A0A5F8HAG2 · A0A5F8HAG2_MONDO

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

  • n ATP + n H2O + a microtubule = n ADP + n phosphate + (n+1) alpha/beta tubulin heterodimers.
    EC:5.6.1.1 (UniProtKB | ENZYME | Rhea)

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.

TypeIDPosition(s)Description
Binding site385-392ATP (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcentrosome
Cellular Componentendoplasmic reticulum
Cellular Componentendosome
Cellular Componentmembrane
Cellular Componentmicrotubule
Cellular Componentmidbody
Cellular Componentnucleus
Cellular Componentperinuclear region of cytoplasm
Cellular Componentspindle
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular Functionisomerase activity
Molecular Functionmicrotubule binding
Molecular Functionmicrotubule severing ATPase activity
Biological Processaxonogenesis
Biological Processcytokinetic process
Biological Processendoplasmic reticulum to Golgi vesicle-mediated transport
Biological Processmicrotubule severing
Biological Processpositive regulation of microtubule depolymerization
Biological Processprotein hexamerization

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Spastin
  • EC number

Gene names

    • Name
      SPAST
    • Synonyms
      SPG4

Organism names

Accessions

  • Primary accession
    A0A5F8HAG2

Proteomes

Subcellular Location

Membrane
; Peripheral membrane protein
Endoplasmic reticulum
Midbody
Cytoplasm, cytoskeleton
Cytoplasm, perinuclear region
Nucleus
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.

Features

Showing features for topological domain, intramembrane, transmembrane.

TypeIDPosition(s)Description
Topological domain1-49Cytoplasmic
Intramembrane50-70Helical
Transmembrane50-71Helical
Topological domain71-595Cytoplasmic

Keywords

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.

Family & Domains

Features

Showing features for region, motif, compositional bias, domain.

TypeIDPosition(s)Description
Region1-33Disordered
Motif4-11Nuclear localization signal
Compositional bias17-33Pro residues
Motif52-60Nuclear export signal
Domain119-197MIT
Region225-312Disordered
Compositional bias241-308Polar residues
Motif312-315Nuclear localization signal
Domain377-489AAA+ ATPase

Sequence similarities

Belongs to the AAA ATPase family. Spastin subfamily.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    595
  • Mass (Da)
    64,733
  • Last updated
    2019-12-11 v1
  • Checksum
    A6247B41AF830E45
MNSPGGRGKKKGSGTAAPAGPPPPCAGPAPPAAAGPSPHKRNLFYFSYPLLAAFALLRFVAFHLGLLFVWLCQRFSRALMAAKRSTRAAATAATGSGAAAAASASAPPPVPAGGEAERVRAFHKQAFEYISFALRIDEDEKAGQKDQAVEWYKKGIEELEKGIAVAVTGQGDQYDRARRLQAKMMTNLVMAKDRLQLLEKLQPVLQFPKSQTDVYNDSTNLTCRNGHLQSESGAVPKKKDPLTHTSNSLPRSKTVAKTTSTGLSGHHRAPSCSGLSMVSSARQGTVPATTSHKGTPKTNRTNKPSTPMTAARKKKDLKNFRNVDSNLANLIMNEIVDNGTAVKFDDIAGQELAKQALQEIVILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIEFDGVQSAGDDRVLVMGATNRPQELDEAVLRRFIKRVYVSLPNEETRLLLLKNLLSKQGSPLTQKELAQLARMTEGYSGSDLTALAKDAALGPIRELKPEQVKNMSASEMRNIRLSDFTESLKKIKRSVSPQTLEAYIRWNKDFGDTTV

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
F6WWB5F6WWB5_MONDOSPAST619
A0A5F8G2P3A0A5F8G2P3_MONDOSPAST570
A0A5F8HE08A0A5F8HE08_MONDOSPAST587

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias17-33Pro residues
Compositional bias241-308Polar residues

Keywords

Genome annotation databases

Similar Proteins

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