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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UBP0: Variant p.Cys448Tyr

Spastin
Gene: SPAST
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Variant information Variant position: help 448 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Cysteine (C) to Tyrosine (Y) at position 448 (C448Y, p.Cys448Tyr). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from medium size and polar (C) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In SPG4; abrogates binding to the tail of beta-3-tubulin, abolishes microtubule severing and promotes the formation of thick microtubule bundles. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 448 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 616 The length of the canonical sequence.
Location on the sequence: help AVARELQPSIIFIDEVDSLL C ERREGEHDASRRLKTEFLIE The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         AVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIE

Mouse                         AVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIE

Rat                           AVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIE

Pig                           AVARELQPSIIFIDEVDSLLRERREGEHDASRRLKTEFLIE

Bovine                        AVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIE

Chicken                       AVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIE

Xenopus laevis                SVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIE

Xenopus tropicalis            SVARELQPSIIFIDEVDSLLCERREGEHDASRRLKTEFLIE

Zebrafish                     AVARELQPSIIFIDEIDSLLCERREGEHDASRRLKTEFLIE

Caenorhabditis elegans        QIARNAQPSIIFIDEIDSILCERSEKDAEVSRRMKTEFLVQ

Drosophila                    AVARHMQPSIIFIDEVDSLLSERSSSEHEASRRLKTEFLVE

Slime mold                    AVATHFQPSIIFIDEIDSLLTERSSNESEASRRLKTEILVQ
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 616 Spastin
Topological domain 78 – 616 Cytoplasmic
Region 228 – 616 Sufficient for microtubule severing
Mutagenesis 442 – 442 E -> Q. Abrogates ATP hydrolysis, abolishes microtubule severing, stabilizes the homohexameric form, and promotes microtubule binding and redistribution from the endosome to microtubules.
Mutagenesis 448 – 448 C -> AG. Abolishes ATPase activity.
Mutagenesis 448 – 448 C -> S. Does not affect ATPase activity.
Mutagenesis 451 – 451 R -> G. Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing.
Mutagenesis 457 – 457 A -> E. Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin and abolishes microtubule severing.



Literature citations
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)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1); TISSUE SPECIFICITY; DEVELOPMENTAL STAGE; VARIANTS SPG4 CYS-362; TYR-448 AND CYS-499; Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics.
Errico A.; Ballabio A.; Rugarli E.I.;
Hum. Mol. Genet. 11:153-163(2002)
Cited for: FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS SPG4 ARG-370; CYS-381; LYS-386; ARG-388; VAL-426; TYR-448; LEU-460; CYS-499 AND VAL-556; Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing.
White S.R.; Evans K.J.; Lary J.; Cole J.L.; Lauring B.P.;
J. Cell Biol. 176:995-1005(2007)
Cited for: FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; HOMOHEXAMERIZATION; INTERACTION WITH TUBULIN AND MICROTUBULES; SUBCELLULAR LOCATION; MUTAGENESIS OF TYR-415; GLU-442; ARG-451 AND ALA-457; CHARACTERIZATION OF VARIANT SPG4 TYR-448; Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia.
Fonknechten N.; Mavel D.; Byrne P.; Davoine C.-S.; Cruaud C.; Bonsch D.; Samson D.; Coutinho P.; Hutchinson M.; McMonagle P.; Burgunder J.-M.; Tartaglione A.; Heinzlef O.; Feki I.; Deufel T.; Parfrey N.; Brice A.; Fontaine B.; Prud'homme J.-F.; Weissenbach J.; Duerr A.; Hazan J.;
Hum. Mol. Genet. 9:637-644(2000)
Cited for: VARIANTS SPG4 CYS-362; ARG-370; CYS-381; LYS-386; ARG-388; VAL-426; TYR-448; LEU-460; CYS-499; ASN-555 AND VAL-556;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.