ID   TLR6_HUMAN              Reviewed;         796 AA.
AC   Q9Y2C9; B3Y640; B6CH35; B6RFS4; B6RFS5; Q2NKL3;
DT   31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 2.
DT   05-FEB-2025, entry version 207.
DE   RecName: Full=Toll-like receptor 6;
DE   AltName: CD_antigen=CD286;
DE   Flags: Precursor;
GN   Name=TLR6;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Placenta;
RX   PubMed=10231569; DOI=10.1016/s0378-1119(99)00098-0;
RA   Takeuchi O., Kawai T., Sanjo H., Copeland N.G., Gilbert D.J., Jenkins N.A.,
RA   Takeda K., Akira S.;
RT   "TLR6: a novel member of an expanding Toll-like receptor family.";
RL   Gene 231:59-65(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-249.
RX   PubMed=18810425; DOI=10.1007/s00251-008-0332-0;
RA   Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.;
RT   "Natural selection in the TLR-related genes in the course of primate
RT   evolution.";
RL   Immunogenetics 60:727-735(2008).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-120 AND PRO-249;
RP   MET-327.
RA   Liu Z., Xiao W., Wang J., Li N., Tai Y.;
RT   "The novel allele of toll-like receptor 6 gene.";
RL   Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-249.
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT PRO-249.
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   FUNCTION.
RX   PubMed=11441107; DOI=10.4049/jimmunol.167.2.987;
RA   Bulut Y., Faure E., Thomas L., Equils O., Arditi M.;
RT   "Cooperation of Toll-like receptor 2 and 6 for cellular activation by
RT   soluble tuberculosis factor and Borrelia burgdorferi outer surface protein
RT   A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling
RT   molecules in Toll-like receptor 2 signaling.";
RL   J. Immunol. 167:987-994(2001).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TLR2; CD14 AND CD36.
RX   PubMed=16880211; DOI=10.1074/jbc.m602794200;
RA   Triantafilou M., Gamper F.G., Haston R.M., Mouratis M.A., Morath S.,
RA   Hartung T., Triantafilou K.;
RT   "Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers
RT   at the cell surface determines heterotypic associations with CD36 and
RT   intracellular targeting.";
RL   J. Biol. Chem. 281:31002-31011(2006).
RN   [9]
RP   FUNCTION, INTERACTION WITH CD36 AND TLR4, AND SUBCELLULAR LOCATION.
RX   PubMed=20037584; DOI=10.1038/ni.1836;
RA   Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A.,
RA   Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A.,
RA   El Khoury J., Golenbock D.T., Moore K.J.;
RT   "CD36 ligands promote sterile inflammation through assembly of a Toll-like
RT   receptor 4 and 6 heterodimer.";
RL   Nat. Immunol. 11:155-161(2010).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 640-782, SUBUNIT, AND MUTAGENESIS
RP   OF PHE-678; CYS-712 AND LEU-716.
RX   PubMed=25088687; DOI=10.1016/j.jmb.2014.07.024;
RA   Jang T.H., Park H.H.;
RT   "Crystal structure of TIR domain of TLR6 reveals novel dimeric interface of
RT   TIR-TIR interaction for toll-like receptor signaling pathway.";
RL   J. Mol. Biol. 426:3305-3313(2014).
RN   [11]
RP   VARIANTS THR-120; VAL-128; PRO-194; THR-210; GLY-210; LYS-247; PRO-249;
RP   VAL-283; MET-327; ALA-427; ALA-442; ILE-465; THR-474; VAL-474; VAL-592;
RP   THR-690 AND HIS-708, AND CHARACTERIZATION OF VARIANTS VAL-128; PRO-194;
RP   VAL-474; THR-690 AND HIS-708.
RX   PubMed=21618349; DOI=10.1002/humu.21486;
RA   Ben-Ali M., Corre B., Manry J., Barreiro L.B., Quach H., Boniotto M.,
RA   Pellegrini S., Quintana-Murci L.;
RT   "Functional characterization of naturally occurring genetic variants in the
RT   human TLR1-2-6 gene family.";
RL   Hum. Mutat. 32:643-652(2011).
CC   -!- FUNCTION: Participates in the innate immune response to Gram-positive
CC       bacteria and fungi. Specifically recognizes diacylated and, to a lesser
CC       extent, triacylated lipopeptides (PubMed:20037584). In response to
CC       diacylated lipopeptides, forms the activation cluster
CC       TLR2:TLR6:CD14:CD36, this cluster triggers signaling from the cell
CC       surface and subsequently is targeted to the Golgi in a lipid-raft
CC       dependent pathway (PubMed:16880211). Acts via MYD88 and TRAF6, leading
CC       to NF-kappa-B activation, cytokine secretion and the inflammatory
CC       response. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD
CC       (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin
CC       (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L)
CC       cooperatively with TLR2 (PubMed:11441107). In complex with TLR4,
CC       promotes sterile inflammation in monocytes/macrophages in response to
CC       oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this
CC       context, the initial signal is provided by oxLDL- or amyloid-beta 42-
CC       binding to CD36. This event induces the formation of a heterodimer of
CC       TLR4 and TLR6, which is rapidly internalized and triggers inflammatory
CC       response, leading to the NF-kappa-B-dependent production of CXCL1,
CC       CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5
CC       cytokine, via TICAM1 signaling pathway, as well as IL1B secretion
CC       (PubMed:11441107, PubMed:20037584). {ECO:0000269|PubMed:11441107,
CC       ECO:0000269|PubMed:16880211, ECO:0000269|PubMed:20037584}.
CC   -!- SUBUNIT: Homodimer (via cytoplasmic TIR domain) (PubMed:25088687).
CC       Heterodimer with TLR2 via their respective extracellular domains
CC       (PubMed:16880211). Binds MYD88 via their respective TIR domains
CC       (Probable). Interacts with CD36, following CD36 stimulation by oxLDL or
CC       amyloid-beta 42, and forms a heterodimer with TLR4. The trimeric
CC       complex is internalized and triggers inflammatory response. LYN kinase
CC       activity facilitates TLR4:TLR6 heterodimerization and signal initiation
CC       (PubMed:20037584). The heterodimer TLR2:TLR6 interacts with CD14 and
CC       CD36 in response to triacylated lipopeptides (PubMed:16880211).
CC       {ECO:0000269|PubMed:16880211, ECO:0000269|PubMed:20037584,
CC       ECO:0000269|PubMed:25088687, ECO:0000305}.
CC   -!- INTERACTION:
CC       Q9Y2C9; Q15399: TLR1; NbExp=3; IntAct=EBI-13940779, EBI-9009517;
CC       Q9Y2C9; O60603: TLR2; NbExp=5; IntAct=EBI-13940779, EBI-973722;
CC       Q9Y2C9; O00206: TLR4; NbExp=2; IntAct=EBI-13940779, EBI-528701;
CC       Q9Y2C9; Q9Y2C9: TLR6; NbExp=4; IntAct=EBI-13940779, EBI-13940779;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20037584};
CC       Single-pass type I membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC       phagosome membrane {ECO:0000250|UniProtKB:Q9EPW9}; Single-pass type I
CC       membrane protein {ECO:0000255}. Membrane raft
CC       {ECO:0000269|PubMed:16880211}. Golgi apparatus
CC       {ECO:0000269|PubMed:16880211}. Note=Upon complex formation with CD36
CC       and TLR4, internalized through dynamin-dependent endocytosis. Does not
CC       reside in lipid rafts before stimulation but accumulates increasingly
CC       in the raft upon the presence of the microbial ligand. In response to
CC       diacylated lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid
CC       rafts, this recruitment determine the intracellular targeting to the
CC       Golgi apparatus (PubMed:16880211). {ECO:0000269|PubMed:16880211,
CC       ECO:0000269|PubMed:20037584}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9Y2C9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9Y2C9-2; Sequence=VSP_056851;
CC   -!- TISSUE SPECIFICITY: Detected in monocytes, CD11c+ immature dendritic
CC       cells, plasmacytoid pre-dendritic cells and dermal microvessel
CC       endothelial cells.
CC   -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
CC   -!- CAUTION: In some plant proteins and in human SARM1, the TIR domain has
CC       NAD(+) hydrolase (NADase) activity (By similarity). However, despite
CC       the presence of the catalytic Asp residue, the isolated TIR domain of
CC       human TLR4 lacks NADase activity (By similarity). Based on this, it is
CC       unlikely that Toll-like receptors have NADase activity.
CC       {ECO:0000250|UniProtKB:O00206, ECO:0000305}.
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DR   EMBL; AB020807; BAA78631.1; -; mRNA.
DR   EMBL; AB445652; BAG55049.1; -; mRNA.
DR   EMBL; EU170528; ABW37063.1; -; Genomic_DNA.
DR   EMBL; EU170529; ABW37064.1; -; Genomic_DNA.
DR   EMBL; EU170531; ABW37066.1; -; Genomic_DNA.
DR   EMBL; EU170532; ABW37067.1; -; Genomic_DNA.
DR   EMBL; EU170533; ABW37068.1; -; Genomic_DNA.
DR   EMBL; EU170534; ABW37069.1; -; Genomic_DNA.
DR   EMBL; EU170536; ABW37071.1; -; Genomic_DNA.
DR   EMBL; EU195537; ABY67113.1; -; Genomic_DNA.
DR   EMBL; EU195538; ABY67114.1; -; Genomic_DNA.
DR   EMBL; EU195539; ABY67115.1; -; Genomic_DNA.
DR   EMBL; EU195541; ABY67117.1; -; Genomic_DNA.
DR   EMBL; EU195542; ABY67118.1; -; Genomic_DNA.
DR   EMBL; EU195543; ABY67119.1; -; Genomic_DNA.
DR   EMBL; EU195544; ABY67120.1; -; Genomic_DNA.
DR   EMBL; EU195545; ABY67121.1; -; Genomic_DNA.
DR   EMBL; EU195546; ABY67122.1; -; Genomic_DNA.
DR   EMBL; EU195547; ABY67123.1; -; Genomic_DNA.
DR   EMBL; EU195548; ABY67124.1; -; Genomic_DNA.
DR   EMBL; EU195550; ABY67126.1; -; Genomic_DNA.
DR   EMBL; EU195551; ABY67127.1; -; Genomic_DNA.
DR   EMBL; EU195553; ABY67129.1; -; Genomic_DNA.
DR   EMBL; EU195554; ABY67130.1; -; Genomic_DNA.
DR   EMBL; EU195555; ABY67131.1; -; Genomic_DNA.
DR   EMBL; EU195557; ABY67133.1; -; Genomic_DNA.
DR   EMBL; AC108044; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471069; EAW92902.1; -; Genomic_DNA.
DR   EMBL; BC111755; AAI11756.1; -; mRNA.
DR   CCDS; CCDS3446.1; -. [Q9Y2C9-1]
DR   RefSeq; NP_006059.2; NM_006068.4. [Q9Y2C9-1]
DR   RefSeq; XP_005262694.1; XM_005262637.4. [Q9Y2C9-1]
DR   RefSeq; XP_011511914.1; XM_011513612.2.
DR   RefSeq; XP_011511915.1; XM_011513613.2. [Q9Y2C9-1]
DR   RefSeq; XP_011511916.1; XM_011513614.2.
DR   PDB; 4OM7; X-ray; 2.20 A; A/B=640-796.
DR   PDBsum; 4OM7; -.
DR   AlphaFoldDB; Q9Y2C9; -.
DR   SMR; Q9Y2C9; -.
DR   BioGRID; 115616; 45.
DR   ComplexPortal; CPX-892; TLR2-TLR6 toll-like receptor complex.
DR   ComplexPortal; CPX-945; TLR4-TLR6 toll-like receptor complex.
DR   IntAct; Q9Y2C9; 10.
DR   MINT; Q9Y2C9; -.
DR   STRING; 9606.ENSP00000389600; -.
DR   BindingDB; Q9Y2C9; -.
DR   ChEMBL; CHEMBL3259477; -.
DR   DrugBank; DB16474; Pam2csk4.
DR   GlyCosmos; Q9Y2C9; 9 sites, No reported glycans.
DR   GlyGen; Q9Y2C9; 10 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR   iPTMnet; Q9Y2C9; -.
DR   PhosphoSitePlus; Q9Y2C9; -.
DR   BioMuta; TLR6; -.
DR   DMDM; 296452933; -.
DR   jPOST; Q9Y2C9; -.
DR   MassIVE; Q9Y2C9; -.
DR   PaxDb; 9606-ENSP00000389600; -.
DR   PeptideAtlas; Q9Y2C9; -.
DR   ProteomicsDB; 85731; -. [Q9Y2C9-1]
DR   Antibodypedia; 10461; 941 antibodies from 45 providers.
DR   DNASU; 10333; -.
DR   Ensembl; ENST00000381950.2; ENSP00000371376.1; ENSG00000174130.13. [Q9Y2C9-1]
DR   Ensembl; ENST00000508254.6; ENSP00000424718.2; ENSG00000174130.13. [Q9Y2C9-1]
DR   GeneID; 10333; -.
DR   KEGG; hsa:10333; -.
DR   MANE-Select; ENST00000508254.6; ENSP00000424718.2; NM_006068.5; NP_006059.2.
DR   UCSC; uc010ifg.3; human. [Q9Y2C9-1]
DR   AGR; HGNC:16711; -.
DR   CTD; 10333; -.
DR   DisGeNET; 10333; -.
DR   GeneCards; TLR6; -.
DR   HGNC; HGNC:16711; TLR6.
DR   HPA; ENSG00000174130; Tissue enhanced (lymphoid).
DR   MIM; 605403; gene.
DR   neXtProt; NX_Q9Y2C9; -.
DR   OpenTargets; ENSG00000174130; -.
DR   PharmGKB; PA38183; -.
DR   VEuPathDB; HostDB:ENSG00000174130; -.
DR   eggNOG; KOG4641; Eukaryota.
DR   GeneTree; ENSGT00940000162201; -.
DR   HOGENOM; CLU_006000_3_0_1; -.
DR   InParanoid; Q9Y2C9; -.
DR   OMA; SWNSLEY; -.
DR   OrthoDB; 1081807at2759; -.
DR   PhylomeDB; Q9Y2C9; -.
DR   TreeFam; TF351113; -.
DR   PathwayCommons; Q9Y2C9; -.
DR   Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR   Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR   Reactome; R-HSA-168188; Toll Like Receptor TLR6:TLR2 Cascade.
DR   Reactome; R-HSA-5602498; MyD88 deficiency (TLR2/4).
DR   Reactome; R-HSA-5603041; IRAK4 deficiency (TLR2/4).
DR   Reactome; R-HSA-5686938; Regulation of TLR by endogenous ligand.
DR   Reactome; R-HSA-9833110; RSV-host interactions.
DR   SignaLink; Q9Y2C9; -.
DR   BioGRID-ORCS; 10333; 7 hits in 1149 CRISPR screens.
DR   ChiTaRS; TLR6; human.
DR   EvolutionaryTrace; Q9Y2C9; -.
DR   GeneWiki; TLR6; -.
DR   GenomeRNAi; 10333; -.
DR   Pharos; Q9Y2C9; Tbio.
DR   PRO; PR:Q9Y2C9; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q9Y2C9; protein.
DR   Bgee; ENSG00000174130; Expressed in monocyte and 99 other cell types or tissues.
DR   ExpressionAtlas; Q9Y2C9; baseline and differential.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR   GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR   GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0043235; C:receptor complex; IPI:ARUK-UCL.
DR   GO; GO:0035355; C:Toll-like receptor 2-Toll-like receptor 6 protein complex; IDA:UniProt.
DR   GO; GO:0001540; F:amyloid-beta binding; IC:ARUK-UCL.
DR   GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR   GO; GO:0071723; F:lipopeptide binding; ISS:UniProtKB.
DR   GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR   GO; GO:0046982; F:protein heterodimerization activity; IPI:ARUK-UCL.
DR   GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL.
DR   GO; GO:0035663; F:Toll-like receptor 2 binding; IPI:UniProtKB.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR   GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; NAS:UniProtKB.
DR   GO; GO:1904646; P:cellular response to amyloid-beta; IDA:ComplexPortal.
DR   GO; GO:0071726; P:cellular response to diacyl bacterial lipopeptide; IDA:UniProtKB.
DR   GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; IDA:ComplexPortal.
DR   GO; GO:0042742; P:defense response to bacterium; TAS:ProtInc.
DR   GO; GO:0042496; P:detection of diacyl bacterial lipopeptide; IDA:MGI.
DR   GO; GO:0006955; P:immune response; TAS:ProtInc.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0045087; P:innate immune response; NAS:ComplexPortal.
DR   GO; GO:0001774; P:microglial cell activation; IEA:Ensembl.
DR   GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IDA:ComplexPortal.
DR   GO; GO:0032717; P:negative regulation of interleukin-8 production; IGI:ARUK-UCL.
DR   GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IGI:ARUK-UCL.
DR   GO; GO:0046209; P:nitric oxide metabolic process; IEA:Ensembl.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:MGI.
DR   GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISS:ARUK-UCL.
DR   GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; ISS:ARUK-UCL.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL.
DR   GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR   GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:MGI.
DR   GO; GO:0043032; P:positive regulation of macrophage activation; ISS:ARUK-UCL.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:ARUK-UCL.
DR   GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR   GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISS:ARUK-UCL.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0002224; P:toll-like receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; IDA:ComplexPortal.
DR   GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; ISS:ARUK-UCL.
DR   FunFam; 3.40.50.10140:FF:000001; Toll-like receptor 2; 1.
DR   FunFam; 3.80.10.10:FF:000046; Toll-like receptor 2; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR   Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 1.
DR   InterPro; IPR000483; Cys-rich_flank_reg_C.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   InterPro; IPR000157; TIR_dom.
DR   InterPro; IPR017241; Toll-like_receptor.
DR   InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR   PANTHER; PTHR24365; TOLL-LIKE RECEPTOR; 1.
DR   PANTHER; PTHR24365:SF422; TOLL-LIKE RECEPTOR 6; 1.
DR   Pfam; PF13855; LRR_8; 2.
DR   Pfam; PF01463; LRRCT; 1.
DR   Pfam; PF01582; TIR; 1.
DR   PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR   PRINTS; PR01537; INTRLKN1R1F.
DR   PRINTS; PR00019; LEURICHRPT.
DR   SMART; SM00369; LRR_TYP; 5.
DR   SMART; SM00082; LRRCT; 1.
DR   SMART; SM00255; TIR; 1.
DR   SUPFAM; SSF52058; L domain-like; 2.
DR   SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1.
DR   PROSITE; PS51450; LRR; 9.
DR   PROSITE; PS50104; TIR; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Cytoplasmic vesicle;
KW   Disulfide bond; Glycoprotein; Golgi apparatus; Immunity;
KW   Inflammatory response; Innate immunity; Leucine-rich repeat; Membrane; NAD;
KW   Proteomics identification; Receptor; Reference proteome; Repeat; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255"
FT   CHAIN           32..796
FT                   /note="Toll-like receptor 6"
FT                   /id="PRO_0000034731"
FT   TOPO_DOM        32..586
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        587..607
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        608..796
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          54..77
FT                   /note="LRR 1"
FT   REPEAT          78..101
FT                   /note="LRR 2"
FT   REPEAT          102..122
FT                   /note="LRR 3"
FT   REPEAT          123..147
FT                   /note="LRR 4"
FT   REPEAT          148..168
FT                   /note="LRR 5"
FT   REPEAT          169..196
FT                   /note="LRR 6"
FT   REPEAT          197..219
FT                   /note="LRR 7"
FT   REPEAT          220..250
FT                   /note="LRR 8"
FT   REPEAT          251..277
FT                   /note="LRR 9"
FT   REPEAT          278..303
FT                   /note="LRR 10"
FT   REPEAT          304..330
FT                   /note="LRR 11"
FT   REPEAT          331..354
FT                   /note="LRR 12"
FT   REPEAT          355..378
FT                   /note="LRR 13"
FT   REPEAT          379..404
FT                   /note="LRR 14"
FT   REPEAT          405..429
FT                   /note="LRR 15"
FT   REPEAT          430..450
FT                   /note="LRR 16"
FT   REPEAT          451..474
FT                   /note="LRR 17"
FT   REPEAT          475..496
FT                   /note="LRR 18"
FT   REPEAT          497..520
FT                   /note="LRR 19"
FT   DOMAIN          521..575
FT                   /note="LRRCT"
FT   DOMAIN          640..781
FT                   /note="TIR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   CARBOHYD        144
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        214
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        253
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        285
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        359
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        423
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        434
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        583
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        117..139
FT                   /evidence="ECO:0000250"
FT   DISULFID        235..265
FT                   /evidence="ECO:0000250"
FT   DISULFID        348..373
FT                   /evidence="ECO:0000250"
FT   DISULFID        424..447
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         383..698
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_056851"
FT   VARIANT         120
FT                   /note="I -> T (in dbSNP:rs5743808)"
FT                   /evidence="ECO:0000269|PubMed:21618349, ECO:0000269|Ref.3"
FT                   /id="VAR_057289"
FT   VARIANT         128
FT                   /note="L -> V (impairs the ability to induce NF-kappa-B
FT                   activation; dbSNP:rs137853178)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_066352"
FT   VARIANT         194
FT                   /note="L -> P (impairs the ability to induce NF-kappa-B
FT                   activation; dbSNP:rs5743809)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_057290"
FT   VARIANT         210
FT                   /note="A -> G (in dbSNP:rs137853180)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_066353"
FT   VARIANT         210
FT                   /note="A -> T (in dbSNP:rs137853179)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_066354"
FT   VARIANT         247
FT                   /note="R -> K (in dbSNP:rs35220466)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_057291"
FT   VARIANT         249
FT                   /note="S -> P (in dbSNP:rs5743810)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:15815621, ECO:0000269|PubMed:18810425,
FT                   ECO:0000269|PubMed:21618349, ECO:0000269|Ref.3"
FT                   /id="VAR_063110"
FT   VARIANT         283
FT                   /note="I -> V (in dbSNP:rs137853181)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_066355"
FT   VARIANT         327
FT                   /note="V -> M (in dbSNP:rs3796508)"
FT                   /evidence="ECO:0000269|PubMed:21618349, ECO:0000269|Ref.3"
FT                   /id="VAR_057292"
FT   VARIANT         345
FT                   /note="H -> Y (in dbSNP:rs5743813)"
FT                   /id="VAR_057293"
FT   VARIANT         427
FT                   /note="V -> A (in dbSNP:rs5743815)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_057294"
FT   VARIANT         442
FT                   /note="D -> A (in dbSNP:rs137853182)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_066356"
FT   VARIANT         465
FT                   /note="V -> I (in dbSNP:rs5743816)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_057295"
FT   VARIANT         474
FT                   /note="A -> T (in dbSNP:rs5743817)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_057296"
FT   VARIANT         474
FT                   /note="A -> V (impairs the ability to induce NF-kappa-B
FT                   activation; dbSNP:rs1302799168)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_066357"
FT   VARIANT         592
FT                   /note="G -> V (in dbSNP:rs75244616)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_066358"
FT   VARIANT         690
FT                   /note="N -> T (impairs the ability to induce NF-kappa-B
FT                   activation; dbSNP:rs114855575)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_066359"
FT   VARIANT         708
FT                   /note="Q -> H (impairs the ability to induce NF-kappa-B
FT                   activation; dbSNP:rs137853183)"
FT                   /evidence="ECO:0000269|PubMed:21618349"
FT                   /id="VAR_066360"
FT   VARIANT         783
FT                   /note="M -> V (in dbSNP:rs5743822)"
FT                   /id="VAR_057297"
FT   MUTAGEN         678
FT                   /note="F->A: Does not inhibit homodimer formation."
FT                   /evidence="ECO:0000269|PubMed:25088687"
FT   MUTAGEN         712
FT                   /note="C->R: Inhibits homodimer formation."
FT                   /evidence="ECO:0000269|PubMed:25088687"
FT   MUTAGEN         716
FT                   /note="L->R: Inhibits homodimer formation."
FT                   /evidence="ECO:0000269|PubMed:25088687"
FT   STRAND          642..647
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           650..652
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           653..658
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           660..666
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           674..677
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           684..694
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   STRAND          695..702
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           704..709
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           711..717
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           722..724
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   STRAND          725..727
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   STRAND          731..737
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           741..743
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           749..757
FT                   /evidence="ECO:0007829|PDB:4OM7"
FT   HELIX           772..780
FT                   /evidence="ECO:0007829|PDB:4OM7"
SQ   SEQUENCE   796 AA;  91880 MW;  9ACEAEC084CB466C CRC64;
     MTKDKEPIVK SFHFVCLMII IVGTRIQFSD GNEFAVDKSK RGLIHVPKDL PLKTKVLDMS
     QNYIAELQVS DMSFLSELTV LRLSHNRIQL LDLSVFKFNQ DLEYLDLSHN QLQKISCHPI
     VSFRHLDLSF NDFKALPICK EFGNLSQLNF LGLSAMKLQK LDLLPIAHLH LSYILLDLRN
     YYIKENETES LQILNAKTLH LVFHPTSLFA IQVNISVNTL GCLQLTNIKL NDDNCQVFIK
     FLSELTRGST LLNFTLNHIE TTWKCLVRVF QFLWPKPVEY LNIYNLTIIE SIREEDFTYS
     KTTLKALTIE HITNQVFLFS QTALYTVFSE MNIMMLTISD TPFIHMLCPH APSTFKFLNF
     TQNVFTDSIF EKCSTLVKLE TLILQKNGLK DLFKVGLMTK DMPSLEILDV SWNSLESGRH
     KENCTWVESI VVLNLSSNML TDSVFRCLPP RIKVLDLHSN KIKSVPKQVV KLEALQELNV
     AFNSLTDLPG CGSFSSLSVL IIDHNSVSHP SADFFQSCQK MRSIKAGDNP FQCTCELREF
     VKNIDQVSSE VLEGWPDSYK CDYPESYRGS PLKDFHMSEL SCNITLLIVT IGATMLVLAV
     TVTSLCIYLD LPWYLRMVCQ WTQTRRRARN IPLEELQRNL QFHAFISYSE HDSAWVKSEL
     VPYLEKEDIQ ICLHERNFVP GKSIVENIIN CIEKSYKSIF VLSPNFVQSE WCHYELYFAH
     HNLFHEGSNN LILILLEPIP QNSIPNKYHK LKALMTQRTY LQWPKEKSKR GLFWANIRAA
     FNMKLTLVTE NNDVKS
//