UniProtKB/SwissProt variant VAR

Variant information

Variant position:

504

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 Proline (P) to Serine (S) at position 504 (P504S, p.Pro504Ser).

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 hydrophobic (P) to small size and polar (S)

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

BLOSUM score:

-1

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 GM2G2; decreases the isozyme A transport out of the endoplasmic reticulum. Lowers its heat stability. Affects the ability of isozyme A to hydrolyze GM2 ganglioside.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121907985 [ dbSNP | Ensembl ]

Sequence information

Variant position:

504

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

Protein sequence length:

556

The length of the canonical sequence.

Location on the sequence:

GEACLWGEYVDATNLTPRLW P RASAVGERLWSSKDVRDMDD

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                         GEACLWGEYVDATNLTPRLWPRASAVGERLWSSKDVRDMDD

Mouse                         GEACLWGEFVDATNLTPRLWPRASAVGERLWSPKTVTDLEN

Rat                           GEACLWGEYVDATNLIPRLWPRASAVGERLWSPRIITNLEN

Pig                           GEACLWGEYVDATNLTPRLWPRASAVGERLWSHKDVRDIHD

Cat                           GEACLWGEFVDATNLTPRLWPRASAVGERLWSPEDITSVGN

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	122 – 556	Beta-hexosaminidase subunit beta
Chain	315 – 556	Beta-hexosaminidase subunit beta chain A
Site	497 – 497	Not glycosylated

Literature citations

A Pro504 --> Ser substitution in the beta-subunit of beta-hexosaminidase A inhibits alpha-subunit hydrolysis of GM2 ganglioside, resulting in chronic Sandhoff disease.
Hou Y.; McInnes B.; Hinek A.; Karpati G.; Mahuran D.;
J. Biol. Chem. 273:21386-21392(1998)
Cited for: VARIANT GM2G2 SER-504; CATALYTIC ACTIVITY; FUNCTION; CHARACTERIZATION OF VARIANT GM2G2 SER-504; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P07686: Variant p.Pro504Ser