SPAST_PIG
ID SPAST_PIG Reviewed; 616 AA.
AC Q719N1; F1S3Z2;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 3.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-616.
RX PubMed=17868079; DOI=10.1111/j.1439-0388.2007.00673.x;
RA Genini S., Kratzsch A., Korczak B., Neuenschwander S., Brenig B., Jorg H.,
RA Burgi E., Ossent P., Stranzinger G., Vogeli P.;
RT "Analysis and mapping of CACNB4, CHRNA1, KCNJ3, SCN2A and SPG4,
RT physiological candidate genes for porcine congenital progressive ataxia and
RT spastic paresis.";
RL J. Anim. Breed. Genet. 124:269-276(2007).
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 -!- SIMILARITY: Belongs to the AAA ATPase family. Spastin subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03021}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ11224.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CU694619; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=FP583344; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CU694619; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP583344; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF540879; AAQ11224.1; ALT_INIT; mRNA.
DR RefSeq; NP_998914.1; NM_213749.1.
DR AlphaFoldDB; Q719N1; -.
DR SMR; Q719N1; -.
DR STRING; 9823.ENSSSCP00000009083; -.
DR PaxDb; Q719N1; -.
DR PeptideAtlas; Q719N1; -.
DR PRIDE; Q719N1; -.
DR Ensembl; ENSSSCT00015075466; ENSSSCP00015030272; ENSSSCG00015056092.
DR Ensembl; ENSSSCT00030045517; ENSSSCP00030020483; ENSSSCG00030032740.
DR Ensembl; ENSSSCT00040010438; ENSSSCP00040004060; ENSSSCG00040007869.
DR Ensembl; ENSSSCT00045026529; ENSSSCP00045018309; ENSSSCG00045015548.
DR Ensembl; ENSSSCT00050065540; ENSSSCP00050028228; ENSSSCG00050048078.
DR Ensembl; ENSSSCT00055023599; ENSSSCP00055018661; ENSSSCG00055011862.
DR Ensembl; ENSSSCT00060065463; ENSSSCP00060028026; ENSSSCG00060048175.
DR GeneID; 396584; -.
DR KEGG; ssc:396584; -.
DR CTD; 6683; -.
DR eggNOG; KOG0740; Eukaryota.
DR InParanoid; Q719N1; -.
DR OrthoDB; 1176820at2759; -.
DR TreeFam; TF105014; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
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: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: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: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 2: Evidence at transcript level;
KW Allosteric enzyme; ATP-binding; Cell cycle; Cell division; Cell projection;
KW Cytoplasm; Cytoskeleton; Developmental protein; Differentiation;
KW Endoplasmic reticulum; Isomerase; Membrane; Microtubule; Neurogenesis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..616
FT /note="Spastin"
FT /id="PRO_0000367134"
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..616
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
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:0000250|UniProtKB:Q9UBP0"
FT REGION 1..194
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..44
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 112..196
FT /note="Sufficient for interaction with CHMP1B"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 114..200
FT /note="Required for interaction with microtubules"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 223..266
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 226..328
FT /note="Sufficient for interaction with microtubules"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 228..616
FT /note="Sufficient for microtubule severing"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 270..328
FT /note="Required for interaction with microtubules and
FT microtubule severing"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 278..311
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 310..312
FT /note="Required for interaction with microtubules"
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 309..312
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT COMPBIAS 17..44
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..264
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 MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT MOD_RES 306
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT MOD_RES 597
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
SQ SEQUENCE 616 AA; 67713 MW; DE982CF334F790D9 CRC64;
MNSPGGRGKK KGSGGPSSPV PPRPPPPCLA SSRPAPRPAP PPQSPHKRNL YYFSYPLFLG
FALLRLVAFH LGLLFVWLCQ RFSRALMAAK RSSRAAPAPA SASPPAPVPG GEVERVRAFH
KQAFEYISVA LRIDEDEKVG QKEQAVEWYK KGIEELEKGI AVVVTGQGEQ CERARRLQAK
MMTNLVMAKD RLQLLEKLQP VLQFSKSQMD VYNDSTNLTC RNGHLQSESG AVPKRKDPLT
HPSNSLPRSK AIMKTGSTGL SGHHRAPSCS GLSIVSGMRQ GPGPTTATHK STPKTNRTNK
PSTPTTAPRK KKDLKNFRNV DSNLANFIMN EIVDNGTAVK FDDIAGQELA KQALQEIVIL
PSLRPELFTG LRAPARGLLL FGPPGNGKTM LAKAVAAESN ATFFNISAAS LTSKYVGEGE
KLVRALFAVA RELQPSIIFI DEVDSLLRER REGEHDASRR LKTEFLIEFD GVQSAGDDRV
LVMGATNRPQ ELDEAVLRRF IKRVYVSLPN EETRLLLLKN LLCKQGSPLT QKELAQLARL
TDGYSGSDLT ALAKDAALGP IRELKPEQVK NMSASEMRNI RLSDFTESLK KIKRSVSPQT
LEAYIRWNKD FGDTTV
