Home  |  Contact

UniProtKB/Swiss-Prot P07225: Variant p.Asn258Ser

Vitamin K-dependent protein S
Gene: PROS1
Chromosomal location: 3q11.2
Variant information

Variant position:  258
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 Asparagine (N) to Serine (S) at position 258 (N258S, p.Asn258Ser).
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 (N) 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

Involvement in disease:  Thrombophilia due to protein S deficiency, autosomal dominant (THPH5) [MIM:612336]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Based on the plasma levels of total and free PROS1 as well as the serine protease-activated protein C cofactor activity, three types of THPH5 have been described: type I, characterized by reduced total and free PROS1 levels together with reduced anticoagulant activity; type III, in which only free PROS1 antigen and PROS1 activity levels are reduced; and the rare type II which is characterized by normal concentrations of both total and free PROS1 antigen, but low cofactor activity. {ECO:0000269|PubMed:10447256, ECO:0000269|PubMed:10613647, ECO:0000269|PubMed:10706858, ECO:0000269|PubMed:10790208, ECO:0000269|PubMed:11372770, ECO:0000269|PubMed:11776305, ECO:0000269|PubMed:11858485, ECO:0000269|PubMed:11927129, ECO:0000269|PubMed:12351389, ECO:0000269|PubMed:12632031, ECO:0000269|PubMed:15238143, ECO:0000269|PubMed:15712227, ECO:0000269|PubMed:18322254, ECO:0000269|PubMed:7482398, ECO:0000269|PubMed:7545463, ECO:0000269|PubMed:7579449, ECO:0000269|PubMed:7803790, ECO:0000269|PubMed:8298131, ECO:0000269|PubMed:8639833, ECO:0000269|PubMed:8701404, ECO:0000269|PubMed:8765219, ECO:0000269|PubMed:8781426, ECO:0000269|PubMed:8943854, ECO:0000269|PubMed:8977443, ECO:0000269|PubMed:9031443, ECO:0000269|PubMed:9241758, ECO:0000269|Ref.15}. 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 THPH5; produces around 30% of PROS1 levels compared to wild-type; has impaired secretion; intracellular degradation of unsecreted material is found.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  258
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  676
The length of the canonical sequence.

Location on the sequence:   SKSCEDIDECSENMCAQLCV  N YPGGYTCYCDGKKGFKLAQD
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.

TypePositionsDescription
Chain 42 – 676 Vitamin K-dependent protein S
Domain 243 – 283 EGF-like 4; calcium-binding
Disulfide bond 252 – 265


Literature citations

Submission
Cooper D.N.;
Cited for: VARIANT THPH5 SER-258;

Detection and characterization of seven novel protein S (PROS) gene lesions: evaluation of reverse transcript-polymerase chain reaction as a mutation screening strategy.
Formstone C.J.; Wacey A.I.; Berg L.-P.; Rahman S.; Bevan D.; Rowley M.; Voke J.; Bernardi F.; Legnani C.; Simioni P.; Girolami A.; Tuddenham E.G.D.; Kakkar V.V.; Cooper D.N.;
Blood 86:2632-2641(1995)
Cited for: VARIANTS THPH5 SER-258 AND THR-611;

Genetic and phenotypic variability between families with hereditary protein S deficiency.
Rezende S.M.; Lane D.A.; Zoeller B.; Mille-Baker B.; Laffan M.; Dalhbaeck B.; Simmonds R.E.;
Thromb. Haemost. 87:258-265(2002)
Cited for: VARIANTS THPH5 GLU-18; CYS-90; SER-258; VAL-336 AND PRO-664; CHARACTERIZATION OF VARIANTS THPH5 GLU-18; CYS-90; SER-258 VAL-336 AND PRO-664;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.