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Protein

Spastin

Gene

SPAST

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).UniRule annotation11 Publications
Isoform 1: Involved in lipid metabolism by regulating the size and distribution of lipid droplets.1 Publication

Catalytic activityi

ATP + H2O = ADP + phosphate.UniRule annotation6 Publications

Enzyme regulationi

Allosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers (PubMed:22637577). Microtubule binding promotes cooperative interactions among spastin subunits (PubMed:22637577). ATP-bound enzyme interacts strongly and cooperatively with microtubules; this interaction stimulates ATP hydrolysis (PubMed:23745751).UniRule annotation2 Publications

Kineticsi

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).1 Publication

Manual assertion based on experiment ini

  1. KM=0.45 mM for ATP3 Publications
  1. Vmax=1.2 nmol/min/µg enzyme3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi382 – 389ATPUniRule annotation1 Publication8

GO - Molecular functioni

  • alpha-tubulin binding Source: UniProtKB
  • ATP binding Source: UniProtKB-HAMAP
  • beta-tubulin binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • microtubule-severing ATPase activity Source: UniProtKB

GO - Biological processi

  • anterograde axonal transport Source: UniProtKB
  • axonal transport of mitochondrion Source: UniProtKB
  • axonogenesis Source: UniProtKB-HAMAP
  • cytokinetic process Source: UniProtKB-HAMAP
  • cytoplasmic microtubule organization Source: GO_Central
  • ER to Golgi vesicle-mediated transport Source: UniProtKB
  • exit from mitosis Source: UniProtKB
  • membrane fission Source: UniProtKB
  • metabolic process Source: UniProtKB-KW
  • microtubule bundle formation Source: UniProtKB
  • microtubule severing Source: UniProtKB
  • mitotic cytokinesis Source: UniProtKB
  • mitotic spindle disassembly Source: UniProtKB
  • nuclear envelope reassembly Source: UniProtKB
  • positive regulation of cytokinesis Source: UniProtKB
  • positive regulation of microtubule depolymerization Source: UniProtKB-HAMAP
  • protein hexamerization Source: UniProtKB
  • protein homooligomerization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase

Keywords - Biological processi

Cell cycle, Cell division, Differentiation, Neurogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00411-MONOMER.
BRENDAi3.6.4.3. 2681.
SABIO-RKQ9UBP0.

Names & Taxonomyi

Protein namesi
Recommended name:
Spastin1 PublicationUniRule annotation (EC:3.6.4.3UniRule annotation6 Publications)
Alternative name(s):
Spastic paraplegia 4 protein
Gene namesi
Name:SPASTUniRule annotationImported
Synonyms:ADPSP, FSP2, KIAA10831 Publication, SPG4UniRule annotation
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:11233. SPAST.

Subcellular locationi

Isoform 1 :
Isoform 3 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 56CytoplasmicUniRule annotation1 PublicationAdd BLAST56
Intramembranei57 – 77HelicalUniRule annotation1 PublicationAdd BLAST21
Topological domaini78 – 616CytoplasmicUniRule annotation1 PublicationAdd BLAST539

GO - Cellular componenti

  • axon cytoplasm Source: GOC
  • centrosome Source: UniProtKB-HAMAP
  • cytoplasm Source: UniProtKB
  • cytoplasmic vesicle Source: MGI
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • endoplasmic reticulum tubular network Source: UniProtKB
  • endosome Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-HAMAP
  • lipid particle Source: UniProtKB-SubCell
  • microtubule Source: UniProtKB-HAMAP
  • midbody Source: UniProtKB
  • nuclear membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • spindle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Endoplasmic reticulum, Endosome, Lipid droplet, Membrane, Microtubule, Nucleus

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 4, autosomal dominant (SPG4)37 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:182601
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07582744 – 616Missing in SPG4. 1 PublicationAdd BLAST573
Natural variantiVAR_01019444S → L in SPG4; rare variant; acts as a disease modifier; may decrease the activity of the alternative promoter which directs the synthesis of isoform 3 and isoform 4. 7 PublicationsCorresponds to variant rs121908515dbSNPEnsembl.1
Natural variantiVAR_02720545P → Q in SPG4; rare variant; acts as a disease modifier. 1 PublicationCorresponds to variant rs121908517dbSNPEnsembl.1
Natural variantiVAR_07582895A → T in SPG4. 1 Publication1
Natural variantiVAR_075829112 – 616Missing in SPG4. 1 PublicationAdd BLAST505
Natural variantiVAR_075830135 – 616Missing in SPG4. 1 PublicationAdd BLAST482
Natural variantiVAR_026758195L → V in SPG4. 1 Publication1
Natural variantiVAR_075831244 – 616Missing in SPG4. 1 PublicationAdd BLAST373
Natural variantiVAR_075832245 – 616Missing in SPG4. 1 PublicationAdd BLAST372
Natural variantiVAR_075833254 – 616Missing in SPG4. 1 PublicationAdd BLAST363
Natural variantiVAR_067631287Missing in SPG4. 1 Publication1
Natural variantiVAR_067632293P → L in SPG4. 1 PublicationCorresponds to variant rs773193617dbSNPEnsembl.1
Natural variantiVAR_075834309R → H in SPG4. 1 PublicationCorresponds to variant rs202152835dbSNPEnsembl.1
Natural variantiVAR_019448344I → K in SPG4; abrogates ATPase activity and promotes microtubule binding. 2 PublicationsCorresponds to variant rs121908513dbSNPEnsembl.1
Natural variantiVAR_027206347Q → K in SPG4; promotes microtubule binding. 2 Publications1
Natural variantiVAR_027207361P → L in SPG4. 1 Publication1
Natural variantiVAR_010195362S → C in SPG4. 2 PublicationsCorresponds to variant rs121908509dbSNPEnsembl.1
Natural variantiVAR_075835363L → P in SPG4. 1 Publication1
Natural variantiVAR_075836364R → M in SPG4. 1 Publication1
Natural variantiVAR_067636364R → T in SPG4. 1 Publication1
Natural variantiVAR_075837368F → L in SPG4. 1 Publication1
Natural variantiVAR_027208370G → R in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications1
Natural variantiVAR_075838372R → G in SPG4. 1 Publication1
Natural variantiVAR_075839377G → E in SPG4. 1 Publication1
Natural variantiVAR_019439378L → Q in SPG4. 1 Publication1
Natural variantiVAR_067637378L → R in SPG4. 1 Publication1
Natural variantiVAR_067638380L → H in SPG4. 2 Publications1
Natural variantiVAR_027209381F → C in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications1
Natural variantiVAR_027210386N → K in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles. 3 Publications1
Natural variantiVAR_019440386N → S in SPG4. 1 PublicationCorresponds to variant rs121908514dbSNPEnsembl.1
Natural variantiVAR_027211388K → R in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles and impairs traffic from the ER to Golgi. 7 Publications1
Natural variantiVAR_019441390M → V in SPG4. 1 Publication1
Natural variantiVAR_067639391L → P in SPG4. 1 Publication1
Natural variantiVAR_067640393 – 396Missing in SPG4. 1 Publication4
Natural variantiVAR_027212399S → L in SPG4. 4 Publications1
Natural variantiVAR_019449404Missing in SPG4. 1 Publication1
Natural variantiVAR_075840406I → R in SPG4. 1 Publication1
Natural variantiVAR_026759406I → V in SPG4. 1 PublicationCorresponds to variant rs587777757dbSNPEnsembl.1
Natural variantiVAR_019450407S → R in SPG4. 1 Publication1
Natural variantiVAR_067641409A → T in SPG4. 2 Publications1
Natural variantiVAR_067642410S → R in SPG4. 1 Publication1
Natural variantiVAR_067568413S → L in SPG4. 1 Publication1
Natural variantiVAR_010196424R → G in SPG4. 1 Publication1
Natural variantiVAR_067643426L → F in SPG4. 1 Publication1
Natural variantiVAR_027213426L → V in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 4 Publications1
Natural variantiVAR_075841431 – 616Missing in SPG4. 1 PublicationAdd BLAST186
Natural variantiVAR_027214435P → L in SPG4. 1 Publication1
Natural variantiVAR_027215436S → F in SPG4. 1 Publication1
Natural variantiVAR_067644436S → P in SPG4. 1 Publication1
Natural variantiVAR_027216441D → G in SPG4. 1 PublicationCorresponds to variant rs121908512dbSNPEnsembl.1
Natural variantiVAR_067645441D → N in SPG4. 1 Publication1
Natural variantiVAR_075842441D → V in SPG4. 1 Publication1
Natural variantiVAR_010197448C → Y in SPG4; abrogates binding to the tail of beta-3-tubulin, abolishes microtubule severing and promotes the formation of thick microtubule bundles. 4 PublicationsCorresponds to variant rs121908510dbSNPEnsembl.1
Natural variantiVAR_075843450R → S in SPG4. 1 Publication1
Natural variantiVAR_075844451Missing in SPG4. 1 Publication1
Natural variantiVAR_067571454E → K in SPG4. 1 Publication1
Natural variantiVAR_075845458S → R in SPG4. 1 Publication1
Natural variantiVAR_027217459R → G in SPG4. 1 Publication1
Natural variantiVAR_027218460R → C in SPG4. 2 Publications1
Natural variantiVAR_027219460R → L in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications1
Natural variantiVAR_067572460R → S in SPG4. 3 Publications1
Natural variantiVAR_075846461L → P in SPG4. 1 Publication1
Natural variantiVAR_067646463T → A in SPG4. 1 Publication1
Natural variantiVAR_027220470D → V in SPG4. 1 PublicationCorresponds to variant rs28939368dbSNPEnsembl.1
Natural variantiVAR_027221485A → V in SPG4. 1 Publication1
Natural variantiVAR_027222489P → L in SPG4. 1 Publication1
Natural variantiVAR_075847490 – 616Missing in SPG4. 1 PublicationAdd BLAST127
Natural variantiVAR_067648492L → F in SPG4. 1 Publication1
Natural variantiVAR_026760493D → G in SPG4. 1 Publication1
Natural variantiVAR_067649498R → G in SPG4. 2 Publications1
Natural variantiVAR_010198499R → C in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles. 6 PublicationsCorresponds to variant rs121908511dbSNPEnsembl.1
Natural variantiVAR_026761499R → H in SPG4. 2 Publications1
Natural variantiVAR_019442503R → L in SPG4. 1 Publication1
Natural variantiVAR_067650503R → RR in SPG4. 1 Publication1
Natural variantiVAR_026762503R → W in SPG4. 2 Publications1
Natural variantiVAR_027223512E → D in SPG4. 1 Publication1
Natural variantiVAR_067651514R → G in SPG4. 1 Publication1
Natural variantiVAR_019443515Missing in SPG4. 1 Publication1
Natural variantiVAR_019444534L → P in SPG4. 1 Publication1
Natural variantiVAR_019451551A → Y in SPG4; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_075848555D → G in SPG4. 1 Publication1
Natural variantiVAR_027224555D → N in SPG4. 1 Publication1
Natural variantiVAR_027225556A → V in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications1
Natural variantiVAR_027226559G → D in SPG4. 2 Publications1
Natural variantiVAR_075849559G → R in SPG4. 1 Publication1
Natural variantiVAR_075850562 – 616Missing in SPG4. 1 PublicationAdd BLAST55
Natural variantiVAR_027227562R → G in SPG4. 2 PublicationsCorresponds to variant rs121908518dbSNPEnsembl.1
Natural variantiVAR_027228562R → Q in SPG4. 1 Publication1
Natural variantiVAR_067654580I → T in SPG4. 1 Publication1
Natural variantiVAR_075851581 – 616Missing in SPG4. 2 PublicationsAdd BLAST36
Natural variantiVAR_010199584D → H in SPG4. 1 Publication1
Natural variantiVAR_075852595S → R in SPG4. 1 Publication1
Natural variantiVAR_026763607W → C in SPG4. 1 Publication1
Natural variantiVAR_019445614T → I in SPG4; variant form with congenital arachnoid cysts. 1 Publication1
Natural variantiVAR_019452615T → I in SPG4. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1M → V: Cytoplasmic and nuclear. 1 Publication1
Mutagenesisi65R → G: Abolishes localization to lipid droplets. 1 Publication1
Mutagenesisi81 – 84RFSR → GFSG: Does not affect localization to lipid droplets. 1 Publication4
Mutagenesisi87M → V: Exclusively cytoplasmic. 1 Publication1
Mutagenesisi120H → D: Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-124. 1 Publication1
Mutagenesisi124F → A: Impairs binding to CHMP1B. 1 Publication1
Mutagenesisi124F → D: Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-120. 1 Publication1
Mutagenesisi310 – 312KKK → QQQ: Loss of microtubule-binding. 1 Publication3
Mutagenesisi388K → A: Abrogates ATPase activity and abolishes microtubule severing. 1 Publication1
Mutagenesisi415Y → A: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing. 1 Publication1
Mutagenesisi442E → Q: Abrogates ATP hydrolysis, abolishes microtubule severing, stabilizes the homohexameric form, and promotes microtubule binding and redistribution from the endosome to microtubules. 8 Publications1
Mutagenesisi448C → A or G: Abolishes ATPase activity. 1 Publication1
Mutagenesisi448C → S: Does not affect ATPase activity. 1 Publication1
Mutagenesisi451R → G: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing. 1 Publication1
Mutagenesisi457A → E: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin and abolishes microtubule severing. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary spastic paraplegia, Neurodegeneration

Organism-specific databases

DisGeNETi6683.
MalaCardsiSPAST.
MIMi182601. phenotype.
OpenTargetsiENSG00000021574.
Orphaneti100985. Autosomal dominant spastic paraplegia type 4.
PharmGKBiPA36063.

Polymorphism and mutation databases

BioMutaiSPAST.
DMDMi12230611.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000847631 – 616SpastinAdd BLAST616

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei245PhosphoserineCombined sources1
Modified residuei268PhosphoserineCombined sources1
Modified residuei306PhosphothreonineCombined sources1
Modified residuei597PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UBP0.
PaxDbiQ9UBP0.
PeptideAtlasiQ9UBP0.
PRIDEiQ9UBP0.

PTM databases

iPTMnetiQ9UBP0.
PhosphoSitePlusiQ9UBP0.

Expressioni

Tissue specificityi

Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. The short isoforms may predominate in brain and spinal cord.1 Publication

Developmental stagei

Expressed in fetal brain, heart, kidney, liver, lung, skeletal muscle, spleen and thymus.1 Publication

Gene expression databases

BgeeiENSG00000021574.
CleanExiHS_SPAST.
ExpressionAtlasiQ9UBP0. baseline and differential.
GenevisibleiQ9UBP0. HS.

Organism-specific databases

HPAiHPA017311.

Interactioni

Subunit structurei

Homohexamer (PubMed:17389232, PubMed:22637577). Mostly monomeric, but assembles into hexameric structure for short periods of time. Oligomerization seems to be a prerequisite for catalytic activity (PubMed:17389232, PubMed:22637577). Binding to ATP in a cleft between two adjacent subunits stabilizes the homohexameric form (PubMed:17389232, PubMed:22637577). Binds to microtubules at least in part via the alpha-tubulin and beta-tubulin tails (PubMed:15269182, PubMed:15716377, PubMed:23272056). The hexamer adopts a ring conformation through which microtubules pass prior to being severed (PubMed:17389232, PubMed:22637577). Does not interact strongly with tubulin heterodimers (PubMed:15269182, PubMed:15716377, PubMed:23272056). Interacts (via MIT domain) with CHMP1B; the interaction is direct (PubMed:15537668, PubMed:18997780). Interacts with SSNA1 (PubMed:15269182). Interacts with ATL1 (PubMed:16339213, PubMed:16815977). Interacts with RTN1 (PubMed:16602018). Interacts with ZFYVE27 (PubMed:16826525, PubMed:23969831). Isoform 1 but not isoform 3 interacts with RTN2 (PubMed:22232211). Interacts with REEP1 (PubMed:20200447). Interacts (via MIT domain) with IST1 (PubMed:23897888, PubMed:26040712).UniRule annotation16 Publications

GO - Molecular functioni

  • alpha-tubulin binding Source: UniProtKB
  • beta-tubulin binding Source: UniProtKB
  • microtubule binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112562. 26 interactors.
DIPiDIP-38418N.
IntActiQ9UBP0. 13 interactors.
STRINGi9606.ENSP00000320885.

Structurei

Secondary structure

1616
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi112 – 136Combined sources25
Beta strandi139 – 141Combined sources3
Helixi142 – 144Combined sources3
Helixi146 – 161Combined sources16
Helixi169 – 195Combined sources27
Helixi328 – 330Combined sources3
Helixi341 – 343Combined sources3
Helixi348 – 357Combined sources10
Helixi359 – 363Combined sources5
Turni365 – 367Combined sources3
Helixi370 – 372Combined sources3
Beta strandi376 – 383Combined sources8
Helixi388 – 398Combined sources11
Beta strandi402 – 406Combined sources5
Helixi420 – 432Combined sources13
Beta strandi433 – 441Combined sources9
Helixi443 – 446Combined sources4
Helixi458 – 472Combined sources15
Beta strandi480 – 487Combined sources8
Helixi489 – 491Combined sources3
Helixi494 – 497Combined sources4
Beta strandi502 – 505Combined sources4
Helixi511 – 522Combined sources12
Helixi531 – 540Combined sources10
Turni541 – 543Combined sources3
Helixi546 – 556Combined sources11
Helixi559 – 562Combined sources4
Beta strandi573 – 575Combined sources3
Helixi582 – 591Combined sources10
Helixi598 – 610Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3EABX-ray2.50A/B/C/D/E/F112-196[»]
3VFDX-ray3.30A228-616[»]
ProteinModelPortaliQ9UBP0.
SMRiQ9UBP0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UBP0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini120 – 195MITSequence analysisAdd BLAST76

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 300Required for interaction with RTN11 PublicationAdd BLAST300
Regioni1 – 194Required for midbody localization1 PublicationAdd BLAST194
Regioni1 – 80Required for interaction with ATL12 PublicationsAdd BLAST80
Regioni1 – 50Required for nuclear localization1 PublicationAdd BLAST50
Regioni50 – 87Required for interaction with SSNA1 and microtubules1 PublicationAdd BLAST38
Regioni112 – 196Sufficient for interaction with CHMP1B1 PublicationAdd BLAST85
Regioni114 – 200Required for interaction with microtubules1 PublicationAdd BLAST87
Regioni228 – 616Sufficient for microtubule severing1 PublicationAdd BLAST389
Regioni270 – 328Required for interaction with microtubules and microtubule severing1 PublicationAdd BLAST59
Regioni310 – 312Required for interaction with microtubules1 Publication3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi4 – 11Nuclear localization signalUniRule annotation1 Publication8
Motifi59 – 67Nuclear export signalUniRule annotation1 Publication9
Motifi309 – 312Nuclear localization signalUniRule annotation1 Publication4

Sequence similaritiesi

Belongs to the AAA ATPase family. Spastin subfamily.UniRule annotation
Contains 1 MIT domain.Sequence analysis

Phylogenomic databases

eggNOGiKOG0740. Eukaryota.
COG0464. LUCA.
GeneTreeiENSGT00570000078874.
HOGENOMiHOG000225146.
HOVERGENiHBG108502.
InParanoidiQ9UBP0.
KOiK13254.
OMAiGNPDGDR.
OrthoDBiEOG091G0Q8J.
PhylomeDBiQ9UBP0.
TreeFamiTF105014.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_03021. Spastin. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR007330. MIT.
IPR027417. P-loop_NTPase.
IPR017179. Spastin.
IPR015415. Vps4_C.
[Graphical view]
PfamiPF00004. AAA. 1 hit.
PF09336. Vps4_C. 1 hit.
[Graphical view]
PIRSFiPIRSF037338. Spastin. 1 hit.
SMARTiSM00382. AAA. 1 hit.
SM00745. MIT. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS00674. AAA. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative promoter usage, alternative splicing and alternative initiation. AlignAdd to basket

Note: Alternative promoter usage of a cryptic promoter in exon 1 can direct the synthesis of N-terminally truncated isoforms, which may also arise from alternative initiation.2 Publications
Isoform 1 (identifier: Q9UBP0-1) [UniParc]FASTAAdd to basket
Also known as: Long, Long variant 1, 68 kDa1 Publication, M11 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNSPGGRGKK KGSGGASNPV PPRPPPPCLA PAPPAAGPAP PPESPHKRNL
60 70 80 90 100
YYFSYPLFVG FALLRLVAFH LGLLFVWLCQ RFSRALMAAK RSSGAAPAPA
110 120 130 140 150
SASAPAPVPG GEAERVRVFH KQAFEYISIA LRIDEDEKAG QKEQAVEWYK
160 170 180 190 200
KGIEELEKGI AVIVTGQGEQ CERARRLQAK MMTNLVMAKD RLQLLEKMQP
210 220 230 240 250
VLPFSKSQTD VYNDSTNLAC RNGHLQSESG AVPKRKDPLT HTSNSLPRSK
260 270 280 290 300
TVMKTGSAGL SGHHRAPSYS GLSMVSGVKQ GSGPAPTTHK GTPKTNRTNK
310 320 330 340 350
PSTPTTATRK KKDLKNFRNV DSNLANLIMN EIVDNGTAVK FDDIAGQDLA
360 370 380 390 400
KQALQEIVIL PSLRPELFTG LRAPARGLLL FGPPGNGKTM LAKAVAAESN
410 420 430 440 450
ATFFNISAAS LTSKYVGEGE KLVRALFAVA RELQPSIIFI DEVDSLLCER
460 470 480 490 500
REGEHDASRR LKTEFLIEFD GVQSAGDDRV LVMGATNRPQ ELDEAVLRRF
510 520 530 540 550
IKRVYVSLPN EETRLLLLKN LLCKQGSPLT QKELAQLARM TDGYSGSDLT
560 570 580 590 600
ALAKDAALGP IRELKPEQVK NMSASEMRNI RLSDFTESLK KIKRSVSPQT
610
LEAYIRWNKD FGDTTV
Length:616
Mass (Da):67,197
Last modified:May 1, 2000 - v1
Checksum:i75E5FC5787132B4C
GO
Isoform 2 (identifier: Q9UBP0-2) [UniParc]FASTAAdd to basket
Also known as: Long variant 2

The sequence of this isoform differs from the canonical sequence as follows:
     197-228: Missing.

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Length:584
Mass (Da):63,606
Checksum:i502F0FCB78ECED14
GO
Isoform 3 (identifier: Q9UBP0-3) [UniParc]FASTAAdd to basket
Also known as: Short, Short variant 1, 60 kDa1 Publication, M871 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-86: Missing.

Note: Produced by alternative promoter usage. May also be produced by alternative initiation at Met-87 of isoform 1. Major isoform.
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Length:530
Mass (Da):58,009
Checksum:i0A4DB33B07801675
GO
Isoform 4 (identifier: Q9UBP0-4) [UniParc]FASTAAdd to basket
Also known as: Short variant 2

The sequence of this isoform differs from the canonical sequence as follows:
     1-86: Missing.
     197-228: Missing.

Note: Produced by alternative promoter usage and alternative splicing. May also be produced by alternative initiation at Met-87 of isoform 2.
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Length:498
Mass (Da):54,418
Checksum:iF8BB32A6C8CB1D73
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07582744 – 616Missing in SPG4. 1 PublicationAdd BLAST573
Natural variantiVAR_01019444S → L in SPG4; rare variant; acts as a disease modifier; may decrease the activity of the alternative promoter which directs the synthesis of isoform 3 and isoform 4. 7 PublicationsCorresponds to variant rs121908515dbSNPEnsembl.1
Natural variantiVAR_02720545P → Q in SPG4; rare variant; acts as a disease modifier. 1 PublicationCorresponds to variant rs121908517dbSNPEnsembl.1
Natural variantiVAR_07582895A → T in SPG4. 1 Publication1
Natural variantiVAR_06762897P → T in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 PublicationCorresponds to variant rs372005558dbSNPEnsembl.1
Natural variantiVAR_075829112 – 616Missing in SPG4. 1 Publication