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Identification
HMDB Protein ID HMDBP12412
Secondary Accession Numbers None
Name Toll-like receptor 2
Synonyms
  1. Toll/interleukin-1 receptor-like protein 4
Gene Name TLR2
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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).
Pathways
  • Amoebiasis
  • Chagas disease
  • Coronavirus disease - COVID-19
  • Epstein-Barr virus infection
  • Hepatitis B
  • Herpes simplex virus 1 infection
  • Human immunodeficiency virus 1 infection
  • Inflammatory bowel disease
  • Legionellosis
  • Leishmaniasis
  • Lipid and atherosclerosis
  • Malaria
  • Measles
  • Neutrophil extracellular trap formation
  • PD-L1 expression and PD-1 checkpoint pathway in cancer
  • Phagosome
  • PI3K-Akt signaling pathway
  • Proteoglycans in cancer
  • Rheumatoid arthritis
  • Salmonella infection
  • Toll-like receptor signaling pathway
  • Toxoplasmosis
  • Tuberculosis
Reactions Not Available
GO Classification
Biological Process
signal transduction
positive regulation of chemokine production
cellular response to lipoteichoic acid
cellular response to triacyl bacterial lipopeptide
detection of triacyl bacterial lipopeptide
interleukin-10 production
microglia development
modulation by symbiont of host defense response
response to progesterone stimulus
negative regulation of phagocytosis
negative regulation of synapse assembly
neutrophil degranulation
positive regulation of cellular response to macrophage colony-stimulating factor stimulus
I-kappaB phosphorylation
positive regulation of interleukin-10 production
positive regulation of interleukin-18 production
positive regulation of interleukin-8 production
positive regulation of matrix metallopeptidase secretion
positive regulation of toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
apoptotic process
positive regulation of inflammatory response
inflammatory response
positive regulation of interleukin-12 production
response to insulin stimulus
positive regulation of nitric-oxide synthase biosynthetic process
positive regulation of interferon-beta production
central nervous system myelin formation
defense response to Gram-positive bacterium
leukotriene metabolic process
defense response to virus
innate immune response
immune response
positive regulation of transcription from RNA polymerase II promoter
learning
positive regulation of oligodendrocyte differentiation
response to fatty acid
positive regulation of tumor necrosis factor production
toll-like receptor signaling pathway
cell activation
cellular response to bacterial lipopeptide
cellular response to diacyl bacterial lipopeptide
response to toxin
detection of diacyl bacterial lipopeptide
negative regulation of cell proliferation
MyD88-dependent toll-like receptor signaling pathway
microglial cell activation
nitric oxide metabolic process
positive regulation of interleukin-6 production
positive regulation of gene expression
toll-like receptor 2 signaling pathway
positive regulation of NF-kappaB transcription factor activity
toll-like receptor TLR6:TLR2 signaling pathway
response to hypoxia
cellular response to interferon-gamma
positive regulation of NIK/NF-kappaB signaling
positive regulation of Wnt receptor signaling pathway
Cellular Component
cell surface
membrane raft
Toll-like receptor 1-Toll-like receptor 2 protein complex
cell projection
intrinsic component of plasma membrane
cytoplasm
plasma membrane
Golgi apparatus
cell body
phagocytic vesicle membrane
secretory granule membrane
integral to plasma membrane
Molecular Function
lipopolysaccharide binding
lipopolysaccharide immune receptor activity
pattern recognition receptor activity
Toll-like receptor binding
triacyl lipopeptide binding
peptidoglycan binding
protein-containing complex binding
beta-amyloid binding
transmembrane signaling receptor activity
NAD(P)+ nucleosidase activity
NAD+ nucleotidase, cyclic ADP-ribose generating
signaling receptor activity
identical protein binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 784
Molecular Weight 89836.575
Theoretical pI 6.608
Pfam Domain Function
Signals
  • 1-20;
Transmembrane Regions
  • 589-609;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O60603
UniProtKB/Swiss-Prot Entry Name TLR2_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  12. Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K, Akira S: Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol. 2002 Dec 15;169(12):6668-72. doi: 10.4049/jimmunol.169.12.6668. [PubMed:12471095 ]
  13. Weber AN, Morse MA, Gay NJ: Four N-linked glycosylation sites in human toll-like receptor 2 cooperate to direct efficient biosynthesis and secretion. J Biol Chem. 2004 Aug 13;279(33):34589-94. doi: 10.1074/jbc.M403830200. Epub 2004 Jun 1. [PubMed:15173186 ]
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  19. Boada-Romero E, Letek M, Fleischer A, Pallauf K, Ramon-Barros C, Pimentel-Muinos FX: TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3. EMBO J. 2013 Feb 20;32(4):566-82. doi: 10.1038/emboj.2013.8. Epub 2013 Feb 1. [PubMed:23376921 ]
  20. Stack J, Doyle SL, Connolly DJ, Reinert LS, O'Keeffe KM, McLoughlin RM, Paludan SR, Bowie AG: TRAM is required for TLR2 endosomal signaling to type I IFN induction. J Immunol. 2014 Dec 15;193(12):6090-102. doi: 10.4049/jimmunol.1401605. Epub 2014 Nov 10. [PubMed:25385819 ]
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