SPAST
entrez
6683
canonical
uniprot
Q9UBP0
canonical
ensembl
ENSG00000021574
resolver
ensp
ENSP00000320885
resolver
ensp
ENSP00000482496
resolver
ensp
ENSP00000493827
resolver
ensp
ENSP00000495015
resolver
ensp
ENSP00000495478
resolver
enst
ENST00000621856
resolver
enst
ENST00000642455
resolver
enst
ENST00000642751
resolver
genesymbol
SPAST
resolver
genesymbol_syn
ADPSP
resolver
genesymbol_syn
FSP2
resolver
genesymbol_syn
KIAA1083
resolver
genesymbol_syn
SPG4
resolver
hgnc
HGNC:11233
resolver
uniprot
A0A2R8Y4I8
resolver
uniprot
A0A2R8YFW8
resolver
uniprot
A0A2U3TZR0
resolver
uniprot
A7E2A7
resolver
uniprot
E5KRP5
resolver
uniprot
E5KRP6
resolver
uniprot
Q9UPR9
resolver
uniprot_entry
A0A2R8Y4I8_HUMAN
resolver
uniprot_entry
A0A2R8YFW8_HUMAN
resolver
uniprot_entry
A0A2U3TZR0_HUMAN
resolver
uniprot_entry
E5KRP5_HUMAN
resolver
uniprot_entry
E5KRP6_HUMAN
resolver
uniprot_entry
SPAST_HUMAN
resolver
uniprot_sec
A7E2A7
resolver
uniprot_sec
Q9UPR9
resolver
activity_regulation
ACTIVITY REGULATION: Allosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers (PubMed:22637577). Microtubule binding promotes cooperative interactions among spastin subunits (PubMed:22637577). ATP-bound enzyme interacts strongly and cooperatively with microtubules; this interaction stimulates ATP hydrolysis (PubMed:23745751). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23745751}.
uniprot
proteins
amino_acid_sequence
MNSPGGRGKKKGSGGASNPVPPRPPPPCLAPAPPAAGPAPPPESPHKRNLYYFSYPLFVGFALLRLVAFHLGLLFVWLCQRFSRALMAAKRSSGAAPAPASASAPAPVPGGEAERVRVFHKQAFEYISIALRIDEDEKAGQKEQAVEWYKKGIEELEKGIAVIVTGQGEQCERARRLQAKMMTNLVMAKDRLQLLEKMQPVLPFSKSQTDVYNDSTNLACRNGHLQSESGAVPKRKDPLTHTSNSLPRSKTVMKTGSAGLSGHHRAPSYSGLSMVSGVKQGSGPAPTTHKGTPKTNRTNKPSTPTTATRKKKDLKNFRNVDSNLANLIMNEIVDNGTAVKFDDIAGQDLAKQALQEIVILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAESNATFFNISAASLTSKYVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIEFDGVQSAGDDRVLVMGATNRPQELDEAVLRRFIKRVYVSLPNEETRLLLLKNLLCKQGSPLTQKELAQLARMTDGYSGSDLTALAKDAALGPIRELKPEQVKNMSASEMRNIRLSDFTESLKKIKRSVSPQTLEAYIRWNKDFGDTTV
uniprot
proteins
disease_involvement
DISEASE: Spastic paraplegia 4, autosomal dominant (SPG4) [MIM:182601]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:10610178, ECO:0000269|PubMed:10699187, ECO:0000269|PubMed:11015453, ECO:0000269|PubMed:11039577, ECO:0000269|PubMed:11087788, ECO:0000269|PubMed:11309678, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:11843700, ECO:0000269|PubMed:11985387, ECO:0000269|PubMed:12124993, ECO:0000269|PubMed:12161613, ECO:0000269|PubMed:12163196, ECO:0000269|PubMed:12202986, ECO:0000269|PubMed:12460147, ECO:0000269|PubMed:12552568, ECO:0000269|PubMed:12939659, ECO:0000269|PubMed:14732620, ECO:0000269|PubMed:15159500, ECO:0000269|PubMed:15210521, ECO:0000269|PubMed:15248095, ECO:0000269|PubMed:15326248, ECO:0000269|PubMed:15482961, ECO:0000269|PubMed:15667412, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:15891913, ECO:0000269|PubMed:16339213, ECO:0000269|PubMed:16682546, ECO:0000269|PubMed:16684598, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:17594340, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20214791, ECO:0000269|PubMed:20550563, ECO:0000269|PubMed:20562464, ECO:0000269|PubMed:20718791, ECO:0000269|PubMed:20932283, ECO:0000269|PubMed:21546041, ECO:0000269|PubMed:22960362, ECO:0000269|PubMed:23279441, ECO:0000269|PubMed:24824479, ECO:0000269|PubMed:25045380, ECO:0000269|PubMed:25421405, ECO:0000269|PubMed:28572275}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
5.6.1.1
uniprot
proteins
function
FUNCTION: ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, PubMed:20530212, PubMed:22637577, PubMed:26875866). 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 (PubMed:26875866). Severing activity is not dependent on tubulin acetylation or detyrosination (PubMed:26875866). 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 (PubMed:19000169, PubMed:21310966, PubMed:26040712). Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex (PubMed:21310966). Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling (PubMed:23897888). Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing (PubMed:23897888). Probably plays a role in axon growth and the formation of axonal branches (PubMed:15716377). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:16219033, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20530212, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23897888, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:26875866}.; FUNCTION: [Isoform 1]: Involved in lipid metabolism by regulating the size and distribution of lipid droplets. {ECO:0000269|PubMed:25875445}.
uniprot
proteins
mass_dalton
67197
uniprot
proteins
mutagenesis
MUTAGEN 1; /note="M->V: Cytoplasmic and nuclear."; /evidence="ECO:0000269|PubMed:16026783"; MUTAGEN 65; /note="R->G: Abolishes localization to lipid droplets."; /evidence="ECO:0000269|PubMed:25875445"; MUTAGEN 81..84; /note="RFSR->GFSG: Does not affect localization to lipid droplets."; /evidence="ECO:0000269|PubMed:25875445"; MUTAGEN 87; /note="M->V: Exclusively cytoplasmic."; /evidence="ECO:0000269|PubMed:16026783"; MUTAGEN 120; /note="H->D: Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-124."; /evidence="ECO:0000269|PubMed:18997780"; MUTAGEN 124; /note="F->A: Impairs binding to CHMP1B."; /evidence="ECO:0000269|PubMed:18997780"; MUTAGEN 124; /note="F->D: Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-120."; /evidence="ECO:0000269|PubMed:18997780"; MUTAGEN 310..312; /note="KKK->QQQ: Loss of microtubule-binding."; /evidence="ECO:0000269|PubMed:23272056"; MUTAGEN 388; /note="K->A: Abrogates ATPase activity and abolishes microtubule severing."; /evidence="ECO:0000269|PubMed:15716377"; MUTAGEN 415; /note="Y->A: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing."; /evidence="ECO:0000269|PubMed:17389232"; MUTAGEN 442; /note="E->Q: Abrogates ATP hydrolysis, abolishes microtubule severing, stabilizes the homohexameric form, and promotes microtubule binding and redistribution from the endosome to microtubules."; /evidence="ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:16815977, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:18410514, ECO:0000269|PubMed:22446388, ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23272056, ECO:0000269|PubMed:23745751"; MUTAGEN 448; /note="C->A,G: Abolishes ATPase activity."; /evidence="ECO:0000269|PubMed:23745751"; MUTAGEN 448; /note="C->S: Does not affect ATPase activity."; /evidence="ECO:0000269|PubMed:23745751"; MUTAGEN 451; /note="R->G: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing."; /evidence="ECO:0000269|PubMed:17389232"; MUTAGEN 457; /note="A->E: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin and abolishes microtubule severing."; /evidence="ECO:0000269|PubMed:17389232
uniprot
proteins
protein_family
AAA ATPase family
uniprot
proteins
protein_family
Spastin subfamily
uniprot
proteins
pubmed
10470851
uniprot
proteins
pubmed
10610178
uniprot
proteins
pubmed
10699187
uniprot
proteins
pubmed
11015453
uniprot
proteins
pubmed
11039577
uniprot
proteins
pubmed
11087788
uniprot
proteins
pubmed
11309678
uniprot
proteins
pubmed
11809724
uniprot
proteins
pubmed
11843700
uniprot
proteins
pubmed
11985387
uniprot
proteins
pubmed
12124993
uniprot
proteins
pubmed
12161613
uniprot
proteins
pubmed
12163196
uniprot
proteins
pubmed
12202986
uniprot
proteins
pubmed
12460147
uniprot
proteins
pubmed
12552568
uniprot
proteins
pubmed
12676568
uniprot
proteins
pubmed
12939659
uniprot
proteins
pubmed
14732620
uniprot
proteins
pubmed
15147984
uniprot
proteins
pubmed
15159500
uniprot
proteins
pubmed
15210521
uniprot
proteins
pubmed
15248095
uniprot
proteins
pubmed
15269182
uniprot
proteins
pubmed
15326248
uniprot
proteins
pubmed
15482961
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15537668
uniprot
proteins
pubmed
15667412
uniprot
proteins
pubmed
15716377
uniprot
proteins
pubmed
15891913
uniprot
proteins
pubmed
16026783
uniprot
proteins
pubmed
16219033
uniprot
proteins
pubmed
16339213
uniprot
proteins
pubmed
16602018
uniprot
proteins
pubmed
16682546
uniprot
proteins
pubmed
16684598
uniprot
proteins
pubmed
16815977
uniprot
proteins
pubmed
16826525
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17389232
uniprot
proteins
pubmed
17594340
uniprot
proteins
pubmed
18410514
uniprot
proteins
pubmed
18613979
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18997780
uniprot
proteins
pubmed
19000169
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20200447
uniprot
proteins
pubmed
20214791
uniprot
proteins
pubmed
20530212
uniprot
proteins
pubmed
20550563
uniprot
proteins
pubmed
20562464
uniprot
proteins
pubmed
20718791
uniprot
proteins
pubmed
20932283
uniprot
proteins
pubmed
21310966
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21546041
uniprot
proteins
pubmed
22232211
uniprot
proteins
pubmed
22446388
uniprot
proteins
pubmed
22637577
uniprot
proteins
pubmed
22960362
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23272056
uniprot
proteins
pubmed
23279441
uniprot
proteins
pubmed
23745751
uniprot
proteins
pubmed
23897888
uniprot
proteins
pubmed
23969831
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24824479
uniprot
proteins
pubmed
25045380
uniprot
proteins
pubmed
25390646
uniprot
proteins
pubmed
25421405
uniprot
proteins
pubmed
25875445
uniprot
proteins
pubmed
26040712
uniprot
proteins
pubmed
26875866
uniprot
proteins
pubmed
28572275
uniprot
proteins
pubmed
37316325
uniprot
proteins
sequence_length
616
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Membrane {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:19000169}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000305|PubMed:20200447}. Endoplasmic reticulum {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:16602018}. Midbody {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:18997780, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:25390646}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15891913, ECO:0000269|PubMed:25390646}. Cytoplasm, cytoskeleton {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:18410514, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20200447}. Cytoplasm, perinuclear region {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:15147984, ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15537668}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15147984, ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:16026783}. Cytoplasm, cytoskeleton, spindle {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15269182}. Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:16026783, ECO:0000269|PubMed:20200447}. Cell projection, axon {ECO:0000269|PubMed:15269182}. Note=Forms an intramembrane hairpin-like structure in the membrane (PubMed:20200447). Localization to the centrosome is independent of microtubules (PubMed:15891913). Localizes to the midbody of dividing cells, and this requires CHMP1B (PubMed:18997780). Enriched in the distal axons and branches of postmitotic neurons (PubMed:15269182). Mainly nuclear in interphase cells and becomes associated with the centrosomes, spindle microtubules, midzone and finally the midbody during cell division (PubMed:15269182). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:15269182, ECO:0000269|PubMed:15891913, ECO:0000269|PubMed:18997780, ECO:0000305|PubMed:20200447}.; SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:23969831}; Peripheral membrane protein {ECO:0000305|PubMed:20200447}. Nucleus membrane {ECO:0000269|PubMed:26040712}. Lipid droplet {ECO:0000269|PubMed:25875445}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20200447}. Endosome {ECO:0000269|PubMed:23897888}. Note=Forms an intramembrane hairpin-like structure in the membrane (PubMed:20200447). Recruited to nuclear membrane by IST1 during late anaphase (PubMed:26040712). Localizes to endoplasmic reticulum tubular network (PubMed:23969831). {ECO:0000269|PubMed:23969831, ECO:0000269|PubMed:26040712, ECO:0000305|PubMed:20200447}.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm {ECO:0000269|PubMed:20200447, ECO:0000269|PubMed:23969831}. Endosome {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:23897888}. Nucleus membrane {ECO:0000269|PubMed:16026783, ECO:0000269|PubMed:26040712}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:25390646}. Note=Constitutes the main endosomal form (PubMed:19000169). Recruited to nuclear membrane by IST1 during late anaphase (PubMed:26040712). {ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:26040712}.
uniprot
proteins