SPAST_HUMAN
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 03-AUG-2022, entry version 203.
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, ECO:0000312|HGNC:HGNC:11233};
GN Synonyms=ADPSP, FSP2, KIAA1083 {ECO:0000303|PubMed:10470851},
GN SPG4 {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-; PHE-422; ASN-445;
RP SER-460; LEU-482; GLU-512 DEL; VAL-534 AND PRO-562, AND VARIANT 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. N-
CC terminally truncated spastin (residues 228-616), which has been shown
CC to exhibit full severing activity, shows a basal ATP turnover rate of
CC 0.78 sec(-1) in the absence of microtubules, a KM of 0.16 mM for ATP,
CC and the ATP turnover rate is extrapolated to 3.83 sec(-1) in the
CC presence of microtubules. ATPase activity shows non-Michaelis-Menten
CC kinetics in the presence of microtubules, but is close to non-
CC 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; Q5T4F4: ZFYVE27; NbExp=3; IntAct=EBI-1222832, EBI-3892947;
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";
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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 PDBsum; 3EAB; -.
DR PDBsum; 3VFD; -.
DR PDBsum; 5Z6Q; -.
DR PDBsum; 5Z6R; -.
DR PDBsum; 6PEK; -.
DR PDBsum; 6PEN; -.
DR AlphaFoldDB; Q9UBP0; -.
DR SMR; Q9UBP0; -.
DR BioGRID; 112562; 40.
DR CORUM; Q9UBP0; -.
DR DIP; DIP-38418N; -.
DR ELM; Q9UBP0; -.
DR IntAct; Q9UBP0; 28.
DR MINT; Q9UBP0; -.
DR STRING; 9606.ENSP00000480893; -.
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; Q9UBP0; -.
DR PeptideAtlas; Q9UBP0; -.
DR PRIDE; Q9UBP0; -.
DR ProteomicsDB; 84020; -. [Q9UBP0-1]
DR ProteomicsDB; 84021; -. [Q9UBP0-2]
DR ProteomicsDB; 84022; -. [Q9UBP0-3]
DR ProteomicsDB; 84023; -. [Q9UBP0-4]
DR Antibodypedia; 2246; 255 antibodies from 30 providers.
DR DNASU; 6683; -.
DR Ensembl; ENST00000315285.9; ENSP00000320885.3; ENSG00000021574.13. [Q9UBP0-1]
DR Ensembl; ENST00000642999.1; ENSP00000496589.1; ENSG00000021574.13. [Q9UBP0-3]
DR Ensembl; ENST00000644954.1; ENSP00000494312.1; ENSG00000021574.13. [Q9UBP0-4]
DR Ensembl; ENST00000646571.1; ENSP00000495015.1; ENSG00000021574.13. [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 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; GMTNEPM; -.
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; 21 hits in 1080 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 197 other tissues.
DR ExpressionAtlas; Q9UBP0; baseline and differential.
DR Genevisible; Q9UBP0; HS.
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: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: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 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 InterPro; IPR035106; Spastin_chordate.
DR InterPro; IPR015415; Vps4_C.
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; SSF52540; 1.
DR PROSITE; PS00674; AAA; 1.
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; unknown pathological 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 variant;
FT 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; unknown pathological 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; unknown pathological significance;
FT dbSNP:rs1553315215)"
FT /evidence="ECO:0000269|PubMed:20718791"
FT /id="VAR_067633"
FT VARIANT 328
FT /note="I -> K (in SPG4; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28572275"
FT /id="VAR_079314"
FT VARIANT 328
FT /note="I -> L (in SPG4; unknown pathological 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; unknown pathological significance;
FT dbSNP:rs1057519181)"
FT /evidence="ECO:0000269|PubMed:20562464"
FT /id="VAR_067564"
FT VARIANT 360
FT /note="L -> V (in SPG4; unknown pathological 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; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:20562464"
FT /id="VAR_067565"
FT VARIANT 366
FT /note="E -> K (in SPG4; unknown pathological 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; unknown pathological 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; unknown pathological 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; unknown pathological 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; unknown pathological 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; unknown pathological 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; unknown pathological 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)"
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; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28572275"
FT /id="VAR_079320"
FT VARIANT 422
FT /note="L -> F (in SPG4; unknown pathological significance)"
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)"
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; unknown pathological 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; unknown pathological 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; unknown pathological significance;
FT dbSNP:rs1553318261)"
FT /evidence="ECO:0000269|PubMed:28572275"
FT /id="VAR_079321"
FT VARIANT 482
FT /note="V -> L (in SPG4; unknown pathological significance;
FT dbSNP:rs1553318315)"
FT /evidence="ECO:0000269|PubMed:20562464"
FT /id="VAR_067573"
FT VARIANT 485
FT /note="A -> T (in SPG4; unknown pathological 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)"
FT /evidence="ECO:0000269|PubMed:20718791,
FT ECO:0000269|PubMed:20932283"
FT /id="VAR_067649"
FT VARIANT 498
FT /note="R -> M (in SPG4; unknown pathological 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; unknown pathological
FT 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; unknown pathological 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; unknown pathological 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; unknown pathological 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; unknown pathological 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 112..136
FT /evidence="ECO:0007829|PDB:3EAB"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:3EAB"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:3EAB"
FT HELIX 146..161
FT /evidence="ECO:0007829|PDB:3EAB"
FT HELIX 169..195
FT /evidence="ECO:0007829|PDB:3EAB"
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
