Tbio SPAST Spastin

Protein Summary

Description

ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, PubMed:20530212, PubMed:22637577, PubMed:26875866). 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 (PubMed:26875866). Severing activity is not dependent on tubulin acetylation or detyrosination (PubMed:26875866). 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 (PubMed:19000169, PubMed:21310966, PubMed:26040712). Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex (PubMed:21310966). Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling (PubMed:23897888). Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing (PubMed:23897888). Probably plays a role in axon growth and the formation of axonal branches (PubMed:15716377). Isoform 1: Involved in lipid metabolism by regulating the size and distribution of lipid droplets. This gene encodes a member of the AAA (ATPases associated with a variety of cellular activities) protein family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. The use of alternative translational initiation sites in this gene results in a single transcript variant that can produce isoforms that differ in the length of their N-terminus and which thereby differ in the efficiency of their export from the nucleus to the cytoplasm. In addition, alternative splicing results in multiple transcript variants that encode isoforms that differ in other protein regions as well. One isoform of this gene has been shown to be a microtubule-severing enzyme that regulates microtubule abundance, mobility, and plus-end distribution. Mutations in this gene cause the most frequent form of autosomal dominant spastic paraplegia 4. [provided by RefSeq, May 2018]

Uniprot Accession IDs

• Q9UBP0
• A7E2A7
• Q9UPR9

Gene Name

• SPAST

Ensembl ID

• ENST00000315285
• ENSP00000320885
• ENSG00000021574
• ENST00000345662
• ENSP00000340817
• ENST00000615843
• ENSP00000480893
• ENST00000642999
• ENSP00000496589
• ENST00000644954
• ENSP00000494312
• ENST00000646571
• ENSP00000495015

Symbol

• ADPSP
• FSP2
• KIAA1083
• SPG4
• FSP2
• SPG4
• ADPSP

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.99
histone modification site profile	0.89
biological term	0.87
protein domain	0.85
virus perturbation	0.85

Protein Classes

PANTHER Classes

Protein / Cytoskeletal Protein / Microtubule Family Cytoskeletal Protein / Non-motor Microtubule Binding Protein / Spastin

DTO Classes

Protein / Cellular Structure / Microtubule Family Cytoskeletal Protein / Non-motor Microtubule Binding Protein / Spastin

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 517.04   (req: < 5)

Gene RIFs: 169   (req: <= 3)

Antibodies: 214   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 517.04   (req: >= 5)

Gene RIFs: 169   (req: > 3)

Antibodies: 214   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 27

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0