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Protein

Spastin

Gene

SPAST

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

ATP-dependent microtubule severing protein that specifically recognizes 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 in 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.UniRule annotation

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

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

Organism-specific databases

VGNCiVGNC:35174 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 – 56CytoplasmicUniRule annotationAdd BLAST56
Intramembranei57 – 77HelicalUniRule annotationAdd BLAST21
Topological domaini78 – 614CytoplasmicUniRule annotationAdd BLAST537

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.1 Publication

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003671331 – 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

PaxDbiA2VDN5
PRIDEiA2VDN5

Expressioni

Gene expression databases

BgeeiENSBTAG00000021694

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

STRINGi9913.ENSBTAP00000044166

Structurei

3D structure databases

ProteinModelPortaliA2VDN5
SMRiA2VDN5
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 – 80Required for interaction with ATL1By similarityAdd BLAST80
Regioni1 – 50Required for nuclear localizationBy similarityAdd BLAST50
Regioni50 – 87Required 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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi4 – 11Nuclear localization signalUniRule annotation8
Motifi59 – 67Nuclear 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
InParanoidiA2VDN5
KOiK13254
OMAiSEMRNIK
OrthoDBiEOG091G0Q8J
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

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)DescriptionActionsGraphical viewLength
Natural varianti560R → Q in BSD. 1 Publication1

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

Similar proteinsi

Entry informationi

Entry nameiSPAST_BOVIN
AccessioniPrimary (citable) accession number: A2VDN5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 24, 2009
Last sequence update: March 20, 2007
Last modified: March 28, 2018
This is version 91 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health