UniProtKB/SwissProt variant VAR

Variant information

Variant position:

715

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 Tyrosine (Y) to Asparagine (N) at position 715 (Y715N, p.Tyr715Asn).

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 aromatic (Y) to medium size and polar (N)

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:

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 rs5743706 [ dbSNP | Ensembl ]

Sequence information

Variant position:

715

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:

KSHKTVFVLSENFVKSEWCK Y ELDFSHFRLFDENNDAAILI

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                         KSHKTVFVLSENFVKSEWCKYELDFSHFRLFDENNDAAILI

Gorilla                       KSHKTVFVLSENFVKSEWCKYELDFSHFRLFDENNDAAILI

                              KSRKTIFVLSENFVKSEWCKYELDFSHFRLFDENSDAAILI

Rhesus macaque                KSHKTVFVLSENFVKSEWCKYELDFSHFRLFDENNDAAILV

Chimpanzee                    KSHKTVFVLSENFVKSEWCKYELDFSHFRLFDENNDAAILI

Mouse                         KSHKTVFVLSENFVRSEWCKYELDFSHFRLFDENNDAAILV

Bovine                        KSHKTIFVLSENFVKSEWCKYELDFSHFRLFDENNDAAILI

Goat                          KSRKTIFVLSENFVRSEWCKYELDFSHFRLFDENNDAAILI

Sheep                         KSRKTIFVLSESFVRSEWCKYELDFSHFRLFDENNDAAILI

Horse                         KSHKTIFVLSENFVKSEWCKYELDFSHFRLFDENNDAAILI

Drosophila                    -VGTEPFSRRENLTSRYSCSGSPDHNRIKRNDTQKSILYTC

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
Active site	716 – 716
Mutagenesis	709 – 709	K -> R. Reduced protein stability.
Mutagenesis	714 – 714	K -> R. Reduced protein stability.
Helix	713 – 716

Literature citations

No reference for the current variant in UniProtKB/Swiss-Prot.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O60603: Variant p.Tyr715Asn