hexamer adopts a ring CC conformation through which microtubules pass prior to being severed CC (PubMed:17389232, PubMed:22637577). Does not interact strongly with CC tubulin heterodimers (PubMed:15269182, PubMed:15716377, CC PubMed:23272056). Interacts (via MIT domain) with CHMP1B; the CC interaction is direct (PubMed:15537668, PubMed:18997780). Interacts CC with SSNA1 (PubMed:15269182, PubMed:25390646). Interacts with ATL1 CC (PubMed:16339213, PubMed:16815977). Interacts with RTN1 CC (PubMed:16602018). Interacts with ZFYVE27 (PubMed:16826525, CC PubMed:23969831). Isoform 1 but not isoform 3 interacts with RTN2 CC (PubMed:22232211). Interacts with REEP1 (PubMed:20200447). Interacts CC (via MIT domain) with IST1 (PubMed:23897888, PubMed:26040712). CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15269182, CC ECO:0000269|PubMed:15537668, ECO:0000269|PubMed:15716377, CC ECO:0000269|PubMed:16339213, ECO:0000269|PubMed:16602018, CC ECO:0000269|PubMed:16815977, ECO:0000269|PubMed:16826525, CC ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:18997780, CC ECO:0000269|PubMed:20200447, ECO:0000269|PubMed:22232211, CC ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23272056, CC ECO:0000269|PubMed:23897888, ECO:0000269|PubMed:23969831, CC ECO:0000269|PubMed:25390646, ECO:0000269|PubMed:26040712}. CC -!- INTERACTION: CC Q9UBP0; Q8WXF7-1: ATL1; NbExp=4; IntAct=EBI-1222832, EBI-15590227; CC Q9UBP0; Q9UF56: FBXL17; NbExp=3; IntAct=EBI-1222832, EBI-8835653; CC Q9UBP0; Q5T4F4: ZFYVE27; NbExp=3; IntAct=EBI-1222832, EBI-3892947; CC Q9UBP0-1; Q9UF56: FBXL17; NbExp=4; IntAct=EBI-36485974, EBI-8835653; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255|HAMAP-Rule:MF_03021, CC ECO:0000269|PubMed:19000169}; Peripheral membrane protein CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000305|PubMed:20200447}. CC Endoplasmic reticulum {ECO:0000255|HAMAP-Rule:MF_03021, CC ECO:0000269|PubMed:16602018}. Midbody {ECO:0000255|HAMAP-Rule:MF_03021, CC ECO:0000269|PubMed:18997780, ECO:0000269|PubMed:21310966, CC ECO:0000269|PubMed:25390646}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000255|HAMAP-Rule:MF_03021, CC ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15891913, CC ECO:0000269|PubMed:25390646}. Cytoplasm, cytoskeleton CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15716377, CC ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:18410514, CC ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20200447}. Cytoplasm, CC perinuclear region {ECO:0000255|HAMAP-Rule:MF_03021, CC ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:15147984, CC ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15537668}. Nucleus CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15147984, CC ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:16026783}. Cytoplasm, CC cytoskeleton, spindle {ECO:0000255|HAMAP-Rule:MF_03021, CC ECO:0000269|PubMed:15269182}. Cytoplasm {ECO:0000255|HAMAP- CC Rule:MF_03021, ECO:0000269|PubMed:16026783, CC ECO:0000269|PubMed:20200447}. Cell projection, axon CC {ECO:0000269|PubMed:15269182}. Note=Forms an intramembrane hairpin-like CC structure in the membrane (PubMed:20200447). Localization to the CC centrosome is independent of microtubules (PubMed:15891913). Localizes CC to the midbody of dividing cells, and this requires CHMP1B CC (PubMed:18997780). Enriched in the distal axons and branches of CC postmitotic neurons (PubMed:15269182). Mainly nuclear in interphase CC cells and becomes associated with the centrosomes, spindle CC microtubules, midzone and finally the midbody during cell division CC (PubMed:15269182). {ECO:0000255|HAMAP-Rule:MF_03021, CC ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15891913, CC ECO:0000269|PubMed:18997780, ECO:0000305|PubMed:20200447}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:23969831}; Peripheral CC membrane protein {ECO:0000305|PubMed:20200447}. Nucleus membrane CC {ECO:0000269|PubMed:26040712}. Lipid droplet CC {ECO:0000269|PubMed:25875445}. Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20200447}. Endosome CC {ECO:0000269|PubMed:23897888}. Note=Forms an intramembrane hairpin-like CC structure in the membrane (PubMed:20200447). Recruited to nuclear CC membrane by IST1 during late anaphase (PubMed:26040712). Localizes to CC endoplasmic reticulum tubular network (PubMed:23969831). CC {ECO:0000269|PubMed:23969831, ECO:0000269|PubMed:26040712, CC ECO:0000305|PubMed:20200447}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm CC {ECO:0000269|PubMed:20200447, ECO:0000269|PubMed:23969831}. Endosome CC {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:23897888}. Nucleus CC membrane {ECO:0000269|PubMed:16026783, ECO:0000269|PubMed:26040712}. CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000269|PubMed:25390646}. Note=Constitutes the main endosomal form CC (PubMed:19000169). Recruited to nuclear membrane by IST1 during late CC anaphase (PubMed:26040712). {ECO:0000269|PubMed:19000169, CC ECO:0000269|PubMed:26040712}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing, Alternative initiation; Named isoforms=4; CC Comment=Alternative promoter usage of a cryptic promoter in exon 1 CC can direct the synthesis of N-terminally truncated isoforms, which CC may also arise from alternative initiation. CC {ECO:0000269|PubMed:16026783, ECO:0000269|PubMed:18613979}; CC Name=1; Synonyms=Long, Long variant 1, 68 kDa CC {ECO:0000303|PubMed:19000169}, M1 {ECO:0000303|PubMed:20200447}; CC IsoId=Q9UBP0-1; Sequence=Displayed; CC Name=2; Synonyms=Long variant 2; CC IsoId=Q9UBP0-2; Sequence=VSP_000024; CC Name=3; Synonyms=Short, Short variant 1, 60 kDa CC {ECO:0000303|PubMed:19000169}, M87 {ECO:0000303|PubMed:20200447}; CC IsoId=Q9UBP0-3; Sequence=VSP_036650; CC Name=4; Synonyms=Short variant 2; CC IsoId=Q9UBP0-4; Sequence=VSP_036650, VSP_000024; CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver, lung, CC pancreas, placenta and skeletal muscle. The short isoforms may CC predominate in brain and spinal cord. {ECO:0000269|PubMed:10610178}. CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain, heart, kidney, liver, CC lung, skeletal muscle, spleen and thymus. CC {ECO:0000269|PubMed:10610178}. CC -!- DISEASE: Spastic paraplegia 4, autosomal dominant (SPG4) [MIM:182601]: CC A form of spastic paraplegia, a neurodegenerative disorder CC characterized by a slow, gradual, progressive weakness and spasticity CC of the lower limbs. Rate of progression and the severity of symptoms CC are quite variable. Initial symptoms may include difficulty with CC balance, weakness and stiffness in the legs, muscle spasms, and CC dragging the toes when walking. In some forms of the disorder, bladder CC symptoms (such as incontinence) may appear, or the weakness and CC stiffness may spread to other parts of the body. CC {ECO:0000269|PubMed:10610178, ECO:0000269|PubMed:10699187, CC ECO:0000269|PubMed:11015453, ECO:0000269|PubMed:11039577, CC ECO:0000269|PubMed:11087788, ECO:0000269|PubMed:11309678, CC ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:11843700, CC ECO:0000269|PubMed:11985387, ECO:0000269|PubMed:12124993, CC ECO:0000269|PubMed:12161613, ECO:0000269|PubMed:12163196, CC ECO:0000269|PubMed:12202986, ECO:0000269|PubMed:12460147, CC ECO:0000269|PubMed:12552568, ECO:0000269|PubMed:12939659, CC ECO:0000269|PubMed:14732620, ECO:0000269|PubMed:15159500, CC ECO:0000269|PubMed:15210521, ECO:0000269|PubMed:15248095, CC ECO:0000269|PubMed:15326248, ECO:0000269|PubMed:15482961, CC ECO:0000269|PubMed:15667412, ECO:0000269|PubMed:15716377, CC ECO:0000269|PubMed:15891913, ECO:0000269|PubMed:16339213, CC ECO:0000269|PubMed:16682546, ECO:0000269|PubMed:16684598, CC ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:17594340, CC ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20214791, CC ECO:0000269|PubMed:20550563, ECO:0000269|PubMed:20562464, CC ECO:0000269|PubMed:20718791, ECO:0000269|PubMed:20932283, CC ECO:0000269|PubMed:21546041, ECO:0000269|PubMed:22960362, CC ECO:0000269|PubMed:23279441, ECO:0000269|PubMed:24824479, CC ECO:0000269|PubMed:25045380, ECO:0000269|PubMed:25421405, CC ECO:0000269|PubMed:28572275}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative promoter usage. May CC also be produced by alternative initiation at Met-87 of isoform 1. CC Major isoform. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative promoter usage and CC alternative splicing. May also be produced by alternative initiation at CC Met-87 of isoform 2. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the AAA ATPase family. Spastin subfamily. CC {ECO:0000255|HAMAP-Rule:MF_03021}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The making of crooked CC - Issue 104 of April 2009; CC URL="https://web.expasy.org/spotlight/back_issues/104"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ246001; CAB60141.1; -; mRNA. DR EMBL; AJ246003; CAB60208.1; -; Genomic_DNA. DR EMBL; AB029006; BAA83035.1; -; mRNA. DR EMBL; CH471053; EAX00462.1; -; Genomic_DNA. DR EMBL; BC150260; AAI50261.1; -; mRNA. DR CCDS; CCDS1778.1; -. [Q9UBP0-1] DR CCDS; CCDS1779.1; -. [Q9UBP0-2] DR RefSeq; NP_055761.2; NM_014946.3. [Q9UBP0-1] DR RefSeq; NP_955468.1; NM_199436.1. [Q9UBP0-2] DR PDB; 3EAB; X-ray; 2.50 A; A/B/C/D/E/F=112-196. DR PDB; 3VFD; X-ray; 3.30 A; A=228-616. DR PDB; 5Z6Q; X-ray; 3.00 A; A=229-616. DR PDB; 5Z6R; X-ray; 3.00 A; A=229-616. DR PDB; 6PEK; EM; 4.20 A; A/B/C/D/E=87-616. DR PDB; 6PEN; EM; 4.20 A; A/B/C/D/E/F=87-616. DR PDB; 7S7J; X-ray; 1.15 A; A=112-195. DR PDBsum; 3EAB; -. DR PDBsum; 3VFD; -. DR PDBsum; 5Z6Q; -. DR PDBsum; 5Z6R; -. DR PDBsum; 6PEK; -. DR PDBsum; 6PEN; -. DR PDBsum; 7S7J; -. DR AlphaFoldDB; Q9UBP0; -. DR EMDB; EMD-20327; -. DR SMR; Q9UBP0; -. DR BioGRID; 112562; 60. DR CORUM; Q9UBP0; -. DR DIP; DIP-38418N; -. DR ELM; Q9UBP0; -. DR IntAct; Q9UBP0; 37. DR MINT; Q9UBP0; -. DR STRING; 9606.ENSP00000320885; -. DR BindingDB; Q9UBP0; -. DR ChEMBL; CHEMBL5169203; -. DR TCDB; 1.R.1.1.1; the membrane contact site (mcs) family. DR iPTMnet; Q9UBP0; -. DR PhosphoSitePlus; Q9UBP0; -. DR BioMuta; SPAST; -. DR DMDM; 12230611; -. DR EPD; Q9UBP0; -. DR jPOST; Q9UBP0; -. DR MassIVE; Q9UBP0; -. DR MaxQB; Q9UBP0; -. DR PaxDb; 9606-ENSP00000480893; -. DR PeptideAtlas; Q9UBP0; -. DR ProteomicsDB; 84020; -. [Q9UBP0-1] DR ProteomicsDB; 84021; -. [Q9UBP0-2] DR ProteomicsDB; 84022; -. [Q9UBP0-3] DR ProteomicsDB; 84023; -. [Q9UBP0-4] DR Pumba; Q9UBP0; -. DR Antibodypedia; 2246; 277 antibodies from 30 providers. DR DNASU; 6683; -. DR Ensembl; ENST00000315285.9; ENSP00000320885.3; ENSG00000021574.14. [Q9UBP0-1] DR Ensembl; ENST00000642999.1; ENSP00000496589.1; ENSG00000021574.14. [Q9UBP0-3] DR Ensembl; ENST00000644954.1; ENSP00000494312.1; ENSG00000021574.14. [Q9UBP0-4] DR Ensembl; ENST00000646571.1; ENSP00000495015.1; ENSG00000021574.14. [Q9UBP0-2] DR GeneID; 6683; -. DR KEGG; hsa:6683; -. DR MANE-Select; ENST00000315285.9; ENSP00000320885.3; NM_014946.4; NP_055761.2. DR UCSC; uc002roc.4; human. [Q9UBP0-1] DR AGR; HGNC:11233; -. DR CTD; 6683; -. DR DisGeNET; 6683; -. DR GeneCards; SPAST; -. DR GeneReviews; SPAST; -. DR HGNC; HGNC:11233; SPAST. DR HPA; ENSG00000021574; Low tissue specificity. DR MalaCards; SPAST; -. DR MIM; 182601; phenotype. DR MIM; 604277; gene. DR neXtProt; NX_Q9UBP0; -. DR OpenTargets; ENSG00000021574; -. DR Orphanet; 100985; Autosomal dominant spastic paraplegia type 4. DR PharmGKB; PA36063; -. DR VEuPathDB; HostDB:ENSG00000021574; -. DR eggNOG; KOG0740; Eukaryota. DR GeneTree; ENSGT00940000156258; -. DR HOGENOM; CLU_000688_21_5_1; -. DR InParanoid; Q9UBP0; -. DR OMA; KSREPML; -. DR OrthoDB; 276256at2759; -. DR PhylomeDB; Q9UBP0; -. DR TreeFam; TF105014; -. DR BRENDA; 5.6.1.1; 2681. DR PathwayCommons; Q9UBP0; -. DR Reactome; R-HSA-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III. DR SABIO-RK; Q9UBP0; -. DR SignaLink; Q9UBP0; -. DR SIGNOR; Q9UBP0; -. DR BioGRID-ORCS; 6683; 23 hits in 1159 CRISPR screens. DR ChiTaRS; SPAST; human. DR EvolutionaryTrace; Q9UBP0; -. DR GeneWiki; Spastin; -. DR GenomeRNAi; 6683; -. DR Pharos; Q9UBP0; Tbio. DR PRO; PR:Q9UBP0; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9UBP0; Protein. DR Bgee; ENSG00000021574; Expressed in cortical plate and 198 other cell types or tissues. DR ExpressionAtlas; Q9UBP0; baseline and differential. DR GO; GO:0030424; C:axon; IDA:UniProtKB. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0071782; C:endoplasmic reticulum tubular network; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell. DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-UniRule. DR GO; GO:0030496; C:midbody; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB. DR GO; GO:0043014; F:alpha-tubulin binding; IPI:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB. DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW. DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB. DR GO; GO:0008568; F:microtubule severing ATPase activity; IDA:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; TAS:ARUK-UCL. DR GO; GO:0008089; P:anterograde axonal transport; ISS:UniProtKB. DR GO; GO:0019896; P:axonal transport of mitochondrion; ISS:UniProtKB. DR GO; GO:0007409; P:axonogenesis; IEA:UniProtKB-UniRule. DR GO; GO:0032506; P:cytokinetic process; IMP:UniProtKB. DR GO; GO:0061640; P:cytoskeleton-dependent cytokinesis; TAS:ARUK-UCL. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IMP:UniProtKB. DR GO; GO:0010458; P:exit from mitosis; IMP:UniProtKB. DR GO; GO:0090148; P:membrane fission; IMP:UniProtKB. DR GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW. DR GO; GO:0001578; P:microtubule bundle formation; IDA:UniProtKB. DR GO; GO:0051013; P:microtubule severing; IDA:UniProtKB. DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB. DR GO; GO:0007084; P:mitotic nuclear membrane reassembly; TAS:Reactome. DR GO; GO:0051228; P:mitotic spindle disassembly; IMP:UniProtKB. DR GO; GO:0031468; P:nuclear membrane reassembly; IMP:UniProtKB. DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB. DR GO; GO:0031117; P:positive regulation of microtubule depolymerization; IEA:UniProtKB-UniRule. DR GO; GO:0034214; P:protein hexamerization; IDA:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR CDD; cd02679; MIT_spastin; 1. DR CDD; cd19524; RecA-like_spastin; 1. DR Gene3D; 1.10.8.60; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 1.20.58.80; Phosphotransferase system, lactose/cellobiose-type IIA subunit; 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; IPR015415; Spast_Vps4_C. DR InterPro; IPR017179; Spastin. DR InterPro; IPR035106; Spastin_chordate. DR PANTHER; PTHR23074; AAA DOMAIN-CONTAINING; 1. DR PANTHER; PTHR23074:SF86; SPASTIN; 1. DR Pfam; PF00004; AAA; 1. DR Pfam; PF17862; AAA_lid_3; 1. DR Pfam; PF09336; Vps4_C; 1. DR PIRSF; PIRSF037338; Spastin; 1. DR SMART; SM00382; AAA; 1. DR SMART; SM00745; MIT; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00674; AAA; 1. DR Genevisible; Q9UBP0; HS. PE 1: Evidence at protein level; KW 3D-structure; Allosteric enzyme; Alternative initiation; KW Alternative promoter usage; Alternative splicing; ATP-binding; Cell cycle; KW Cell division; Cell projection; Cytoplasm; Cytoskeleton; KW Developmental protein; Differentiation; Disease variant; KW Endoplasmic reticulum; Endosome; Hereditary spastic paraplegia; Isomerase; KW Lipid droplet; Membrane; Microtubule; Neurodegeneration; Neurogenesis; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..616 FT /note="Spastin" FT /id="PRO_0000084763" FT TOPO_DOM 1..56 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021, FT ECO:0000305|PubMed:20200447" FT INTRAMEM 57..77 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021, FT ECO:0000305|PubMed:20200447" FT TOPO_DOM 78..616 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021, FT ECO:0000305|PubMed:20200447" FT DOMAIN 120..195 FT /note="MIT" FT /evidence="ECO:0000255" FT REGION 1..300 FT /note="Required for interaction with RTN1" FT /evidence="ECO:0000269|PubMed:16602018" FT REGION 1..194 FT /note="Required for midbody localization" FT /evidence="ECO:0000269|PubMed:18997780" FT REGION 1..80 FT /note="Required for interaction with ATL1" FT /evidence="ECO:0000269|PubMed:16339213, FT ECO:0000269|PubMed:16815977" FT REGION 1..50 FT /note="Required for nuclear localization" FT /evidence="ECO:0000269|PubMed:15147984" FT REGION 1..43 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 50..87 FT /note="Required for interaction with SSNA1 and FT microtubules" FT /evidence="ECO:0000269|PubMed:15269182" FT REGION 112..196 FT /note="Sufficient for interaction with CHMP1B" FT /evidence="ECO:0000269|PubMed:18997780" FT REGION 114..200 FT /note="Required for interaction with microtubules" FT /evidence="ECO:0000269|PubMed:15269182" FT REGION 224..266 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 228..616 FT /note="Sufficient for microtubule severing" FT /evidence="ECO:0000269|PubMed:15269182" FT REGION 270..328 FT /note="Required for interaction with microtubules and FT microtubule severing" FT /evidence="ECO:0000269|PubMed:15269182" FT REGION 278..312 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 310..312 FT /note="Required for interaction with microtubules" FT /evidence="ECO:0000269|PubMed:23272056" FT MOTIF 4..11 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021, FT ECO:0000269|PubMed:15147984" FT MOTIF 59..67 FT /note="Nuclear export signal" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021, FT ECO:0000269|PubMed:16026783" FT MOTIF 309..312 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021, FT ECO:0000269|PubMed:15147984" FT COMPBIAS 18..43 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 238..256 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 278..305 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 382..389 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021, FT ECO:0000305|PubMed:15716377" FT MOD_RES 245 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 268 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 306 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 597 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..86 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_036650" FT VAR_SEQ 197..228 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:10470851, FT ECO:0000303|PubMed:15489334" FT /id="VSP_000024" FT VARIANT 44..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:25045380" FT /id="VAR_075827" FT VARIANT 44 FT /note="S -> L (acts as a disease modifier; patients FT carrying a mutated allele of spastin and L-44 on the other FT allele are affected by severe spastic paraplegia with an FT early age of onset; may decrease the activity of the FT alternative promoter which directs the synthesis of isoform FT 3 and isoform 4; dbSNP:rs121908515)" FT /evidence="ECO:0000269|PubMed:11015453, FT ECO:0000269|PubMed:15248095, ECO:0000269|PubMed:15326248, FT ECO:0000269|PubMed:17594340, ECO:0000269|PubMed:18613979, FT ECO:0000269|PubMed:20214791, ECO:0000269|PubMed:20562464" FT /id="VAR_010194" FT VARIANT 45 FT /note="P -> Q (acts as a disease modifier; patients FT carrying a mutated allele of spastin and Q-45 on the other FT allele are affected by severe spastic paraplegia with an FT early age of onset; dbSNP:rs121908517)" FT /evidence="ECO:0000269|PubMed:15248095" FT /id="VAR_027205" FT VARIANT 95 FT /note="A -> T (in SPG4; dbSNP:rs1343258361)" FT /evidence="ECO:0000269|PubMed:22960362" FT /id="VAR_075828" FT VARIANT 97 FT /note="P -> T (in SPG4; uncertain significance; FT dbSNP:rs372005558)" FT /evidence="ECO:0000269|PubMed:20718791" FT /id="VAR_067628" FT VARIANT 112..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:22960362" FT /id="VAR_075829" FT VARIANT 135..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:22960362" FT /id="VAR_075830" FT VARIANT 162 FT /note="V -> I (in SPG4; likely benign; dbSNP:rs141944844)" FT /evidence="ECO:0000269|PubMed:20214791, FT ECO:0000269|PubMed:20562464" FT /id="VAR_067563" FT VARIANT 195 FT /note="L -> V (in SPG4; dbSNP:rs1553400016)" FT /evidence="ECO:0000269|PubMed:16682546" FT /id="VAR_026758" FT VARIANT 201 FT /note="V -> D (in SPG4; uncertain significance; FT dbSNP:rs1553311831)" FT /evidence="ECO:0000269|PubMed:20718791" FT /id="VAR_067629" FT VARIANT 229 FT /note="S -> G (in dbSNP:rs1182763020)" FT /evidence="ECO:0000269|PubMed:20214791" FT /id="VAR_067630" FT VARIANT 244..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:25421405" FT /id="VAR_075831" FT VARIANT 245..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:25045380" FT /id="VAR_075832" FT VARIANT 254..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:25045380" FT /id="VAR_075833" FT VARIANT 287 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067631" FT VARIANT 293 FT /note="P -> L (in SPG4; dbSNP:rs773193617)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067632" FT VARIANT 309 FT /note="R -> H (in SPG4; dbSNP:rs202152835)" FT /evidence="ECO:0000269|PubMed:23279441" FT /id="VAR_075834" FT VARIANT 314 FT /note="L -> S (in SPG4; uncertain significance; FT dbSNP:rs1553315215)" FT /evidence="ECO:0000269|PubMed:20718791" FT /id="VAR_067633" FT VARIANT 328 FT /note="I -> K (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079314" FT VARIANT 328 FT /note="I -> L (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067634" FT VARIANT 344 FT /note="I -> K (in SPG4; abrogates ATPase activity and FT promotes microtubule binding; dbSNP:rs121908513)" FT /evidence="ECO:0000269|PubMed:12202986, FT ECO:0000269|PubMed:15716377" FT /id="VAR_019448" FT VARIANT 347 FT /note="Q -> K (in SPG4; promotes microtubule binding; FT dbSNP:rs1553315329)" FT /evidence="ECO:0000269|PubMed:12161613, FT ECO:0000269|PubMed:15716377" FT /id="VAR_027206" FT VARIANT 356 FT /note="E -> K (in SPG4; uncertain significance; FT dbSNP:rs1057519181)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067564" FT VARIANT 360 FT /note="L -> V (in SPG4; uncertain significance; FT dbSNP:rs1553315347)" FT /evidence="ECO:0000269|PubMed:20718791" FT /id="VAR_067635" FT VARIANT 361 FT /note="P -> L (in SPG4; dbSNP:rs1553315352)" FT /evidence="ECO:0000269|PubMed:15326248" FT /id="VAR_027207" FT VARIANT 362 FT /note="S -> C (in SPG4; dbSNP:rs121908509)" FT /evidence="ECO:0000269|PubMed:10610178, FT ECO:0000269|PubMed:10699187" FT /id="VAR_010195" FT VARIANT 363 FT /note="L -> P (in SPG4)" FT /evidence="ECO:0000269|PubMed:24824479" FT /id="VAR_075835" FT VARIANT 364 FT /note="R -> M (in SPG4; dbSNP:rs1553315355)" FT /evidence="ECO:0000269|PubMed:21546041" FT /id="VAR_075836" FT VARIANT 364 FT /note="R -> T (in SPG4; dbSNP:rs1553315355)" FT /evidence="ECO:0000269|PubMed:17594340" FT /id="VAR_067636" FT VARIANT 365 FT /note="P -> S (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067565" FT VARIANT 366 FT /note="E -> K (in SPG4; uncertain significance; FT dbSNP:rs1553315356)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079315" FT VARIANT 368 FT /note="F -> L (in SPG4)" FT /evidence="ECO:0000269|PubMed:21546041, FT ECO:0000269|PubMed:28572275" FT /id="VAR_075837" FT VARIANT 368 FT /note="F -> V (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079316" FT VARIANT 370 FT /note="G -> R (in SPG4; promotes microtubule binding and FT the formation of thick microtubule bundles)" FT /evidence="ECO:0000269|PubMed:10699187, FT ECO:0000269|PubMed:11809724" FT /id="VAR_027208" FT VARIANT 372 FT /note="R -> G (in SPG4; dbSNP:rs1553316807)" FT /evidence="ECO:0000269|PubMed:25045380" FT /id="VAR_075838" FT VARIANT 372 FT /note="R -> T (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079317" FT VARIANT 377 FT /note="G -> E (in SPG4)" FT /evidence="ECO:0000269|PubMed:21546041" FT /id="VAR_075839" FT VARIANT 378 FT /note="L -> Q (in SPG4; dbSNP:rs1553316816)" FT /evidence="ECO:0000269|PubMed:14732620" FT /id="VAR_019439" FT VARIANT 378 FT /note="L -> R (in SPG4; dbSNP:rs1553316816)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067637" FT VARIANT 380 FT /note="L -> H (in SPG4; dbSNP:rs1553316819)" FT /evidence="ECO:0000269|PubMed:17594340, FT ECO:0000269|PubMed:20932283" FT /id="VAR_067638" FT VARIANT 381 FT /note="F -> C (in SPG4; promotes microtubule binding and FT the formation of thick microtubule bundles; FT dbSNP:rs1553316822)" FT /evidence="ECO:0000269|PubMed:10699187, FT ECO:0000269|PubMed:11809724" FT /id="VAR_027209" FT VARIANT 382 FT /note="G -> R (in SPG4; uncertain significance; FT dbSNP:rs1553316826)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067566" FT VARIANT 386 FT /note="N -> K (in SPG4; abrogates ATPase activity, promotes FT microtubule binding and the formation of thick microtubule FT bundles; dbSNP:rs1553316834)" FT /evidence="ECO:0000269|PubMed:10699187, FT ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:15716377" FT /id="VAR_027210" FT VARIANT 386 FT /note="N -> S (in SPG4; dbSNP:rs121908514)" FT /evidence="ECO:0000269|PubMed:15210521" FT /id="VAR_019440" FT VARIANT 386 FT /note="N -> Y (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079318" FT VARIANT 388 FT /note="K -> R (in SPG4; abrogates ATPase activity, promotes FT microtubule binding and the formation of thick microtubule FT bundles and impairs traffic from the ER to Golgi; FT dbSNP:rs1553316837)" FT /evidence="ECO:0000269|PubMed:10699187, FT ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:12161613, FT ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:15891913, FT ECO:0000269|PubMed:16339213, ECO:0000269|PubMed:19000169" FT /id="VAR_027211" FT VARIANT 390 FT /note="M -> T (in SPG4; uncertain significance; FT dbSNP:rs1131691977)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079319" FT VARIANT 390 FT /note="M -> V (in SPG4; dbSNP:rs797044850)" FT /evidence="ECO:0000269|PubMed:14732620" FT /id="VAR_019441" FT VARIANT 391 FT /note="L -> P (in SPG4; dbSNP:rs1553316845)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067639" FT VARIANT 393..396 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067640" FT VARIANT 399 FT /note="S -> L (in SPG4; dbSNP:rs1553317025)" FT /evidence="ECO:0000269|PubMed:11843700, FT ECO:0000269|PubMed:22960362, ECO:0000269|PubMed:24824479, FT ECO:0000269|PubMed:25045380" FT /id="VAR_027212" FT VARIANT 404 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:12163196" FT /id="VAR_019449" FT VARIANT 406 FT /note="I -> R (in SPG4; dbSNP:rs1553317038)" FT /evidence="ECO:0000269|PubMed:22960362" FT /id="VAR_075840" FT VARIANT 406 FT /note="I -> V (in SPG4; dbSNP:rs587777757)" FT /evidence="ECO:0000269|PubMed:16682546" FT /id="VAR_026759" FT VARIANT 407 FT /note="S -> I (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067567" FT VARIANT 407 FT /note="S -> R (in SPG4; dbSNP:rs1553317041)" FT /evidence="ECO:0000269|PubMed:12124993" FT /id="VAR_019450" FT VARIANT 409 FT /note="A -> T (in SPG4; dbSNP:rs1064793273)" FT /evidence="ECO:0000269|PubMed:20932283, FT ECO:0000269|PubMed:22960362" FT /id="VAR_067641" FT VARIANT 410 FT /note="S -> R (in SPG4; dbSNP:rs1679266894)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067642" FT VARIANT 413 FT /note="S -> L (in SPG4; dbSNP:rs1553317045)" FT /evidence="ECO:0000269|PubMed:20550563" FT /id="VAR_067568" FT VARIANT 418 FT /note="E -> A (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079320" FT VARIANT 422 FT /note="L -> F (in SPG4; uncertain significance; FT dbSNP:rs1679543653)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067569" FT VARIANT 423 FT /note="V -> L (in a breast cancer sample; somatic mutation; FT dbSNP:rs1553318168)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035902" FT VARIANT 424 FT /note="R -> G (in SPG4; dbSNP:rs1553318169)" FT /evidence="ECO:0000269|PubMed:11015453" FT /id="VAR_010196" FT VARIANT 426 FT /note="L -> F (in SPG4; dbSNP:rs1060502227)" FT /evidence="ECO:0000269|PubMed:20214791" FT /id="VAR_067643" FT VARIANT 426 FT /note="L -> V (in SPG4; promotes microtubule binding and FT the formation of thick microtubule bundles; FT dbSNP:rs1060502227)" FT /evidence="ECO:0000269|PubMed:10699187, FT ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:11843700, FT ECO:0000269|PubMed:22960362" FT /id="VAR_027213" FT VARIANT 431..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:22960362" FT /id="VAR_075841" FT VARIANT 435 FT /note="P -> L (in SPG4; dbSNP:rs1553318182)" FT /evidence="ECO:0000269|PubMed:16684598" FT /id="VAR_027214" FT VARIANT 436 FT /note="S -> F (in SPG4; dbSNP:rs1553318184)" FT /evidence="ECO:0000269|PubMed:11087788" FT /id="VAR_027215" FT VARIANT 436 FT /note="S -> P (in SPG4)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067644" FT VARIANT 441 FT /note="D -> G (in SPG4; dbSNP:rs121908512)" FT /evidence="ECO:0000269|PubMed:11039577" FT /id="VAR_027216" FT VARIANT 441 FT /note="D -> N (in SPG4; dbSNP:rs1553318188)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067645" FT VARIANT 441 FT /note="D -> V (in SPG4)" FT /evidence="ECO:0000269|PubMed:24824479" FT /id="VAR_075842" FT VARIANT 445 FT /note="S -> N (in SPG4; uncertain significance; FT dbSNP:rs1131691838)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067570" FT VARIANT 448 FT /note="C -> Y (in SPG4; abrogates binding to the tail of FT beta-3-tubulin, abolishes microtubule severing and promotes FT the formation of thick microtubule bundles; FT dbSNP:rs121908510)" FT /evidence="ECO:0000269|PubMed:10610178, FT ECO:0000269|PubMed:10699187, ECO:0000269|PubMed:11809724, FT ECO:0000269|PubMed:17389232" FT /id="VAR_010197" FT VARIANT 450 FT /note="R -> S (in SPG4; dbSNP:rs1553318224)" FT /evidence="ECO:0000269|PubMed:21546041" FT /id="VAR_075843" FT VARIANT 451 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:25045380" FT /id="VAR_075844" FT VARIANT 454 FT /note="E -> K (in SPG4; dbSNP:rs1553318230)" FT /evidence="ECO:0000269|PubMed:20550563" FT /id="VAR_067571" FT VARIANT 458 FT /note="S -> R (in SPG4; dbSNP:rs1036039694)" FT /evidence="ECO:0000269|PubMed:25045380" FT /id="VAR_075845" FT VARIANT 459 FT /note="R -> G (in SPG4; dbSNP:rs1553318238)" FT /evidence="ECO:0000269|PubMed:15482961" FT /id="VAR_027217" FT VARIANT 460 FT /note="R -> C (in SPG4; dbSNP:rs878854990)" FT /evidence="ECO:0000269|PubMed:15482961, FT ECO:0000269|PubMed:22960362" FT /id="VAR_027218" FT VARIANT 460 FT /note="R -> L (in SPG4; promotes microtubule binding and FT the formation of thick microtubule bundles; FT dbSNP:rs1553318241)" FT /evidence="ECO:0000269|PubMed:10699187, FT ECO:0000269|PubMed:11809724" FT /id="VAR_027219" FT VARIANT 460 FT /note="R -> S (in SPG4; dbSNP:rs878854990)" FT /evidence="ECO:0000269|PubMed:20214791, FT ECO:0000269|PubMed:20562464, ECO:0000269|PubMed:20932283" FT /id="VAR_067572" FT VARIANT 461 FT /note="L -> P (in SPG4; dbSNP:rs1553318242)" FT /evidence="ECO:0000269|PubMed:25421405" FT /id="VAR_075846" FT VARIANT 463 FT /note="T -> A (in SPG4; dbSNP:rs1553318248)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067646" FT VARIANT 464 FT /note="E -> A (in SPG4; uncertain significance; FT dbSNP:rs1553318251)" FT /evidence="ECO:0000269|PubMed:20718791" FT /id="VAR_067647" FT VARIANT 470 FT /note="D -> V (in SPG4; dbSNP:rs121908516)" FT /evidence="ECO:0000269|PubMed:15248095" FT /id="VAR_027220" FT VARIANT 470 FT /note="D -> Y (in SPG4; uncertain significance; FT dbSNP:rs1553318261)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079321" FT VARIANT 482 FT /note="V -> L (in SPG4; uncertain significance; FT dbSNP:rs1553318315)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067573" FT VARIANT 485 FT /note="A -> T (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079322" FT VARIANT 485 FT /note="A -> V (in SPG4; dbSNP:rs536599683)" FT /evidence="ECO:0000269|PubMed:12460147" FT /id="VAR_027221" FT VARIANT 489 FT /note="P -> L (in SPG4; dbSNP:rs1553318331)" FT /evidence="ECO:0000269|PubMed:11843700" FT /id="VAR_027222" FT VARIANT 490..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:15667412" FT /id="VAR_075847" FT VARIANT 492 FT /note="L -> F (in SPG4; dbSNP:rs1553318337)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067648" FT VARIANT 493 FT /note="D -> G (in SPG4; dbSNP:rs1553318342)" FT /evidence="ECO:0000269|PubMed:16682546" FT /id="VAR_026760" FT VARIANT 498 FT /note="R -> G (in SPG4; dbSNP:rs1553318350)" FT /evidence="ECO:0000269|PubMed:20718791, FT ECO:0000269|PubMed:20932283" FT /id="VAR_067649" FT VARIANT 498 FT /note="R -> M (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079323" FT VARIANT 499 FT /note="R -> C (in SPG4; abrogates ATPase activity, promotes FT microtubule binding and the formation of thick microtubule FT bundles; dbSNP:rs121908511)" FT /evidence="ECO:0000269|PubMed:10610178, FT ECO:0000269|PubMed:10699187, ECO:0000269|PubMed:11309678, FT ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:12161613, FT ECO:0000269|PubMed:15716377" FT /id="VAR_010198" FT VARIANT 499 FT /note="R -> H (in SPG4; dbSNP:rs878854991)" FT /evidence="ECO:0000269|PubMed:16682546, FT ECO:0000269|PubMed:25045380" FT /id="VAR_026761" FT VARIANT 503 FT /note="R -> L (in SPG4; dbSNP:rs1553319087)" FT /evidence="ECO:0000269|PubMed:12552568" FT /id="VAR_019442" FT VARIANT 503 FT /note="R -> RR (in SPG4)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067650" FT VARIANT 503 FT /note="R -> W (in SPG4; dbSNP:rs864622162)" FT /evidence="ECO:0000269|PubMed:16682546, FT ECO:0000269|PubMed:22960362" FT /id="VAR_026762" FT VARIANT 512 FT /note="E -> D (in SPG4; dbSNP:rs1553319093)" FT /evidence="ECO:0000269|PubMed:11985387" FT /id="VAR_027223" FT VARIANT 512 FT /note="Missing (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067574" FT VARIANT 514 FT /note="R -> G (in SPG4; dbSNP:rs1553319286)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067651" FT VARIANT 515 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:14732620" FT /id="VAR_019443" FT VARIANT 534 FT /note="L -> P (in SPG4; dbSNP:rs1553319317)" FT /evidence="ECO:0000269|PubMed:12939659" FT /id="VAR_019444" FT VARIANT 534 FT /note="L -> V (in SPG4; uncertain significance; FT dbSNP:rs1553319314)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067575" FT VARIANT 546..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:28572275" FT /id="VAR_079324" FT VARIANT 550 FT /note="T -> I (in SPG4; uncertain significance; FT dbSNP:rs1553319537)" FT /evidence="ECO:0000269|PubMed:20718791" FT /id="VAR_067652" FT VARIANT 551 FT /note="A -> Y (in SPG4; requires 2 nucleotide FT substitutions)" FT /evidence="ECO:0000269|PubMed:12124993" FT /id="VAR_019451" FT VARIANT 555 FT /note="D -> G (in SPG4; dbSNP:rs1553319548)" FT /evidence="ECO:0000269|PubMed:25421405" FT /id="VAR_075848" FT VARIANT 555 FT /note="D -> N (in SPG4; dbSNP:rs1553319546)" FT /evidence="ECO:0000269|PubMed:10699187" FT /id="VAR_027224" FT VARIANT 556 FT /note="A -> V (in SPG4; promotes microtubule binding and FT the formation of thick microtubule bundles)" FT /evidence="ECO:0000269|PubMed:10699187, FT ECO:0000269|PubMed:11809724" FT /id="VAR_027225" FT VARIANT 559 FT /note="G -> D (in SPG4; dbSNP:rs864622179)" FT /evidence="ECO:0000269|PubMed:11087788, FT ECO:0000269|PubMed:11843700" FT /id="VAR_027226" FT VARIANT 559 FT /note="G -> R (in SPG4; dbSNP:rs878854992)" FT /evidence="ECO:0000269|PubMed:22960362" FT /id="VAR_075849" FT VARIANT 562..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:22960362" FT /id="VAR_075850" FT VARIANT 562 FT /note="R -> G (in SPG4; dbSNP:rs121908518)" FT /evidence="ECO:0000269|PubMed:11309678, FT ECO:0000269|PubMed:15248095" FT /id="VAR_027227" FT VARIANT 562 FT /note="R -> P (in SPG4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20562464" FT /id="VAR_067576" FT VARIANT 562 FT /note="R -> Q (in SPG4; dbSNP:rs863224923)" FT /evidence="ECO:0000269|PubMed:11843700" FT /id="VAR_027228" FT VARIANT 579 FT /note="N -> H (in SPG4; uncertain significance; FT dbSNP:rs144594804)" FT /evidence="ECO:0000269|PubMed:17594340" FT /id="VAR_067653" FT VARIANT 580 FT /note="I -> T (in SPG4; dbSNP:rs1553321202)" FT /evidence="ECO:0000269|PubMed:20932283" FT /id="VAR_067654" FT VARIANT 581..616 FT /note="Missing (in SPG4)" FT /evidence="ECO:0000269|PubMed:25045380, FT ECO:0000269|PubMed:25421405" FT /id="VAR_075851" FT VARIANT 584 FT /note="D -> H (in SPG4)" FT /evidence="ECO:0000269|PubMed:11015453" FT /id="VAR_010199" FT VARIANT 595 FT /note="S -> R (in SPG4; dbSNP:rs1553321245)" FT /evidence="ECO:0000269|PubMed:24824479" FT /id="VAR_075852" FT VARIANT 607 FT /note="W -> C (in SPG4; dbSNP:rs1553321266)" FT /evidence="ECO:0000269|PubMed:16682546" FT /id="VAR_026763" FT VARIANT 614 FT /note="T -> I (in SPG4; variant form with congenital FT arachnoid cysts; dbSNP:rs1573186691)" FT /evidence="ECO:0000269|PubMed:15159500" FT /id="VAR_019445" FT VARIANT 615 FT /note="T -> I (in SPG4; dbSNP:rs765941217)" FT /evidence="ECO:0000269|PubMed:12124993" FT /id="VAR_019452" FT MUTAGEN 1 FT /note="M->V: Cytoplasmic and nuclear." FT /evidence="ECO:0000269|PubMed:16026783" FT MUTAGEN 65 FT /note="R->G: Abolishes localization to lipid droplets." FT /evidence="ECO:0000269|PubMed:25875445" FT MUTAGEN 81..84 FT /note="RFSR->GFSG: Does not affect localization to lipid FT droplets." FT /evidence="ECO:0000269|PubMed:25875445" FT MUTAGEN 87 FT /note="M->V: Exclusively cytoplasmic." FT /evidence="ECO:0000269|PubMed:16026783" FT MUTAGEN 120 FT /note="H->D: Impairs binding to CHMP1B. Impairs midbody FT localization; when associated with D-124." FT /evidence="ECO:0000269|PubMed:18997780" FT MUTAGEN 124 FT /note="F->A: Impairs binding to CHMP1B." FT /evidence="ECO:0000269|PubMed:18997780" FT MUTAGEN 124 FT /note="F->D: Impairs binding to CHMP1B. Impairs midbody FT localization; when associated with D-120." FT /evidence="ECO:0000269|PubMed:18997780" FT MUTAGEN 310..312 FT /note="KKK->QQQ: Loss of microtubule-binding." FT /evidence="ECO:0000269|PubMed:23272056" FT MUTAGEN 388 FT /note="K->A: Abrogates ATPase activity and abolishes FT microtubule severing." FT /evidence="ECO:0000269|PubMed:15716377" FT MUTAGEN 415 FT /note="Y->A: Abrogates binding to the tail of alpha-tubulin FT and beta-3-tubulin, impairs ATPase activity and abolishes FT microtubule severing." FT /evidence="ECO:0000269|PubMed:17389232" FT MUTAGEN 442 FT /note="E->Q: Abrogates ATP hydrolysis, abolishes FT microtubule severing, stabilizes the homohexameric form, FT and promotes microtubule binding and redistribution from FT the endosome to microtubules." FT /evidence="ECO:0000269|PubMed:15716377, FT ECO:0000269|PubMed:16815977, ECO:0000269|PubMed:17389232, FT ECO:0000269|PubMed:18410514, ECO:0000269|PubMed:22446388, FT ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23272056, FT ECO:0000269|PubMed:23745751" FT MUTAGEN 448 FT /note="C->A,G: Abolishes ATPase activity." FT /evidence="ECO:0000269|PubMed:23745751" FT MUTAGEN 448 FT /note="C->S: Does not affect ATPase activity." FT /evidence="ECO:0000269|PubMed:23745751" FT MUTAGEN 451 FT /note="R->G: Abrogates binding to the tail of alpha-tubulin FT and beta-3-tubulin, impairs ATPase activity and abolishes FT microtubule severing." FT /evidence="ECO:0000269|PubMed:17389232" FT MUTAGEN 457 FT /note="A->E: Abrogates binding to the tail of alpha-tubulin FT and beta-3-tubulin and abolishes microtubule severing." FT /evidence="ECO:0000269|PubMed:17389232" FT HELIX 113..135 FT /evidence="ECO:0007829|PDB:7S7J" FT STRAND 138..140 FT /evidence="ECO:0007829|PDB:7S7J" FT HELIX 142..161 FT /evidence="ECO:0007829|PDB:7S7J" FT HELIX 169..192 FT /evidence="ECO:0007829|PDB:7S7J" FT HELIX 326..331 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 341..343 FT /evidence="ECO:0007829|PDB:5Z6R" FT HELIX 348..357 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 359..363 FT /evidence="ECO:0007829|PDB:5Z6Q" FT TURN 365..367 FT /evidence="ECO:0007829|PDB:5Z6R" FT HELIX 370..372 FT /evidence="ECO:0007829|PDB:5Z6R" FT STRAND 376..386 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 388..398 FT /evidence="ECO:0007829|PDB:5Z6Q" FT STRAND 402..407 FT /evidence="ECO:0007829|PDB:5Z6Q" FT TURN 408..412 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 425..432 FT /evidence="ECO:0007829|PDB:5Z6Q" FT STRAND 435..442 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 443..446 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 462..473 FT /evidence="ECO:0007829|PDB:5Z6Q" FT STRAND 480..487 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 489..491 FT /evidence="ECO:0007829|PDB:5Z6Q" FT TURN 494..496 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 497..499 FT /evidence="ECO:0007829|PDB:5Z6Q" FT STRAND 501..505 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 511..523 FT /evidence="ECO:0007829|PDB:5Z6Q" FT TURN 524..526 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 531..540 FT /evidence="ECO:0007829|PDB:5Z6Q" FT TURN 541..543 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 546..557 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 559..563 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 566..571 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 574..576 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 582..588 FT /evidence="ECO:0007829|PDB:5Z6Q" FT TURN 589..591 FT /evidence="ECO:0007829|PDB:5Z6Q" FT HELIX 598..609 FT /evidence="ECO:0007829|PDB:5Z6Q" SQ SEQUENCE 616 AA; 67197 MW; 75E5FC5787132B4C CRC64; MNSPGGRGKK KGSGGASNPV PPRPPPPCLA PAPPAAGPAP PPESPHKRNL YYFSYPLFVG FALLRLVAFH LGLLFVWLCQ RFSRALMAAK RSSGAAPAPA SASAPAPVPG GEAERVRVFH KQAFEYISIA LRIDEDEKAG QKEQAVEWYK KGIEELEKGI AVIVTGQGEQ CERARRLQAK MMTNLVMAKD RLQLLEKMQP VLPFSKSQTD VYNDSTNLAC RNGHLQSESG AVPKRKDPLT HTSNSLPRSK TVMKTGSAGL SGHHRAPSYS GLSMVSGVKQ GSGPAPTTHK GTPKTNRTNK PSTPTTATRK KKDLKNFRNV DSNLANLIMN EIVDNGTAVK FDDIAGQDLA KQALQEIVIL PSLRPELFTG LRAPARGLLL FGPPGNGKTM LAKAVAAESN ATFFNISAAS LTSKYVGEGE KLVRALFAVA RELQPSIIFI DEVDSLLCER REGEHDASRR LKTEFLIEFD GVQSAGDDRV LVMGATNRPQ ELDEAVLRRF IKRVYVSLPN EETRLLLLKN LLCKQGSPLT QKELAQLARM TDGYSGSDLT ALAKDAALGP IRELKPEQVK NMSASEMRNI RLSDFTESLK KIKRSVSPQT LEAYIRWNKD FGDTTV //