TISIDB

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell membrane Single-pass type I membrane protein Cytoplasmic vesicle, phagosome membrane Single-pass type I membrane protein Membrane raft Golgi apparatus Note=Upon complex formation with CD36 and TLR4, internalized through dynamin-dependent endocytosis. Does not reside in lipid rafts before stimulation but accumulates increasingly in the raft upon the presence of the microbial ligand. In response to diacylated lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid rafts, this recruitment determine the intracellular targeting to the Golgi apparatus (PubMed:16880211).
Domain	PF13855 Leucine rich repeat PF01463 Leucine rich repeat C-terminal domain PF01582 TIR domain
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).

> Gene Ontology [ TOP ]
Biological Process	GO:0001774 microglial cell activation GO:0001819 positive regulation of cytokine production GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002237 response to molecule of bacterial origin GO:0002250 adaptive immune response GO:0002274 myeloid leukocyte activation GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002755 MyD88-dependent toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0007250 activation of NF-kappaB-inducing kinase activity GO:0007254 JNK cascade GO:0009306 protein secretion GO:0009595 detection of biotic stimulus GO:0016045 detection of bacterium GO:0031098 stress-activated protein kinase signaling cascade GO:0031334 positive regulation of protein complex assembly GO:0031349 positive regulation of defense response GO:0032147 activation of protein kinase activity GO:0032490 detection of molecule of bacterial origin GO:0032493 response to bacterial lipoprotein GO:0032611 interleukin-1 beta production GO:0032612 interleukin-1 production GO:0032635 interleukin-6 production GO:0032675 regulation of interleukin-6 production GO:0032755 positive regulation of interleukin-6 production GO:0032872 regulation of stress-activated MAPK cascade GO:0032874 positive regulation of stress-activated MAPK cascade GO:0033674 positive regulation of kinase activity GO:0034150 toll-like receptor 6 signaling pathway GO:0038061 NIK/NF-kappaB signaling GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway GO:0042035 regulation of cytokine biosynthetic process GO:0042088 T-helper 1 type immune response GO:0042089 cytokine biosynthetic process GO:0042107 cytokine metabolic process GO:0042108 positive regulation of cytokine biosynthetic process GO:0042116 macrophage activation GO:0042226 interleukin-6 biosynthetic process GO:0042494 detection of bacterial lipoprotein GO:0042496 detection of diacyl bacterial lipopeptide GO:0042742 defense response to bacterium GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043254 regulation of protein complex assembly GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043506 regulation of JUN kinase activity GO:0043507 positive regulation of JUN kinase activity GO:0044089 positive regulation of cellular component biogenesis GO:0044546 NLRP3 inflammasome complex assembly GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045408 regulation of interleukin-6 biosynthetic process GO:0045410 positive regulation of interleukin-6 biosynthetic process GO:0045860 positive regulation of protein kinase activity GO:0046209 nitric oxide metabolic process GO:0046328 regulation of JNK cascade GO:0046330 positive regulation of JNK cascade GO:0050663 cytokine secretion GO:0050701 interleukin-1 secretion GO:0050702 interleukin-1 beta secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0051403 stress-activated MAPK cascade GO:0070302 regulation of stress-activated protein kinase signaling cascade GO:0070304 positive regulation of stress-activated protein kinase signaling cascade GO:0070339 response to bacterial lipopeptide GO:0070340 detection of bacterial lipopeptide GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071220 cellular response to bacterial lipoprotein GO:0071221 cellular response to bacterial lipopeptide GO:0071724 response to diacyl bacterial lipopeptide GO:0071726 cellular response to diacyl bacterial lipopeptide GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0072593 reactive oxygen species metabolic process GO:0098542 defense response to other organism GO:0098543 detection of other organism GO:0098581 detection of external biotic stimulus GO:1900225 regulation of NLRP3 inflammasome complex assembly GO:1900227 positive regulation of NLRP3 inflammasome complex assembly GO:1901222 regulation of NIK/NF-kappaB signaling GO:1901224 positive regulation of NIK/NF-kappaB signaling GO:2001057 reactive nitrogen species metabolic process
Molecular Function	GO:0033218 amide binding GO:0035325 Toll-like receptor binding GO:0035663 Toll-like receptor 2 binding GO:0042277 peptide binding GO:0071723 lipopeptide binding
Cellular Component	GO:0030139 endocytic vesicle GO:0030659 cytoplasmic vesicle membrane GO:0030666 endocytic vesicle membrane GO:0030670 phagocytic vesicle membrane GO:0035355 Toll-like receptor 2-Toll-like receptor 6 protein complex GO:0043235 receptor complex GO:0045121 membrane raft GO:0045335 phagocytic vesicle GO:0098589 membrane region GO:0098802 plasma membrane receptor complex GO:0098857 membrane microdomain

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04145 Phagosome hsa04620 Toll-like receptor signaling pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-1280218: Adaptive Immune System R-HSA-1236975: Antigen processing-Cross presentation R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-1643685: Disease R-HSA-5602358: Diseases associated with the TLR signaling cascade R-HSA-5260271: Diseases of Immune System R-HSA-1236974: ER-Phagosome pathway R-HSA-5603041: IRAK4 deficiency (TLR2/4) R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-5602498: MyD88 deficiency (TLR2/4) R-HSA-166058: MyD88 R-HSA-5686938: Regulation of TLR by endogenous ligand R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179: Toll Like Receptor TLR1 R-HSA-168188: Toll Like Receptor TLR6 R-HSA-168898: Toll-Like Receptors Cascades

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04145 Phagosome
hsa04620 Toll-like receptor signaling pathway

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-1280218: Adaptive Immune System
R-HSA-1236975: Antigen processing-Cross presentation
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1643685: Disease
R-HSA-5602358: Diseases associated with the TLR signaling cascade
R-HSA-5260271: Diseases of Immune System
R-HSA-1236974: ER-Phagosome pathway
R-HSA-5603041: IRAK4 deficiency (TLR2/4)
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-5602498: MyD88 deficiency (TLR2/4)
R-HSA-166058: MyD88
R-HSA-5686938: Regulation of TLR by endogenous ligand
R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179: Toll Like Receptor TLR1
R-HSA-168188: Toll Like Receptor TLR6
R-HSA-168898: Toll-Like Receptors Cascades

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TLR6 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between TLR6 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25765738	Melanoma	Promote immunity (infiltration)	TLR2/6 agonists and interferon-gamma induce human melanoma cells to produce CXCL10. CXCL10 has been implicated as a critical chemokine supporting T-cell infiltration into the TME.

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of TLR6 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of TLR6 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.416	0.264
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.728	0.323
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.185	0.765
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.026	0.961
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.536	0.679
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.633	0.743
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.329	0.448
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.157	0.886
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.529	0.659
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.728	0.247
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.189	0.164
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.186	0.321

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TLR6 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	11.8	-11.8	0.193
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	18.2	-18.2	0.199
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TLR6. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TLR6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TLR6. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TLR6. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TLR6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TLR6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TLR6
Name	toll-like receptor 6
Aliases	CD286; CD antigen CD286
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TLR6 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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