SPAST_DANRE
ID SPAST_DANRE Reviewed; 570 AA.
AC Q6NW58; Q6JUU0;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Spastin {ECO:0000255|HAMAP-Rule:MF_03021};
DE EC=5.6.1.1 {ECO:0000255|HAMAP-Rule:MF_03021};
GN Name=spast {ECO:0000255|HAMAP-Rule:MF_03021};
GN Synonyms=spg4 {ECO:0000255|HAMAP-Rule:MF_03021};
GN ORFNames=si:ch73-233a22.3, zgc:85952;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16893913; DOI=10.1093/hmg/ddl212;
RA Wood J.D., Landers J.A., Bingley M., McDermott C.J., Thomas-McArthur V.,
RA Gleadall L.J., Shaw P.J., Cunliffe V.T.;
RT "The microtubule-severing protein spastin is essential for axon outgrowth
RT in the zebrafish embryo.";
RL Hum. Mol. Genet. 15:2763-2771(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
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).
CC -!- FUNCTION: ATP-dependent microtubule severing protein that specifically
CC recognizes and cuts microtubules that are polyglutamylated.
CC Preferentially recognizes and acts on microtubules decorated with short
CC polyglutamate tails: severing activity increases as the number of
CC glutamates per tubulin rises from one to eight, but decreases beyond
CC this glutamylation threshold. Microtubule severing promotes
CC reorganization of cellular microtubule arrays and the release of
CC microtubules from the centrosome following nucleation. Required for
CC membrane traffic from the endoplasmic reticulum (ER) to the Golgi and
CC for completion of the abscission stage of cytokinesis. Also plays a
CC role in axon growth and the formation of axonal branches.
CC {ECO:0000255|HAMAP-Rule:MF_03021}.
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 -!- SUBUNIT: Homohexamer. The homohexamer is stabilized by ATP-binding. The
CC homohexamer may adopt a ring conformation through which microtubules
CC pass prior to being severed. Interacts with microtubules.
CC {ECO:0000255|HAMAP-Rule:MF_03021}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255|HAMAP-Rule:MF_03021};
CC Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_03021}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm, cytoskeleton
CC {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm, perinuclear region
CC {ECO:0000255|HAMAP-Rule:MF_03021}. Nucleus {ECO:0000255|HAMAP-
CC Rule:MF_03021}. Note=Forms an intramembrane hairpin-like structure in
CC the membrane. {ECO:0000255|HAMAP-Rule:MF_03021}.
CC -!- DEVELOPMENTAL STAGE: Maternally expressed. Expressed at low levels
CC throughout the embryo up to 24 hours post-fertilization (hpf).
CC {ECO:0000269|PubMed:16893913}.
CC -!- DISRUPTION PHENOTYPE: Branchiomotor neurons exhibit reduced axonal
CC outgrowth and aberrant positioning of neuronal cell bodies. Outgrowth
CC of motor axons from the spinal cord is impaired, the number and length
CC of spinal motor neurons is reduced, and elevated levels of apoptosis
CC are observed in the CNS. Thickened bundles of axonal microtubules are
CC observed in the spinal cord. Longitudinal fascicles in the hindbrain
CC are disordered. Most embryos are immotile and fail to hatch, while
CC those that do exhibit reduced motility and swimming defects. Morpholino
CC knockdown results in abnormal morphological features, including
CC hydrocephalia, perturbed yolk sac extension and an arched-back
CC phenotype, disorganized microtubule networks in the spinal cord and
CC thinner microtubules in the spinal motor neuron axons, and in increased
CC oxidative stress (PubMed:26744324). These phenotypes are rescued
CC following exposure to the drugs methylene blue, guanabenz, salubrinal
CC or phenazine (PubMed:26744324). {ECO:0000269|PubMed:16893913,
CC ECO:0000269|PubMed:26744324}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. Spastin subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03021}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY304504; AAQ74774.1; -; mRNA.
DR EMBL; CU651563; CAX13091.1; -; Genomic_DNA.
DR EMBL; BC067715; AAH67715.1; -; mRNA.
DR RefSeq; NP_998080.2; NM_212915.2.
DR AlphaFoldDB; Q6NW58; -.
DR SMR; Q6NW58; -.
DR STRING; 7955.ENSDARP00000029675; -.
DR PaxDb; Q6NW58; -.
DR Ensembl; ENSDART00000035150; ENSDARP00000029675; ENSDARG00000024933.
DR GeneID; 405851; -.
DR KEGG; dre:405851; -.
DR CTD; 6683; -.
DR ZFIN; ZDB-GENE-040426-2331; spast.
DR eggNOG; KOG0740; Eukaryota.
DR GeneTree; ENSGT00940000156258; -.
DR HOGENOM; CLU_000688_21_5_1; -.
DR InParanoid; Q6NW58; -.
DR OMA; GMTNEPM; -.
DR OrthoDB; 1176820at2759; -.
DR PhylomeDB; Q6NW58; -.
DR TreeFam; TF105014; -.
DR BRENDA; 5.6.1.1; 928.
DR Reactome; R-DRE-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR PRO; PR:Q6NW58; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 1.
DR Bgee; ENSDARG00000024933; Expressed in mature ovarian follicle and 21 other tissues.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-UniRule.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-UniRule.
DR GO; GO:0015630; C:microtubule cytoskeleton; IBA:GO_Central.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-UniRule.
DR GO; GO:0043014; F:alpha-tubulin binding; ISS: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; ISS:UniProtKB.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0008568; F:microtubule severing ATPase activity; ISS:UniProtKB.
DR GO; GO:0008089; P:anterograde axonal transport; ISS:UniProtKB.
DR GO; GO:0048675; P:axon extension; IMP:ZFIN.
DR GO; GO:0007411; P:axon guidance; IMP:ZFIN.
DR GO; GO:0019896; P:axonal transport of mitochondrion; ISS:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; IMP:ZFIN.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; IMP:ZFIN.
DR GO; GO:0032506; P:cytokinetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IMP:ZFIN.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IEA:UniProtKB-UniRule.
DR GO; GO:0007032; P:endosome organization; IMP:ZFIN.
DR GO; GO:0010458; P:exit from mitosis; ISS:UniProtKB.
DR GO; GO:0090148; P:membrane fission; ISS:UniProtKB.
DR GO; GO:0001578; P:microtubule bundle formation; ISS:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:ZFIN.
DR GO; GO:0051013; P:microtubule severing; ISS:UniProtKB.
DR GO; GO:0000281; P:mitotic cytokinesis; ISS:UniProtKB.
DR GO; GO:0051228; P:mitotic spindle disassembly; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ZFIN.
DR GO; GO:0031468; P:nuclear membrane reassembly; ISS:UniProtKB.
DR GO; GO:0045773; P:positive regulation of axon extension; IMP:ZFIN.
DR GO; GO:0031117; P:positive regulation of microtubule depolymerization; IMP:ZFIN.
DR GO; GO:0034214; P:protein hexamerization; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:ZFIN.
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 2: Evidence at transcript level;
KW ATP-binding; Cell cycle; Cell division; Cytoplasm; Cytoskeleton;
KW Developmental protein; Differentiation; Isomerase; Membrane; Microtubule;
KW Neurogenesis; Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..570
FT /note="Spastin"
FT /id="PRO_0000367137"
FT TOPO_DOM 1..35
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT INTRAMEM 36..52
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT TOPO_DOM 53..570
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT DOMAIN 83..158
FT /note="MIT"
FT /evidence="ECO:0000255"
FT REGION 186..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..263
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 335..342
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT CONFLICT 224
FT /note="C -> R (in Ref. 3; AAH67715)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 570 AA; 63086 MW; 2EE116D8B18DD9AA CRC64;
MNSGHKARLR GGRACGPVSD GSARGNRLLF YTRSLSRVPE WLLRVLLLLL RWLFQPIRRA
MAARAKECGP DGSEETGERI RNYHKQAFEF ISVALQIDED EKGDKQKAVQ WYRKGIAELE
KGIQIQVTGA GEKADRARKL QDKMITNLSM AEDRLKLLGN LLSQSPAESS SDDSFYSFSN
GNLRPAPASG AVSKKKDTLT ITNQTSLRPK NPPKSTPNAS GLNCTPSAAQ SSRTGPQNNQ
KGPTVKGKNN VKASTTATAS PQRKRDMKNF KNVDSKLASL ILNEIVDSGS VVRFDDIAGQ
DLAKQALQEI VILPALRPEL FTGLRAPARG LLLFGPPGNG KTMLAKAVAM ESNATFFNIS
AATLTSKYVG EGEKLVRALF AVARELQPSI IFIDEIDSLL CERREGEHDA SRRLKTEFLI
EFDGVQSGGD ERVLVMGATN RPQELDEAVL RRFAKRIYVA LPTEETRLKL LKNLLSKHRN
PLSQKELSQL ARLTDGYSGS DLTSLAKDAA LGPIRELKPE QVRNMSAHEM RDIRISDFLE
SLKRIKRSVS PQTLDQYVRW NREYGDTTGV
