UniProtKB/SwissProt variant VAR

Variant information

Variant position:

517

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 Glutamate (E) to Valine (V) at position 517 (E517V, p.Glu517Val).

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 acidic (E) to medium size and hydrophobic (V)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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 NPDB.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs142787001 [ dbSNP | Ensembl ]

Sequence information

Variant position:

517

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

Protein sequence length:

631

The length of the canonical sequence.

Location on the sequence:

YRVYQIDGNYSGSSHVVLDH E TYILNLTQANIPGAIPHWQL

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                         YRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQL

Mouse                         YRVYQIDGNYPGSSHVVLDHETYILNLTQANAAGGTPSWKR

Bovine                        YRVYQIDGNYSGSSHVVLDHETYIMNLTEANEPGATPHWYL

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	47 – 631	Sphingomyelin phosphodiesterase
Modified residue	510 – 510	Phosphoserine; by PKC/PRKCD
Glycosylation	505 – 505	N-linked (GlcNAc...) asparagine
Glycosylation	522 – 522	N-linked (GlcNAc...) asparagine
Mutagenesis	505 – 505	N -> G. Loss of sphingomyelin phosphodiesterase activity. Loss of secretion.
Mutagenesis	510 – 510	S -> A. Abolishes constitutive secretion and decreases secretion in response to IL1B. No effect on lysosomal targeting. No effect on sphingomyelin phosphodiesterase activity. No effect on endolysosome location. Abolishes phosphorylation by PRKCD.
Mutagenesis	522 – 522	N -> G. Loss of sphingomyelin phosphodiesterase activity. Loss of secretion.
Beta strand	513 – 520

Literature citations

The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations.
Simonaro C.M.; Desnick R.J.; McGovern M.M.; Wasserstein M.P.; Schuchman E.H.;
Am. J. Hum. Genet. 71:1413-1419(2002)
Cited for: VARIANTS NPDB VAL-51; TRP-94; PRO-139; ARG-159; PRO-198; CYS-202; MET-227; CYS-230; ASP-234; SER-247; ARG-250; HIS-291; ALA-325; ARG-332; ASP-359; HIS-378; LEU-378; PRO-381; VAL-415; TYR-423; ARG-433; PRO-434; CYS-437; VAL-454; ASP-458; TRP-476; LEU-477; LEU-482; ASN-490; SER-496; CYS-498; GLN-516; VAL-517; ARG-535; PRO-551; ASN-578; HIS-602 AND PRO-602; VARIANT VAL-487;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17405: Variant p.Glu517Val