UniProtKB/Swiss-Prot O15118: Variant p.Cys113Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 113 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 113 (C113R, p.Cys113Arg). 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 NPC1; partially mislocalized from late endocytic organelles diffusely to the cell periphery; localizes to the endoplasmic reticulum Rab7-negative endosomes and the cell surface; does not clear the lysosomal cholesterol accumulation in NPC1-deficient cells. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs120074136 [ dbSNP | Ensembl ]

Sequence information

Variant position: 113 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 1278 The length of the canonical sequence.
Location on the sequence: FLSRCPSCFYNLLNLFCELT C SPRQSQFLNVTATEDYVDPV 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.
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	23 – 1278	NPC intracellular cholesterol transporter 1
Topological domain	23 – 261	Lumenal
Site	108 – 108	Important for cholesterol binding
Glycosylation	122 – 122	N-linked (GlcNAc...) asparagine
Disulfide bond	75 – 113
Disulfide bond	97 – 238
Disulfide bond	100 – 160
Alternative sequence	1 – 267	Missing. In isoform 2.
Mutagenesis	25 – 257	Missing. Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1.
Mutagenesis	96 – 96	R -> A. Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-88 and A-92.
Mutagenesis	97 – 97	C -> S. Loss of function.
Mutagenesis	122 – 122	N -> Q. Reduces glycosylation; when associated with Q-70 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding.
Helix	98 – 113

Literature citations

Defective endocytic trafficking of NPC1 and NPC2 underlying infantile Niemann-Pick type C disease.
Blom T.S.; Linder M.D.; Snow K.; Pihko H.; Hess M.W.; Jokitalo E.; Veckman V.; Syvaenen A.-C.; Ikonen E.;
Hum. Mol. Genet. 12:257-272(2003)
Cited for: FUNCTION; SUBCELLULAR LOCATION; VARIANT NPC1 ARG-113; VARIANT SER-237; CHARACTERIZATION OF VARIANT NPC1 ARG-113; CHARACTERIZATION OF VARIANT SER-237;