SPAST_HUMAN
Source:
PM19886704
PM23856902
Marked as 'Integral membrane protein'
Confidence:
low (only semi-automatic identification from reviews)
Search PubMed for
(RBC AND this entry)
Gene names:
SPAST
, ADPSP, FSP2, KIAA1083, SPG4
Protein names and data:
SPAST_HUMAN
, Spastin; 3.6.4.3
, Spastic paraplegia 4 protein
Lenght: 616 a.a.
Mass: 67197 Da
fasta formatted sequence
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. May also play a role in axon growth and the formation of axonal branches.
Catalytic activity:
ATP + H(2)O = ADP + phosphate.
Disease:
( OMIM:
182601
604277
)
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. Note=The disease is caused by mutations affecting the gene represented in this entry.
Cellular location:
Membrane; Single-pass membrane protein (Potential). Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton. Cytoplasm, perinuclear region. Endoplasmic reticulum. Endosome. Nucleus. Cytoplasm, cytoskeleton, spindle. Note=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. Isoform 3 is the main endosomal form.
Tissue specificity:
Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. The short isoforms may predominate in brain and spinal cord.
Genetic variants
44 - 44
S -> L (rare polymorphism which modifies the phenotype of SPG4 disease; may decrease the activity of the alternative promoter which directs the synthesis of isoform 3 and isoform 4; dbSNP:rs121908515). VAR_010194
121908515
45 - 45
P -> Q (rare polymorphism which modifies the phenotype of SPG4 disease). VAR_027205
97 - 97
P -> T (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067628
162 - 162
V -> I (in a patient with hereditary spastic paraplegia; unknown pathological significance; dbSNP:rs141944844). VAR_067563
141944844
195 - 195
L -> V (in SPG4). VAR_026758
201 - 201
V -> D (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067629
229 - 229
S -> G. VAR_067630
287 - 287
Missing (in SPG4). VAR_067631
293 - 293
P -> L (in SPG4). VAR_067632
314 - 314
L -> S (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067633
328 - 328
I -> L (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067634
344 - 344
I -> K (in SPG4; abrogates ATPase activity and promotes microtubule binding). VAR_019448
347 - 347
Q -> K (in SPG4; promotes microtubule binding). VAR_027206
356 - 356
E -> K (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067564
360 - 360
L -> V (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067635
361 - 361
P -> L (in SPG4). VAR_027207
362 - 362
S -> C (in SPG4). VAR_010195
364 - 364
R -> T (in SPG4). VAR_067636
365 - 365
P -> S (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067565
370 - 370
G -> R (in SPG4; promotes microtubule binding and the formation of thick microtubule bundles). VAR_027208
378 - 378
L -> Q (in SPG4). VAR_019439
378 - 378
L -> R (in SPG4). VAR_067637
380 - 380
L -> H (in SPG4). VAR_067638
381 - 381
F -> C (in SPG4; promotes microtubule binding and the formation of thick microtubule bundles). VAR_027209
382 - 382
G -> R (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067566
386 - 386
N -> K (in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles). VAR_027210
386 - 386
N -> S (in SPG4). VAR_019440
388 - 388
K -> R (in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles and impairs traffic from the ER to Golgi). VAR_027211
390 - 390
M -> V (in SPG4). VAR_019441
391 - 391
L -> P (in SPG4). VAR_067639
393 - 396
Missing (in SPG4). VAR_067640
399 - 399
S -> L (in SPG4). VAR_027212
404 - 404
Missing (in SPG4). VAR_019449
406 - 406
I -> V (in SPG4). VAR_026759
407 - 407
S -> I (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067567
407 - 407
S -> R (in SPG4). VAR_019450
409 - 409
A -> T (in SPG4). VAR_067641
410 - 410
S -> R (in SPG4). VAR_067642
413 - 413
S -> L (in SPG4). VAR_067568
422 - 422
L -> F (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067569
423 - 423
V -> L (in a breast cancer sample; somatic mutation). VAR_035902
424 - 424
R -> G (in SPG4). VAR_010196
426 - 426
L -> F (in SPG4). VAR_067643
426 - 426
L -> V (in SPG4; promotes microtubule binding and the formation of thick microtubule bundles). VAR_027213
435 - 435
P -> L (in SPG4). VAR_027214
436 - 436
S -> F (in SPG4). VAR_027215
436 - 436
S -> P (in SPG4). VAR_067644
441 - 441
D -> G (in SPG4). VAR_027216
441 - 441
D -> N (in SPG4). VAR_067645
445 - 445
S -> N (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067570
448 - 448
C -> Y (in SPG4; abrogates binding to the tail of beta-3-tubulin, abolishes microtubule severing and promotes the formation of thick microtubule bundles). VAR_010197
454 - 454
E -> K (in SPG4). VAR_067571
459 - 459
R -> G (in SPG4). VAR_027217
460 - 460
R -> C (in SPG4; promotes microtubule binding and the formation of thick microtubule bundles). VAR_027218
460 - 460
R -> L (in SPG4). VAR_027219
460 - 460
R -> S (in SPG4). VAR_067572
463 - 463
T -> A (in SPG4). VAR_067646
464 - 464
E -> A (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067647
470 - 470
D -> V (in SPG4; dbSNP:rs28939368). VAR_027220
28939368
482 - 482
V -> L (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067573
485 - 485
A -> V (in SPG4). VAR_027221
489 - 489
P -> L (in SPG4). VAR_027222
492 - 492
L -> F (in SPG4). VAR_067648
493 - 493
D -> G (in SPG4). VAR_026760
498 - 498
R -> G (in SPG4). VAR_067649
499 - 499
R -> C (in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles). VAR_010198
499 - 499
R -> H (in SPG4). VAR_026761
503 - 503
R -> L (in SPG4). VAR_019442
503 - 503
R -> RR (in SPG4). VAR_067650
503 - 503
R -> W (in SPG4). VAR_026762
512 - 512
E -> D (in SPG4). VAR_027223
512 - 512
Missing (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067574
514 - 514
R -> G (in SPG4). VAR_067651
515 - 515
Missing (in SPG4). VAR_019443
534 - 534
L -> P (in SPG4). VAR_019444
534 - 534
L -> V (found at homozygosity in two children with hereditary spastic paraplegia; unknown pathological significance). VAR_067575
550 - 550
T -> I (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067652
551 - 551
A -> Y (in SPG4; requires 2 nucleotide substitutions). VAR_019451
555 - 555
D -> N (in SPG4). VAR_027224
556 - 556
A -> V (in SPG4; promotes microtubule binding and the formation of thick microtubule bundles). VAR_027225
559 - 559
G -> D (in SPG4). VAR_027226
562 - 562
R -> G (in SPG4). VAR_027227
562 - 562
R -> P (in a patient with hereditary spastic paraplegia; unknown pathological significance). VAR_067576
562 - 562
R -> Q (in SPG4). VAR_027228
579 - 579
N -> H (found in patients with hereditary spastic paraplegia; unknown pathological significance; dbSNP:rs144594804). VAR_067653
144594804
580 - 580
I -> T (in SPG4). VAR_067654
584 - 584
D -> H (in SPG4). VAR_010199
607 - 607
W -> C (in SPG4). VAR_026763
614 - 614
T -> I (in SPG4; variant form with congenital arachnoid cysts). VAR_019445
615 - 615
T -> I (in SPG4). VAR_019452
Database cross-references
UniProt:
Q9UBP0
Ensembl:
ENST00000315285
Ensembl:
ENST00000345662
MIM:
182601
MIM:
604277
neXtProt:
NX_Q9UBP0
Antibodypedia:
Q9UBP0
(may not find the protein thus also not any antibody)
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