HAMAP rule MF_03021
General rule information
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| 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
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Identifier, protein and gene names
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| 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
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| case <OC:Mammalia> | |
| FUNCTION | ATP-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 REGULATION | Allosteric 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. |
| SUBUNIT | Homohexamer. 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 LOCATION | Membrane; 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> | |
| FUNCTION | ATP-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. |
| SUBUNIT | Homohexamer. 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 LOCATION | Membrane; 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> | |
| FUNCTION | ATP-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. |
| SUBUNIT | Homohexamer. 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 LOCATION | Membrane; 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 | |
| FUNCTION | ATP-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. |
| SUBUNIT | Homohexamer. 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 LOCATION | Membrane; 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; |
| SIMILARITY | Belongs to the AAA ATPase family. Spastin subfamily. |
Keywords
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| 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
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| 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
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Features
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| 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
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| Size range | 570-827 amino acids |
| Related rules |
None |
| Fusion | Nter: None Cter: None |