UniProtKB/Swiss-Prot O60603: Variant p.Pro631His

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

631 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 Proline (P) to Histidine (H) at position 631 (P631H, p.Pro631His). 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 medium size and polar (H) 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.
Variant description:

Reduces TLR2-mediated NF-kappa-B activation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs5743704 [ dbSNP | Ensembl ]

Sequence information Variant position:

631 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:

RFHGLWYMKMMWAWLQAKRK P RKAPSRNICYDAFVSYSERD 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                         RFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERD

Gorilla                       RFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERD

                              RFHGLWYMRMMWAWLQAKRKPRKAPSRDVCYDAFVSYSEHD

Rhesus macaque                RFHGLWYMKMMWAWLQAKRKPRKAPNRDICYDAFVSYSERD

Chimpanzee                    RFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERD

Mouse                         HFHGLWYLRMMWAWLQAKRKPKKAPCRDVCYDAFVSYSEQD

Bovine                        RFHGLWYMKMMWAWLQAKRKPRKAPRRDICYDAFVSYSERD

Goat                          RFHGLWYMKMMWAWLQAKRKPRKAPRRDLCYDAFVSYSEQD

Sheep                         RFHGLWYMKMMWAWLQAKRKPRKAPRRDLCYDAFVSYSERD

Horse                         HFHGLWYMKMMWAWLQAKRKPRTAPQRDICYDAFVSYSERD

Drosophila                    -MSNSMYNPIIYCWMNSRFR----------------YG---

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

Literature citations
The heterogeneous allelic repertoire of human Toll-Like receptor (TLR) genes.
Georgel P.; Macquin C.; Bahram S.;
PLoS ONE 4:E7803-E7803(2009)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS HIS-631 AND GLN-753; Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family.
Ben-Ali M.; Corre B.; Manry J.; Barreiro L.B.; Quach H.; Boniotto M.; Pellegrini S.; Quintana-Murci L.;
Hum. Mutat. 32:643-652(2011)
Cited for: VARIANTS ASP-89; ILE-411; HIS-571; HIS-631; ARG-636 AND GLN-753; CHARACTERIZATION OF VARIANTS ILE-411; HIS-631 AND GLN-753;

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.