Toll-like receptor 6

Details

Name
Toll-like receptor 6
Synonyms
  • 3.2.2.6
Gene Name
TLR6
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052605|Toll-like receptor 6
MTKDKEPIVKSFHFVCLMIIIVGTRIQFSDGNEFAVDKSKRGLIHVPKDLPLKTKVLDMS
QNYIAELQVSDMSFLSELTVLRLSHNRIQLLDLSVFKFNQDLEYLDLSHNQLQKISCHPI
VSFRHLDLSFNDFKALPICKEFGNLSQLNFLGLSAMKLQKLDLLPIAHLHLSYILLDLRN
YYIKENETESLQILNAKTLHLVFHPTSLFAIQVNISVNTLGCLQLTNIKLNDDNCQVFIK
FLSELTRGSTLLNFTLNHIETTWKCLVRVFQFLWPKPVEYLNIYNLTIIESIREEDFTYS
KTTLKALTIEHITNQVFLFSQTALYTVFSEMNIMMLTISDTPFIHMLCPHAPSTFKFLNF
TQNVFTDSIFEKCSTLVKLETLILQKNGLKDLFKVGLMTKDMPSLEILDVSWNSLESGRH
KENCTWVESIVVLNLSSNMLTDSVFRCLPPRIKVLDLHSNKIKSVPKQVVKLEALQELNV
AFNSLTDLPGCGSFSSLSVLIIDHNSVSHPSADFFQSCQKMRSIKAGDNPFQCTCELREF
VKNIDQVSSEVLEGWPDSYKCDYPESYRGSPLKDFHMSELSCNITLLIVTIGATMLVLAV
TVTSLCIYLDLPWYLRMVCQWTQTRRRARNIPLEELQRNLQFHAFISYSEHDSAWVKSEL
VPYLEKEDIQICLHERNFVPGKSIVENIINCIEKSYKSIFVLSPNFVQSEWCHYELYFAH
HNLFHEGSNNLILILLEPIPQNSIPNKYHKLKALMTQRTYLQWPKEKSKRGLFWANIRAA
FNMKLTLVTENNDVKS
Number of residues
796
Molecular Weight
91878.845
Theoretical pI
Not Available
GO Classification
Functions
amyloid-beta binding / identical protein binding / lipopeptide binding / NAD(P)+ nucleosidase activity / NAD+ nucleotidase, cyclic ADP-ribose generating / protein heterodimerization activity / signaling receptor activity / signaling receptor binding / Toll-like receptor 2 binding / transmembrane signaling receptor activity
Processes
activation of NF-kappaB-inducing 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 / defense response to bacterium / detection of diacyl bacterial lipopeptide / immune response / inflammatory response / innate immune response / microglial cell activation / MyD88-dependent toll-like receptor signaling pathway / negative regulation of interleukin-8 production / negative regulation of toll-like receptor 2 signaling pathway / nitric oxide metabolic process / positive regulation of cytokine production involved in inflammatory response / positive regulation of gene expression / positive regulation of I-kappaB kinase/NF-kappaB signaling / positive regulation of interleukin-1 beta production / positive regulation of interleukin-6 production / positive regulation of JUN kinase activity / positive regulation of macrophage activation / positive regulation of NF-kappaB transcription factor activity / positive regulation of nitric oxide biosynthetic process / positive regulation of NLRP3 inflammasome complex assembly / positive regulation of oxidative stress-induced neuron death / positive regulation of reactive oxygen species biosynthetic process / signal transduction / toll-like receptor 6 signaling pathway / toll-like receptor signaling pathway / toll-like receptor TLR6 / TRIF-dependent toll-like receptor signaling pathway
Components
Golgi apparatus / integral component of plasma membrane / membrane raft / phagocytic vesicle membrane / plasma membrane / receptor complex / Toll-like receptor 2-Toll-like receptor 6 protein complex
General 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).
Specific Function
Amyloid-beta binding
Pfam Domain Function
Transmembrane Regions
587-607
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0052606|Toll-like receptor 6 (TLR6)
ATGACCAAAGACAAAGAACCTATTGTTAAAAGCTTCCATTTTGTTTGCCTTATGATCATA
ATAGTTGGAACCAGAATCCAGTTCTCCGACGGAAATGAATTTGCAGTAGACAAGTCAAAA
AGAGGTCTTATTCATGTTCCAAAAGACCTACCGCTGAAAACCAAAGTCTTAGATATGTCT
CAGAACTACATCGCTGAGCTTCAGGTCTCTGACATGAGCTTTCTATCAGAGTTGACAGTT
TTGAGACTTTCCCATAACAGAATCCAGCTACTTGATTTAAGTGTTTTCAAGTTCAACCAG
GATTTAGAATATTTGGATTTATCTCATAATCAGTTGCAAAAGATATCCTGCCATCCTATT
GTGAGTTTCAGGCATTTAGATCTCTCATTCAATGATTTCAAGGCCCTGCCCATCTGTAAG
GAATTTGGCAACTTATCACAACTGAATTTCTTGGGATTGAGTGCTATGAAGCTGCAAAAA
TTAGATTTGCTGCCAATTGCTCACTTGCATCTAAGTTATATCCTTCTGGATTTAAGAAAT
TATTATATAAAAGAAAATGAGACAGAAAGTCTACAAATTCTGAATGCAAAAACCCTTCAC
CTTGTTTTTCACCCAACTAGTTTATTCGCTATCCAAGTGAACATATCAGTTAATACTTTA
GGGTGCTTACAACTGACTAATATTAAATTGAATGATGACAACTGTCAAGTTTTCATTAAA
TTTTTATCAGAACTCACCAGAGGTTCAACCTTACTGAATTTTACCCTCAACCACATAGAA
ACGACTTGGAAATGCCTGGTCAGAGTCTTTCAATTTCTTTGGCCCAAACCTGTGGAATAT
CTCAATATTTACAATTTAACAATAATTGAAAGCATTCGTGAAGAAGATTTTACTTATTCT
AAAACGACATTGAAAGCATTGACAATAGAACATATCACGAACCAAGTTTTTCTGTTTTCA
CAGACAGCTTTGTACACCGTGTTTTCTGAGATGAACATTATGATGTTAACCATTTCAGAT
ACACCTTTTATACACATGCTGTGTCCTCATGCACCAAGCACATTCAAGTTTTTGAACTTT
ACCCAGAACGTTTTCACAGATAGTATTTTTGAAAAATGTTCCACGTTAGTTAAATTGGAG
ACACTTATCTTACAAAAGAATGGATTAAAAGACCTTTTCAAAGTAGGTCTCATGACGAAG
GATATGCCTTCTTTGGAAATACTGGATGTTAGCTGGAATTCTTTGGAATCTGGTAGACAT
AAAGAAAACTGCACTTGGGTTGAGAGTATAGTGGTGTTAAATTTGTCTTCAAATATGCTT
ACTGACTCTGTTTTCAGATGTTTACCTCCCAGGATCAAGGTACTTGATCTTCACAGCAAT
AAAATAAAGAGCGTTCCTAAACAAGTCGTAAAACTGGAAGCTTTGCAAGAACTCAATGTT
GCTTTCAATTCTTTAACTGACCTTCCTGGATGTGGCAGCTTTAGCAGCCTTTCTGTATTG
ATCATTGATCACAATTCAGTTTCCCACCCATCGGCTGATTTCTTCCAGAGCTGCCAGAAG
ATGAGGTCAATAAAAGCAGGGGACAATCCATTCCAATGTACCTGTGAGCTAAGAGAATTT
GTCAAAAATATAGACCAAGTATCAAGTGAAGTGTTAGAGGGCTGGCCTGATTCTTATAAG
TGTGACTACCCAGAAAGTTATAGAGGAAGCCCACTAAAGGACTTTCACATGTCTGAATTA
TCCTGCAACATAACTCTGCTGATCGTCACCATCGGTGCCACCATGCTGGTGTTGGCTGTG
ACTGTGACCTCCCTCTGCATCTACTTGGATCTGCCCTGGTATCTCAGGATGGTGTGCCAG
TGGACCCAGACTCGGCGCAGGGCCAGGAACATACCCTTAGAAGAACTCCAAAGAAACCTC
CAGTTTCATGCTTTTATTTCATATAGTGAACATGATTCTGCCTGGGTGAAAAGTGAATTG
GTACCTTACCTAGAAAAAGAAGATATACAGATTTGTCTTCATGAGAGAAACTTTGTCCCT
GGCAAGAGCATTGTGGAAAATATCATCAACTGCATTGAGAAGAGTTACAAGTCCATCTTT
GTTTTGTCTCCCAACTTTGTCCAGAGTGAGTGGTGCCATTACGAACTCTATTTTGCCCAT
CACAATCTCTTTCATGAAGGATCTAATAACTTAATCCTCATCTTACTGGAACCCATTCCA
CAGAACAGCATTCCCAACAAGTACCACAAGCTGAAGGCTCTCATGACGCAGCGGACTTAT
TTGCAGTGGCCCAAGGAGAAAAGCAAACGTGGGCTCTTTTGGGCTAACATTAGAGCCGCT
TTTAATATGAAATTAACACTAGTCACTGAAAACAATGATGTGAAATCTTAA
Chromosome Location
4
Locus
4p14
External Identifiers
ResourceLink
UniProtKB IDQ9Y2C9
UniProtKB Entry NameTLR6_HUMAN
HGNC IDHGNC:16711
General References
  1. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  4. 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. [Article]
  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. [Article]
  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. Epub 2006 Jul 31. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB16474Pam2csk4investigationalunknownagonistDetails