InnateDB: Systems Biology of the Innate Immune Response

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

IDBP-154820

toll-like receptor 2

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 18768838

Tlr2 expression in astrocytes is induced by TNF alpha and NF Kappa B-dependent pathways.

PMID 18621910

Tlr2 recognition of Staphylococcal peptidoglycan leads to induction of beta-defensin-2.

PMID 19019963

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.

PMID 19865078

Tlr4, Tlr2, or Tlr3 cooperate with proteinase-activated receptors (PARs) for activation of nuclear factor-kappaB-dependent signaling in mucosal epithelial cell lines.

PMID 9751057

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.

PMID 10364168

Tlr2 is a signal transducer for soluble Peptidoglycan and lipoteichoic acid (LTA) in addition to LPS.

PMID 10384090

Tlr2 recognizes Gram-positive bacterial cell wall components, leading to the activation of the innate immune system.

PMID 10426996

Tlr2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.

PMID 20167866

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.

PMID 20385881

Tlr2 and Tlr4 activate murine macrophages and this is negatively regulated by a Lyn/PI3K module and promoted by SHIP1.

PMID 20407745

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.

PMID 20422028

Tlr2 activation induces type I interferon responses from endolysosomal compartments where it is translocated to upon ligand engagement.

PMID 20368346

Tlr2 and Myd88-dependent phosphatidylinositol 3-kinase and Rac1 activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophages.

PMID 21439957

Tlr1 :: Tlr2 dimeric pairs recognize malarial glycosylphosphatidylinositols (GPI) to initiates intracellular signalling and the production of pro-inflammatory cytokines.

PMID 21454596

Tlr2 recognizes Thermus aquaticus extracellular polysacchride, YT-1, and induces the production of cytokines TNF and IL6 in peritoneal macrophages.

PMID 21482737

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.

PMID 21512004

Tlr2 is activated by gut commensal microbe, Bacteroides fragilis, to establish host-microbial symbiosis by promoting immunological tolerance.

PMID 21566133

Tlr2 and Tnfsf11 signalling pathways are modulated by Porphromonas gingivalis to alter the differentiation states of osteoclasts resulting in bacteria-mediated bone loss.

PMID 21602496

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.

PMID 21698237

Tlr2 is required for rapid inflammasome activation in response to infection by cytosolic bacterial pathogens such as Francisella novicida.

PMID 21862586

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.

PMID 21873606

Tlr2 directly recognizes glycogen, resulting in the activation of immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines.

PMID 22096480

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.

PMID 22102818

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).

PMID 22174456

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.

PMID 22216191

Mycobacterium abscessus glycopeptidolipid (GPL) prevents Tlr2-mediate induction of Il8 and Defb4a in respiratory epithelial cells. (Demonstrated in human)

PMID 23994200

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

PMID 25423082

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.

PMID 25505250

Adaptor proteins Ticam1 and Ticam2 have a novel function in Tlr2-mediated signal transduction.

PMID 25826367

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.

PMID 25586105

Proline-proline-glutamic acid 57 (PPE57), located on the mycobacterial cell surface, induces a T helper 1 immune response via Tlr2-mediated macrophage functions.

PMID 26078314

Tlr2 is essential for the immune responses to cholera vaccination.

PMID 26283364

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.

PMID 26310831

Peli3 is involved in endotoxin tolerance and functions as a negative regulator of Tlr2/4 signalling.

PMID 26423153

Cytokine activation as a result of Tlr2 stimulation is mediated by the phagosomal trafficking molecule Ap3b1 (AP-3).

InnateDB Annotation from Orthologs

Summary

PMID 20505832

[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.

PMID 20927103

[Homo sapiens] TLR2 functions as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.

PMID 21439957

[Homo sapiens] TLR1 :: TLR2 dimeric pairs recognize malarial glycosylphosphatidylinositols (GPI) to initiates intracellular signalling and the production of pro-inflammatory cytokines.

PMID 21454596

[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)

PMID 21482737

[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.

PMID 21512004

[Homo sapiens] TLR2 is activated by gut commensal microbe, Bacteroides fragilis, to establish host-microbial symbiosis by promoting immunological tolerance. (Demonstrated in murine model)

PMID 21566133

[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)

PMID 21602496

[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.

PMID 21698237

[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)

PMID 21862586

[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)

PMID 21873606

[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.

PMID 22096480

[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)

PMID 22102818

[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)

PMID 22174456

[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)

PMID 22216191

[Homo sapiens] Mycobacterium abscessus glycopeptidolipid (GPL) prevents TLR2-mediate induction of IL8 and DEFB4A in respiratory epithelial cells.

PMID 25353353

[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.

PMID 25456159

[Homo sapiens] Cutaneous bacteria can negatively regulate skin-driven immune responses by inducing Gr1(+)CD11b(+) myeloid-derived suppressor cells via TLR2-6 activation.

PMID 25531754

[Homo sapiens] Soluble TLR2 (sTLR2) generated by metalloproteinase activation inhibits TLR2-induced cytokine production in THP-1 cell line.

PMID 25977263

[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.

PMID 25955717

[Homo sapiens] Human Cytomegalovirus (HCMV) miR-UL112-3p efficiently targets TLR2 during HCMV infection, resulting in the inhibition of TLR2-mediated NFκB signalling.

PMID 26610398

[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.

PMID 26283364

[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.

PMID 26310831

[Homo sapiens] PELI3 is involved in endotoxin tolerance and functions as a negative regulator of TLR2/4 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

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