TISIDB

Summary
Symbol	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
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	Membrane Single-pass type I membrane protein
Domain	PF13855 Leucine rich repeat PF01582 TIR domain
Function	Participates in the innate immune response to microbial agents. Mediates detection of bacterial flagellins. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.

> Gene Ontology [ TOP ]
Biological Process	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: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:0006809 nitric oxide biosynthetic process GO:0007548 sex differentiation GO:0008406 gonad development GO:0008584 male gonad development GO:0009306 protein secretion GO:0009612 response to mechanical stimulus GO:0031349 positive regulation of defense response GO:0032496 response to lipopolysaccharide GO:0032637 interleukin-8 production GO:0032677 regulation of interleukin-8 production GO:0032757 positive regulation of interleukin-8 production GO:0034121 regulation of toll-like receptor signaling pathway GO:0034123 positive regulation of toll-like receptor signaling pathway GO:0034146 toll-like receptor 5 signaling pathway GO:0042742 defense response to bacterium GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045137 development of primary sexual characteristics GO:0045428 regulation of nitric oxide biosynthetic process GO:0045429 positive regulation of nitric oxide biosynthetic process GO:0046209 nitric oxide metabolic process GO:0046546 development of primary male sexual characteristics GO:0046661 male sex differentiation GO:0048608 reproductive structure development GO:0050663 cytokine secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0050829 defense response to Gram-negative bacterium GO:0061458 reproductive system development GO:0071214 cellular response to abiotic stimulus GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071260 cellular response to mechanical stimulus GO:0071396 cellular response to lipid GO:0071496 cellular response to external stimulus GO:0072593 reactive oxygen species metabolic process GO:0098542 defense response to other organism GO:1903409 reactive oxygen species biosynthetic process GO:1903426 regulation of reactive oxygen species biosynthetic process GO:1903428 positive regulation of reactive oxygen species biosynthetic process GO:1904407 positive regulation of nitric oxide metabolic process GO:2000377 regulation of reactive oxygen species metabolic process GO:2000379 positive regulation of reactive oxygen species metabolic process GO:2001057 reactive nitrogen species metabolic process
Molecular Function	GO:0005126 cytokine receptor binding GO:0005149 interleukin-1 receptor binding GO:0070851 growth factor receptor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04620 Toll-like receptor signaling pathway
Reactome	R-HSA-1643685: Disease R-HSA-5602358: Diseases associated with the TLR signaling cascade R-HSA-5260271: Diseases of Immune System R-HSA-5603037: IRAK4 deficiency (TLR5) R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-975871: MyD88 cascade initiated on plasma membrane R-HSA-5602680: MyD88 deficiency (TLR5) R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade R-HSA-168176: Toll Like Receptor 5 (TLR5) Cascade R-HSA-168898: Toll-Like Receptors Cascades

> KEGG and Reactome Pathway

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KEGG

hsa04620 Toll-like receptor signaling pathway

Reactome

R-HSA-1643685: Disease
R-HSA-5602358: Diseases associated with the TLR signaling cascade
R-HSA-5260271: Diseases of Immune System
R-HSA-5603037: IRAK4 deficiency (TLR5)
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-975871: MyD88 cascade initiated on plasma membrane
R-HSA-5602680: MyD88 deficiency (TLR5)
R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168176: Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168898: Toll-Like Receptors Cascades

Summary
Symbol	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TLR5 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 TLR5 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26831100	Colorectal Carcinoma	Promote immunity	Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8+ T-cell axis.
19620771	Ovarian Carcinoma	Promote immunity	Here we demonstrated that linear polyethylenimine-based (PEI-based) nanoparticles encapsulating siRNA were preferentially and avidly engulfed by regulatory DCs expressing CD11c and programmed cell death 1-ligand 1 (PD-L1) at ovarian cancer locations in mice. PEI triggered robust and selective TLR5 activation in vitro and elicited the production of hallmark TLR5-inducible cytokines in WT mice, but not in Tlr5-/- littermates. Our results demonstrate that the intrinsic TLR5 and TLR7 stimulation of siRNA-PEI nanoparticles synergizes with the gene-specific silencing activity of siRNA to transform tumor-infiltrating regulatory DCs into DCs capable of promoting therapeutic antitumor immunity.
21427357	Breast Carcinoma	Promote immunity	Activation of Toll-like receptor 5 on breast cancer cells by flagellin suppresses cell proliferation and tumor growth. These findings indicate that TLR5 activation by flagellin mediates innate immune response to elicit potent antitumor activity in breast cancer cells themselves, which may serve as a novel therapeutic target for human breast cancer therapy.
20483744	Prostate Carcinoma	Promote immunity	Overall, these data show for the first time that TLR3 and TLR5 stimulation of human prostate cancer cells triggers the production of chemokines, which, in turn, favor the attraction of immune effectors, thereby representing a tool to enhance the efficacy of conventional therapies by stimulating anticancer immune responses.
25223833	melanoma	Promote immunity	Taken together, our results report a new immunotherapeutic approach based on TLR-5 activation and IFN-gamma production capable to control the metastatic growth of B16F10-Nex2 melanoma, being a promising alternative to be associated with chemotherapeutic drugs for an effective anti-tumor responses.
21804019	lymphoma; lung carcinoma; colon carcinoma	Promote immunity	We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells

Summary
Symbol	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
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 TLR5 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	Second most enriched score: 0.53	Sensitive to T cell-mediated killing
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	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
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 TLR5 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	0.333	0.212
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.423	0.426
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.269	0.531
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.501	0.172
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.805	0.564
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.119	0.945
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.391	0.292
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.891	0.315
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.219	0.834
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.624	0.553
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	1.554	0.267
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.358	0.00653

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TLR5 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	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	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	7.4	1.4	6	0.177
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	7.4	1.7	5.7	0.231
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	5.9	8.4	0.613
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	9.1	6.3	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
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	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	3.7	4.2	0.636
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TLR5. 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	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TLR5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TLR5. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TLR5. 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	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TLR5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TLR5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TLR5
Name	toll-like receptor 5
Aliases	TIL3; MGC126430; MGC126431; Toll/interleukin-1 receptor-like protein 3; SLEB1; systemic lupus erythematosus ......
Chromosomal Location	1q32.3-q42
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TLR5 collected from DrugBank database.

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

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