ID H9FYV4_MACMU Unreviewed; 614 AA.
AC H9FYV4; F7F0D1;
DT 16-MAY-2012, integrated into UniProtKB/TrEMBL.
DT 16-MAY-2012, sequence version 1.
DT 27-MAR-2024, entry version 79.
DE RecName: Full=Spastin {ECO:0000256|HAMAP-Rule:MF_03021};
DE EC=5.6.1.1 {ECO:0000256|HAMAP-Rule:MF_03021};
GN Name=SPAST {ECO:0000256|HAMAP-Rule:MF_03021,
GN ECO:0000313|EMBL:AFE79813.1, ECO:0000313|Ensembl:ENSMMUP00000028561.3,
GN ECO:0000313|VGNC:VGNC:77857};
GN Synonyms=SPG4 {ECO:0000256|HAMAP-Rule:MF_03021};
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544 {ECO:0000313|EMBL:AFE79813.1};
RN [1] {ECO:0000313|Proteomes:UP000006718}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17573 {ECO:0000313|Proteomes:UP000006718};
RX PubMed=17431167; DOI=10.1126/science.1139247;
RA Gibbs R.A., Rogers J., Katze M.G., Bumgarner R., Weinstock G.M.,
RA Mardis E.R., Remington K.A., Strausberg R.L., Venter J.C., Wilson R.K.,
RA Batzer M.A., Bustamante C.D., Eichler E.E., Hahn M.W., Hardison R.C.,
RA Makova K.D., Miller W., Milosavljevic A., Palermo R.E., Siepel A.,
RA Sikela J.M., Attaway T., Bell S., Bernard K.E., Buhay C.J.,
RA Chandrabose M.N., Dao M., Davis C., Delehaunty K.D., Ding Y., Dinh H.H.,
RA Dugan-Rocha S., Fulton L.A., Gabisi R.A., Garner T.T., Godfrey J.,
RA Hawes A.C., Hernandez J., Hines S., Holder M., Hume J., Jhangiani S.N.,
RA Joshi V., Khan Z.M., Kirkness E.F., Cree A., Fowler R.G., Lee S.,
RA Lewis L.R., Li Z., Liu Y.-S., Moore S.M., Muzny D., Nazareth L.V.,
RA Ngo D.N., Okwuonu G.O., Pai G., Parker D., Paul H.A., Pfannkoch C.,
RA Pohl C.S., Rogers Y.-H.C., Ruiz S.J., Sabo A., Santibanez J.,
RA Schneider B.W., Smith S.M., Sodergren E., Svatek A.F., Utterback T.R.,
RA Vattathil S., Warren W., White C.S., Chinwalla A.T., Feng Y., Halpern A.L.,
RA Hillier L.W., Huang X., Minx P., Nelson J.O., Pepin K.H., Qin X.,
RA Sutton G.G., Venter E., Walenz B.P., Wallis J.W., Worley K.C., Yang S.-P.,
RA Jones S.M., Marra M.A., Rocchi M., Schein J.E., Baertsch R., Clarke L.,
RA Csuros M., Glasscock J., Harris R.A., Havlak P., Jackson A.R., Jiang H.,
RA Liu Y., Messina D.N., Shen Y., Song H.X.-Z., Wylie T., Zhang L., Birney E.,
RA Han K., Konkel M.K., Lee J., Smit A.F.A., Ullmer B., Wang H., Xing J.,
RA Burhans R., Cheng Z., Karro J.E., Ma J., Raney B., She X., Cox M.J.,
RA Demuth J.P., Dumas L.J., Han S.-G., Hopkins J., Karimpour-Fard A.,
RA Kim Y.H., Pollack J.R., Vinar T., Addo-Quaye C., Degenhardt J., Denby A.,
RA Hubisz M.J., Indap A., Kosiol C., Lahn B.T., Lawson H.A., Marklein A.,
RA Nielsen R., Vallender E.J., Clark A.G., Ferguson B., Hernandez R.D.,
RA Hirani K., Kehrer-Sawatzki H., Kolb J., Patil S., Pu L.-L., Ren Y.,
RA Smith D.G., Wheeler D.A., Schenck I., Ball E.V., Chen R., Cooper D.N.,
RA Giardine B., Hsu F., Kent W.J., Lesk A., Nelson D.L., O'brien W.E.,
RA Pruefer K., Stenson P.D., Wallace J.C., Ke H., Liu X.-M., Wang P.,
RA Xiang A.P., Yang F., Barber G.P., Haussler D., Karolchik D., Kern A.D.,
RA Kuhn R.M., Smith K.E., Zwieg A.S.;
RT "Evolutionary and biomedical insights from the rhesus macaque genome.";
RL Science 316:222-234(2007).
RN [2] {ECO:0000313|EMBL:AFE79813.1}
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Caudate {ECO:0000313|EMBL:AFE79813.1}, and Thymus
RC {ECO:0000313|EMBL:AFH33725.1};
RX PubMed=25319552; DOI=10.1186/1745-6150-9-20;
RA Zimin A.V., Cornish A.S., Maudhoo M.D., Gibbs R.M., Zhang X., Pandey S.,
RA Meehan D.T., Wipfler K., Bosinger S.E., Johnson Z.P., Tharp G.K.,
RA Marcais G., Roberts M., Ferguson B., Fox H.S., Treangen T., Salzberg S.L.,
RA Yorke J.A., Norgren R.B.Jr.;
RT "A new rhesus macaque assembly and annotation for next-generation
RT sequencing analyses.";
RL Biol. Direct 9:20-20(2014).
RN [3] {ECO:0000313|Ensembl:ENSMMUP00000028561.3}
RP IDENTIFICATION.
RC STRAIN=17573 {ECO:0000313|Ensembl:ENSMMUP00000028561.3};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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. Severing activity is not dependent on
CC tubulin acetylation or detyrosination. Microtubule severing promotes
CC reorganization of cellular microtubule arrays and the release of
CC microtubules from the centrosome following nucleation. It is critical
CC for the biogenesis and maintenance of complex microtubule arrays in
CC axons, spindles and cilia. SPAST is involved in abscission step of
CC cytokinesis and nuclear envelope reassembly during anaphase in
CC cooperation with the ESCRT-III complex. Recruited at the midbody,
CC probably by IST1, and participates in membrane fission during
CC abscission together with the ESCRT-III complex. Recruited to the
CC nuclear membrane by IST1 and mediates microtubule severing, promoting
CC nuclear envelope sealing and mitotic spindle disassembly during late
CC anaphase. Required for membrane traffic from the endoplasmic reticulum
CC (ER) to the Golgi and endosome recycling. Recruited by IST1 to
CC endosomes and regulates early endosomal tubulation and recycling by
CC mediating microtubule severing. Probably plays a role in axon growth
CC and the formation of axonal branches. {ECO:0000256|HAMAP-
CC 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:0000256|ARBA:ARBA00036378, ECO:0000256|HAMAP-
CC Rule:MF_03021};
CC -!- ACTIVITY REGULATION: Allosteric enzyme with a cooperative mechanism; at
CC least two neighbor subunits influence each other strongly in spastin
CC hexamers. Microtubule binding promotes cooperative interactions among
CC spastin subunits. {ECO:0000256|HAMAP-Rule:MF_03021}.
CC -!- SUBUNIT: Homohexamer. Mostly monomeric, but assembles into hexameric
CC structure for short periods of time. Oligomerization seems to be a
CC prerequisite for catalytic activity. Binding to ATP in a cleft between
CC two adjacent subunits stabilizes the homohexameric form. Binds to
CC microtubules at least in part via the alpha-tubulin and beta-tubulin
CC tails. The hexamer adopts a ring conformation through which
CC microtubules pass prior to being severed. Does not interact strongly
CC with tubulin heterodimers. Interacts (via MIT domain) with CHMP1B; the
CC interaction is direct. Interacts with SSNA1. Interacts with ATL1.
CC Interacts with RTN1. Interacts with ZFYVE27. Interacts with REEP1.
CC Interacts (via MIT domain) with IST1. {ECO:0000256|HAMAP-
CC Rule:MF_03021}.
CC -!- SUBCELLULAR LOCATION: Cell projection, axon
CC {ECO:0000256|ARBA:ARBA00004489}. Membrane {ECO:0000256|HAMAP-
CC Rule:MF_03021}; Peripheral membrane protein {ECO:0000256|HAMAP-
CC Rule:MF_03021}. Endoplasmic reticulum {ECO:0000256|HAMAP-
CC Rule:MF_03021}. Midbody {ECO:0000256|HAMAP-Rule:MF_03021}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000256|HAMAP-Rule:MF_03021}. Cytoplasm, cytoskeleton
CC {ECO:0000256|HAMAP-Rule:MF_03021}. Cytoplasm, perinuclear region
CC {ECO:0000256|HAMAP-Rule:MF_03021}. Nucleus {ECO:0000256|HAMAP-
CC Rule:MF_03021}. Cytoplasm, cytoskeleton, spindle {ECO:0000256|HAMAP-
CC Rule:MF_03021}. Cytoplasm {ECO:0000256|HAMAP-Rule:MF_03021}. Note=Forms
CC an intramembrane hairpin-like structure in the membrane. Localization
CC to the centrosome is independent of microtubules. Localizes to the
CC midbody of dividing cells, and this requires CHMP1B. Enriched in the
CC distal axons and branches of postmitotic neurons. Localizes to
CC endoplasmic reticulum tubular network. {ECO:0000256|HAMAP-
CC Rule:MF_03021}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. Spastin subfamily.
CC {ECO:0000256|HAMAP-Rule:MF_03021}.
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DR EMBL; JU336060; AFE79813.1; -; mRNA.
DR EMBL; JU476921; AFH33725.1; -; mRNA.
DR EMBL; JU476922; AFH33726.1; -; mRNA.
DR RefSeq; XP_014967546.1; XM_015112060.1.
DR STRING; 9544.ENSMMUP00000028561; -.
DR Ensembl; ENSMMUT00000030520.4; ENSMMUP00000028561.3; ENSMMUG00000021691.4.
DR GeneID; 706264; -.
DR KEGG; mcc:706264; -.
DR CTD; 6683; -.
DR VEuPathDB; HostDB:ENSMMUG00000021691; -.
DR VGNC; VGNC:77857; SPAST.
DR GeneTree; ENSGT00940000156258; -.
DR OMA; KSREPML; -.
DR OrthoDB; 276256at2759; -.
DR TreeFam; TF105014; -.
DR Proteomes; UP000006718; Chromosome 13.
DR Bgee; ENSMMUG00000021691; Expressed in ileum and 23 other cell types or tissues.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; 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; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000922; C:spindle pole; IEA:Ensembl.
DR GO; GO:0043014; F:alpha-tubulin binding; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008568; F:microtubule severing ATPase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008089; P:anterograde axonal transport; IEA:Ensembl.
DR GO; GO:0019896; P:axonal transport of mitochondrion; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; IEA:UniProtKB-UniRule.
DR GO; GO:0032506; P:cytokinetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IEA:UniProtKB-UniRule.
DR GO; GO:0010458; P:exit from mitosis; IEA:Ensembl.
DR GO; GO:0090148; P:membrane fission; IEA:Ensembl.
DR GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0001578; P:microtubule bundle formation; IEA:Ensembl.
DR GO; GO:0051013; P:microtubule severing; IEA:UniProtKB-UniRule.
DR GO; GO:0000281; P:mitotic cytokinesis; IEA:Ensembl.
DR GO; GO:0051228; P:mitotic spindle disassembly; IEA:Ensembl.
DR GO; GO:0031468; P:nuclear membrane reassembly; IEA:Ensembl.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IEA:Ensembl.
DR GO; GO:0031117; P:positive regulation of microtubule depolymerization; IEA:UniProtKB-UniRule.
DR GO; GO:0034214; P:protein hexamerization; IEA:UniProtKB-UniRule.
DR GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl.
DR CDD; cd02679; MIT_spastin; 1.
DR CDD; cd19524; RecA-like_spastin; 1.
DR Gene3D; 1.10.8.60; -; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR Gene3D; 1.20.58.80; Phosphotransferase system, lactose/cellobiose-type IIA subunit; 1.
DR HAMAP; MF_03021; Spastin; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR007330; MIT_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR015415; Spast_Vps4_C.
DR InterPro; IPR017179; Spastin.
DR InterPro; IPR035106; Spastin_chordate.
DR PANTHER; PTHR23074; AAA DOMAIN-CONTAINING; 1.
DR PANTHER; PTHR23074:SF86; SPASTIN; 1.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR Pfam; PF09336; Vps4_C; 1.
DR PIRSF; PIRSF037338; Spastin; 1.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00745; MIT; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR PROSITE; PS00674; AAA; 1.
PE 2: Evidence at transcript level;
KW Allosteric enzyme {ECO:0000256|HAMAP-Rule:MF_03021};
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|HAMAP-
KW Rule:MF_03021}; Cell cycle {ECO:0000256|HAMAP-Rule:MF_03021};
KW Cell division {ECO:0000256|HAMAP-Rule:MF_03021};
KW Cytoplasm {ECO:0000256|HAMAP-Rule:MF_03021};
KW Cytoskeleton {ECO:0000256|ARBA:ARBA00023212, ECO:0000256|HAMAP-
KW Rule:MF_03021}; Developmental protein {ECO:0000256|HAMAP-Rule:MF_03021};
KW Differentiation {ECO:0000256|HAMAP-Rule:MF_03021};
KW Endoplasmic reticulum {ECO:0000256|HAMAP-Rule:MF_03021};
KW Isomerase {ECO:0000256|ARBA:ARBA00023235, ECO:0000256|HAMAP-Rule:MF_03021};
KW Membrane {ECO:0000256|HAMAP-Rule:MF_03021, ECO:0000256|SAM:Phobius};
KW Microtubule {ECO:0000256|ARBA:ARBA00022701, ECO:0000256|HAMAP-
KW Rule:MF_03021}; Neurogenesis {ECO:0000256|HAMAP-Rule:MF_03021};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|HAMAP-
KW Rule:MF_03021}; Nucleus {ECO:0000256|HAMAP-Rule:MF_03021};
KW Reference proteome {ECO:0000313|Proteomes:UP000006718};
KW Transmembrane {ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|SAM:Phobius}.
FT TOPO_DOM 1..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03021"
FT TRANSMEM 57..78
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT INTRAMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03021"
FT TOPO_DOM 78..614
FT /note="Cytoplasmic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03021"
FT DOMAIN 114..192
FT /note="MIT"
FT /evidence="ECO:0000259|SMART:SM00745"
FT DOMAIN 372..508
FT /note="AAA+ ATPase"
FT /evidence="ECO:0000259|SMART:SM00382"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..260
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4..11
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03021"
FT MOTIF 59..67
FT /note="Nuclear export signal"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03021"
FT MOTIF 307..310
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03021"
FT COMPBIAS 18..43
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 287..303
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 380..387
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03021"
SQ SEQUENCE 614 AA; 66937 MW; 0E7E914077C7FC2E CRC64;
MNSPGGRGKK KGSGGASNPV PPRPPPPCLA SAPPAAGPAP PPESPHKRNL YYFSYPLFVG
FALLRLVAFH LGLLFVWLCQ RFSRALMAAK RSSGAAPAPA SAPAPVPGGE AERVRVFHKQ
AFEYISIALR IDEDEKAGQK EQAVGWYKKG IEELEKGIAV IVTGQGEQCE RARRLQAKMM
TNLVMAKDRL QLLEKMQPVL PFSKSQTDVY NDSTNVACRN GHLQSESGAV PKRKDPLTHT
SNSLPRSKTI MKTGSAGLSG HHRAPSYSGL SMVSGVKQGP GPAPTTHKGT PKTNRTNKPS
TPTTAARKKK DLKNFRNVDS NLANLIMNEI VDNGTAVKFD DIAGQDLAKQ ALQEIVILPS
LRPELFTGLR APARGLLLFG PPGNGKTMLA KAVAAESNAT FFNISAASLT SKYVGEGEKL
VRALFAVARE LQPSIIFIDE VDSLLCERRE GEHDASRRLK TEFLIEFDGV QSAGDDRVLV
MGATNRPQEL DEAVLRRFIK RVYVSLPNEE TRLLLLKNLL CKQGSPLTQK ELAQLARMTD
GYSGSDLTAL AKDAALGPIR ELKPEQVKNM SASEMRNIRL SDFTESLKKI KRSVSPQTLE
AYIRWNKDFG DTTV
//
