Q9QYY8 (SPAST_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Spastin
EC=3.6.4.3

Gene names

Name:	Spast
Synonyms:	Kiaa1083, Spg4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	614 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	ATP-dependent microtubule severing protein. Microtubule severing may promote reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and for completion of the abscission stage of cytokinesis By similarity. Required for development of axonal processes and for axonal branching. Ref.7 Ref.9
Catalytic activity	ATP + H2O = ADP + phosphate. HAMAP-Rule MF_03021
Subunit structure	Homohexamer. Binding to ATP stabilizes the homohexameric form. Binds to microtubules at least in part via the alpha-tubulin and beta-tubulin tails. The hexamer may adopt 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 ATL1, RTN1, SSNA1 and ZFYVE27 By similarity. Interacts with RTN2 By similarity. Interacts with REEP1 By similarity.
Subcellular location	Membrane; Single-pass membrane protein Potential. Cytoplasm › cytoskeleton › centrosome By similarity. Cytoplasm › cytoskeleton By similarity. Cytoplasm › perinuclear region By similarity. Endoplasmic reticulum By similarity. Endosome By similarity. Nucleus By similarity. Cytoplasm › cytoskeleton › spindle By similarity. Note: Localization to the centrosome is independent of microtubules. Localizes to the midbody of dividing cells, and this requires CHMP1B By similarity. Evenly distributed along early axons and concentrates in the growth cone of the axons of late stage 3 neurons. Ref.7
Tissue specificity	Expressed in brain, heart, liver, lung, skeletal muscle, spinal cord, spleen and testis. Ref.4 Ref.5
Induction	Expressed is decreased following activation of the Notch pathway by JAG1/Jagged1. Ref.8
Disruption phenotype	Progressive axonal degeneration characterized by focal axonal swellings and the accumulation of organelles and cytoskeletal components, which is suggestive of impaired axonal transport. Late development of mild motor defects. Adults are sterile. Primary cortical neurons develop swellings at the border between stable and dynamic microtubules. Ref.6
Sequence similarities	Belongs to the AAA ATPase family. Spastin subfamily. Contains 1 MIT domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Differentiation Neurogenesis
Cellular component	Cytoplasm Cytoskeleton Endoplasmic reticulum Endosome Membrane Microtubule Nucleus
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER to Golgi vesicle-mediated transport Inferred from sequence or structural similarity. Source: UniProtKB cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cytokinesis, completion of separation Inferred from sequence or structural similarity. Source: UniProtKB microtubule bundle formation Inferred from sequence or structural similarity. Source: UniProtKB microtubule severing Inferred from sequence or structural similarity. Source: UniProtKB nervous system development Inferred from electronic annotation. Source: UniProtKB-KW protein hexamerization Inferred from sequence or structural similarity. Source: UniProtKB protein homooligomerization Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasmic vesicle Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell endosome Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microtubule Inferred from direct assay PubMed 20530212. Source: MGI microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell midbody Inferred from electronic annotation. Source: Compara nucleus Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell spindle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW alpha-tubulin binding Inferred from sequence or structural similarity. Source: UniProtKB beta-tubulin binding Inferred from sequence or structural similarity. Source: UniProtKB microtubule binding Inferred from sequence or structural similarity. Source: UniProtKB microtubule-severing ATPase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 614	614	Spastin HAMAP-Rule MF_03021		PRO_0000084764
Regions
	Transmembrane	55 – 77	23	Helical; Potential
	Domain	118 – 193	76	MIT
	Nucleotide binding	380 – 387	8	ATP Potential
	Region	1 – 298	298	Required for interaction with RTN1 By similarity
	Region	1 – 192	192	Required for midbody localization By similarity
	Region	1 – 78	78	Required for interaction with ATL1 By similarity
	Region	1 – 48	48	Required for nuclear localization By similarity
	Region	48 – 85	38	Required for interaction with SSNA1 and microtubules By similarity
	Region	110 – 194	85	Sufficient for interaction with CHMP1B By similarity
	Region	112 – 198	87	Required for interaction with microtubules By similarity
	Region	224 – 326	103	Sufficient for interaction with microtubules By similarity
	Region	226 – 614	389	Sufficient for microtubule severing By similarity
	Region	268 – 326	59	Required for interaction with microtubules and microtubule severing By similarity
	Motif	4 – 11	8	Nuclear localization signal By similarity
	Motif	57 – 65	9	Nuclear export signal By similarity
	Motif	307 – 310	4	Nuclear localization signal By similarity
Amino acid modifications
	Modified residue	243	1	Phosphoserine By similarity
	Modified residue	266	1	Phosphoserine By similarity
	Modified residue	304	1	Phosphothreonine By similarity
Experimental info
	Sequence conflict	104	1	E → A in BAC98092. Ref.1
	Sequence conflict	104	1	E → A in AAH46286. Ref.2
	Sequence conflict	137	1	Missing in AAH46286. Ref.2
	Sequence conflict	137	1	Missing in BAB25259. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9QYY8 [UniParc]. Last modified March 24, 2009. Version 3. Checksum: C0D235031A7E4C8F	FASTA	614	66,456
	10 20 30 40 50 60 MSSPAGRRKK KGSGGASPAP ARPPPPAAVP APAAGPAPAA GSPPKRNPSS FSSPLVVGFA 70 80 90 100 110 120 LLRLLACHLG LLFAWLCQRF SRALMAAKRS SGTAPAPASP SPPEPGPGGE AESVRVFHKQ 130 140 150 160 170 180 AFEYISIALR IDEEEKAGQK EQAVEWYKKG IEELEKGIAV IVTGQGEQYE RARRLQAKMM 190 200 210 220 230 240 TNLVMAKDRL QLLEKLQPVL QFSKSQTDVY NESTNLTCRN GHLQSESGAV PKRKDPLTHA 250 260 270 280 290 300 SNSLPRSKTV LKSGSAGLSG HHRAPSCSGL SMVSGARPGP GPAATTHKGT PKPNRTNKPS 310 320 330 340 350 360 TPTTAVRKKK DLKNFRNVDS NLANLIMNEI VDNGTAVKFD DIAGQELAKQ ALQEIVILPS 370 380 390 400 410 420 LRPELFTGLR APARGLLLFG PPGNGKTMLA KAVAAESNAT FFNISAASLT SKYVGEGEKL 430 440 450 460 470 480 VRALFAVARE LQPSIIFIDE VDSLLCERRE GEHDASRRLK TEFLIEFDGV QSAGDDRVLV 490 500 510 520 530 540 MGATNRPQEL DEAVLRRFIK RVYVSLPNEE TRLLLLKNLL CKQGSPLTQK ELAQLARMTD 550 560 570 580 590 600 GYSGSDLTAL AKDAALGPIR ELKPEQVKNM SASEMRNIRL SDFTESLKKI KRSVSPQTLE 610 AYIRWNKDFG DTTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Embryonic tail.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N-3. Tissue: Mammary tumor.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-614. Strain: C57BL/6J. Tissue: Pancreas.
[4]	"Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia." Hazan J., Fonknechten N., Mavel D., Paternotte C., Samson D., Artiguenave F., Davoine C.-S., Cruaud C., Durr A., Wincker P., Brottier P., Cattolico L., Barbe V., Burgunder J.-M., Prud'homme J.-F., Brice A., Fontaine B., Heilig R., Weissenbach J. Nat. Genet. 23:296-303(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 111-614, TISSUE SPECIFICITY.
[5]	"Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus." Claudiani P., Riano E., Errico A., Andolfi G., Rugarli E.I. Exp. Cell Res. 309:358-369(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition." Tarrade A., Fassier C., Courageot S., Charvin D., Vitte J., Peris L., Thorel A., Mouisel E., Fonknechten N., Roblot N., Seilhean D., Dierich A., Hauw J.J., Melki J. Hum. Mol. Genet. 15:3544-3558(2006) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[7]	"The microtubule-severing proteins spastin and katanin participate differently in the formation of axonal branches." Yu W., Qiang L., Solowska J.M., Karabay A., Korulu S., Baas P.W. Mol. Biol. Cell 19:1485-1498(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"Microtubule stabilizing effect of notch activation in primary cortical neurons." Ferrari-Toninelli G., Bonini S.A., Bettinsoli P., Uberti D., Memo M. Neuroscience 154:946-952(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[9]	"Pleiotropic effects of spastin on neurite growth depending on expression levels." Riano E., Martignoni M., Mancuso G., Cartelli D., Crippa F., Toldo I., Siciliano G., Di Bella D., Taroni F., Bassi M.T., Cappelletti G., Rugarli E.I. J. Neurochem. 108:1277-1288(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK129282 mRNA. Translation: BAC98092.1. BC046286 mRNA. Translation: AAH46286.1. AK007793 mRNA. Translation: BAB25259.1. AJ246002 mRNA. Translation: CAB60143.1.
IPI	IPI00420580.
RefSeq	NP_001156342.1. NM_001162870.1. NP_058658.2. NM_016962.2.
UniGene	Mm.19804.
3D structure databases
ProteinModelPortal	Q9QYY8.
SMR	Q9QYY8. Positions 110-194, 322-610.
ModBase	Search...
PTM databases
PhosphoSite	Q9QYY8.
Proteomic databases
PaxDb	Q9QYY8.
PRIDE	Q9QYY8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000024869; ENSMUSP00000024869; ENSMUSG00000024068.
GeneID	50850.
KEGG	mmu:50850.
UCSC	uc008dnz.2. mouse.
Organism-specific databases
CTD	6683.
MGI	MGI:1858896. Spast.
Rouge	Search...
Phylogenomic databases
eggNOG	COG0464.
GeneTree	ENSGT00570000078874.
HOGENOM	HOG000225146.
HOVERGEN	HBG108502.
InParanoid	Q9QYY8.
KO	K13254.
OMA	HKSTPKT.
OrthoDB	EOG4NZTTF.
Gene expression databases
Bgee	Q9QYY8.
CleanEx	MM_SPAST.
Genevestigator	Q9QYY8.
GermOnline	ENSMUSG00000024068. Mus musculus.
Family and domain databases
HAMAP	MF_03021. Spastin.
InterPro	IPR003593. AAA+_ATPase. IPR003959. ATPase_AAA_core. IPR003960. ATPase_AAA_CS. IPR007330. MIT. IPR027417. P-loop_NTPase. IPR017179. Spastin. [Graphical view]
PANTHER	PTHR23074:SF15. PTHR23074:SF15. 1 hit.
Pfam	PF00004. AAA. 1 hit. PF04212. MIT. 1 hit. [Graphical view]
PIRSF	PIRSF037338. Spastin. 1 hit.
SMART	SM00382. AAA. 1 hit. SM00745. MIT. 1 hit. [Graphical view]
SUPFAM	SSF52540. SSF52540. 1 hit.
PROSITE	PS00674. AAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	307827.
SOURCE	Search...

Entry information

Entry name

SPAST_MOUSE

Accession

Primary (citable) accession number: Q9QYY8
Secondary accession number(s): Q6ZPY6, Q80VE0, Q9CVK0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	March 24, 2009
Last modified:	May 29, 2013
This is version 114 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program