TLR6_HUMAN
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 03-AUG-2022, entry version 194.
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; 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. [Q9Y2C9-1]
DR PDB; 4OM7; X-ray; 2.20 A; A/B=640-796.
DR PDBsum; 4OM7; -.
DR AlphaFoldDB; Q9Y2C9; -.
DR SMR; Q9Y2C9; -.
DR BioGRID; 115616; 44.
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 ChEMBL; CHEMBL3259477; -.
DR GlyGen; Q9Y2C9; 9 sites.
DR iPTMnet; Q9Y2C9; -.
DR PhosphoSitePlus; Q9Y2C9; -.
DR BioMuta; TLR6; -.
DR DMDM; 296452933; -.
DR jPOST; Q9Y2C9; -.
DR MassIVE; Q9Y2C9; -.
DR MaxQB; Q9Y2C9; -.
DR PaxDb; Q9Y2C9; -.
DR PeptideAtlas; Q9Y2C9; -.
DR PRIDE; Q9Y2C9; -.
DR ProteomicsDB; 85731; -. [Q9Y2C9-1]
DR Antibodypedia; 10461; 876 antibodies from 46 providers.
DR DNASU; 10333; -.
DR Ensembl; ENST00000381950.1; ENSP00000371376.1; ENSG00000174130.12. [Q9Y2C9-1]
DR Ensembl; ENST00000436693.6; ENSP00000389600.2; ENSG00000174130.12. [Q9Y2C9-1]
DR Ensembl; ENST00000610323.2; ENSP00000480266.1; ENSG00000174130.12. [Q9Y2C9-2]
DR GeneID; 10333; -.
DR KEGG; hsa:10333; -.
DR UCSC; uc010ifg.3; human. [Q9Y2C9-1]
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; IHMLCPQ; -.
DR OrthoDB; 282372at2759; -.
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 SignaLink; Q9Y2C9; -.
DR BioGRID-ORCS; 10333; 7 hits in 1072 CRISPR screens.
DR ChiTaRS; TLR6; human.
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 tissues.
DR ExpressionAtlas; Q9Y2C9; baseline and differential.
DR Genevisible; Q9Y2C9; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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; TAS:Reactome.
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; IPI:ComplexPortal.
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:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC.
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:0001775; P:cell activation; IDA:AgBase.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IDA:ComplexPortal.
DR GO; GO:0071221; P:cellular response to bacterial lipopeptide; IBA:GO_Central.
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; IC:ComplexPortal.
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:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISS:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
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:0051092; P:positive regulation of NF-kappaB transcription factor activity; IGI: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:1903223; P:positive regulation of oxidative stress-induced neuron death; ISS:ARUK-UCL.
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:0034150; P:toll-like receptor 6 signaling pathway; IEA:InterPro.
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 Gene3D; 3.40.50.10140; -; 1.
DR Gene3D; 3.80.10.10; -; 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; IPR027187; TLR6.
DR InterPro; IPR017241; Toll-like_receptor.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR24365; PTHR24365; 1.
DR PANTHER; PTHR24365:SF422; PTHR24365:SF422; 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 SMART; SM00369; LRR_TYP; 5.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 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 Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW 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
