UniProtKB/SwissProt variant VAR

Variant information

Variant position:

135

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Lysine (K) to Glutamate (E) at position 135 (K135E, p.Lys135Glu).

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 (K) to medium size and acidic (E)

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

Involvement in disease:

Werner syndrome (WRN) [MIM:277700]: A rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction. {ECO:0000269|PubMed:16673358}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In WRN.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs267607008 [ dbSNP | Ensembl ]

Sequence information

Variant position:

135

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

Protein sequence length:

1432

The length of the canonical sequence.

Location on the sequence:

SSMSVFPQGLKMLLENKAVK K AGVGIEGDQWKLLRDFDIKL

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                         SSMSVFPQGLKMLLENKAVKKAGVGIEGDQWKLLRDFDIKL

Mouse                         SSMSVFPQGLKMLLENKSIKKAGVGIEGDQWKLLRDFDVKL

Xenopus laevis                SPMAGFPKGLKRLLEDESVRKVGVGIEGDQWKLMSDYELKL

Caenorhabditis elegans        --------------DNDELPETEPESDSDKPTVTSN-----

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	2 – 1432	Werner syndrome ATP-dependent helicase
Domain	60 – 228	3'-5' exonuclease
Region	2 – 277	Interaction with WRNIP1
Site	145 – 145	Interaction with DNA
Cross	154 – 154	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis	145 – 145	W -> A. Reduces exonuclease activity.
Beta strand	133 – 139

Literature citations

The spectrum of WRN mutations in Werner syndrome patients.
Huang S.; Lee L.; Hanson N.B.; Lenaerts C.; Hoehn H.; Poot M.; Rubin C.D.; Chen D.-F.; Yang C.-C.; Juch H.; Dorn T.; Spiegel R.; Oral E.A.; Abid M.; Battisti C.; Lucci-Cordisco E.; Neri G.; Steed E.H.; Kidd A.; Isley W.; Showalter D.; Vittone J.L.; Konstantinow A.; Ring J.; Meyer P.; Wenger S.L.; Herbay A.V.; Wollina U.; Schuelke M.; Huizenga C.R.; Leistritz D.F.; Martin G.M.; Mian I.S.; Oshima J.;
Hum. Mutat. 27:558-567(2006)
Cited for: VARIANTS WRN ASN-125 AND GLU-135;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14191: Variant p.Lys135Glu