UniProtKB/Swiss-Prot Q9UBP0: Variant p.Arg499Cys

Spastin
Gene: SPAST
Feedback?

Variant information Variant position:

499 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 Arginine (R) to Cysteine (C) at position 499 (R499C, p.Arg499Cys). 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:

Change from large size and basic (R) to medium size and polar (C) 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; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121908511 [ dbSNP | Ensembl ]

Sequence information Variant position:

499 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:

RVLVMGATNRPQELDEAVLR R FIKRVYVSLPNEETRLLLLK 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                         RVLVMGATNRPQELDEAVLRRFIKRVYVSLPNEETRLLLLK

Mouse                         RVLVMGATNRPQELDEAVLRRFIKRVYVSLPNEETRLLLLK

Rat                           RVLVMGATNRPQELDEAVLRRFIKRVYVSLPNEETRLLLLK

Pig                           RVLVMGATNRPQELDEAVLRRFIKRVYVSLPNEETRLLLLK

Bovine                        RVLVMGATNRPQELDEAVLRRFTKRVYVSLPNEETRLLLLK

Chicken                       RILVMGATNRPQELDDAVLRRFTKRVYVSLPNEETRLILLK

Xenopus laevis                RVLVMGATNRPQELDDAVLRRFTKRVYVALPNEETRLVLLK

Xenopus tropicalis            RVLVMGATNRPQELDDAVLRRFTKRVYVSLPNEETRLLLLK

Zebrafish                     RVLVMGATNRPQELDEAVLRRFAKRIYVALPTEETRLKLLK

Caenorhabditis elegans        RILVIGATNRPHELDDAVLRRFPKRIMLNLPDEEARKELIT

Drosophila                    RIVVLAATNRPQELDEAALRRFTKRVYVSLPDEQTRELLLN

Slime mold                    RVLVMGATNRPEDLDDAALRRLVKRIYVGLPELETRLQIIQ

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.

Type	Positions	Description
Chain	1 – 616	Spastin
Topological domain	78 – 616	Cytoplasmic
Region	228 – 616	Sufficient for microtubule severing
Helix	497 – 499

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; Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing.
Evans K.J.; Gomes E.R.; Reisenweber S.M.; Gundersen G.G.; Lauring B.P.;
J. Cell Biol. 168:599-606(2005)
Cited for: FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; INTERACTION WITH MICROTUBULES; SUBCELLULAR LOCATION; MUTAGENESIS OF LYS-388 AND GLU-442; CHARACTERIZATION OF VARIANTS SPG4 LYS-344; LYS-347; LYS-386; ARG-388 AND CYS-499; 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; Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia.
Svenson I.K.; Ashley-Koch A.E.; Gaskell P.C.; Riney T.J.; Cumming W.J.K.; Kingston H.M.; Hogan E.L.; Boustany R.-M.N.; Vance J.M.; Nance M.A.; Pericak-Vance M.A.; Marchuk D.A.;
Am. J. Hum. Genet. 68:1077-1085(2001)
Cited for: VARIANTS SPG4 CYS-499 AND GLY-562; Spastin gene mutation in Japanese with hereditary spastic paraplegia.
Yabe I.; Sasaki H.; Tashiro K.; Matsuura T.; Takegami T.; Satoh T.;
J. Med. Genet. 39:E46-E46(2002)
Cited for: VARIANTS SPG4 LYS-347; ARG-388 AND CYS-499;

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.