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UniProtKB/Swiss-Prot Q9UBP0: Variant p.Pro435Leu

Spastin
Gene: SPAST
Variant information

Variant position:  435
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Proline (P) to Leucine (L) at position 435 (P435L, p.Pro435Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  In SPG4.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  435
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  616
The length of the canonical sequence.

Location on the sequence:   YVGEGEKLVRALFAVARELQ  P SIIFIDEVDSLLCERREGEH
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         YVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEH

Mouse                         YVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEH

Rat                           YVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEH

Pig                           YVGEGEKLVRALFAVARELQPSIIFIDEVDSLLRERREGEH

Bovine                        YVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEH

Chicken                       YVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCERREGEH

Xenopus laevis                YVGEGEKLVRALFSVARELQPSIIFIDEVDSLLCERREGEH

Xenopus tropicalis            YVGEGEKLVRALFSVARELQPSIIFIDEVDSLLCERREGEH

Zebrafish                     YVGEGEKLVRALFAVARELQPSIIFIDEIDSLLCERREGEH

Caenorhabditis elegans        WVGDSEKTIRGLFQIARNAQPSIIFIDEIDSILCERSEKDA

Drosophila                    YVGDGEKLVRALFAVARHMQPSIIFIDEVDSLLSERSSSEH

Slime mold                    YVGDGEKLVRALFAVATHFQPSIIFIDEIDSLLTERSSNES

Sequence annotation in neighborhood:  
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 415 – 415 Y -> A. Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes 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.
Beta strand 435 – 442


Literature citations

Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia.
Magariello A.; Muglia M.; Patitucci A.; Mazzei R.; Conforti F.L.; Gabriele A.L.; Sprovieri T.; Ungaro C.; Gambardella A.; Mancuso M.; Siciliano G.; Branca D.; Aguglia U.; de Angelis M.V.; Longo K.; Quattrone A.;
Neuromuscul. Disord. 16:387-390(2006)
Cited for: VARIANT SPG4 LEU-435;

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.