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UniProtKB/Swiss-Prot O00206: Variant p.Lys694Arg

Toll-like receptor 4
Gene: TLR4
Variant information

Variant position:  694
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Arginine (R) at position 694 (K694R, p.Lys694Arg).
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:  Similar physico-chemical property. Both residues are large size and basic.
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

Polymorphism:  Allele TLR4*B (Gly-299, Ile-399) is associated with a blunted response to inhaled LPS.
Additional information on the polymorphism described.

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



Sequence information

Variant position:  694
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  839
The length of the canonical sequence.

Location on the sequence:   YDAFVIYSSQDEDWVRNELV  K NLEEGVPPFQLCLHYRDFIP
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                         YDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIP

Gorilla                       YDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIP

Mouse                         YDAFVIYSSQNEDWVRNELVKNLEEGVPRFHLCLHYRDFIP

Rat                           YDAFVIYSSQNEDWVRNELVKNLEEGVPRFQLCLHYRDFIP

Pig                           YDAFVIYSSQDEDWVRNELVKNLEEGVPPFHLCLHYRDFIP

Bovine                        YDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIP

Cat                           YDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIP

Horse                         YDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIP

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 24 – 839 Toll-like receptor 4
Topological domain 653 – 839 Cytoplasmic
Domain 672 – 815 TIR
Mutagenesis 697 – 697 E -> R. Abolishes LPS-response.
Mutagenesis 710 – 710 R -> E. Abolishes LPS-response.
Mutagenesis 711 – 711 D -> K. Abolishes LPS-response.
Mutagenesis 714 – 714 P -> HRE. Abolishes MYD88-binding and LPS-response.


Literature citations

Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in humans.
Smirnova I.; Hamblin M.T.; McBride C.; Beutler B.; Di Rienzo A.;
Genetics 158:1657-1664(2001)
Cited for: VARIANTS ARG-188; SER-246; GLY-299; SER-329; ILE-399; LEU-443; LYS-474; HIS-510; ARG-694; HIS-763 AND HIS-834;

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.