SPAST_BOVIN
ID SPAST_BOVIN Reviewed; 614 AA.
AC A2VDN5;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 111.
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};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Brain cortex;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INVOLVEMENT IN BSD, AND VARIANT BSD GLN-560.
RX PubMed=19714378; DOI=10.1007/s10048-009-0214-0;
RA Thomsen B., Nissen P.H., Agerholm J.S., Bendixen C.;
RT "Congenital bovine spinal dysmyelination is caused by a missense mutation
RT in the SPAST gene.";
RL Neurogenetics 11:175-183(2010).
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:0000255|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:0000255|HAMAP-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:0000255|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:0000255|HAMAP-
CC Rule:MF_03021}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255|HAMAP-Rule:MF_03021};
CC Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_03021}.
CC Endoplasmic reticulum {ECO:0000255|HAMAP-Rule:MF_03021}. Midbody
CC {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000255|HAMAP-Rule:MF_03021}.
CC Cytoplasm, cytoskeleton {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm,
CC perinuclear region {ECO:0000255|HAMAP-Rule:MF_03021}. Nucleus
CC {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000255|HAMAP-Rule:MF_03021}. Cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_03021}. Cell projection, axon {ECO:0000250|UniProtKB:Q9UBP0}.
CC Note=Forms an intramembrane hairpin-like structure in the membrane.
CC Localization to the centrosome is independent of microtubules.
CC Localizes to the midbody of dividing cells, and this requires CHMP1B.
CC Enriched in the distal axons and branches of postmitotic neurons.
CC Localizes to endoplasmic reticulum tubular network. Mainly nuclear in
CC interphase cells and becomes associated with the centrosomes, spindle
CC microtubules, midzone and finally the midbody during cell division (By
CC similarity). {ECO:0000250|UniProtKB:Q9UBP0, ECO:0000255|HAMAP-
CC Rule:MF_03021}.
CC -!- DISEASE: Note=Defects in SPAST are the cause of bovine spinal
CC dysmyelination (BSD), a neurodegenerative disorder characterized by
CC pathological changes of the myelin sheaths in the spinal cord. Defects
CC appear immediately at birth and include lateral recumbency with slight
CC to moderate opisthotonos, body tremor, and spastic extension of the
CC limbs. General muscle atrophy due to denervation occurs to variable
CC degrees and is most obvious in the hind limbs. BSD is a longstanding
CC problem in the American Brown Swiss (ABS) breed and in several European
CC cattle breeds upgraded with ABS. The morphological cause of the
CC phenotype is bilateral symmetrical hypo- and demyelination of axons in
CC the cervical and thoracic segments of the spinal cord. The disease is
CC caused by variants affecting the gene represented in this entry.
CC {ECO:0000269|PubMed:19714378}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. Spastin subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03021}.
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DR EMBL; BC133327; AAI33328.1; -; mRNA.
DR RefSeq; NP_001075060.1; NM_001081591.1.
DR AlphaFoldDB; A2VDN5; -.
DR SMR; A2VDN5; -.
DR STRING; 9913.ENSBTAP00000044166; -.
DR PaxDb; A2VDN5; -.
DR PRIDE; A2VDN5; -.
DR Ensembl; ENSBTAT00000046919; ENSBTAP00000044166; ENSBTAG00000021694.
DR Ensembl; ENSBTAT00000069887; ENSBTAP00000058511; ENSBTAG00000021694.
DR GeneID; 521442; -.
DR KEGG; bta:521442; -.
DR CTD; 6683; -.
DR VEuPathDB; HostDB:ENSBTAG00000021694; -.
DR VGNC; VGNC:35174; SPAST.
DR eggNOG; KOG0740; Eukaryota.
DR GeneTree; ENSGT00940000156258; -.
DR HOGENOM; CLU_000688_21_5_1; -.
DR InParanoid; A2VDN5; -.
DR OMA; GMTNEPM; -.
DR OrthoDB; 1176820at2759; -.
DR TreeFam; TF105014; -.
DR Proteomes; UP000009136; Chromosome 11.
DR Bgee; ENSBTAG00000021694; Expressed in spermatocyte and 106 other tissues.
DR ExpressionAtlas; A2VDN5; baseline and differential.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-UniRule.
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: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:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000922; C:spindle pole; ISS:UniProtKB.
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:0019896; P:axonal transport of mitochondrion; ISS:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; IEA:UniProtKB-UniRule.
DR GO; GO:0032506; P:cytokinetic process; ISS:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; ISS:UniProtKB.
DR GO; GO:0010458; P:exit from mitosis; ISS:UniProtKB.
DR GO; GO:0090148; P:membrane fission; ISS:UniProtKB.
DR GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0001578; P:microtubule bundle formation; ISS:UniProtKB.
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:0031468; P:nuclear membrane reassembly; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; ISS: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 Allosteric enzyme; ATP-binding; Cell cycle; Cell division; Cell projection;
KW Cytoplasm; Cytoskeleton; Developmental protein; Differentiation;
KW Disease variant; Endoplasmic reticulum; Isomerase; Membrane; Microtubule;
KW Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..614
FT /note="Spastin"
FT /id="PRO_0000367133"
FT TOPO_DOM 1..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT INTRAMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT TOPO_DOM 78..614
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT DOMAIN 118..193
FT /note="MIT"
FT /evidence="ECO:0000255"
FT REGION 1..298
FT /note="Required for interaction with RTN1"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 1..192
FT /note="Required for midbody localization"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 1..80
FT /note="Required for interaction with ATL1"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 1..50
FT /note="Required for nuclear localization"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 1..45
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:0000250|UniProtKB:Q9UBP0"
FT REGION 110..194
FT /note="Sufficient for interaction with CHMP1B"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 112..198
FT /note="Required for interaction with microtubules"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 220..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 226..614
FT /note="Sufficient for microtubule severing"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 268..326
FT /note="Required for interaction with microtubules and
FT microtubule severing"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT MOTIF 4..11
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT MOTIF 59..67
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT MOTIF 307..310
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT COMPBIAS 17..45
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..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:0000255|HAMAP-Rule:MF_03021"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT MOD_RES 304
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT MOD_RES 595
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT VARIANT 560
FT /note="R -> Q (in BSD)"
FT /evidence="ECO:0000269|PubMed:19714378"
SQ SEQUENCE 614 AA; 67225 MW; B284B6EBF04D358F CRC64;
MNSPGGRGKK KGSGGPSSPV PPRPPPPCQA RSRPAPKPAP PPQSPHKRNL YYFSYPLFLG
FALLRLVAFH LGLLFVWLCQ RFSRALMAAK RSSGAAPASA SPPAPVPGGE AERVRAFHKQ
AFEYISVALR IDEDEKVGQK DQAVEWYKKG IEELEKGIAV VVTGQGEQCE RARRLQAKMM
TNLVMAKDRL QLLEKLQPSL QFSKSQTDVY NDSTNLTCRN GHLQSESGAV PKRKDPLTHA
SNSLPRSKTV MKTGPTGLSG HHRAPSCSGL SMVSGVRQGP GSAAATHKST PKTNRTNKPS
TPTTAARKKK DLKNFRNVDS NLANLIMNEI VDNGTAVKFD DIAGQELAKQ ALQEIVILPS
LRPELFTGLR APARGLLLFG PPGNGKTMLA KAVAAESNAT FFNISAASLT SKYVGEGEKL
VRALFAVARE LQPSIIFIDE VDSLLCERRE GEHDASRRLK TEFLIEFDGV QSAGDDRVLV
MGATNRPQEL DEAVLRRFTK RVYVSLPNEE TRLLLLKNLL CKQGSPLTQK ELAQLARMTN
GYSGSDLTAL AKDAALGPIR ELKPEQVKNM SASEMRNIRL SDFTESLKKI KRSVSPQTLE
AYIRWNKDFG DTTV
