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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 TLR6 that 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 0.47–0.75
Genetic87%Literature14%

Open Targets aggregate 0.37 · 2 independent evidence families

Chronic rhinosinusitisLimited support
0.39
agreement 0.27–0.51
Genetic100%

Open Targets aggregate 0.24 · 1 independent evidence family

Immunologic Deficiency SyndromesPreliminary
0.24
agreement 0.01–0.47
Pathway100%

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

Cardiovascular DiseasesPreliminary
0.20
agreement 0.06–0.34
Genetic97%Literature3%

Open Targets aggregate 0.12 · 2 independent evidence families

Lyme DiseasePreliminary
0.14
agreement 0.02–0.26
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
Infections0.09
Lyme Disease0.08

Tractability

Antibodies — Emerging

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

Protein degraders — Emerging

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.