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Identification
HMDB Protein ID HMDBP12384
Secondary Accession Numbers None
Name Toll-like receptor 6
Synonyms Not Available
Gene Name TLR6
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Participates in the innate immune response to Gram-positive bacteria and fungi. Specifically recognizes diacylated and, to a lesser extent, triacylated lipopeptides (PubMed:20037584). In response to diacylated lipopeptides, forms the activation cluster TLR2:TLR6:CD14:CD36, this cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (PubMed:16880211). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR2 (PubMed:11441107). In complex with TLR4, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion (PubMed:11441107, PubMed:20037584).
Pathways
  • Chagas disease
  • Lipid and atherosclerosis
  • Phagosome
  • Salmonella infection
  • Toll-like receptor signaling pathway
  • Tuberculosis
Reactions Not Available
GO Classification
Biological Process
signal transduction
defense response to bacterium
inflammatory response
positive regulation of nitric oxide biosynthetic process
activation of NF-kappaB-inducing kinase activity
innate immune response
immune response
positive regulation of I-kappaB kinase/NF-kappaB cascade
toll-like receptor signaling pathway
positive regulation of JUN kinase activity
cell activation
cellular response to amyloid-beta
cellular response to bacterial lipopeptide
cellular response to diacyl bacterial lipopeptide
cellular response to oxidised low-density lipoprotein particle stimulus
detection of diacyl bacterial lipopeptide
MyD88-dependent toll-like receptor signaling pathway
microglial cell activation
nitric oxide metabolic process
negative regulation of interleukin-8 production
negative regulation of toll-like receptor 2 signaling pathway
positive regulation of cytokine production involved in inflammatory response
positive regulation of interleukin-1 beta production
positive regulation of interleukin-6 production
positive regulation of gene expression
positive regulation of macrophage activation
positive regulation of NLRP3 inflammasome complex assembly
positive regulation of NF-kappaB transcription factor activity
positive regulation of oxidative stress-induced neuron death
positive regulation of reactive oxygen species biosynthetic process
TRIF-dependent toll-like receptor signaling pathway
toll-like receptor 6 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
Cellular Component
membrane raft
receptor complex
plasma membrane
Golgi apparatus
phagocytic vesicle membrane
Toll-like receptor 2-Toll-like receptor 6 protein complex
integral to plasma membrane
Molecular Function
beta-amyloid binding
receptor binding
transmembrane signaling receptor activity
NAD(P)+ nucleosidase activity
NAD+ nucleotidase, cyclic ADP-ribose generating
signaling receptor activity
lipopeptide binding
Toll-like receptor 2 binding
identical protein binding
protein heterodimerization activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 796
Molecular Weight 91878.845
Theoretical pI 7.231
Pfam Domain Function
Signals
  • 1-31;
Transmembrane Regions
  • 587-607;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9Y2C9
UniProtKB/Swiss-Prot Entry Name TLR6_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Nakajima T, Ohtani H, Satta Y, Uno Y, Akari H, Ishida T, Kimura A: Natural selection in the TLR-related genes in the course of primate evolution. Immunogenetics. 2008 Dec;60(12):727-35. doi: 10.1007/s00251-008-0332-0. Epub 2008 Sep 23. [PubMed:18810425 ]
  4. Takeuchi O, Kawai T, Sanjo H, Copeland NG, Gilbert DJ, Jenkins NA, Takeda K, Akira S: TLR6: A novel member of an expanding toll-like receptor family. Gene. 1999 Apr 29;231(1-2):59-65. doi: 10.1016/s0378-1119(99)00098-0. [PubMed:10231569 ]
  5. Bulut Y, Faure E, Thomas L, Equils O, Arditi M: Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J Immunol. 2001 Jul 15;167(2):987-94. doi: 10.4049/jimmunol.167.2.987. [PubMed:11441107 ]
  6. Triantafilou M, Gamper FG, Haston RM, Mouratis MA, Morath S, Hartung T, Triantafilou K: Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J Biol Chem. 2006 Oct 13;281(41):31002-11. doi: 10.1074/jbc.M602794200. Epub 2006 Jul 31. [PubMed:16880211 ]
  7. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulbert A, El Khoury J, Golenbock DT, Moore KJ: CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010 Feb;11(2):155-61. doi: 10.1038/ni.1836. Epub 2009 Dec 27. [PubMed:20037584 ]
  8. Jang TH, Park HH: Crystal structure of TIR domain of TLR6 reveals novel dimeric interface of TIR-TIR interaction for toll-like receptor signaling pathway. J Mol Biol. 2014 Sep 23;426(19):3305-3313. doi: 10.1016/j.jmb.2014.07.024. Epub 2014 Jul 31. [PubMed:25088687 ]
  9. Ben-Ali M, Corre B, Manry J, Barreiro LB, Quach H, Boniotto M, Pellegrini S, Quintana-Murci L: Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family. Hum Mutat. 2011 Jun;32(6):643-52. doi: 10.1002/humu.21486. [PubMed:21618349 ]