TLR2

Domain

Ester-bound lipid substrates are bound through a crevice formed between the LRR 11 and LRR 12.

The ATG16L1-binding motif mediates interaction with ATG16L1.

The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.

Function

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:21078852, PubMed:17889651). 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).

Post-translational modifications

Glycosylation of Asn-442 is critical for secretion of the N-terminal ectodomain of TLR2.

Ubiquitinated at Lys-754 by PPP1R11, leading to its degradation (PubMed:27805901). Deubiquitinated by USP2 (By similarity).

Sequence similarities

Belongs to the Toll-like receptor family.

Tissue specificity

Highly expressed in peripheral blood leukocytes, in particular in monocytes, in bone marrow, lymph node and in spleen. Also detected in lung and in fetal liver. Levels are low in other tissues.

Cellular localization

• Membrane
• Single-pass type I membrane protein
• Cytoplasmic vesicle
• Phagosome membrane
• Single-pass type I membrane protein
• Membrane raft
• 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 determines the intracellular targeting to the Golgi apparatus. Triacylated lipoproteins induce the same mechanism for TLR2:TLR1 heterodimers.

Alternative names

• Toll-like receptor 2
• Toll/interleukin-1 receptor-like protein 4
• TLR2
• TIL4

Database links

• entrezGene:7097
• omim:603028
• swissprot:O60603

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Other research areas

• Immuno-oncology

Molecular weight

89838Da