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Protein

Spastin

Gene

SPAST

Organism
Bos taurus (Bovine)
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. 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. Severing activity is not dependent on tubulin acetylation or detyrosination. 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. Recruited at the midbody, probably by IST1, and participates to membrane fission during abscission together with the ESCRT-III complex. Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling. Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing. Probably plays a role in axon growth and the formation of axonal branches.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 (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi380 – 3878ATPUniRule annotation

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:SPG4UniRule annotation
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 11

Subcellular locationi

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

  • 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. Enriched in the distal axons and branches of postmitotic neurons.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5656CytoplasmicBy similarityAdd
BLAST
Intramembranei57 – 7721HelicalBy similarityAdd
BLAST
Topological domaini78 – 614537CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Endoplasmic reticulum, Membrane, Microtubule, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in SPAST are the cause of bovine spinal dysmyelination (BSD), a neurodegenerative disorder characterized by pathological changes of the myelin sheaths in the spinal cord. Defects appear immediately at birth and include lateral recumbency with slight to moderate opisthotonos, body tremor, and spastic extension of the limbs. General muscle atrophy due to denervation occurs to variable degrees and is most obvious in the hind limbs. BSD is a longstanding problem in the American Brown Swiss (ABS) breed and in several European cattle breeds upgraded with ABS. The morphological cause of the phenotype is bilateral symmetrical hypo- and demyelination of axons in the cervical and thoracic segments of the spinal cord. The disease is caused by mutations affecting the gene represented in this entry.

Keywords - Diseasei

Disease mutation, Neurodegeneration

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 614614SpastinPRO_0000367133Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei243 – 2431PhosphoserineBy similarity
Modified residuei266 – 2661PhosphoserineBy similarity
Modified residuei304 – 3041PhosphothreonineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiA2VDN5.

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.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000044166.

Structurei

3D structure databases

ProteinModelPortaliA2VDN5.
SMRiA2VDN5. Positions 322-606.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini118 – 19376MITUniRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 298298Required for interaction with RTN1By similarityAdd
BLAST
Regioni1 – 192192Required for midbody localizationBy similarityAdd
BLAST
Regioni1 – 8080Required for interaction with ATL1By similarityAdd
BLAST
Regioni1 – 5050Required for nuclear localizationBy similarityAdd
BLAST
Regioni50 – 8738Required for interaction with SSNA1 and microtubulesBy similarityAdd
BLAST
Regioni110 – 19485Sufficient for interaction with CHMP1BBy similarityAdd
BLAST
Regioni112 – 19887Required for interaction with microtubulesBy similarityAdd
BLAST
Regioni226 – 614389Sufficient for microtubule severingBy similarityAdd
BLAST
Regioni268 – 32659Required for interaction with microtubules and microtubule severingBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi4 – 118Nuclear localization signalUniRule annotation
Motifi59 – 679Nuclear export signalUniRule annotation
Motifi307 – 3104Nuclear localization signalUniRule annotation

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0740. Eukaryota.
COG0464. LUCA.
GeneTreeiENSGT00570000078874.
HOGENOMiHOG000225146.
HOVERGENiHBG108502.
InParanoidiA2VDN5.
KOiK13254.
OMAiFCIFRYL.
OrthoDBiEOG7GXPCR.
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]

Sequencei

Sequence statusi: Complete.

A2VDN5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNSPGGRGKK KGSGGPSSPV PPRPPPPCQA RSRPAPKPAP PPQSPHKRNL
60 70 80 90 100
YYFSYPLFLG FALLRLVAFH LGLLFVWLCQ RFSRALMAAK RSSGAAPASA
110 120 130 140 150
SPPAPVPGGE AERVRAFHKQ AFEYISVALR IDEDEKVGQK DQAVEWYKKG
160 170 180 190 200
IEELEKGIAV VVTGQGEQCE RARRLQAKMM TNLVMAKDRL QLLEKLQPSL
210 220 230 240 250
QFSKSQTDVY NDSTNLTCRN GHLQSESGAV PKRKDPLTHA SNSLPRSKTV
260 270 280 290 300
MKTGPTGLSG HHRAPSCSGL SMVSGVRQGP GSAAATHKST PKTNRTNKPS
310 320 330 340 350
TPTTAARKKK 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 DEAVLRRFTK
510 520 530 540 550
RVYVSLPNEE TRLLLLKNLL CKQGSPLTQK ELAQLARMTN GYSGSDLTAL
560 570 580 590 600
AKDAALGPIR ELKPEQVKNM SASEMRNIRL SDFTESLKKI KRSVSPQTLE
610
AYIRWNKDFG DTTV
Length:614
Mass (Da):67,225
Last modified:March 20, 2007 - v1
Checksum:iB284B6EBF04D358F
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti560 – 5601R → Q in BSD. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC133327 mRNA. Translation: AAI33328.1.
RefSeqiNP_001075060.1. NM_001081591.1.
UniGeneiBt.46123.

Genome annotation databases

EnsembliENSBTAT00000046919; ENSBTAP00000044166; ENSBTAG00000021694.
GeneIDi521442.
KEGGibta:521442.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC133327 mRNA. Translation: AAI33328.1.
RefSeqiNP_001075060.1. NM_001081591.1.
UniGeneiBt.46123.

3D structure databases

ProteinModelPortaliA2VDN5.
SMRiA2VDN5. Positions 322-606.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000044166.

Proteomic databases

PaxDbiA2VDN5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000046919; ENSBTAP00000044166; ENSBTAG00000021694.
GeneIDi521442.
KEGGibta:521442.

Organism-specific databases

CTDi6683.

Phylogenomic databases

eggNOGiKOG0740. Eukaryota.
COG0464. LUCA.
GeneTreeiENSGT00570000078874.
HOGENOMiHOG000225146.
HOVERGENiHBG108502.
InParanoidiA2VDN5.
KOiK13254.
OMAiFCIFRYL.
OrthoDBiEOG7GXPCR.
TreeFamiTF105014.

Miscellaneous databases

NextBioi20873307.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Brain cortex.
  2. "Congenital bovine spinal dysmyelination is caused by a missense mutation in the SPAST gene."
    Thomsen B., Nissen P.H., Agerholm J.S., Bendixen C.
    Neurogenetics 11:175-183(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN BSD, VARIANT BSD GLN-560.

Entry informationi

Entry nameiSPAST_BOVIN
AccessioniPrimary (citable) accession number: A2VDN5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 24, 2009
Last sequence update: March 20, 2007
Last modified: May 11, 2016
This is version 77 of the entry and version 1 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. 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.