A0A5F8HAG2 · A0A5F8HAG2_MONDO
- ProteinSpastin
- GeneSPAST
- StatusUniProtKB unreviewed (TrEMBL)
- Amino acids595 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
Function
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.
Catalytic activity
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.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | centrosome | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endosome | |
Cellular Component | membrane | |
Cellular Component | microtubule | |
Cellular Component | midbody | |
Cellular Component | nucleus | |
Cellular Component | perinuclear region of cytoplasm | |
Cellular Component | spindle | |
Molecular Function | ATP binding | |
Molecular Function | ATP hydrolysis activity | |
Molecular Function | isomerase activity | |
Molecular Function | microtubule binding | |
Molecular Function | microtubule severing ATPase activity | |
Biological Process | axonogenesis | |
Biological Process | cytokinetic process | |
Biological Process | endoplasmic reticulum to Golgi vesicle-mediated transport | |
Biological Process | microtubule severing | |
Biological Process | positive regulation of microtubule depolymerization | |
Biological Process | protein hexamerization |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSpastin
- EC number
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Metatheria > Didelphimorphia > Didelphidae > Monodelphis
Accessions
- Primary accessionA0A5F8HAG2
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Peripheral membrane protein
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.
Features
Showing features for topological domain, intramembrane, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-49 | Cytoplasmic | ||||
Sequence: MNSPGGRGKKKGSGTAAPAGPPPPCAGPAPPAAAGPSPHKRNLFYFSYP | ||||||
Intramembrane | 50-70 | Helical | ||||
Sequence: LLAAFALLRFVAFHLGLLFVW | ||||||
Transmembrane | 50-71 | Helical | ||||
Sequence: LLAAFALLRFVAFHLGLLFVWL | ||||||
Topological domain | 71-595 | Cytoplasmic | ||||
Sequence: LCQRFSRALMAAKRSTRAAATAATGSGAAAAASASAPPPVPAGGEAERVRAFHKQAFEYISFALRIDEDEKAGQKDQAVEWYKKGIEELEKGIAVAVTGQGDQYDRARRLQAKMMTNLVMAKDRLQLLEKLQPVLQFPKSQTDVYNDSTNLTCRNGHLQSESGAVPKKKDPLTHTSNSLPRSKTVAKTTSTGLSGHHRAPSCSGLSMVSSARQGTVPATTSHKGTPKTNRTNKPSTPMTAARKKKDLKNFRNVDSNLANLIMNEIVDNGTAVKFDDIAGQELAKQALQEIVILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIEFDGVQSAGDDRVLVMGATNRPQELDEAVLRRFIKRVYVSLPNEETRLLLLKNLLSKQGSPLTQKELAQLARMTEGYSGSDLTALAKDAALGPIRELKPEQVKNMSASEMRNIRLSDFTESLKKIKRSVSPQTLEAYIRWNKDFGDTTV |
Keywords
- Cellular component
Expression
Gene expression databases
Interaction
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.
Structure
Family & Domains
Features
Showing features for region, motif, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-33 | Disordered | ||||
Sequence: MNSPGGRGKKKGSGTAAPAGPPPPCAGPAPPAA | ||||||
Motif | 4-11 | Nuclear localization signal | ||||
Sequence: PGGRGKKK | ||||||
Compositional bias | 17-33 | Pro residues | ||||
Sequence: APAGPPPPCAGPAPPAA | ||||||
Motif | 52-60 | Nuclear export signal | ||||
Sequence: AAFALLRFV | ||||||
Domain | 119-197 | MIT | ||||
Sequence: VRAFHKQAFEYISFALRIDEDEKAGQKDQAVEWYKKGIEELEKGIAVAVTGQGDQYDRARRLQAKMMTNLVMAKDRLQL | ||||||
Region | 225-312 | Disordered | ||||
Sequence: NGHLQSESGAVPKKKDPLTHTSNSLPRSKTVAKTTSTGLSGHHRAPSCSGLSMVSSARQGTVPATTSHKGTPKTNRTNKPSTPMTAAR | ||||||
Compositional bias | 241-308 | Polar residues | ||||
Sequence: PLTHTSNSLPRSKTVAKTTSTGLSGHHRAPSCSGLSMVSSARQGTVPATTSHKGTPKTNRTNKPSTPM | ||||||
Motif | 312-315 | Nuclear localization signal | ||||
Sequence: RKKK | ||||||
Domain | 377-489 | AAA+ ATPase | ||||
Sequence: PARGLLLFGPPGNGKTMLVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIEFDGVQSAGDDRVLVMGATNRPQELDEAVLRRFIKRVYVSLPN |
Sequence similarities
Belongs to the AAA ATPase family. Spastin subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length595
- Mass (Da)64,733
- Last updated2019-12-11 v1
- ChecksumA6247B41AF830E45
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F6WWB5 | F6WWB5_MONDO | SPAST | 619 | ||
A0A5F8G2P3 | A0A5F8G2P3_MONDO | SPAST | 570 | ||
A0A5F8HE08 | A0A5F8HE08_MONDO | SPAST | 587 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 17-33 | Pro residues | ||||
Sequence: APAGPPPPCAGPAPPAA | ||||||
Compositional bias | 241-308 | Polar residues | ||||
Sequence: PLTHTSNSLPRSKTVAKTTSTGLSGHHRAPSCSGLSMVSSARQGTVPATTSHKGTPKTNRTNKPSTPM |
Keywords
- Technical term