Mus musculus Gene: Tlr2
Summary
InnateDB Gene IDBG-154818.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Tlr2
Gene Name toll-like receptor 2
Synonyms Ly105;
Species Mus musculus
Ensembl Gene ENSMUSG00000027995
Encoded Proteins
toll-like receptor 2
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
Tlr2 expression in astrocytes is induced by TNF alpha and NF Kappa B-dependent pathways.
Tlr2 recognition of Staphylococcal peptidoglycan leads to induction of beta-defensin-2.
Tlr2 is involved in Respiratory syncytial virus (RSV) recognition and subsequent innate immune activation by promoting neutrophil migration and dendritic cell activation within the lung.
Tlr4, Tlr2, or Tlr3 cooperate with proteinase-activated receptors (PARs) for activation of nuclear factor-kappaB-dependent signaling in mucosal epithelial cell lines.
Tlr2 is a signaling receptor that is activated by lipopolysaccharide (LPS) in a response that depends on LPS-binding protein and is enhanced by CD14.
Tlr2 is a signal transducer for soluble Peptidoglycan and lipoteichoic acid (LTA) in addition to LPS.
Tlr2 recognizes Gram-positive bacterial cell wall components, leading to the activation of the innate immune system.
Tlr2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.
TLR2/MyD88/PI3K/Rac1/Akt pathway mediates the activation of LTA-induced mitogen-activated protein kinases (MAPKs), which in turn initiates the activation of NF-kappaB, and ultimately induces cPLA2/COX-2-dependent PGE2 and IL-6 generation.
Tlr2 and Tlr4 activate murine macrophages and this is negatively regulated by a Lyn/PI3K module and promoted by SHIP1.
Tlr2 is a molecular link between increased dietary lipid intake and the regulation of glucose homeostasis, via regulation of energy substrate utilization and tissue inflammation.
Tlr2 activation induces type I interferon responses from endolysosomal compartments where it is translocated to upon ligand engagement.
Tlr2 and Myd88-dependent phosphatidylinositol 3-kinase and Rac1 activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophages.
Tlr1 :: Tlr2 dimeric pairs recognize malarial glycosylphosphatidylinositols (GPI) to initiates intracellular signalling and the production of pro-inflammatory cytokines.
Tlr2 recognizes Thermus aquaticus extracellular polysacchride, YT-1, and induces the production of cytokines TNF and IL6 in peritoneal macrophages.
Tlr2::Tlr6 synergistically interacts with Tlr9 in lung epithelium to induce rapid pathogen killing, and can be used as a therapeutic target to treat otherwise lethal pneumonia.
Tlr2 is activated by gut commensal microbe, Bacteroides fragilis, to establish host-microbial symbiosis by promoting immunological tolerance.
Tlr2 and Tnfsf11 signalling pathways are modulated by Porphromonas gingivalis to alter the differentiation states of osteoclasts resulting in bacteria-mediated bone loss.
Tlr2 is expressed by Muller cells, principal glia of retina, and is responsible for generating robust bactericidal activity against Staphylococcus aureusand contributing to retinal innate defence.
Tlr2 is required for rapid inflammasome activation in response to infection by cytosolic bacterial pathogens such as Francisella novicida.
Tlr2-driven integration of inducible nitric oxide synthase (iNOS), Wnt-beta-Catenin and Notch1 signalling contributes to its capacity to regulate a battery of genes associated with T regulatory cell lineage commitment and towards modulation of defined set of effector functions in macrophages.
Tlr2 directly recognizes glycogen, resulting in the activation of immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines.
Tlr2 and Tlr4 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr2/4 double-deficient mice were unable to control pneumonia caused by C. pneumoniae.
Tlr2 signalling promotes protective vaccine-enhancing Th17 cell responses when cells are stimulated with early secreted antigenic target protein 6 (ESAT-6) expressed by the virulent Mycobacterium tuberculosis strain H37Rv but not by tuberculosis vaccine Bacillus Calmette-Guérin (BCG).
Tlr2 recognizes Mycobacterium tuberculosis H37Rv cell surface lipoprotein MPT83, which induces the production of Tnf, Il6, and Il12b cytokines by macrophages and upregulates macrophage function.
Mycobacterium abscessus glycopeptidolipid (GPL) prevents Tlr2-mediate induction of Il8 and Defb4a in respiratory epithelial cells. (Demonstrated in human)
Tlr2 is expressed in the enteric nervous system (ENS) and intestinal smooth muscle layers. Its absence induces architectural and neurochemical coding changes in the ENS, leading to gut dysmotility and to higher inflammatory bowel diseases susceptibility
Salmonella enterica serovar Typhimurium ?msbB that possesses a modified lipid A triggers exacerbated colitis in the absence of Nod1 and/or Nod2, which is likely due to increased Tlr2 stimulation.
Adaptor proteins Ticam1 and Ticam2 have a novel function in Tlr2-mediated signal transduction.
Retinoic acid treatment enhances Tlr2-dependent Il10 production from T cells and this, in turn, potentiates T regulatory cell generation without the need for activation of antigen presenting cells.
Proline-proline-glutamic acid 57 (PPE57), located on the mycobacterial cell surface, induces a T helper 1 immune response via Tlr2-mediated macrophage functions.
Tlr2 is essential for the immune responses to cholera vaccination.
Staphylococcal superantigen-like protein 3 (SSL3) interferes with Tlr2 activation at two stages. First by binding to Tlr2 and blocking ligand binding and second by interacting with an already formed Tlr2-lipopeptide complex, thus preventing TLR heterodimerization and downstream signalling.
InnateDB Annotation from Orthologs
Summary
[Homo sapiens] TLR2 plays a critical role in the ability of innate immunity to determine M. pulmonis numbers in the lung, and early after respiratory infection TLR2 recognition of M. pulmonis triggers initial cytokine responses of host cells.
[Homo sapiens] TLR2 functions as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.
[Homo sapiens] TLR1 :: TLR2 dimeric pairs recognize malarial glycosylphosphatidylinositols (GPI) to initiates intracellular signalling and the production of pro-inflammatory cytokines.
[Homo sapiens] TLR2 recognizes Thermus aquaticus extracellular polysacchride, YT-1, and induces the production of cytokines TNF and IL6 in peritoneal macrophages. (Demonstrated in murine model)
[Homo sapiens] TLR2::TLR6 synergistically interacts with TLR9 in lung epithelium to induce rapid pathogen killing, and can be used as a therapeutic target to treat otherwise lethal pneumonia.
[Homo sapiens] TLR2 is activated by gut commensal microbe, Bacteroides fragilis, to establish host-microbial symbiosis by promoting immunological tolerance. (Demonstrated in murine model)
[Homo sapiens] TLR2 and TNFSF11 signalling pathways are modulated by Porphromonas gingivalis to alter the differentiation states of osteoclasts resulting in bacteria-mediated bone loss. (Demonstrated in murine model)
[Homo sapiens] TLR2 is expressed by Muller cells, principal glia of retina, and is responsible for generating robust bactericidal activity against Staphylococcus aureus and contributing to retinal innate defence.
[Homo sapiens] TLR2 is required for rapid inflammasome activation in response to infection by cytosolic bacterial pathogens such as Francisella novicida. (Demonstrated in murine model)
[Homo sapiens] TLR2-driven integration of inducible nitric oxide synthase (iNOS), Wnt-beta-Catenin and NOTCH1 signalling contributes to its capacity to regulate a battery of genes associated with T regulatory cell lineage commitment and towards modulation of defined set of effector functions in macrophages. (Demonstrated in murine model)
[Homo sapiens] TLR2 directly recognizes glycogen, resulting in the activation of immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines.
[Homo sapiens] TLR2 and TLR4 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr2/4 double-deficient mice were unable to control pneumonia caused by C. pneumoniae. (Demonstrated in mice)
[Homo sapiens] TLR2 signalling promotes protective vaccine-enhancing Th17 cell responses when cells are stimulated with early secreted antigenic target protein 6 (ESAT-6) expressed by the virulent Mycobacterium tuberculosis strain H37Rv but not by tuberculosis vaccine Bacillus Calmette-Guérin (BCG). (Demonstrated in mice)
[Homo sapiens] TLR2 recognizes Mycobacterium tuberculosis H37Rv cell surface lipoprotein MPT83, which induces the production of TNF, IL6, and IL12B cytokines by macrophages and upregulates macrophage function. (Demonstrated in mouse)
[Homo sapiens] Mycobacterium abscessus glycopeptidolipid (GPL) prevents TLR2-mediate induction of IL8 and DEFB4A in respiratory epithelial cells.
[Homo sapiens] Interaction of filamentous hemagglutinin (FHA) with TLR2 induces an innate immune response against Bordetella pertussis and the TLR2-binding domain of FHA may contribute to immunoprotection against pertussis infection.
[Homo sapiens] Cutaneous bacteria can negatively regulate skin-driven immune responses by inducing Gr1(+)CD11b(+) myeloid-derived suppressor cells via TLR2-6 activation.
[Homo sapiens] Soluble TLR2 (sTLR2) generated by metalloproteinase activation inhibits TLR2-induced cytokine production in THP-1 cell line.
[Homo sapiens] TLR10 is a functional receptor involved in the innate immune response to H. pylori infection and the TLR2/TLR10 heterodimer functions in H. pylori lipopolysaccharide recognition.
[Homo sapiens] Human Cytomegalovirus (HCMV) miR-UL112-3p efficiently targets TLR2 during HCMV infection, resulting in the inhibition of TLR2-mediated NFκB signalling.
[Homo sapiens] H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in neutrophils and this activation is independent of a functional type IV secretion system, TLR2 and TLR4.
[Homo sapiens] Staphylococcal superantigen-like protein 3 (SSL3) interferes with TLR2 activation at two stages. First by binding to TLR2 and blocking ligand binding and second by interacting with an already formed TLR2-lipopeptide complex, thus preventing TLR heterodimerization and downstream signalling.
Entrez Gene
Summary This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000137462:
The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is expressed most abundantly in peripheral blood leukocytes, and mediates host response to Gram-positive bacteria and yeast via stimulation of NF-kappaB. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 3:83836273-83841767
Strand Reverse strand
Band E3
Transcripts
ENSMUST00000029623 ENSMUSP00000029623
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 15 experimentally validated interaction(s) in this database.
They are also associated with 30 interaction(s) predicted by orthology.
Experimentally validated
Total 15 [view]
Protein-Protein 15 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 30 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004872 receptor activity
GO:0004888 transmembrane signaling receptor activity
GO:0005515 protein binding
GO:0008329 signaling pattern recognition receptor activity
GO:0042497 triacyl lipopeptide binding
GO:0042498 diacyl lipopeptide binding
GO:0042834 peptidoglycan binding
GO:0046982 protein heterodimerization activity
GO:0070891 lipoteichoic acid binding
GO:0071723 lipopeptide binding
Biological Process
GO:0001666 response to hypoxia
GO:0001774 microglial cell activation
GO:0002224 toll-like receptor signaling pathway
GO:0002238 response to molecule of fungal origin
GO:0002282 microglial cell activation involved in immune response
GO:0002687 positive regulation of leukocyte migration
GO:0002752 cell surface pattern recognition receptor signaling pathway
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0006691 leukotriene metabolic process
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0007165 signal transduction
GO:0007252 I-kappaB phosphorylation
GO:0008285 negative regulation of cell proliferation
GO:0009617 response to bacterium
GO:0009636 response to toxic substance
GO:0030177 positive regulation of Wnt signaling pathway
GO:0032289 central nervous system myelin formation
GO:0032493 response to bacterial lipoprotein
GO:0032494 response to peptidoglycan
GO:0032496 response to lipopolysaccharide
GO:0032570 response to progesterone
GO:0032695 negative regulation of interleukin-12 production
GO:0032700 negative regulation of interleukin-17 production
GO:0032722 positive regulation of chemokine production
GO:0032733 positive regulation of interleukin-10 production
GO:0032755 positive regulation of interleukin-6 production
GO:0032757 positive regulation of interleukin-8 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0032868 response to insulin
GO:0034123 positive regulation of toll-like receptor signaling pathway
GO:0034134 toll-like receptor 2 signaling pathway
GO:0042346 positive regulation of NF-kappaB import into nucleus
GO:0042495 detection of triacyl bacterial lipopeptide
GO:0042496 detection of diacyl bacterial lipopeptide
GO:0042535 positive regulation of tumor necrosis factor biosynthetic process
GO:0042892 chloramphenicol transport
GO:0044130 negative regulation of growth of symbiont in host
GO:0045087 innate immune response (InnateDB)
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0046209 nitric oxide metabolic process
GO:0048714 positive regulation of oligodendrocyte differentiation
GO:0050715 positive regulation of cytokine secretion
GO:0050729 positive regulation of inflammatory response
GO:0050830 defense response to Gram-positive bacterium
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0052033 pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response
GO:0052063 induction by symbiont of defense-related host nitric oxide production
GO:0060907 positive regulation of macrophage cytokine production
GO:0070542 response to fatty acid
GO:0071221 cellular response to bacterial lipopeptide
GO:0071223 cellular response to lipoteichoic acid
GO:0071224 cellular response to peptidoglycan
GO:0071726 cellular response to diacyl bacterial lipopeptide
GO:0071727 cellular response to triacyl bacterial lipopeptide
Cellular Component
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0009897 external side of plasma membrane
GO:0009986 cell surface
GO:0016021 integral component of membrane
GO:0035354 Toll-like receptor 1-Toll-like receptor 2 protein complex
GO:0035355 Toll-like receptor 2-Toll-like receptor 6 protein complex
GO:0042995 cell projection
GO:0044297 cell body
Orthologs
Species
Homo sapiens
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
KEGG
Phagosome pathway
Toll-like receptor signaling pathway pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
Malaria pathway
Toxoplasmosis pathway
Amoebiasis pathway
INOH
PID BIOCARTA
PID NCI
Pathway Predictions based on Human Orthology Data
NETPATH
REACTOME
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
Defensins pathway
Innate Immune System pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
Beta defensins pathway
Immune System pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
KEGG
Phagosome pathway
Toll-like receptor signaling pathway pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
Malaria pathway
Toxoplasmosis pathway
Amoebiasis pathway
INOH
PID BIOCARTA
Toll-like receptor pathway [Biocarta view]
Nfkb activation by nontypeable hemophilus influenzae [Biocarta view]
PID NCI
Endogenous TLR signaling
Cross-References
SwissProt
TrEMBL G3X8Y8
UniProt Splice Variant
Entrez Gene 24088
UniGene Mm.87596
RefSeq NM_011905
OMIM
CCDS CCDS17435
HPRD
IMGT
MGI ID MGI:1346060
MGI Symbol Tlr2
EMBL AC133160 CH466547
GenPept EDL15415
RNA Seq Atlas 24088