| http://purl.uniprot.org/citations/15248095 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15248095 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15248095 | http://www.w3.org/2000/01/rdf-schema#comment | "Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurodegenerative disease characterized by wide variability in phenotypic expression, both within and among families. The most-common cause of autosomal dominant HSP is mutation of the gene encoding spastin, a protein of uncertain function. We report the existence of intragenic polymorphisms of spastin that modify the HSP phenotype. One (S44L) is a previously described recessively acting allele and the second is a novel allele affecting the adjacent amino acid residue (P45Q). In 4 HSP families in which either L44 or Q45 segregates independently of a missense or splicing mutation in the AAA domain of spastin, L44 and Q45 are each associated with a striking decrease in age at onset in the presence of the AAA domain mutations. Using a bioinformatics approach, we found that the highly conserved S44 is predicted to be phosphorylated by a number of family members of the proline-directed serine/threonine cyclin-dependent kinases (Cdks). Cdk1 and Cdk5 showed no kinase activity toward synthetic spastin peptide in an in vitro kinase assay, suggesting that this serine residue may be phosphorylated by a different Cdk. Our identification of S44L and P45Q as modifiers of the HSP phenotype suggests a role for spastin phosphorylation by Cdks in the neurodegeneration of the most-common form of HSP."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.org/dc/terms/identifier | "doi:10.1007/s10048-004-0186-z"xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.org/dc/terms/identifier | "doi:10.1007/s10048-004-0186-z"xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Hisanaga S."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Hisanaga S."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Pericak-Vance M.A."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Pericak-Vance M.A."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Garbern J.Y."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Garbern J.Y."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Gaskell P.C."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Gaskell P.C."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Marchuk D.A."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Marchuk D.A."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Svenson I.K."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Svenson I.K."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Nance M.A."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Nance M.A."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Ashley-Koch A.E."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Ashley-Koch A.E."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Kloos M.T."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/author | "Kloos M.T."xsd:string |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15248095 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |