SPAST_RAT
ID SPAST_RAT Reviewed; 581 AA.
AC B2RYN7;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 99.
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}; Synonyms=Spg4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP FUNCTION.
RX PubMed=18234839; DOI=10.1091/mbc.e07-09-0878;
RA Yu W., Qiang L., Solowska J.M., Karabay A., Korulu S., Baas P.W.;
RT "The microtubule-severing proteins spastin and katanin participate
RT differently in the formation of axonal branches.";
RL Mol. Biol. Cell 19:1485-1498(2008).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (By similarity). Probably plays a role
CC in axon growth and the formation of axonal branches (PubMed:18234839).
CC {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:18234839}.
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}.
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DR EMBL; BC166846; AAI66846.1; -; mRNA.
DR RefSeq; NP_001102172.2; NM_001108702.2.
DR AlphaFoldDB; B2RYN7; -.
DR SMR; B2RYN7; -.
DR IntAct; B2RYN7; 1.
DR STRING; 10116.ENSRNOP00000033763; -.
DR iPTMnet; B2RYN7; -.
DR PhosphoSitePlus; B2RYN7; -.
DR PaxDb; B2RYN7; -.
DR PeptideAtlas; B2RYN7; -.
DR PRIDE; B2RYN7; -.
DR GeneID; 362700; -.
DR KEGG; rno:362700; -.
DR UCSC; RGD:1308494; rat.
DR CTD; 6683; -.
DR RGD; 1308494; Spast.
DR VEuPathDB; HostDB:ENSRNOG00000027136; -.
DR eggNOG; KOG0740; Eukaryota.
DR InParanoid; B2RYN7; -.
DR OMA; CERKENE; -.
DR OrthoDB; 1176820at2759; -.
DR Reactome; R-RNO-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR PRO; PR:B2RYN7; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000027136; Expressed in testis and 20 other tissues.
DR ExpressionAtlas; B2RYN7; baseline and differential.
DR Genevisible; B2RYN7; RN.
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:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
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; ISO:RGD.
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; ISO:RGD.
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; ISO:RGD.
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 Endoplasmic reticulum; Isomerase; Membrane; Microtubule; Neurogenesis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..581
FT /note="Spastin"
FT /id="PRO_0000367135"
FT TOPO_DOM 1..54
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT INTRAMEM 55..75
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT TOPO_DOM 76..581
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT DOMAIN 118..192
FT /note="MIT"
FT /evidence="ECO:0000255"
FT REGION 1..265
FT /note="Required for interaction with RTN1"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 1..191
FT /note="Required for midbody localization"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 1..78
FT /note="Required for interaction with ATL1"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 1..48
FT /note="Required for nuclear localization"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 48..85
FT /note="Required for interaction with SSNA1 and
FT microtubules"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 90..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..581
FT /note="Sufficient for microtubule severing"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT REGION 195..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..293
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 57..65
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT MOTIF 274..277
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT COMPBIAS 18..39
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..229
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 251..270
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 347..354
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03021"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT MOD_RES 271
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP0"
SQ SEQUENCE 581 AA; 63022 MW; A404A3B676F9F224 CRC64;
MSSPAGRRKK KGSGGASPAP ARPPPPAAVP APAAGPAPAP GSPHKRNLYY FSYPLVVGFA
LLRLLACHLG LLFVWLCQRF SRALMAAKRS SGTAPAPASP STPAPGPGGE AESVRVFHKQ
AFEYISIALR IDEEEKGQKE QAVEWYKKGI EELEKGIAVI VTGQGEQYER ARRLQAKMMT
NLVMAKDRLQ LLESGAVPKK KDPLTHASNS LPRSKTVMKS GSTGLSGHHR APSCSGLSMV
SGARPGSGPA ATTHKGTSKP NRTNKPSTPT TAVRKKKDLK NFRNVDSNLA NLIMNEIVDN
GTAVKFDDIA GQELAKQALQ EIVILPSLRP ELFTGLRAPA RGLLLFGPPG NGKTMLAKAV
AAESNATFFN ISAASLTSKY VGEGEKLVRA LFAVARELQP SIIFIDEVDS LLCERREGEH
DASRRLKTEF LIEFDGVQSA GDDRVLVMGA TNRPQELDEA VLRRFIKRVY VSLPNEETRL
LLLKNLLCKQ GSPLTQKELA QLARMTDGYS GSDLTALAKD AALGPIRELK PEQVKNMSAS
EMRNIRLSDF TESLKKIKRS VSPQTLEAYI RWNKDFGDTT V
