AC   MF_03021;
DC   Protein; auto
TR   HAMAP; MF_03021; -; 1; level=0
XX
Names: Spastin
XX
ID   SPAST
DE   RecName: Full=Spastin;
DE            EC=5.6.1.1;
case <OC:Vertebrata>
GN   Name=SPAST; Synonyms=SPG4;
else case <OC:Drosophilidae>
GN   Name=spas;
end case
XX
case <OC:Mammalia>
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.
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.
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.
CC   -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC       Endoplasmic reticulum. Midbody. Cytoplasm, cytoskeleton, microtubule
CC       organizing center, centrosome. Cytoplasm, cytoskeleton. Cytoplasm,
CC       perinuclear region. Nucleus. Cytoplasm, cytoskeleton, spindle.
CC       Cytoplasm. Note=Forms an intramembrane hairpin-like structure in the
CC       membrane. Localization to the centrosome is independent of
CC       microtubules. Localizes to the midbody of dividing cells, and this
CC       requires CHMP1B. Enriched in the distal axons and branches of
CC       postmitotic neurons. Localizes to endoplasmic reticulum tubular
CC       network.
else case <OC:Vertebrata>
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   -!- 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   -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein. Cytoplasm,
CC       cytoskeleton, microtubule organizing center, centrosome. Cytoplasm,
CC       cytoskeleton. Cytoplasm, perinuclear region. Nucleus. Note=Forms an
CC       intramembrane hairpin-like structure in the membrane.
else case <OC:Drosophilidae>
CC   -!- FUNCTION: ATP-dependent microtubule severing protein. Stimulates
CC       microtubule minus-end depolymerization and poleward microtubule flux in
CC       the mitotic spindle. Regulates microtubule stability in the
CC       neuromuscular junction synapse. Involved in lipid metabolism by
CC       regulating the size and distribution of lipid droplets. Involved in
CC       axon regeneration by regulating microtubule severing.
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. Interacts
CC       with atl; may be involved in microtubule dynamics.
CC   -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein. Cytoplasm,
CC       cytoskeleton, microtubule organizing center, centrosome. Cytoplasm,
CC       cytoskeleton. Chromosome. Lipid droplet. Note=Forms an intramembrane
CC       hairpin-like structure in the membrane. Colocalizes with cellular
CC       microtubule arrays. Localizes to chromosomes from
CC       prometaphase/metaphase to anaphase, and this requires microtubules.
CC       Localizes to discrete punctate cytoplasmic foci which may correspond to
CC       secretory vesicles.
else
CC   -!- FUNCTION: ATP-dependent microtubule severing protein. Microtubule
CC       severing may promote reorganization of cellular microtubule arrays and
CC       the release of microtubules from the microtubule organizing center
CC       following nucleation.
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   -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein. Cytoplasm,
CC       cytoskeleton, microtubule organizing center, centrosome. Cytoplasm,
CC       cytoskeleton. Note=Forms an intramembrane hairpin-like structure in the
CC       membrane.
end case
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   -!- SIMILARITY: Belongs to the AAA ATPase family. Spastin subfamily.
XX
DR   PROSITE; PS00674; AAA; 1; trigger=no
DR   Pfam; PF00004; AAA; 1; trigger=no
DR   Pfam; PF04212; MIT; 0-1; trigger=yes
DR   Pfam; PF09336; Vps4_C; 1; trigger=no
XX
KW   ATP-binding
KW   Cytoplasm
KW   Cytoskeleton
KW   Isomerase
KW   Membrane
KW   Microtubule
KW   Nucleotide-binding
case <OC:Mammalia>
KW   Allosteric enzyme
KW   Endoplasmic reticulum
end case
case <OC:Vertebrata> or <OC:Drosophilidae>
KW   Cell cycle
KW   Cell division
KW   Developmental protein
KW   Differentiation
KW   Neurogenesis
end case
case <OC:Vertebrata>
KW   Nucleus
end case
case <OC:Drosophilidae>
KW   Chromosome
KW   Lipid droplet
KW   Mitosis
end case
XX
GO   GO:0005524; F:ATP binding
GO   GO:0008017; F:microtubule binding
GO   GO:0008568; F:microtubule severing ATPase activity
GO   GO:0051013; P:microtubule severing
GO   GO:0031117; P:positive regulation of microtubule depolymerization
GO   GO:0034214; P:protein hexamerization
GO   GO:0005813; C:centrosome
GO   GO:0005737; C:cytoplasm
GO   GO:0016020; C:membrane
GO   GO:0005874; C:microtubule
GO   GO:0005819; C:spindle
case <OC:Mammalia>
GO   GO:0005768; C:endosome
GO   GO:0005783; C:endoplasmic reticulum
GO   GO:0030496; C:midbody
end case
case <OC:Vertebrata>
GO   GO:0005634; C:nucleus
GO   GO:0007409; P:axonogenesis
GO   GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport
GO   GO:0032506; P:cytokinetic process
end case
case <OC:Drosophilidae>
GO   GO:0000022; P:mitotic spindle elongation
GO   GO:0007079; P:mitotic chromosome movement towards spindle pole
GO   GO:0008344; P:adult locomotory behavior
GO   GO:0050803; P:regulation of synapse structure or activity
end case
XX
FT   From: SPAST_HUMAN (Q9UBP0)
FT   TOPO_DOM        Nter..56
FT                   /note="Cytoplasmic"
FT   INTRAMEM        57..77
FT                   /note="Helical"
FT   TOPO_DOM        78..Cter
FT                   /note="Cytoplasmic"
FT   BINDING         382..389
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   Condition: G-P-P-G-N-G-K-T
case <OC:Mammalia>
FT   MOTIF           4..11
FT                   /note="Nuclear localization signal"
FT   MOTIF           59..67
FT                   /note="Nuclear export signal"
FT   MOTIF           309..312
FT                   /note="Nuclear localization signal"
FT   Condition: R-K-K-K
end case
XX
Size: 570-827;
Related: None;
Template: Q9UBP0; Q9QYY8; B2RYN7; Q6NW58; Q8I0P1;
Scope:
 Eukaryota
Fusion:
 Nter: None
 Cter: None
Duplicate: None
Plasmid: None
Comments: None
XX
# Revision 1.24 2022/11/19
//