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UniProtKB/Swiss-Prot O15455: Variant p.Pro554Ser

Toll-like receptor 3
Gene: TLR3
Chromosomal location: 4q35
Variant information

Variant position:  554
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 Proline (P) to Serine (S) at position 554 (P554S, p.Pro554Ser).
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

Involvement in disease:  Encephalopathy, acute, infection-induced, Herpes-specific, 2 (IIAE2) [MIM:613002]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269|PubMed:17872438}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system.
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 IIAE2; causes TLR3 deficiency and predisposition to herpes simplex encephalitis.
Any additional useful information about the variant.

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

Sequence information

Variant position:  554
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  904
The length of the canonical sequence.

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.




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.

Chain 24 – 904 Toll-like receptor 3
Topological domain 24 – 704 Lumenal
Mutagenesis 539 – 539 H -> A. No effect.
Mutagenesis 539 – 539 H -> E. Loss of RNA binding. Constitutive activation of NF-kappa-B.
Mutagenesis 541 – 541 N -> A. Loss of RNA binding. Abolishes activation of NF-kappa-B.

Literature citations

TLR3 deficiency in patients with herpes simplex encephalitis.
Zhang S.-Y.; Jouanguy E.; Ugolini S.; Smahi A.; Elain G.; Romero P.; Segal D.; Sancho-Shimizu V.; Lorenzo L.; Puel A.; Picard C.; Chapgier A.; Plancoulaine S.; Titeux M.; Cognet C.; von Bernuth H.; Ku C.-L.; Casrouge A.; Zhang X.-X.; Barreiro L.; Leonard J.; Hamilton C.; Lebon P.; Heron B.; Vallee L.; Quintana-Murci L.; Hovnanian A.; Rozenberg F.; Vivier E.; Geissmann F.; Tardieu M.; Abel L.; Casanova J.-L.;
Science 317:1522-1527(2007)
Cited for: VARIANT IIAE2 SER-554;

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.