Spastin

SPAST
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3EAB, 3VFD
Identifiers
Aliases	SPAST , ADPSP, FSP2, SPG4, spastin
External IDs	OMIM: 604277 MGI: 1858896 HomoloGene: 8970 GeneCards: SPAST
Gene location (Human) Chr. Chromosome 2 (human) [1] Band 2p22.3 Start 32,063,556 bp [1] End 32,157,637 bp [1]
Gene location (Mouse) Chr. Chromosome 17 (mouse) [2] Band 17|17 E2 Start 74,645,982 bp [2] End 74,698,110 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte ganglionic eminence Achilles tendon palpebral conjunctiva germinal epithelium endothelial cell tibia amniotic fluid monocyte Top expressed in secondary oocyte barrel cortex medullary collecting duct medial ganglionic eminence trigeminal ganglion sexually immature organism superior cervical ganglion spermatocyte vastus lateralis muscle triceps brachii muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding alpha-tubulin binding microtubule-severing ATPase activity protein binding catalytic activity hydrolase activity ATP binding beta-tubulin binding microtubule binding isomerase activity ATPase activity protein-containing complex binding Cellular component cytoplasm endosome membrane microtubule cytoskeleton spindle microtubule organizing center midbody endoplasmic reticulum perinuclear region of cytoplasm microtubule extracellular exosome cytoplasmic vesicle nucleus cytoskeleton axon cytoplasm nuclear membrane lipid droplet endoplasmic reticulum membrane nucleoplasm cytosol endoplasmic reticulum tubular network ESCRT III complex centrosome integral component of membrane Biological process cell differentiation nervous system development positive regulation of cytokinesis multicellular organism development cell division microtubule bundle formation cell cycle metabolism protein homooligomerization nuclear membrane reassembly exit from mitosis mitotic cytokinesis cytoplasmic microtubule organization microtubule severing anterograde axonal transport mitotic spindle disassembly axonal transport of mitochondrion membrane fission endoplasmic reticulum to Golgi vesicle-mediated transport protein hexamerization cytokinetic process axonogenesis positive regulation of microtubule depolymerization cytoskeleton-dependent cytokinesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6683 50850 Ensembl ENSG00000021574 ENSMUSG00000024068 UniProt Q9UBP0 Q9QYY8 RefSeq (mRNA) NM_014946 NM_199436 NM_001363823 NM_001363875 NM_001377959 NM_001162870 NM_016962 NM_001357738 RefSeq (protein) NP_055761 NP_955468 NP_001350752 NP_001350804 NP_001364888 NP_001156342 NP_058658 NP_001344667 Location (UCSC) Chr 2: 32.06 – 32.16 Mb Chr 17: 74.65 – 74.7 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The human gene SPAST codes for the microtubule-severing protein of the same name, commonly known as spastin. ^[5]

This gene encodes a member of the AAA (ATPases associated with a variety of cellular activities) protein family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. The encoded ATPase may be involved in the assembly or function of nuclear protein complexes. Two transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described but their full length sequences have not been determined. Mutations associated with this gene cause the most frequent form of autosomal dominant spastic paraplegia 4. ^[6]

See also

Spastic paraplegia

References

1. GRCh38: Ensembl release 89: ENSG00000021574 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024068 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Roll-Mecak A, Vale RD (2008). "Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin". Nature . 451 (7176): 363–7. Bibcode:2008Natur.451..363R. doi:10.1038/nature06482. PMC   2882799 . PMID   18202664.
6. "Entrez Gene: SPAST spastin".

Further reading

• Kikuno R, Nagase T, Ishikawa K, et al. (1999). "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (3): 197–205. doi: 10.1093/dnares/6.3.197 . PMID   10470851.
• Hazan J, Davoine CS, Mavel D, et al. (1999). "A fine integrated map of the SPG4 locus excludes an expanded CAG repeat in chromosome 2p-linked autosomal dominant spastic paraplegia". Genomics . 60 (3): 309–19. doi:10.1006/geno.1999.5932. PMID   10493830.
• Hazan J, Fonknechten N, Mavel D, et al. (1999). "Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia". Nat. Genet. 23 (3): 296–303. doi:10.1038/15472. PMID   10610178. S2CID   23167276.
• Fonknechten N, Mavel D, Byrne P, et al. (2000). "Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia". Hum. Mol. Genet. 9 (4): 637–44. doi: 10.1093/hmg/9.4.637 . PMID   10699187.
• Santorelli FM, Patrono C, Fortini D, et al. (2000). "Intrafamilial variability in hereditary spastic paraplegia associated with an SPG4 gene mutation". Neurology . 55 (5): 702–5. doi:10.1212/wnl.55.5.702. PMID   10980739. S2CID   38129619.
• Lindsey JC, Lusher ME, McDermott CJ, et al. (2001). "Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis". J. Med. Genet. 37 (10): 759–65. doi:10.1136/jmg.37.10.759. PMC   1757167 . PMID   11015453.
• Bürger J, Fonknechten N, Hoeltzenbein M, et al. (2001). "Hereditary spastic paraplegia caused by mutations in the SPG4 gene". Eur. J. Hum. Genet. 8 (10): 771–6. doi: 10.1038/sj.ejhg.5200528 . PMID   11039577.
• Hentati A, Deng HX, Zhai H, et al. (2000). "Novel mutations in spastin gene and absence of correlation with age at onset of symptoms". Neurology . 55 (9): 1388–90. doi:10.1212/wnl.55.9.1388. PMID   11087788. S2CID   41471774.
• Svenson IK, Ashley-Koch AE, Gaskell PC, et al. (2001). "Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia". Am. J. Hum. Genet. 68 (5): 1077–85. doi:10.1086/320111. PMC   1226088 . PMID   11309678.
• Svenson IK, Ashley-Koch AE, Pericak-Vance MA, Marchuk DA (2002). "A second leaky splice-site mutation in the spastin gene". Am. J. Hum. Genet. 69 (6): 1407–9. doi:10.1086/324593. PMC   1235553 . PMID   11704932.
• Errico A, Ballabio A, Rugarli EI (2002). "Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics". Hum. Mol. Genet. 11 (2): 153–63. doi:10.1093/hmg/11.2.153. PMID   11809724.
• Meijer IA, Hand CK, Cossette P, et al. (2002). "Spectrum of SPG4 mutations in a large collection of North American families with hereditary spastic paraplegia". Arch. Neurol. 59 (2): 281–6. doi: 10.1001/archneur.59.2.281 . PMID   11843700.
• Patrono C, Casali C, Tessa A, et al. (2002). "Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia". J. Neurol. 249 (2): 200–5. doi:10.1007/PL00007865. PMID   11985387. S2CID   22503829.
• Morita M, Ho M, Hosler BA, et al. (2002). "A novel mutation in the spastin gene in a family with spastic paraplegia". Neurosci. Lett. 325 (1): 57–61. doi:10.1016/S0304-3940(02)00239-2. PMID   12023066. S2CID   26359975.
• Sauter S, Miterski B, Klimpe S, et al. (2002). "Mutation analysis of the spastin gene (SPG4) in patients in Germany with autosomal dominant hereditary spastic paraplegia". Hum. Mutat. 20 (2): 127–32. doi:10.1002/humu.10105. PMID   12124993. S2CID   28344764.
• Yabe I, Sasaki H, Tashiro K, et al. (2002). "Spastin gene mutation in Japanese with hereditary spastic paraplegia". J. Med. Genet. 39 (8): 46e–46. doi:10.1136/jmg.39.8.e46. PMC   1735214 . PMID   12161613.
• Proukakis C, Hart PE, Cornish A, et al. (2002). "Three novel spastin (SPG4) mutations in families with autosomal dominant hereditary spastic paraplegia". J. Neurol. Sci. 201 (1–2): 65–9. doi:10.1016/S0022-510X(02)00192-2. PMID   12163196. S2CID   44994475.
• Ki CS, Lee WY, Han DH, et al. (2002). "A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia". J. Hum. Genet. 47 (9): 473–7. doi: 10.1007/s100380200068 . PMID   12202986.
• Namekawa M, Takiyama Y, Sakoe K, et al. (2003). "A Japanese SPG4 family with a novel missense mutation of the SPG4 gene: intrafamilial variability in age at onset and clinical severity". Acta Neurol. Scand. 106 (6): 387–91. doi:10.1034/j.1600-0404.2002.01254.x. PMID   12460147. S2CID   43161611.
• Starling A, Rocco P, Passos-Bueno MR, et al. (2003). "Autosomal dominant (AD) pure spastic paraplegia (HSP) linked to locus SPG4 affects almost exclusively males in a large pedigree". J. Med. Genet. 39 (12): 77e–77. doi:10.1136/jmg.39.12.e77. PMC   1757223 . PMID   12471215.

External links

• GeneReviews/NCBI/NIH/UW entry on Spastic Paraplegia Type 4