SPAST_CAEEL
ID SPAST_CAEEL Reviewed; 512 AA.
AC Q8MNV0; G5EEF8; Q7M3K5; Q8MNU9;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Spastin homolog {ECO:0000305};
DE EC=5.6.1.1 {ECO:0000269|PubMed:19619244, ECO:0000269|PubMed:22561316};
GN Name=spas-1 {ECO:0000303|PubMed:17531954, ECO:0000312|WormBase:C24B5.2c};
GN ORFNames=C24B5.2 {ECO:0000312|WormBase:C24B5.2c};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000312|EMBL:BAH80101.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Han C., Hobert O., Lauring B.;
RT "Spastin deficiency in C.elegans results in premature termination of motor
RT axons.";
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-285; TRP-312 AND GLU-339.
RX PubMed=17531954; DOI=10.1016/j.bbrc.2007.05.086;
RA Matsushita-Ishiodori Y., Yamanaka K., Ogura T.;
RT "The C. elegans homologue of the spastic paraplegia protein, spastin,
RT disassembles microtubules.";
RL Biochem. Biophys. Res. Commun. 359:157-162(2007).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP INTERACTION WITH TUBULIN, DOMAIN, AND MUTAGENESIS OF 1-MET--ASN-103;
RP ARG-237; LYS-266; LYS-285; LYS-297; TRP-312; LYS-318; ARG-321; ARG-328;
RP GLU-339; ARG-347; ARG-356 AND ARG-357.
RX PubMed=19619244; DOI=10.1111/j.1365-2443.2009.01320.x;
RA Matsushita-Ishiodori Y., Yamanaka K., Hashimoto H., Esaki M., Ogura T.;
RT "Conserved aromatic and basic amino acid residues in the pore region of
RT Caenorhabditis elegans spastin play critical roles in microtubule
RT severing.";
RL Genes Cells 14:925-940(2009).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ARG-285; LYS-498;
RP LYS-502; 498-SER--CYS-512; 497-GLN--CYS-512 AND 509-SER--CYS-512.
RX PubMed=22561316; DOI=10.1016/j.jsb.2012.04.010;
RA Onitake A., Matsushita-Ishiodori Y., Johjima A., Esaki M., Ogura T.,
RA Yamanaka K.;
RT "The C-terminal alpha-helix of SPAS-1, a Caenorhabditis elegans spastin
RT homologue, is crucial for microtubule severing.";
RL J. Struct. Biol. 179:138-142(2012).
RN [6]
RP FUNCTION.
RX PubMed=26051896; DOI=10.1016/j.cub.2015.04.061;
RA Kurup N., Yan D., Goncharov A., Jin Y.;
RT "Dynamic microtubules drive circuit rewiring in the absence of neurite
RT remodeling.";
RL Curr. Biol. 25:1594-1605(2015).
RN [7]
RP DISRUPTION PHENOTYPE.
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 [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=26744324; DOI=10.1093/hmg/ddv632;
RA Julien C., Lissouba A., Madabattula S., Fardghassemi Y., Rosenfelt C.,
RA Androschuk A., Strautman J., Wong C., Bysice A., O'sullivan J.,
RA Rouleau G.A., Drapeau P., Parker J.A., Bolduc F.V.;
RT "Conserved pharmacological rescue of hereditary spastic paraplegia-related
RT phenotypes across model organisms.";
RL Hum. Mol. Genet. 25:1088-1099(2016).
RN [9]
RP 3D-STRUCTURE MODELING, FUNCTION, SUBUNIT, AND MUTAGENESIS OF GLU-339.
RX PubMed=18202664; DOI=10.1038/nature06482;
RA Roll-Mecak A., Vale R.D.;
RT "Structural basis of microtubule severing by the hereditary spastic
RT paraplegia protein spastin.";
RL Nature 451:363-367(2008).
CC -!- FUNCTION: ATP-dependent microtubule severing protein that specifically
CC recognizes and cuts microtubules (PubMed:17531954, PubMed:19619244,
CC PubMed:22561316, PubMed:18202664). Probably by regulating microtubule
CC remodeling, plays a role in new synapse formation in GABAergic DD
CC (Dorsal D type) neurons (PubMed:26051896).
CC {ECO:0000269|PubMed:17531954, ECO:0000269|PubMed:18202664,
CC ECO:0000269|PubMed:19619244, ECO:0000269|PubMed:22561316,
CC ECO:0000269|PubMed:26051896}.
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:0000269|PubMed:19619244, ECO:0000269|PubMed:22561316};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.53 mM for ATP (at 37 degrees Celsius and pH 8.8)
CC {ECO:0000269|PubMed:19619244};
CC Vmax=115 nmol/min/mg enzyme (at 37 degrees Celsius and pH 8.8)
CC {ECO:0000269|PubMed:19619244};
CC -!- SUBUNIT: Homohexamer (PubMed:19619244, PubMed:22561316). The
CC homohexamer is stabilized by ATP-binding (By similarity). The
CC homohexamer may adopt a ring conformation through which microtubules
CC pass prior to being severed. Interacts with microtubules (By
CC similarity). Interacts (via N-terminus) with tubulin; the interaction
CC is direct (PubMed:19619244). {ECO:0000250|UniProtKB:Q9UBP0,
CC ECO:0000269|PubMed:19619244, ECO:0000269|PubMed:22561316}.
CC -!- INTERACTION:
CC Q8MNV0; Q8MNV0: spas-1; NbExp=3; IntAct=EBI-15680248, EBI-15680248;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q9UBP0}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:17531954}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:17531954}. Note=Forms an intramembrane hairpin-like
CC structure in the membrane (By similarity). Localizes to the
CC cytoskeleton, perinuclear region and cytoplasm in early embryos
CC (PubMed:17531954). {ECO:0000250|UniProtKB:Q9UBP0,
CC ECO:0000269|PubMed:17531954}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=c {ECO:0000312|WormBase:C24B5.2c}; Synonyms=spas-1L
CC {ECO:0000303|PubMed:17531954};
CC IsoId=Q8MNV0-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:C24B5.2a}; Synonyms=spas-1S
CC {ECO:0000303|PubMed:17531954};
CC IsoId=Q8MNV0-2; Sequence=VSP_036645;
CC -!- DEVELOPMENTAL STAGE: [Isoform a]: Expressed at all developmental stages
CC (PubMed:17531954). Highly expressed in the embryo and expressed at
CC lower levels in L3-L4 larvae (PubMed:17531954).
CC {ECO:0000269|PubMed:17531954}.
CC -!- DEVELOPMENTAL STAGE: [Isoform c]: Highly expressed in the embryo
CC (PubMed:17531954). Not expressed in L3-L4 larvae (PubMed:17531954).
CC {ECO:0000269|PubMed:17531954}.
CC -!- DOMAIN: The MTBD (microtubule binding domain) region mediates binding
CC to microtubules and tubulin. {ECO:0000269|PubMed:19619244}.
CC -!- DISRUPTION PHENOTYPE: Slow growth, reduced brood size, abnormal
CC oogenesis and multiple vulvae (PubMed:17531954). Progressive locomotor
CC defects, which is rescued following exposure to the drugs guanabenz,
CC salubrinal, phenazine, or methylene blue (PubMed:26744324). Lifespan is
CC prolonged following exposure to the drugs guanabenz, salubrinal or
CC methylene blue, but not phenazine (PubMed:26744324). Increases numbers
CC of centrosomal microtubules in early embryos (PubMed:17531954). Reduced
CC neutral lipid levels in intestinal cells (PubMed:25875445). RNAi-
CC mediated knockdown results in paralysis due to an increase in the
CC endoplasmic reticulum stress response, which is rescued following
CC exposure to the drugs methylene blue, guanabenz, salubrinal, or
CC phenazine (PubMed:26744324). {ECO:0000269|PubMed:17531954,
CC ECO:0000269|PubMed:25875445, ECO:0000269|PubMed:26744324}.
CC -!- MISCELLANEOUS: [Isoform a]: Produced by alternative splicing and the
CC skipping of exon 4. {ECO:0000269|PubMed:17531954}.
CC -!- MISCELLANEOUS: [Isoform c]: Produced by alternative splicing, which
CC results in the retention of exon 4. {ECO:0000269|PubMed:17531954}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. Spastin subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Lacks the conserved MIT domain, which is one of the features
CC of the spastin family. {ECO:0000303|PubMed:17531954}.
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DR EMBL; AB287436; BAH80101.1; -; mRNA.
DR EMBL; BX284605; CCD61426.1; -; Genomic_DNA.
DR EMBL; BX284605; CCD61430.1; -; Genomic_DNA.
DR RefSeq; NP_001256115.1; NM_001269186.1. [Q8MNV0-1]
DR RefSeq; NP_741586.1; NM_171501.4. [Q8MNV0-2]
DR AlphaFoldDB; Q8MNV0; -.
DR SMR; Q8MNV0; -.
DR BioGRID; 44338; 1.
DR DIP; DIP-59833N; -.
DR STRING; 6239.C24B5.2c; -.
DR EPD; Q8MNV0; -.
DR PaxDb; Q8MNV0; -.
DR PeptideAtlas; Q8MNV0; -.
DR EnsemblMetazoa; C24B5.2a.1; C24B5.2a.1; WBGene00016045. [Q8MNV0-2]
DR EnsemblMetazoa; C24B5.2c.1; C24B5.2c.1; WBGene00016045. [Q8MNV0-1]
DR GeneID; 179300; -.
DR KEGG; cel:CELE_C24B5.2; -.
DR UCSC; C24B5.2a; c. elegans.
DR CTD; 179300; -.
DR WormBase; C24B5.2a; CE30731; WBGene00016045; spas-1. [Q8MNV0-2]
DR WormBase; C24B5.2c; CE20522; WBGene00016045; spas-1. [Q8MNV0-1]
DR eggNOG; KOG0740; Eukaryota.
DR GeneTree; ENSGT00940000156258; -.
DR InParanoid; Q8MNV0; -.
DR OMA; CSTYERV; -.
DR OrthoDB; 1176820at2759; -.
DR PhylomeDB; Q8MNV0; -.
DR BRENDA; 5.6.1.1; 1045.
DR Reactome; R-CEL-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR PRO; PR:Q8MNV0; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00016045; Expressed in germ line (C elegans) and 7 other tissues.
DR ExpressionAtlas; Q8MNV0; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IDA:WormBase.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IPI:WormBase.
DR GO; GO:0005524; F:ATP binding; IMP:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:WormBase.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; IDA:WormBase.
DR GO; GO:0008568; F:microtubule severing ATPase activity; IDA:WormBase.
DR GO; GO:0001578; P:microtubule bundle formation; NAS:UniProtKB.
DR GO; GO:0007019; P:microtubule depolymerization; IDA:WormBase.
DR GO; GO:0051013; P:microtubule severing; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0051647; P:nucleus localization; IMP:WormBase.
DR GO; GO:0048477; P:oogenesis; IMP:WormBase.
DR GO; GO:0031117; P:positive regulation of microtubule depolymerization; IDA:UniProtKB.
DR GO; GO:0040025; P:vulval development; IMP:WormBase.
DR Gene3D; 3.40.50.300; -; 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; IPR027417; P-loop_NTPase.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Coiled coil; Cytoplasm; Cytoskeleton;
KW Isomerase; Membrane; Microtubule; Neurogenesis; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..512
FT /note="Spastin homolog"
FT /id="PRO_0000367132"
FT TOPO_DOM 1..274
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 275..294
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT TOPO_DOM 295..512
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 110..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 115..233
FT /note="MTBD"
FT /evidence="ECO:0000269|PubMed:19619244"
FT COILED 32..97
FT /evidence="ECO:0000255"
FT COMPBIAS 138..173
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 279..286
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00499"
FT VAR_SEQ 139..199
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_036645"
FT MUTAGEN 1..103
FT /note="Missing: Abolishes interaction with tubulin."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 237
FT /note="R->A: Does not abolish microtubule severing.
FT Disperse cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 266
FT /note="K->A: Does not abolish microtubule severing.
FT Disperse cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 285
FT /note="K->R: Abolishes ATP-binding and enzymatic activity.
FT Abolishes microtubule severing. Forms homohexamers."
FT /evidence="ECO:0000269|PubMed:17531954,
FT ECO:0000269|PubMed:19619244, ECO:0000269|PubMed:22561316"
FT MUTAGEN 297
FT /note="K->A: Does not abolish microtubule severing.
FT Disperse cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 312
FT /note="W->A,E,K: Abolishes microtubule severing. Abolishes
FT microtubule localization; in association with A-318."
FT /evidence="ECO:0000269|PubMed:17531954,
FT ECO:0000269|PubMed:19619244"
FT MUTAGEN 312
FT /note="W->F: Does not abolish microtubule severing."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 318
FT /note="K->A: Increases enzymatic activity. Forms
FT homohexamers. Localizes to microtubules, but microtubule
FT severing is abolished. Abolishes microtubule localization;
FT in association with A-312, A-321 or A-357. Does not abolish
FT microtubule localization; in association with A-347 or A-
FT 356."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 321
FT /note="R->A: Abolishes microtubule severing. Disperse
FT cytoplasmic localization. Abolishes microtubule
FT localization; in association with A-318."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 328
FT /note="R->A: Does not abolish microtubule severing.
FT Disperse cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 339
FT /note="E->Q: Abolishes enzymatic activity. Abrogates
FT microtubule severing, promotes homohexamerization and
FT promotes association with microtubules."
FT /evidence="ECO:0000269|PubMed:17531954,
FT ECO:0000269|PubMed:18202664, ECO:0000269|PubMed:19619244"
FT MUTAGEN 347
FT /note="R->A: Abolishes microtubule severing. Disperse
FT cytoplasmic localization. Does not abolish microtubule
FT localization; in association with A-318."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 356
FT /note="R->A: Abolishes microtubule severing. Disperse
FT cytoplasmic localization. Does not abolish microtubule
FT localization; in association with A-318."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 357
FT /note="R->A: Abolishes microtubule severing. Disperse
FT cytoplasmic localization. Abolishes microtubule
FT localization; in association with A-318."
FT /evidence="ECO:0000269|PubMed:19619244"
FT MUTAGEN 494..512
FT /note="Missing: Abolishes ATP-binding and reduces enzymatic
FT activity. Abolishes microtubule severing. Forms
FT homohexamers."
FT /evidence="ECO:0000269|PubMed:22561316"
FT MUTAGEN 497..512
FT /note="Missing: Abolishes microtubule severing."
FT /evidence="ECO:0000269|PubMed:22561316"
FT MUTAGEN 498
FT /note="K->P: Abolishes microtubule severing; in association
FT with P-502."
FT /evidence="ECO:0000269|PubMed:22561316"
FT MUTAGEN 502
FT /note="K->P: Abolishes microtubule severing; in association
FT with P-498."
FT /evidence="ECO:0000269|PubMed:22561316"
FT MUTAGEN 509..512
FT /note="Missing: Does not abolish microtubule severing."
FT /evidence="ECO:0000269|PubMed:22561316"
SQ SEQUENCE 512 AA; 56901 MW; 8CA8E44B54F713AB CRC64;
MFAFSKGPAG SSTYDRVAQK FQDGYEKMRA AIEMDELTKH AGSIQEKLRT AELYKEARSL
LKEANEFNIM DIPETRRSEI RDKRQNMMKL EKSAQDRLIA ICNEVDPNVK QSRSATVGPS
RPASAARVTP RPTRATAPEK KNAAKAKEND ENRHVCSRGD RCGAHHQPVT KKSDTVHPEP
PVQASNRKME TVKRVKVDKA SLPMHQNPVN RAALLNGVDK VIGERLLDEV LDNTGVRMDD
VAGCHSAKAA LEEAVILPAL NPNLFKGLRQ PVKGILLFGP PGNGKTLLAK AVAGESKQMF
FNISASSLTS KWVGDSEKTI RGLFQIARNA QPSIIFIDEI DSILCERSEK DAEVSRRMKT
EFLVQFDGAT SSADDRILVI GATNRPHELD DAVLRRFPKR IMLNLPDEEA RKELITKTLK
KHNMMDGLIS SDIRYIASNT SGFSNSDLVA LCKEAAMVPI REIDRSKLSM TDGEKIRKIR
ASDFDTALRT IRPSTSQKIM SKLSDFSRSF GC
