UniProtKB/SwissProt variant VAR

Variant information

Variant position:

455

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 Cysteine (C) to Arginine (R) at position 455 (C455R, p.Cys455Arg).

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 medium size and polar (C) to large size and basic (R)

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 CADASIL1; impaired ligand-binding; strongly reduced signaling activity; no effect on cell membrane localization; reduced proteolytic processing.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28933698 [ dbSNP | Ensembl ]

Sequence information

Variant position:

455

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

Protein sequence length:

2321

The length of the canonical sequence.

Location on the sequence:

CLSGPCRNQATCLDRIGQFT C ICMAGFTGTYCEVDIDECQS

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                         CLSGPCRNQATCLDRIGQFTCICMAGFTGTYCEVDIDECQS

Mouse                         CLSGPCRNQATCLDRIGQFTCICMAGFTGTYCEVDIDECQS

Rat                           CLSGPCRNQATCLDRIGQFTCICMAGFTGTFCEVDIDECQS

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	40 – 2321	Neurogenic locus notch homolog protein 3
Topological domain	40 – 1643	Extracellular
Domain	431 – 467	EGF-like 11; calcium-binding
Disulfide bond	440 – 455

Literature citations

C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke.
Arboleda-Velasquez J.F.; Lopera F.; Lopez E.; Frosch M.P.; Sepulveda-Falla D.; Gutierrez J.E.; Vargas S.; Medina M.; Martinez De Arrieta C.; Lebo R.V.; Slaugenhaupt S.A.; Betensky R.A.; Villegas A.; Arcos-Burgos M.; Rivera D.; Restrepo J.C.; Kosik K.S.;
Neurology 59:277-279(2002)
Cited for: VARIANT CADASIL1 ARG-455;

CADASIL-associated Notch3 mutations have differential effects both on ligand binding and ligand-induced Notch3 receptor signaling through RBP-Jk.
Peters N.; Opherk C.; Zacherle S.; Capell A.; Gempel P.; Dichgans M.;
Exp. Cell Res. 299:454-464(2004)
Cited for: CHARACTERIZATION OF VARIANTS CADASIL1 CYS-133; SER-183 AND ARG-455; FUNCTION; SUBCELLULAR LOCATION; LIGAND-BINDING DOMAIN; PROTEOLYTIC PROCESSING;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UM47: Variant p.Cys455Arg