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Protein / target

Toll-like receptor 6

Encoded byTLR6Q9Y2C9Homo sapiensSwiss-Prot
Antibody-tractable
Druggability
UniProt loc high conf
3
Research papers

Protein at a glance

Biological role

Transmembrane signaling receptor

Strongest disease association

Asthma

Via encoding gene TLR6 · Genetic evidence · score 0.57

Research activity

Emerging research

3 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Participates in the innate immune response to Gram-positive bacteria and fungi.

View complete UniProt function annotation

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)

Subcellular location

Cell membraneCytoplasmic vesicle, phagosome membraneMembrane raftGolgi apparatus
Domains and Gene Ontology detail (49)

Domains & features

LRRCTTIR

Gene Ontology

  • CGolgi apparatus
  • Cmembrane raft
  • Cphagocytic vesicle membrane
  • Cplasma membrane
  • Creceptor complex
  • CToll-like receptor 2-Toll-like receptor 6 protein complex
  • Famyloid-beta binding
  • Fdiacyl lipopeptide binding
  • Fidentical protein binding
  • Flipopeptide binding
  • Fprotein heterodimerization activity
  • Fsignaling receptor activity

796 aa · 92 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GOImmune signallingUniProt · GOKinase signallingGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·Participates in the innate immune response to Gram-positive bacteria and fungi. Specific…
  • ·cellular response to oxidised low-density lipoprotein particle stimulus

Immune signalling

  • ·Participates in the innate immune response to Gram-positive bacteria and fungi. Specific…
  • ·antibacterial innate immune response
  • ·immune response
  • ·inflammatory response

Kinase signalling

  • ·activation of NF-kappaB-inducing kinase activity
  • ·positive regulation of JUN kinase activity

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene TLR6

Gene-level evidence surfaced through the gene TLR6that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Asthma
0.61Moderately supported

Genetic evidence dominant · Open Targets 0.37

Chronic rhinosinusitis
0.39Limited support

Genetic evidence dominant · Open Targets 0.24

Immunologic Deficiency Syndromes
0.24Preliminary

Pathway evidence dominant · Open Targets 0.37 · no direct causal or clinical evidence

Cardiovascular Diseases
0.20Preliminary

Genetic evidence dominant · Open Targets 0.12

Lyme Disease
0.14Preliminary

Genetic evidence dominant · Open Targets 0.08

View evidence synthesis (5)
AsthmaModerately supported
0.61
agreement 0.470.75
Genetic87%Literature14%

Open Targets aggregate 0.37 · 2 independent evidence families

Chronic rhinosinusitisLimited support
0.39
agreement 0.270.51
Genetic100%

Open Targets aggregate 0.24 · 1 independent evidence family

Immunologic Deficiency SyndromesPreliminary
0.24
agreement 0.010.47
Pathway100%

Open Targets aggregate 0.37 · 1 independent evidence family · no direct causal or clinical evidence

Cardiovascular DiseasesPreliminary
0.20
agreement 0.060.34
Genetic97%Literature3%

Open Targets aggregate 0.12 · 2 independent evidence families

Lyme DiseasePreliminary
0.14
agreement 0.020.26
Genetic100%

Open Targets aggregate 0.08 · 1 independent evidence family

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Immunologic Deficiency Syndromes0.37
Asthma0.37
Chronic rhinosinusitis0.24
Cardiovascular Diseases0.12
Colorectal Neoplasms0.09
Infections0.09
Lyme Disease0.08

Tractability

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
AB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

3 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Olson JK · Journal of immunology (Baltimore, Md. : 1950) · 2004

Zhang X · Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024

Recent

Sustained exposure to Helicobacter pylori induces immune tolerance by desensitizing TLR6.

Zhang X · Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024

Europe PMC papers linked directly to this protein.