UniProtKB/Swiss-Prot O60603: Variant p.Arg677Trp

Toll-like receptor 2
Gene: TLR2
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Variant information Variant position:

677 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Arginine (R) to Tryptophan (W) at position 677 (R677W, p.Arg677Trp). 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 (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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:

Genetic variations in TLR2 are associated with susceptibility to leprosy [MIM:246300]. Leprosy is a chronic disease associated with depressed cellular (but not humoral) immunity, the bacterium requires a lower temperature than 37 degrees Celsius and thrives particularly in peripheral Schwann cells and macrophages. The Trp-677 polymorphism in the intracellular domain of TLR2 has a role in susceptibility to lepromatous leprosy. Wild-type TLR2 mediates CD14-enhanced Mycobacterium leprae-dependent activation of NFKB1, but TLR2 containing the Trp-677 polymorphism did not. The impaired function of the Trp-677 polymorphism provides a molecular mechanism for the poor cellular immune response associated with lepromatous leprosy. Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs121917864 [ dbSNP | Ensembl ]

Sequence information Variant position:

677 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

784 The length of the canonical sequence.
Location on the sequence:

NLMVQELENFNPPFKLCLHK R DFIPGKWIIDNIIDSIEKSH 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                         NLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSH

Gorilla                       NLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSH

                              NLLVQKLEHFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSR

Rhesus macaque                NLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSH

Chimpanzee                    NLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSH

Mouse                         NLMVQQLENSDPPFKLCLHKRDFVPGKWIIDNIIDSIEKSH

Bovine                        NLMVQELEHFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSH

Goat                          NLMVQELEHFNPPFKLCLHKRDFVPGKWIIDNIIDSIEKSR

Sheep                         NLMVQELEHFNPPFKLCLHKRDFVPGKWIIDNIIDSIEKSR

Horse                         NLMVQELEHFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSH

Drosophila                    ---------FKMVFRWCLFVR------------------VG

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	21 – 784	Toll-like receptor 2
Topological domain	610 – 784	Cytoplasmic
Domain	639 – 782	TIR
Mutagenesis	681 – 681	P -> F. Abolishes the interaction with MYD88. No effect on oligomerization or on the structure of the TIR domain.
Helix	675 – 678

Literature citations
Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients.
Kang T.-J.; Chae G.-T.;
FEMS Immunol. Med. Microbiol. 31:53-58(2001)
Cited for: VARIANT TRP-677; ASSOCIATION WITH LEPROSIS; A Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling.
Bochud P.-Y.; Hawn T.R.; Aderem A.;
J. Immunol. 170:3451-3454(2003)
Cited for: VARIANT TRP-677; ASSOCIATION WITH LEPROSIS;

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.