UniProtKB/Swiss-Prot O15118: Variant p.Arg518Trp

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 518 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 Arginine (R) to Tryptophan (W) at position 518 (R518W, p.Arg518Trp). 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 large size and aromatic (W) 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; decreased affinity for NPC2; decreased cholesterol transfer from NPC2 to NPC1. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs377515417 [ dbSNP | Ensembl ]

Sequence information

Variant position: 518 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: KKGDDFFVYADYHTHFLYCV R APASLNDTSLLHDPCLGTFG 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	372 – 620	Lumenal
Glycosylation	524 – 524	N-linked (GlcNAc...) asparagine
Disulfide bond	516 – 533
Mutagenesis	503 – 503	F -> AG. Loss of interaction with ebolavirus glycoprotein.
Mutagenesis	504 – 504	F -> AG. Loss of interaction with ebolavirus glycoprotein.
Mutagenesis	506 – 506	Y -> A. Loss of interaction with ebolavirus glycoprotein.

Literature citations

Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection.
Gong X.; Qian H.; Zhou X.; Wu J.; Wan T.; Cao P.; Huang W.; Zhao X.; Wang X.; Wang P.; Shi Y.; Gao G.F.; Zhou Q.; Yan N.;
Cell 165:1467-1478(2016)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.43 ANGSTROMS); FUNCTION; INTERACTION WITH NPC2 AND WITH EBOLAVIRUS GLYCOPROTEIN GP; TOPOLOGY; GLYCOSYLATION AT ASN-122; ASN-135; ASN-158; ASN-185; ASN-222; ASN-524; ASN-572; ASN-598 AND ASN-1064; DISULFIDE BONDS; CHARACTERIZATION OF VARIANT NPC1 TRP-518; MUTAGENESIS OF 25-CYS--PRO-257; 175-LEU-LEU-176; 202-PRO-PHE-203 AND 249-PRO--PRO-257; Niemann-Pick type C disease: NPC1 mutations associated with severe and mild cellular cholesterol trafficking alterations.
Ribeiro I.; Marcao A.; Amaral O.; Sa Miranda M.C.; Vanier M.T.; Millat G.;
Hum. Genet. 109:24-32(2001)
Cited for: VARIANTS NPC1 ARG-92; TYR-177; TRP-518; CYS-942; CYS-978; ALA-1007; VAL-1035 AND THR-1061; VARIANTS ARG-215; ILE-642 AND VAL-858;