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Protein

Spastin

Gene

Spast

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Activity 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

Keywordsi

Molecular functionAllosteric enzyme, Developmental protein, Hydrolase
Biological processCell cycle, Cell division, Differentiation, Neurogenesis
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1858896 Spast

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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 Expressed in 312 organ(s), highest expression level in zygote
CleanExiMM_SPAST
ExpressionAtlasiQ9QYY8 baseline and differential
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

Phylogenomic databases

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

Family and domain databases

HAMAPiMF_03021 Spastin, 1 hit
InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR003959 ATPase_AAA_core
IPR003960 ATPase_AAA_CS
IPR007330 MIT
IPR027417 P-loop_NTPase
IPR017179 Spastin
IPR035106 Spastin_chordate
IPR015415 Vps4_C
PfamiView protein in Pfam
PF00004 AAA, 1 hit
PF09336 Vps4_C, 1 hit
PIRSFiPIRSF037338 Spastin, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SM00745 MIT, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00674 AAA, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A286YE25A0A286YE25_MOUSE
Spastin
Spast SPAST, SPG4
613Annotation score:
A0A286YCJ4A0A286YCJ4_MOUSE
Spastin
Spast
300Annotation score:

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

Similar proteinsi

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
OMAiSEMRNIK
OrthoDBiEOG091G0Q8J
PhylomeDBiQ9QYY8
TreeFamiTF105014

Miscellaneous databases

PROiPR:Q9QYY8
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024068 Expressed in 312 organ(s), highest expression level in zygote
CleanExiMM_SPAST
ExpressionAtlasiQ9QYY8 baseline and differential
GenevisibleiQ9QYY8 MM

Family and domain databases

HAMAPiMF_03021 Spastin, 1 hit
InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR003959 ATPase_AAA_core
IPR003960 ATPase_AAA_CS
IPR007330 MIT
IPR027417 P-loop_NTPase
IPR017179 Spastin
IPR035106 Spastin_chordate
IPR015415 Vps4_C
PfamiView protein in Pfam
PF00004 AAA, 1 hit
PF09336 Vps4_C, 1 hit
PIRSFiPIRSF037338 Spastin, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SM00745 MIT, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00674 AAA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSPAST_MOUSE
AccessioniPrimary (citable) accession number: Q9QYY8
Secondary accession number(s): Q6ZPY6, Q80VE0, Q9CVK0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: March 24, 2009
Last modified: October 10, 2018
This is version 157 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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