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Gene Symbol |
TLR2 |
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Aliases |
CD282, TIL4 |
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Entrez Gene ID |
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Gene Name |
Toll like receptor 2 |
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Chromosomal Location |
4q31.3 |
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HGNC ID |
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RefSeq DNA |
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RefSeq mRNA |
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e!Ensembl
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Gene Ontology (GO)
| GO ID |
Ontology |
Function |
Evidence |
Reference |
| GO:0001775 |
Biological process |
Cell activation |
IDA |
15294986 |
| GO:0002224 |
Biological process |
Toll-like receptor signaling pathway |
IBA |
21873635 |
| GO:0002374 |
Biological process |
Cytokine secretion involved in immune response |
IMP |
20441518 |
| GO:0006915 |
Biological process |
Apoptotic process |
TAS |
10426996 |
| GO:0006954 |
Biological process |
Inflammatory response |
IBA |
21873635 |
| GO:0006955 |
Biological process |
Immune response |
TAS |
10426995 |
| GO:0007165 |
Biological process |
Signal transduction |
TAS |
11044375 |
| GO:0007252 |
Biological process |
I-kappaB phosphorylation |
IDA |
19740627 |
| GO:0010628 |
Biological process |
Positive regulation of gene expression |
IMP |
23817958, 26649771 |
| GO:0030177 |
Biological process |
Positive regulation of Wnt signaling pathway |
IMP |
16601243 |
| GO:0032613 |
Biological process |
Interleukin-10 production |
IDA |
23826189 |
| GO:0032722 |
Biological process |
Positive regulation of chemokine production |
IDA |
19740627 |
| GO:0032755 |
Biological process |
Positive regulation of interleukin-6 production |
IDA |
19740627 |
| GO:0032757 |
Biological process |
Positive regulation of interleukin-8 production |
IDA |
17128265, 19740627 |
| GO:0034123 |
Biological process |
Positive regulation of toll-like receptor signaling pathway |
IDA |
17128265 |
| GO:0042495 |
Biological process |
Detection of triacyl bacterial lipopeptide |
IDA |
19931471 |
| GO:0042496 |
Biological process |
Detection of diacyl bacterial lipopeptide |
IDA |
19931471 |
| GO:0045087 |
Biological process |
Innate immune response |
TAS |
15356140 |
| GO:0050729 |
Biological process |
Positive regulation of inflammatory response |
IC |
19740627 |
| GO:0050830 |
Biological process |
Defense response to Gram-positive bacterium |
IDA |
11521063 |
| GO:0051092 |
Biological process |
Positive regulation of NF-kappaB transcription factor activity |
IDA |
12594207, 21618349 |
| GO:0071221 |
Biological process |
Cellular response to bacterial lipopeptide |
TAS |
15356140 |
| GO:0071223 |
Biological process |
Cellular response to lipoteichoic acid |
IDA |
12594207 |
| GO:0071223 |
Biological process |
Cellular response to lipoteichoic acid |
IMP |
26649771 |
| GO:0071346 |
Biological process |
Cellular response to interferon-gamma |
IDA |
11672593 |
| GO:0071726 |
Biological process |
Cellular response to diacyl bacterial lipopeptide |
IDA |
16880211, 19931471 |
| GO:0071727 |
Biological process |
Cellular response to triacyl bacterial lipopeptide |
IDA |
16880211, 19931471 |
| GO:1901224 |
Biological process |
Positive regulation of NIK/NF-kappaB signaling |
IDA |
19740627 |
| GO:1903974 |
Biological process |
Positive regulation of cellular response to macrophage colony-stimulating factor stimulus |
IDA |
11672593 |
| GO:2000484 |
Biological process |
Positive regulation of interleukin-8 secretion |
IGI |
22198949 |
| GO:0005737 |
Cellular component |
Cytoplasm |
IDA |
19740627 |
| GO:0005794 |
Cellular component |
Golgi apparatus |
IDA |
16880211 |
| GO:0005886 |
Cellular component |
Plasma membrane |
IDA |
19740627 |
| GO:0005887 |
Cellular component |
Integral component of plasma membrane |
IBA |
21873635 |
| GO:0009986 |
Cellular component |
Cell surface |
IDA |
12443841 |
| GO:0031226 |
Cellular component |
Intrinsic component of plasma membrane |
IBA |
21873635 |
| GO:0031226 |
Cellular component |
Intrinsic component of plasma membrane |
IDA |
11274165 |
| GO:0035354 |
Cellular component |
Toll-like receptor 1-Toll-like receptor 2 protein complex |
IDA |
17889651 |
| GO:0045121 |
Cellular component |
Membrane raft |
IDA |
16880211 |
| GO:0001530 |
Molecular function |
Lipopolysaccharide binding |
IDA |
11274165 |
| GO:0001540 |
Molecular function |
Amyloid-beta binding |
IDA |
22198949 |
| GO:0001875 |
Molecular function |
Lipopolysaccharide receptor activity |
TAS |
11518816 |
| GO:0005515 |
Molecular function |
Protein binding |
IPI |
10854325, 11441107, 12594264, 15657077, 15728506, 16293622, 16622205, 16880211, 17095513, 17126326, 18765807, 19509286, 19880448, 20802527, 23155421, 23376921, 24658140, 29990310 |
| GO:0008329 |
Molecular function |
Signaling pattern recognition receptor activity |
IDA |
10384090 |
| GO:0035325 |
Molecular function |
Toll-like receptor binding |
IPI |
16880211 |
| GO:0038023 |
Molecular function |
Signaling receptor activity |
TAS |
10426995 |
| GO:0042497 |
Molecular function |
Triacyl lipopeptide binding |
IDA |
17889651 |
| GO:0042802 |
Molecular function |
Identical protein binding |
IPI |
23155421 |
| GO:0042834 |
Molecular function |
Peptidoglycan binding |
IDA |
11986301 |
| GO:0044877 |
Molecular function |
Protein-containing complex binding |
IPI |
22198949 |
| GO:0046982 |
Molecular function |
Protein heterodimerization activity |
IDA |
17889651 |
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| Protein Information |
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Protein Name |
Toll-like receptor 2, toll/interleukin-1 receptor-like protein 4 |
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Function |
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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). |
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UniProt |
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PDB |
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Interactions |
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| STRING |
MINT |
IntAct |
| ENSP00000449404 |
P05787 |
P05787 |
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View interactions
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Associated Diseases
| Disease group | Disease Name | References |
| Blood Disorders |
| Eosinophilia |
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| Cardiovascular Diseases |
| Cardiomyopathy |
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| Myocardial Diseases |
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| Digestive System Diseases |
| Cholestasis |
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| Ear Or Mastoid Diseases |
| Meniere Disease |
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| Endocrine System Diseases |
| PCOS |
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| Eye Diseases |
| Keratitis |
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| Immune System Diseases |
| Rheumatoid Arthritis |
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| Neoplasms |
| Colorectal Cancer |
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| Psychiatric/Brain disorders |
| Schizophrenia |
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| Bipolar Disorder |
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| Obstructive Sleep Apnea |
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| Renal Disorder |
| Kidney Failure |
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| Kidney Insufficiency |
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| Reproductive disorders |
| Preeclampsia |
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References |
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| Ojeda-Ojeda Miriam, Martinez-Garcia M Angeles, Alpanes Macarena, Luque-Ramirez Manuel, Escobar-Morreale Hector F |
| Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramon y Cajal & Universidad de Alcala & Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigacion Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Spain. Electronic address: ojedaojedamiriam@gmail.com.| Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramon y Cajal & Universidad de Alcala & Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigacion Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Spain.| Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramon y Cajal & Universidad de Alcala & Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigacion Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Spain.| Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramon y Cajal & Universidad de Alcala & Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigacion Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Spain.| Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramon y Cajal & Universidad de Alcala & Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigacion Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Spain. Electronic address: hectorfrancisco.escobar@salud.madrid.org. |
| J Reprod Immunol. 2016 Feb;113:9-15. doi: 10.1016/j.jri.2015.09.072. Epub 2015 |
Abstract
Toll-like receptors (TLRs) are activated by inflammatory stimuli and influence endothelial functions, contributing to the pathogenesis of atherosclerosis. We investigate the influence of polymorphisms in the genes encoding toll-like receptor 2 (TLR2) and 4 (TLR4) and endothelial adhesion molecules on polycystic ovary syndrome (PCOS) and its interaction with obesity. Ten single nucleotide polymorphisms were genotyped in 305 women with PCOS and 166 non-hyperandrogenic control women. In obese women, TLR2 S450S and ICAM1 K469E polymorphisms differently influenced metabolic variables and PCOS, respectively. Irrespective of PCOS, variant alleles of TLR2 S450S increased triglycerides, fasting insulin levels, and insulin resistance in obese women. TLR2 S450S interacted with obesity and PCOS on androstenedione levels, mutant alleles were associated with increased androstenedione concentrations in all women, with the exception of obese patients with PCOS (P=0.034). Regarding ICAM1 K469E, homozygosis for K469 alleles was more frequent in PCOS, but only in obese women (P=0.014). K469 alleles were also related to increased body mass index (P=0.017) and diastolic blood pressure (P=0.034). Moreover, ICAM1 K469E interacted with obesity and PCOS on serum triglyceride levels (P=0.019) and with PCOS on serum sex hormone-binding globulin concentrations (P=0.006). In conclusion, TLR2 S450S and ICAM1 K469E polymorphisms may be associated with PCOS and metabolic comorbidities in obese women. |
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