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Aliases for SPAST Gene

Aliases for SPAST Gene

  • Spastin 2 3
  • SPG4 3 4 6
  • Spastic Paraplegia 4 (Autosomal Dominant; Spastin) 2 3
  • Spastic Paraplegia 4 Protein 3 4
  • ADPSP 3 4
  • FSP2 3 4
  • EC 3.6.1.3 64
  • EC 3.6.4.3 4
  • KIAA1083 4

External Ids for SPAST Gene

Previous Symbols for SPAST Gene

  • SPG4

Summaries for SPAST Gene

Entrez Gene Summary for SPAST Gene

  • 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 encoded ATPase may be involved in the assembly or function of nuclear protein complexes. Two transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described but their full length sequences have not been determined. Mutations associated with this gene cause the most frequent form of autosomal dominant spastic paraplegia 4. [provided by RefSeq, Jul 2008]

GeneCards Summary for SPAST Gene

SPAST (Spastin) is a Protein Coding gene. Diseases associated with SPAST include spastic paraplegia 4 and spastic paraplegia 4, autosomal dominant. GO annotations related to this gene include microtubule binding and alpha-tubulin binding. An important paralog of this gene is FIGN.

UniProtKB/Swiss-Prot for SPAST Gene

  • ATP-dependent microtubule severing protein. Microtubule severing may promote 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. May also play a role in axon growth and the formation of axonal branches.

Gene Wiki entry for SPAST Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SPAST Gene

Genomics for SPAST Gene

Genomic Location for SPAST Gene

Start:
32,063,592 bp from pter
End:
32,157,637 bp from pter
Size:
94,046 bases
Orientation:
Plus strand

Genomic View for SPAST Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SPAST Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPAST Gene

Regulatory Elements for SPAST Gene

Proteins for SPAST Gene

  • Protein details for SPAST Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UBP0-SPAST_HUMAN
    Recommended name:
    Spastin
    Protein Accession:
    Q9UBP0
    Secondary Accessions:
    • A7E2A7
    • Q9UPR9

    Protein attributes for SPAST Gene

    Size:
    616 amino acids
    Molecular mass:
    67197 Da
    Quaternary structure:
    • 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 ATL1, RTN1, SSNA1 and ZFYVE27. Isoform 1 but not isoform 3 interacts with RTN2. Interacts with REEP1.

    Three dimensional structures from OCA and Proteopedia for SPAST Gene

    Alternative splice isoforms for SPAST Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SPAST Gene

Proteomics data for SPAST Gene at MOPED

Post-translational modifications for SPAST Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SPAST Gene

Domains for SPAST Gene

Gene Families for SPAST Gene

HGNC:
  • AATP :ATPases / AAA-type

Protein Domains for SPAST Gene

UniProtKB/Swiss-Prot:

SPAST_HUMAN
Domain:
  • Contains 1 MIT domain.:
    • Q9UBP0
Family:
  • Belongs to the AAA ATPase family. Spastin subfamily.:
    • Q9UBP0
genes like me logo Genes that share domains with SPAST: view

Function for SPAST Gene

Molecular function for SPAST Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties: Kinetic parameters: KM=0.45 mM for ATP {ECO:0000269 PubMed:15716377, ECO:0000269 PubMed:17389232, ECO:0000269 PubMed:22637577}; Vmax=1.2 nmol/min/ug enzyme {ECO:0000269 PubMed:15716377, ECO:0000269 PubMed:17389232, ECO:0000269 PubMed:22637577}; Note=Kinetic parameters shown are for full length enzyme. N- terminally truncated spastin (residues 228-616), which has been shown to exhibit full severing activity, shows a basal ATP turnover rate of 0.78 sec(-1) in the absence of microtubules, a KM of 0.16 mM for ATP, and the ATP turnover rate is extrapolated to 3.83 sec(-1) in the presence of microtubules. ATPase activity shows non-Michaelis-Menten kinetics in the presence of microtubules, but is close to non-cooperative behavior in their absence (PubMed:22637577). {ECO:0000269 PubMed:22637577};
UniProtKB/Swiss-Prot CatalyticActivity: ATP + H(2)O = ADP + phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation: 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.
UniProtKB/Swiss-Prot Function: ATP-dependent microtubule severing protein. Microtubule severing may promote 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. May also play a role in axon growth and the formation of axonal branches.

Enzyme Numbers (IUBMB) for SPAST Gene

Gene Ontology (GO) - Molecular Function for SPAST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16815977
GO:0005524 ATP binding IEA --
GO:0008017 microtubule binding IDA 15716377
GO:0008568 microtubule-severing ATPase activity IDA 15716377
GO:0009378 four-way junction helicase activity --
genes like me logo Genes that share ontologies with SPAST: view
genes like me logo Genes that share phenotypes with SPAST: view

Animal Models for SPAST Gene

MGI Knock Outs for SPAST:

miRNA for SPAST Gene

miRTarBase miRNAs that target SPAST

No data available for Transcription Factor Targeting and HOMER Transcription for SPAST Gene

Localization for SPAST Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPAST Gene

Membrane; Single-pass membrane protein. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton. Cytoplasm, perinuclear region. Endoplasmic reticulum. Endosome. Nucleus. Cytoplasm, cytoskeleton, spindle. Note=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. Isoform 3 is the main endosomal form.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SPAST Gene COMPARTMENTS Subcellular localization image for SPAST gene
Compartment Confidence
cytoskeleton 5
endoplasmic reticulum 5
endosome 5
nucleus 5
cytosol 3
mitochondrion 1
peroxisome 1
plasma membrane 1

Gene Ontology (GO) - Cellular Components for SPAST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 16026783
GO:0005737 cytoplasm IDA 16026783
GO:0005768 colocalizes_with endosome IDA 19000169
GO:0005783 colocalizes_with endoplasmic reticulum IDA 19000169
GO:0005813 centrosome IEA --
genes like me logo Genes that share ontologies with SPAST: view

Pathways for SPAST Gene

SuperPathways for SPAST Gene

No Data Available

Gene Ontology (GO) - Biological Process for SPAST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001578 microtubule bundle formation IDA 16219033
GO:0006200 obsolete ATP catabolic process --
GO:0006281 DNA repair --
GO:0006310 DNA recombination --
GO:0006888 ER to Golgi vesicle-mediated transport IMP 19000169
genes like me logo Genes that share ontologies with SPAST: view

No data available for Pathways by source for SPAST Gene

Compounds for SPAST Gene

(1) Novoseek inferred chemical compound relationships for SPAST Gene

Compound -log(P) Hits PubMed IDs
atp 0 1
genes like me logo Genes that share compounds with SPAST: view

Transcripts for SPAST Gene

Unigene Clusters for SPAST Gene

Spastin:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SPAST Gene

No ASD Table

Relevant External Links for SPAST Gene

GeneLoc Exon Structure for
SPAST
ECgene alternative splicing isoforms for
SPAST

Expression for SPAST Gene

mRNA expression in normal human tissues for SPAST Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for SPAST Gene

SOURCE GeneReport for Unigene cluster for SPAST Gene Hs.468091

mRNA Expression by UniProt/SwissProt for SPAST Gene

Q9UBP0-SPAST_HUMAN
Tissue specificity: Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. The short isoforms may predominate in brain and spinal cord.
genes like me logo Genes that share expressions with SPAST: view

Orthologs for SPAST Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for SPAST Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SPAST 36
  • 99.89 (n)
  • 100 (a)
SPAST 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SPAST 36
  • 93.07 (n)
  • 94.93 (a)
SPAST 37
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SPAST 36
  • 94.2 (n)
  • 96.28 (a)
SPAST 37
  • 95 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Spast 36
  • 89.12 (n)
  • 94.39 (a)
Spast 16
Spast 37
  • 93 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SPAST 37
  • 91 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SPAST 37
  • 90 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Spast 36
  • 89.59 (n)
  • 95.72 (a)
chicken
(Gallus gallus)
Aves SPAST 36
  • 83.1 (n)
  • 86.65 (a)
SPAST 37
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SPAST 37
  • 76 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.32426 36
tropical clawed frog
(Silurana tropicalis)
Amphibia spast 36
  • 73.37 (n)
  • 79.13 (a)
Str.10574 36
zebrafish
(Danio rerio)
Actinopterygii spast 36
  • 64.98 (n)
  • 69.48 (a)
spast 37
  • 66 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta SPAST_ANOGA 36
  • 54.41 (n)
  • 64.71 (a)
fruit fly
(Drosophila melanogaster)
Insecta spas 36
  • 53.26 (n)
  • 57.53 (a)
spas 37
  • 40 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea spas-1 36
  • 54.27 (n)
  • 49.69 (a)
spas-1 37
  • 35 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SAP1 37
  • 23 (a)
ManyToMany
SAP1 39
YTA6 37
  • 26 (a)
ManyToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G45500 36
  • 53.67 (n)
  • 48.1 (a)
rice
(Oryza sativa)
Liliopsida Os.4292 36
Os06g0130000 36
  • 57.42 (n)
  • 53.66 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.25966 36
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.581 36
Species with no ortholog for SPAST:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for SPAST Gene

ENSEMBL:
Gene Tree for SPAST (if available)
TreeFam:
Gene Tree for SPAST (if available)

Paralogs for SPAST Gene

Paralogs for SPAST Gene

Selected SIMAP similar genes for SPAST Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with SPAST: view

Variants for SPAST Gene

Sequence variations from dbSNP and Humsavar for SPAST Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs191961 -- 32,068,515(+) gacag(C/G)atttc intron-variant
rs216536 -- 32,081,289(+) tgggg(C/T)ttcac intron-variant
rs216537 -- 32,085,566(+) GCACC(A/T)ACTGT intron-variant
rs216538 -- 32,065,262(+) ATCGG(C/G)TCGCC intron-variant
rs216539 -- 32,072,167(+) cctcc(C/T)gagta intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SPAST Gene

Variant ID Type Subtype PubMed ID
esv2659839 CNV Deletion 23128226
nsv820001 CNV Gain 19587683
nsv828698 CNV Gain 20364138
nsv833670 CNV Loss 17160897
nsv873778 CNV Loss 21882294
nsv873779 CNV Loss 21882294
esv2668359 CNV Deletion 23128226

Relevant External Links for SPAST Gene

HapMap Linkage Disequilibrium report
SPAST
Human Gene Mutation Database (HGMD)
SPAST

Disorders for SPAST Gene

(1) OMIM Diseases for SPAST Gene (604277)

UniProtKB/Swiss-Prot

SPAST_HUMAN
  • Spastic paraplegia 4, autosomal dominant (SPG4) [MIM:182601]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269 PubMed:10610178, ECO:0000269 PubMed:10699187, ECO:0000269 PubMed:11015453, ECO:0000269 PubMed:11039577, ECO:0000269 PubMed:11087788, ECO:0000269 PubMed:11309678, ECO:0000269 PubMed:11843700, ECO:0000269 PubMed:11985387, ECO:0000269 PubMed:12124993, ECO:0000269 PubMed:12161613, ECO:0000269 PubMed:12163196, ECO:0000269 PubMed:12202986, ECO:0000269 PubMed:12460147, ECO:0000269 PubMed:12552568, ECO:0000269 PubMed:12939659, ECO:0000269 PubMed:14732620, ECO:0000269 PubMed:15159500, ECO:0000269 PubMed:15210521, ECO:0000269 PubMed:15248095, ECO:0000269 PubMed:15326248, ECO:0000269 PubMed:15482961, ECO:0000269 PubMed:16682546, ECO:0000269 PubMed:16684598, ECO:0000269 PubMed:17594340, ECO:0000269 PubMed:18613979, ECO:0000269 PubMed:20214791, ECO:0000269 PubMed:20550563, ECO:0000269 PubMed:20562464, ECO:0000269 PubMed:20718791, ECO:0000269 PubMed:20932283}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(1) University of Copenhagen DISEASES for SPAST Gene

(15) Novoseek inferred disease relationships for SPAST Gene

Disease -log(P) Hits PubMed IDs
spastic paraplegia hereditary autosomal dominant 98.4 22
spastic paraplegia hereditary 98.2 58
spg3a 96.2 25
spastic paraplegia 91.9 25
neurodegenerative diseases 71.9 5

Relevant External Links for SPAST

GeneTests
SPAST
GeneReviews
SPAST
Genetic Association Database (GAD)
SPAST
Human Genome Epidemiology (HuGE) Navigator
SPAST
genes like me logo Genes that share disorders with SPAST: view

Publications for SPAST Gene

  1. Three novel mutations of the spastin gene in Chinese patients with hereditary spastic paraplegia. (PMID: 14732620) Tang B. … Jiang H. (Arch. Neurol. 2004) 3 4 23 49
  2. Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia. (PMID: 16682546) Crippa F. … Bassi M.T. (Arch. Neurol. 2006) 3 4 23 49
  3. Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia. (PMID: 16684598) Magariello A. … Quattrone A. (Neuromuscul. Disord. 2006) 3 4 23
  4. Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus. (PMID: 16026783) Claudiani P. … Rugarli E.I. (Exp. Cell Res. 2005) 3 4 23
  5. Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance. (PMID: 16815977) Evans K.J. … Lauring B.P. (Proc. Natl. Acad. Sci. U.S.A. 2006) 3 4 23

Products for SPAST Gene

Sources for SPAST Gene

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