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HAMAP rule MF_03021

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General rule information [?]

Accession MF_03021
Dates 24-FEB-2009 (Created)
19-NOV-2022 (Last updated, Version 24)
Name Spastin
Scope(s) Eukaryota
Template(s) Q9UBP0 (SPAST_HUMAN); Q9QYY8 (SPAST_MOUSE); B2RYN7 (SPAST_RAT); Q6NW58 (SPAST_DANRE); Q8I0P1 (SPAST_DROME); [ Recover all ]
Triggered by HAMAP; MF_03021 (Get profile general information and statistics)

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier SPAST
Protein name RecName: Full=Spastin;
                 EC=5.6.1.1;
case <OC:Vertebrata>
Gene name Name=SPAST; Synonyms=SPG4;
else case <OC:Drosophilidae>
Gene name Name=spas;
end case

Comments [?]

case <OC:Mammalia>
FUNCTIONATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated. Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold. Severing activity is not dependent on tubulin acetylation or detyrosination. Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex. Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex. Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling. Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing. Probably plays a role in axon growth and the formation of axonal branches.
ACTIVITY REGULATIONAllosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers. Microtubule binding promotes cooperative interactions among spastin subunits.
SUBUNITHomohexamer. Mostly monomeric, but assembles into hexameric structure for short periods of time. Oligomerization seems to be a prerequisite for catalytic activity. Binding to ATP in a cleft between two adjacent subunits stabilizes the homohexameric form. Binds to microtubules at least in part via the alpha-tubulin and beta-tubulin tails. The hexamer adopts a ring conformation through which microtubules pass prior to being severed. Does not interact strongly with tubulin heterodimers. Interacts (via MIT domain) with CHMP1B; the interaction is direct. Interacts with SSNA1. Interacts with ATL1. Interacts with RTN1. Interacts with ZFYVE27. Interacts with REEP1. Interacts (via MIT domain) with IST1.
SUBCELLULAR LOCATIONMembrane; Peripheral membrane protein. Endoplasmic reticulum. Midbody. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton. Cytoplasm, perinuclear region. Nucleus. Cytoplasm, cytoskeleton, spindle. Cytoplasm. Note=Forms an intramembrane hairpin-like structure in the membrane. Localization to the centrosome is independent of microtubules. Localizes to the midbody of dividing cells, and this requires CHMP1B. Enriched in the distal axons and branches of postmitotic neurons. Localizes to endoplasmic reticulum tubular network.
else case <OC:Vertebrata>
FUNCTIONATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated. Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold. Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and for completion of the abscission stage of cytokinesis. Also plays a role in axon growth and the formation of axonal branches.
SUBUNITHomohexamer. The homohexamer is stabilized by ATP-binding. The homohexamer may adopt a ring conformation through which microtubules pass prior to being severed. Interacts with microtubules.
SUBCELLULAR LOCATIONMembrane; Peripheral membrane protein. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton. Cytoplasm, perinuclear region. Nucleus. Note=Forms an intramembrane hairpin-like structure in the membrane.
else case <OC:Drosophilidae>
FUNCTIONATP-dependent microtubule severing protein. Stimulates microtubule minus-end depolymerization and poleward microtubule flux in the mitotic spindle. Regulates microtubule stability in the neuromuscular junction synapse. Involved in lipid metabolism by regulating the size and distribution of lipid droplets. Involved in axon regeneration by regulating microtubule severing.
SUBUNITHomohexamer. The homohexamer is stabilized by ATP-binding. The homohexamer may adopt a ring conformation through which microtubules pass prior to being severed. Interacts with microtubules. Interacts with atl; may be involved in microtubule dynamics.
SUBCELLULAR LOCATIONMembrane; Peripheral membrane protein. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton. Chromosome. Lipid droplet. Note=Forms an intramembrane hairpin-like structure in the membrane. Colocalizes with cellular microtubule arrays. Localizes to chromosomes from prometaphase/metaphase to anaphase, and this requires microtubules. Localizes to discrete punctate cytoplasmic foci which may correspond to secretory vesicles.
else
FUNCTIONATP-dependent microtubule severing protein. Microtubule severing may promote reorganization of cellular microtubule arrays and the release of microtubules from the microtubule organizing center following nucleation.
SUBUNITHomohexamer. The homohexamer is stabilized by ATP-binding. The homohexamer may adopt a ring conformation through which microtubules pass prior to being severed. Interacts with microtubules.
SUBCELLULAR LOCATIONMembrane; Peripheral membrane protein. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton. Note=Forms an intramembrane hairpin-like structure in the membrane.
end case
CATALYTIC ACTIVITY Reaction=n ATP + n H2O + a microtubule = n ADP + n phosphate + (n+1) alpha/beta tubulin heterodimers.; EC=5.6.1.1;
SIMILARITYBelongs to the AAA ATPase family. Spastin subfamily.

Keywords [?]

ATP-binding
Cytoplasm
Cytoskeleton
Isomerase
Membrane
Microtubule
Nucleotide-binding
case <OC:Mammalia>
Allosteric enzyme
Endoplasmic reticulum
end case
case <OC:Vertebrata> or <OC:Drosophilidae>
Cell cycle
Cell division
Developmental protein
Differentiation
Neurogenesis
end case
case <OC:Vertebrata>
Nucleus
end case
case <OC:Drosophilidae>
Chromosome
Lipid droplet
Mitosis
end case

Gene Ontology [?]

GO:0005524; Molecular function:ATP binding
GO:0008017; Molecular function:microtubule binding
GO:0008568; Molecular function:microtubule severing ATPase activity
GO:0051013; Biological process:microtubule severing
GO:0031117; Biological process:positive regulation of microtubule depolymerization
GO:0034214; Biological process:protein hexamerization
GO:0005813; Cellular component:centrosome
GO:0005737; Cellular component:cytoplasm
GO:0016020; Cellular component:membrane
GO:0005874; Cellular component:microtubule
GO:0005819; Cellular component:spindle
case <OCellular component:Mammalia>
GO:0005768; Cellular component:endosome
GO:0005783; Cellular component:endoplasmic reticulum
GO:0030496; Cellular component:midbody
end case
case <OCellular component:Vertebrata>
GO:0005634; Cellular component:nucleus
GO:0007409; Biological process:axonogenesis
GO:0006888; Biological process:endoplasmic reticulum to Golgi vesicle-mediated transport
GO:0032506; Biological process:cytokinetic process
end case
case <OCellular component:Drosophilidae>
GO:0000022; Biological process:mitotic spindle elongation
GO:0007079; Biological process:mitotic chromosome movement towards spindle pole
GO:0008344; Biological process:adult locomotory behavior
GO:0050803; Biological process:regulation of synapse structure or activity
end case

Cross-references [?]

PROSITE PS00674; AAA; 1;
Pfam PF00004; AAA; 1;
Pfam PF04212; MIT; 0-1;
Pfam PF09336; Vps4_C; 1;

Features [?]

From: SPAST_HUMAN (Q9UBP0)
Key From To Description Tag Condition FTGroup
TOPO_DOM Nter 56 /note="Cytoplasmic"
INTRAMEM 57 77 /note="Helical"
TOPO_DOM 78 Cter /note="Cytoplasmic"
BINDING 382 389 /ligand="ATP"
/ligand_id="ChEBI:CHEBI:30616"
G-P-P-G-N-G-K-T
case <OC:Mammalia>
MOTIF 4 11 /note="Nuclear localization signal"
MOTIF 59 67 /note="Nuclear export signal"
MOTIF 309 312 /note="Nuclear localization signal" R-K-K-K
end case

Additional information [?]

Size range 570-827 amino acids
Related rules None
Fusion Nter: None Cter: None



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