UniProtKB/Swiss-Prot O60602: Variant p.Phe616Leu

Toll-like receptor 5
Gene: TLR5
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Variant information Variant position:

616 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 Phenylalanine (F) to Leucine (L) at position 616 (F616L, p.Phe616Leu). 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 (F) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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:

Individuals with a common stop codon polymorphism in position 392 are unable to mediate flagellin signaling. This polymorphism acts in a dominant fashion and is associated with susceptibility to pneumonia caused by Legionella pneumophila [MIM:608556]. It also provides protection against systemic lupus erythematosus.A nonsense TLR5 polymorphism, resulting in p.Arg392Ter, confers resistance to melioidosis [MIM:615557], an infection caused by the Gram-negative, flagellated soil saprophyte Burkholderia pseudomallei. Carriers of this hypofunctional TLR5 variant may generate impaired inflammatory responses during melioidosis infection that result in reduced organ failure and lower mortality. - Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs5744174 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

HTNVTIAGPPADIYCVYPDS F SGVSLFSLSTEGCDEEEVLK 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                         HTNVTIAGPPADIYCVYPDSFSGVSLFSLSTEGCDEEEVLK

Mouse                         QTNVTLFGSPADVYCMYPNSLLGGSLYNISTEDCDEEEAMR

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 – 858	Toll-like receptor 5
Topological domain	21 – 639	Extracellular
Domain	579 – 631	LRRCT
Glycosylation	598 – 598	N-linked (GlcNAc...) asparagine
Disulfide bond	585 – 629

Literature citations
Cloning and characterization of two Toll/Interleukin-1 receptor-like genes TIL3 and TIL4: evidence for a multi-gene receptor family in humans.
Chaudhary P.M.; Ferguson C.; Nguyen V.; Nguyen O.; Massa H.F.; Eby M.; Jasmin A.; Trask B.J.; Hood L.; Nelson P.S.;
Blood 91:4020-4027(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT LEU-616; A stop codon polymorphism of Toll-like receptor 5 is associated with resistance to systemic lupus erythematosus.
Hawn T.R.; Wu H.; Grossman J.M.; Hahn B.H.; Tsao B.P.; Aderem A.;
Proc. Natl. Acad. Sci. U.S.A. 102:10593-10597(2005)
Cited for: ASSOCIATION WITH RESISTANCE TO SLEB1; VARIANTS SER-592 AND LEU-616; A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease.
Hawn T.R.; Verbon A.; Lettinga K.D.; Zhao L.P.; Li S.S.; Laws R.J.; Skerrett S.J.; Beutler B.; Schroeder L.; Nachman A.; Ozinsky A.; Smith K.D.; Aderem A.;
J. Exp. Med. 198:1563-1572(2003)
Cited for: VARIANTS 392-ARG--SER-858 DEL; SER-592 AND LEU-616;

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.