Protein / target

Toll-like receptor 2

Encoded byTLR2O60603Homo sapiensSwiss-Prot

UniProt: O60603 Ensembl: ENSG00000137462 HGNC: HGNC:11848 NCBI Gene: 7097

Clinical-stage

Therapeutic maturity

Clinical candidates

Small-molecule tractable

Druggability

Advanced Clinical

Research papers

Protein at a glance

Biological role

Lipopolysaccharide immune receptor

Strongest disease association

Tuberculosis

Via encoding gene TLR2 · Literature evidence · score 0.49

Therapeutic position

Clinically advancing target

Small molecules and antibodies

Research activity

Emerging research

8 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

Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components.

View complete UniProt function annotation

Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides (PubMed:17889651, PubMed:21078852). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins (PubMed:10426995, PubMed:10426996). 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 TLR6 (PubMed:11441107). Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor, but also partially via TLR4 (PubMed:16622205). MAPK activation in response to bacterial peptidoglycan also occurs via this receptor (PubMed:16622205). Acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CD36); the lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression (PubMed:15809303). Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse) (By similarity). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides (PubMed:16880211). Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM (By similarity)

Subcellular location

MembraneCytoplasmic vesicle, phagosome membraneMembrane raft

Domains and Gene Ontology detail (61)

Domains & features

LRRCTTIR

Gene Ontology

Ccell surface
Ccytoplasm
CGolgi apparatus
Cmembrane raft
Cphagocytic vesicle membrane
Cplasma membrane
Cplasma membrane raft
Creceptor complex
Csecretory granule membrane
CToll-like receptor 1-Toll-like receptor 2 protein complex
CToll-like receptor 2-Toll-like receptor 6 protein complex
Famyloid-beta binding

784 aa · 90 kDa

Biological roles

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

Synaptic signallingGOLipid & lipoprotein metabolismUniProtImmune signallingUniProt · GOTranscriptional regulationGO

View supporting evidence

Synaptic signalling

·negative regulation of synapse assembly

Lipid & lipoprotein metabolism

·Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and…

Immune signalling

·Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and…
·antibacterial innate immune response
·immune response
·inflammatory response

Transcriptional regulation

·positive regulation of gene expression
·positive regulation of transcription by RNA polymerase II

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 TLR2

Gene-level evidence surfaced through the gene TLR2 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.

Tuberculosis

0.40Preliminary

Pathway evidence dominant · Open Targets 0.49 · no direct causal or clinical evidence

Immunologic Deficiency Syndromes

0.25Preliminary

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

Myelodysplastic syndrome

0.22Preliminary

Literature evidence dominant · Open Targets 0.12

Neurodegenerative Diseases

0.16Preliminary

Pathway evidence dominant · Open Targets 0.22 · no direct causal or clinical evidence

Infections

0.15Preliminary

Literature evidence dominant · Open Targets 0.12 · no direct causal or clinical evidence

View evidence synthesis (5)

TuberculosisPreliminary

0.40

agreement 0.22–0.57

Pathway69%Literature31%

Open Targets aggregate 0.49 · 2 independent evidence families · no direct causal or clinical evidence

Immunologic Deficiency SyndromesPreliminary

0.25

agreement 0.07–0.43

Pathway96%Literature4%

Open Targets aggregate 0.37 · 2 independent evidence families · no direct causal or clinical evidence

Myelodysplastic syndromePreliminary

0.22

agreement 0.06–0.37

Literature50%Clinical50%

Open Targets aggregate 0.12 · 2 independent evidence families

Neurodegenerative DiseasesPreliminary

0.16

agreement 0.00–0.34

Pathway89%Literature12%

Open Targets aggregate 0.22 · 2 independent evidence families · no direct causal or clinical evidence

InfectionsPreliminary

0.15

agreement 0.00–0.42

Literature100%

Open Targets aggregate 0.12 · 1 independent evidence family · no direct causal or clinical evidence

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

Tuberculosis0.49

Immunologic Deficiency Syndromes0.37

Neurodegenerative Diseases0.22

Infections0.12

Neoplasms0.12

Myelodysplastic syndrome0.12

Pulmonary Disease, Chronic Obstructive0.12

Drug development

2 compounds recorded · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (2)

TOMARALIMABPhase 2

VB-201Phase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Advanced Clinical and Structure with Ligand support this modality.

Antibodies — Strong

Advanced Clinical and GO CC high conf support this modality.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (12)

SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Advanced ClinicalAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · UniProt UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.