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Protein

Spastin

Gene

Spast

Organism
Mus musculus (Mouse)
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:19141076 PubMed:20530212). 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 (By similarity). Severing activity is not dependent on tubulin acetylation or detyrosination (By similarity). Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation (By similarity). It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia (By similarity). SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex (By similarity). Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex (By similarity). Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase (By similarity). Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling (By similarity). Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing (By similarity). Probably plays a role in axon growth and the formation of axonal branches (PubMed:18234839).UniRule annotationBy similarity3 Publications
Isoform 1: Involved in lipid metabolism by regulating the size and distribution of lipid droplets.By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.UniRule annotation

Enzyme regulationi

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.UniRule annotation

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi380 – 387ATPUniRule annotation8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase

Keywords - Biological processi

Cell cycle, Cell division, Differentiation, Neurogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
SpastinUniRule annotation (EC:3.6.4.3UniRule annotation)
Gene namesi
Name:SpastUniRule annotation
Synonyms:Kiaa10831 Publication, Spg4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1858896. Spast.

Subcellular locationi

  • Membrane UniRule annotation; Peripheral membrane protein UniRule annotation
  • Endoplasmic reticulum UniRule annotation
  • Midbody UniRule annotation
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome UniRule annotation
  • Cytoplasmcytoskeleton UniRule annotation
  • Cytoplasmperinuclear region UniRule annotation
  • Nucleus UniRule annotation
  • Cytoplasmcytoskeletonspindle UniRule annotation
  • Cytoplasm UniRule annotation

  • Note: Forms a 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 (By similarity). Enriched in the distal axons and branches of postmitotic neurons (By similarity). Evenly distributed along early axons and concentrates in the growth cone of the axons of late stage 3 neurons (PubMed:18234839).UniRule annotation1 Publication
Isoform 1 :
  • Endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity
  • Nucleus membrane By similarity
  • Lipid droplet By similarity
  • Cytoplasmcytoskeleton By similarity
  • Endosome By similarity

  • Note: Forms a intramembrane hairpin-like structure in the membrane. Recruited to nuclear membrane by IST1 during late anaphase. Localizes to endoplasmic reticulum tubular network.By similarity
Isoform 2 :
  • Cytoplasm By similarity
  • Endosome By similarity
  • Nucleus membrane By similarity

  • Note: Constitutes the main endosomal form. Recruited to nuclear membrane by IST1 during late anaphase.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 54CytoplasmicUniRule annotationAdd BLAST54
Intramembranei55 – 75HelicalUniRule annotationAdd BLAST21
Topological domaini76 – 614CytoplasmicUniRule annotationAdd BLAST539

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

Mice develop gait abnormalities that correlate with phenotypes seen in hereditary spastic paraplegia (HSP) patients (PubMed:19453301). Adults are sterile (PubMed:17101632). Progressive axonal degeneration characterized by focal axonal swellings and the accumulation of organelles and cytoskeletal components, which is suggestive of impaired axonal transport (PubMed:17101632, PubMed:19453301). Primary cortical neurons develop swellings at the border between stable and dynamic microtubules (PubMed:17101632). In neurons with axonal swellings, the mitochondrial axonal transport defects are exacerbated: distal to axonal swellings both anterograde and retrograde transport are severely reduced (PubMed:19453301). In cortical neurons, axonal swellings is probably due to impaired microtubule dynamics all along the axons (PubMed:22773755).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi360S → C: Decreased microtubule severing activity. 1 Publication1
Mutagenesisi553D → A: Decreased microtubule severing activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000847641 – 614SpastinAdd BLAST614

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei243PhosphoserineBy similarity1
Modified residuei266PhosphoserineBy similarity1
Modified residuei304PhosphothreonineBy similarity1
Modified residuei595PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9QYY8.
MaxQBiQ9QYY8.
PaxDbiQ9QYY8.
PeptideAtlasiQ9QYY8.
PRIDEiQ9QYY8.

PTM databases

iPTMnetiQ9QYY8.
PhosphoSitePlusiQ9QYY8.

Expressioni

Tissue specificityi

Expressed in brain, heart, liver, lung, skeletal muscle, spinal cord, spleen and testis.2 Publications

Inductioni

Expressed is decreased following activation of the Notch pathway by JAG1/Jagged1.1 Publication

Gene expression databases

BgeeiENSMUSG00000024068.
CleanExiMM_SPAST.
GenevisibleiQ9QYY8. MM.

Interactioni

Subunit structurei

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.UniRule annotation

GO - Molecular functioni

Protein-protein interaction databases

BioGridi206134. 41 interactors.
IntActiQ9QYY8. 41 interactors.
STRINGi10090.ENSMUSP00000024869.

Structurei

3D structure databases

ProteinModelPortaliQ9QYY8.
SMRiQ9QYY8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini118 – 193MITSequence analysisAdd BLAST76

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 298Required for interaction with RTN1By similarityAdd BLAST298
Regioni1 – 192Required for midbody localizationBy similarityAdd BLAST192
Regioni1 – 78Required for interaction with ATL1By similarityAdd BLAST78
Regioni1 – 48Required for nuclear localizationBy similarityAdd BLAST48
Regioni48 – 85Required for interaction with SSNA1 and microtubulesBy similarityAdd BLAST38
Regioni110 – 194Sufficient for interaction with CHMP1BBy similarityAdd BLAST85
Regioni112 – 198Required for interaction with microtubulesBy similarityAdd BLAST87
Regioni226 – 614Sufficient for microtubule severingBy similarityAdd BLAST389
Regioni268 – 326Required for interaction with microtubules and microtubule severingBy similarityAdd BLAST59
Regioni308 – 310Required for interaction with microtubulesBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi4 – 11Nuclear localization signalUniRule annotation8
Motifi57 – 65Nuclear export signalUniRule annotation9
Motifi307 – 310Nuclear localization signalUniRule annotation4

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.
InParanoidiQ9QYY8.
KOiK13254.
OMAiGNPDGDR.
OrthoDBiEOG091G0Q8J.
PhylomeDBiQ9QYY8.
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9QYY8-1) [UniParc]FASTAAdd to basket
Also known as: 68 kDaBy similarity, M1By similarity

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
MSSPAGRRKK KGSGGASPAP ARPPPPAAVP APAAGPAPAA GSPPKRNPSS
60 70 80 90 100
FSSPLVVGFA LLRLLACHLG LLFAWLCQRF SRALMAAKRS SGTAPAPASP
110 120 130 140 150
SPPEPGPGGE AESVRVFHKQ AFEYISIALR IDEEEKAGQK EQAVEWYKKG
160 170 180 190 200
IEELEKGIAV IVTGQGEQYE RARRLQAKMM TNLVMAKDRL QLLEKLQPVL
210 220 230 240 250
QFSKSQTDVY NESTNLTCRN GHLQSESGAV PKRKDPLTHA SNSLPRSKTV
260 270 280 290 300
LKSGSAGLSG HHRAPSCSGL SMVSGARPGP GPAATTHKGT PKPNRTNKPS
310 320 330 340 350
TPTTAVRKKK DLKNFRNVDS NLANLIMNEI VDNGTAVKFD DIAGQELAKQ
360 370 380 390 400
ALQEIVILPS LRPELFTGLR APARGLLLFG PPGNGKTMLA KAVAAESNAT
410 420 430 440 450
FFNISAASLT SKYVGEGEKL VRALFAVARE LQPSIIFIDE VDSLLCERRE
460 470 480 490 500
GEHDASRRLK TEFLIEFDGV QSAGDDRVLV MGATNRPQEL DEAVLRRFIK
510 520 530 540 550
RVYVSLPNEE TRLLLLKNLL CKQGSPLTQK ELAQLARMTD GYSGSDLTAL
560 570 580 590 600
AKDAALGPIR ELKPEQVKNM SASEMRNIRL SDFTESLKKI KRSVSPQTLE
610
AYIRWNKDFG DTTV
Length:614
Mass (Da):66,456
Last modified:March 24, 2009 - v3
Checksum:iC0D235031A7E4C8F
GO
Isoform 2 (identifier: Q9QYY8-2) [UniParc]FASTAAdd to basket
Also known as: Short, Short variant 1, 60 kDaBy similarity, M87By similarity

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.

Show »
Length:530
Mass (Da):58,008
Checksum:iA7568D20A447B36A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti104E → A in BAC98092 (PubMed:14621295).Curated1
Sequence conflicti104E → A in AAH46286 (PubMed:15489334).Curated1
Sequence conflicti137Missing in AAH46286 (PubMed:15489334).Curated1
Sequence conflicti137Missing in BAB25259 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0583351 – 84Missing in isoform 2. CuratedAdd BLAST84

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK129282 mRNA. Translation: BAC98092.1.
BC046286 mRNA. Translation: AAH46286.1.
AK007793 mRNA. Translation: BAB25259.1.
AJ246002 mRNA. Translation: CAB60143.1.
CCDSiCCDS50181.1. [Q9QYY8-1]
RefSeqiNP_001156342.1. NM_001162870.1. [Q9QYY8-1]
NP_058658.2. NM_016962.2.
UniGeneiMm.19804.

Genome annotation databases

EnsembliENSMUST00000024869; ENSMUSP00000024869; ENSMUSG00000024068. [Q9QYY8-1]
GeneIDi50850.
KEGGimmu:50850.
UCSCiuc008dnz.2. mouse. [Q9QYY8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK129282 mRNA. Translation: BAC98092.1.
BC046286 mRNA. Translation: AAH46286.1.
AK007793 mRNA. Translation: BAB25259.1.
AJ246002 mRNA. Translation: CAB60143.1.
CCDSiCCDS50181.1. [Q9QYY8-1]
RefSeqiNP_001156342.1. NM_001162870.1. [Q9QYY8-1]
NP_058658.2. NM_016962.2.
UniGeneiMm.19804.

3D structure databases

ProteinModelPortaliQ9QYY8.
SMRiQ9QYY8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi206134. 41 interactors.
IntActiQ9QYY8. 41 interactors.
STRINGi10090.ENSMUSP00000024869.

PTM databases

iPTMnetiQ9QYY8.
PhosphoSitePlusiQ9QYY8.

Proteomic databases

EPDiQ9QYY8.
MaxQBiQ9QYY8.
PaxDbiQ9QYY8.
PeptideAtlasiQ9QYY8.
PRIDEiQ9QYY8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000024869; ENSMUSP00000024869; ENSMUSG00000024068. [Q9QYY8-1]
GeneIDi50850.
KEGGimmu:50850.
UCSCiuc008dnz.2. mouse. [Q9QYY8-1]

Organism-specific databases

CTDi6683.
MGIiMGI:1858896. Spast.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0740. Eukaryota.
COG0464. LUCA.
GeneTreeiENSGT00570000078874.
HOGENOMiHOG000225146.
HOVERGENiHBG108502.
InParanoidiQ9QYY8.
KOiK13254.
OMAiGNPDGDR.
OrthoDBiEOG091G0Q8J.
PhylomeDBiQ9QYY8.
TreeFamiTF105014.

Miscellaneous databases

PROiQ9QYY8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024068.
CleanExiMM_SPAST.
GenevisibleiQ9QYY8. MM.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiSPAST_MOUSE
AccessioniPrimary (citable) accession number: Q9QYY8
Secondary accession number(s): Q6ZPY6, Q80VE0, Q9CVK0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: March 24, 2009
Last modified: November 2, 2016
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.