Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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 regognizes 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 to 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

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

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi382 – 3898ATPUniRule annotation1 Publication

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
  • axonogenesis Source: UniProtKB-HAMAP
  • axon transport of mitochondrion Source: UniProtKB
  • 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

BRENDAi3.6.4.3. 2681.

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5656CytoplasmicUniRule annotation1 PublicationAdd
BLAST
Intramembranei57 – 7721HelicalUniRule annotation1 PublicationAdd
BLAST
Topological domaini78 – 616539CytoplasmicUniRule annotation1 PublicationAdd
BLAST

GO - Cellular componenti

  • axon cytoplasm Source: GOC
  • centrosome Source: UniProtKB-HAMAP
  • cytoplasm Source: UniProtKB
  • cytoplasmic vesicle Source: MGI
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • endosome Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti44 – 616573Missing in SPG4. 1 Publication
VAR_075827Add
BLAST
Natural varianti44 – 441S → 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 Publications
Corresponds to variant rs121908515 [ dbSNP | Ensembl ].
VAR_010194
Natural varianti45 – 451P → Q in SPG4; rare variant; acts as a disease modifier. 1 Publication
Corresponds to variant rs121908517 [ dbSNP | Ensembl ].
VAR_027205
Natural varianti95 – 951A → T in SPG4. 1 Publication
VAR_075828
Natural varianti112 – 616505Missing in SPG4. 1 Publication
VAR_075829Add
BLAST
Natural varianti135 – 616482Missing in SPG4. 1 Publication
VAR_075830Add
BLAST
Natural varianti195 – 1951L → V in SPG4. 1 Publication
VAR_026758
Natural varianti244 – 616373Missing in SPG4. 1 Publication
VAR_075831Add
BLAST
Natural varianti245 – 616372Missing in SPG4. 1 Publication
VAR_075832Add
BLAST
Natural varianti254 – 616363Missing in SPG4. 1 Publication
VAR_075833Add
BLAST
Natural varianti287 – 2871Missing in SPG4. 1 Publication
VAR_067631
Natural varianti293 – 2931P → L in SPG4. 1 Publication
Corresponds to variant rs773193617 [ dbSNP | Ensembl ].
VAR_067632
Natural varianti309 – 3091R → H in SPG4. 1 Publication
Corresponds to variant rs202152835 [ dbSNP | Ensembl ].
VAR_075834
Natural varianti344 – 3441I → K in SPG4; abrogates ATPase activity and promotes microtubule binding. 2 Publications
Corresponds to variant rs121908513 [ dbSNP | Ensembl ].
VAR_019448
Natural varianti347 – 3471Q → K in SPG4; promotes microtubule binding. 2 Publications
VAR_027206
Natural varianti361 – 3611P → L in SPG4. 1 Publication
VAR_027207
Natural varianti362 – 3621S → C in SPG4. 2 Publications
Corresponds to variant rs121908509 [ dbSNP | Ensembl ].
VAR_010195
Natural varianti363 – 3631L → P in SPG4. 1 Publication
VAR_075835
Natural varianti364 – 3641R → M in SPG4. 1 Publication
VAR_075836
Natural varianti364 – 3641R → T in SPG4. 1 Publication
VAR_067636
Natural varianti368 – 3681F → L in SPG4. 1 Publication
VAR_075837
Natural varianti370 – 3701G → R in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications
VAR_027208
Natural varianti372 – 3721R → G in SPG4. 1 Publication
VAR_075838
Natural varianti377 – 3771G → E in SPG4. 1 Publication
VAR_075839
Natural varianti378 – 3781L → Q in SPG4. 1 Publication
VAR_019439
Natural varianti378 – 3781L → R in SPG4. 1 Publication
VAR_067637
Natural varianti380 – 3801L → H in SPG4. 2 Publications
VAR_067638
Natural varianti381 – 3811F → C in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications
VAR_027209
Natural varianti386 – 3861N → K in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles. 3 Publications
VAR_027210
Natural varianti386 – 3861N → S in SPG4. 1 Publication
Corresponds to variant rs121908514 [ dbSNP | Ensembl ].
VAR_019440
Natural varianti388 – 3881K → 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 Publications
VAR_027211
Natural varianti390 – 3901M → V in SPG4. 1 Publication
VAR_019441
Natural varianti391 – 3911L → P in SPG4. 1 Publication
VAR_067639
Natural varianti393 – 3964Missing in SPG4. 1 Publication
VAR_067640
Natural varianti399 – 3991S → L in SPG4. 4 Publications
VAR_027212
Natural varianti404 – 4041Missing in SPG4. 1 Publication
VAR_019449
Natural varianti406 – 4061I → R in SPG4. 1 Publication
VAR_075840
Natural varianti406 – 4061I → V in SPG4. 1 Publication
Corresponds to variant rs587777757 [ dbSNP | Ensembl ].
VAR_026759
Natural varianti407 – 4071S → R in SPG4. 1 Publication
VAR_019450
Natural varianti409 – 4091A → T in SPG4. 2 Publications
VAR_067641
Natural varianti410 – 4101S → R in SPG4. 1 Publication
VAR_067642
Natural varianti413 – 4131S → L in SPG4. 1 Publication
VAR_067568
Natural varianti424 – 4241R → G in SPG4. 1 Publication
VAR_010196
Natural varianti426 – 4261L → F in SPG4. 1 Publication
VAR_067643
Natural varianti426 – 4261L → V in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 4 Publications
VAR_027213
Natural varianti431 – 616186Missing in SPG4. 1 Publication
VAR_075841Add
BLAST
Natural varianti435 – 4351P → L in SPG4. 1 Publication
VAR_027214
Natural varianti436 – 4361S → F in SPG4. 1 Publication
VAR_027215
Natural varianti436 – 4361S → P in SPG4. 1 Publication
VAR_067644
Natural varianti441 – 4411D → G in SPG4. 1 Publication
Corresponds to variant rs121908512 [ dbSNP | Ensembl ].
VAR_027216
Natural varianti441 – 4411D → N in SPG4. 1 Publication
VAR_067645
Natural varianti441 – 4411D → V in SPG4. 1 Publication
VAR_075842
Natural varianti448 – 4481C → Y in SPG4; abrogates binding to the tail of beta-3-tubulin, abolishes microtubule severing and promotes the formation of thick microtubule bundles. 4 Publications
Corresponds to variant rs121908510 [ dbSNP | Ensembl ].
VAR_010197
Natural varianti450 – 4501R → S in SPG4. 1 Publication
VAR_075843
Natural varianti451 – 4511Missing in SPG4. 1 Publication
VAR_075844
Natural varianti454 – 4541E → K in SPG4. 1 Publication
VAR_067571
Natural varianti458 – 4581S → R in SPG4. 1 Publication
VAR_075845
Natural varianti459 – 4591R → G in SPG4. 1 Publication
VAR_027217
Natural varianti460 – 4601R → C in SPG4. 2 Publications
VAR_027218
Natural varianti460 – 4601R → L in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications
VAR_027219
Natural varianti460 – 4601R → S in SPG4. 3 Publications
VAR_067572
Natural varianti461 – 4611L → P in SPG4. 1 Publication
VAR_075846
Natural varianti463 – 4631T → A in SPG4. 1 Publication
VAR_067646
Natural varianti470 – 4701D → V in SPG4. 1 Publication
Corresponds to variant rs28939368 [ dbSNP | Ensembl ].
VAR_027220
Natural varianti485 – 4851A → V in SPG4. 1 Publication
VAR_027221
Natural varianti489 – 4891P → L in SPG4. 1 Publication
VAR_027222
Natural varianti490 – 616127Missing in SPG4. 1 Publication
VAR_075847Add
BLAST
Natural varianti492 – 4921L → F in SPG4. 1 Publication
VAR_067648
Natural varianti493 – 4931D → G in SPG4. 1 Publication
VAR_026760
Natural varianti498 – 4981R → G in SPG4. 2 Publications
VAR_067649
Natural varianti499 – 4991R → C in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles. 6 Publications
Corresponds to variant rs121908511 [ dbSNP | Ensembl ].
VAR_010198
Natural varianti499 – 4991R → H in SPG4. 2 Publications
VAR_026761
Natural varianti503 – 5031R → L in SPG4. 1 Publication
VAR_019442
Natural varianti503 – 5031R → RR in SPG4. 1 Publication
VAR_067650
Natural varianti503 – 5031R → W in SPG4. 2 Publications
VAR_026762
Natural varianti512 – 5121E → D in SPG4. 1 Publication
VAR_027223
Natural varianti514 – 5141R → G in SPG4. 1 Publication
VAR_067651
Natural varianti515 – 5151Missing in SPG4. 1 Publication
VAR_019443
Natural varianti534 – 5341L → P in SPG4. 1 Publication
VAR_019444
Natural varianti551 – 5511A → Y in SPG4; requires 2 nucleotide substitutions. 1 Publication
VAR_019451
Natural varianti555 – 5551D → G in SPG4. 1 Publication
VAR_075848
Natural varianti555 – 5551D → N in SPG4. 1 Publication
VAR_027224
Natural varianti556 – 5561A → V in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications
VAR_027225
Natural varianti559 – 5591G → D in SPG4. 2 Publications
VAR_027226
Natural varianti559 – 5591G → R in SPG4. 1 Publication
VAR_075849
Natural varianti562 – 61655Missing in SPG4. 1 Publication
VAR_075850Add
BLAST
Natural varianti562 – 5621R → G in SPG4. 2 Publications
Corresponds to variant rs121908518 [ dbSNP | Ensembl ].
VAR_027227
Natural varianti562 – 5621R → Q in SPG4. 1 Publication
VAR_027228
Natural varianti580 – 5801I → T in SPG4. 1 Publication
VAR_067654
Natural varianti581 – 61636Missing in SPG4. 2 Publications
VAR_075851Add
BLAST
Natural varianti584 – 5841D → H in SPG4. 1 Publication
VAR_010199
Natural varianti595 – 5951S → R in SPG4. 1 Publication
VAR_075852
Natural varianti607 – 6071W → C in SPG4. 1 Publication
VAR_026763
Natural varianti614 – 6141T → I in SPG4; variant form with congenital arachnoid cysts. 1 Publication
VAR_019445
Natural varianti615 – 6151T → I in SPG4. 1 Publication
VAR_019452

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1 – 11M → V: Cytoplasmic and nuclear. 1 Publication
Mutagenesisi65 – 651R → G: Abolishes localization to lipid droplets. 1 Publication
Mutagenesisi81 – 844RFSR → GFSG: Does not affect localization to lipid droplets. 1 Publication
Mutagenesisi87 – 871M → V: Exclusively cytoplasmic. 1 Publication
Mutagenesisi120 – 1201H → D: Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-124. 1 Publication
Mutagenesisi124 – 1241F → A: Impairs binding to CHMP1B. 1 Publication
Mutagenesisi124 – 1241F → D: Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-120. 1 Publication
Mutagenesisi310 – 3123KKK → QQQ: Loss of microtubule-binding. 1 Publication
Mutagenesisi388 – 3881K → A: Abrogates ATPase activity and abolishes microtubule severing. 1 Publication
Mutagenesisi415 – 4151Y → A: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing. 1 Publication
Mutagenesisi442 – 4421E → Q: Abrogates ATP hydrolysis, abolishes microtubule severing, stabilizes the homohexameric form, and promotes microtubule binding and redistribution from the endosome to microtubules. 8 Publications
Mutagenesisi448 – 4481C → A or G: Abolishes ATPase activity. 1 Publication
Mutagenesisi448 – 4481C → S: Does not affect ATPase activity. 1 Publication
Mutagenesisi451 – 4511R → G: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing. 1 Publication
Mutagenesisi457 – 4571A → E: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin and abolishes microtubule severing. 1 Publication

Keywords - Diseasei

Hereditary spastic paraplegia, Neurodegeneration

Organism-specific databases

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

Polymorphism and mutation databases

BioMutaiSPAST.
DMDMi12230611.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 616616SpastinPRO_0000084763Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei245 – 2451PhosphoserineCombined sources
Modified residuei268 – 2681PhosphoserineCombined sources
Modified residuei306 – 3061PhosphothreonineCombined sources
Modified residuei597 – 5971PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UBP0.
MaxQBiQ9UBP0.
PaxDbiQ9UBP0.
PeptideAtlasiQ9UBP0.
PRIDEiQ9UBP0.

PTM databases

iPTMnetiQ9UBP0.
PhosphoSiteiQ9UBP0.

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

BgeeiQ9UBP0.
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). 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 annotation15 Publications

GO - Molecular functioni

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

Protein-protein interaction databases

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

Structurei

Secondary structure

1
616
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi112 – 13625Combined sources
Beta strandi139 – 1413Combined sources
Helixi142 – 1443Combined sources
Helixi146 – 16116Combined sources
Helixi169 – 19527Combined sources
Helixi328 – 3303Combined sources
Helixi341 – 3433Combined sources
Helixi348 – 35710Combined sources
Helixi359 – 3635Combined sources
Turni365 – 3673Combined sources
Helixi370 – 3723Combined sources
Beta strandi376 – 3838Combined sources
Helixi388 – 39811Combined sources
Beta strandi402 – 4065Combined sources
Helixi420 – 43213Combined sources
Beta strandi433 – 4419Combined sources
Helixi443 – 4464Combined sources
Helixi458 – 47215Combined sources
Beta strandi480 – 4878Combined sources
Helixi489 – 4913Combined sources
Helixi494 – 4974Combined sources
Beta strandi502 – 5054Combined sources
Helixi511 – 52212Combined sources
Helixi531 – 54010Combined sources
Turni541 – 5433Combined sources
Helixi546 – 55611Combined sources
Helixi559 – 5624Combined sources
Beta strandi573 – 5753Combined sources
Helixi582 – 59110Combined sources
Helixi598 – 61013Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3EABX-ray2.50A/B/C/D/E/F112-196[»]
3VFDX-ray3.30A228-616[»]
ProteinModelPortaliQ9UBP0.
SMRiQ9UBP0. Positions 112-196, 290-612.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UBP0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini120 – 19576MITSequence analysisAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 300300Required for interaction with RTN11 PublicationAdd
BLAST
Regioni1 – 194194Required for midbody localization1 PublicationAdd
BLAST
Regioni1 – 8080Required for interaction with ATL12 PublicationsAdd
BLAST
Regioni1 – 5050Required for nuclear localization1 PublicationAdd
BLAST
Regioni50 – 8738Required for interaction with SSNA1 and microtubules1 PublicationAdd
BLAST
Regioni112 – 19685Sufficient for interaction with CHMP1B1 PublicationAdd
BLAST
Regioni114 – 20087Required for interaction with microtubules1 PublicationAdd
BLAST
Regioni228 – 616389Sufficient for microtubule severing1 PublicationAdd
BLAST
Regioni270 – 32859Required for interaction with microtubules and microtubule severing1 PublicationAdd
BLAST
Regioni310 – 3123Required for interaction with microtubules1 Publication

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi4 – 118Nuclear localization signalUniRule annotation1 Publication
Motifi59 – 679Nuclear export signalUniRule annotation1 Publication
Motifi309 – 3124Nuclear localization signalUniRule annotation1 Publication

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.
OMAiFCIFRYL.
OrthoDBiEOG7GXPCR.
PhylomeDBiQ9UBP0.
TreeFamiTF105014.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_03021. Spastin.
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.

Show »
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.
Show »
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.
Show »
Length:498
Mass (Da):54,418
Checksum:iF8BB32A6C8CB1D73
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti44 – 616573Missing in SPG4. 1 Publication
VAR_075827Add
BLAST
Natural varianti44 – 441S → 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 Publications
Corresponds to variant rs121908515 [ dbSNP | Ensembl ].
VAR_010194
Natural varianti45 – 451P → Q in SPG4; rare variant; acts as a disease modifier. 1 Publication
Corresponds to variant rs121908517 [ dbSNP | Ensembl ].
VAR_027205
Natural varianti95 – 951A → T in SPG4. 1 Publication
VAR_075828
Natural varianti97 – 971P → T in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication