Details of the Drug Therapeutic Target (DTT)
General Information of Drug Therapeutic Target (DTT) (ID: TTY7ZHS)
| DTT Name | Toll-like receptor 2 (TLR2) | ||||
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| Synonyms | Toll/interleukin-1 receptor-like protein 4; TIL4; CD282 | ||||
| Gene Name | TLR2 | ||||
| DTT Type |
Clinical trial target
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| BioChemical Class |
Toll-like receptor
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| UniProt ID | |||||
| TTD ID | |||||
| 3D Structure | |||||
| Sequence |
MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLS
NNRITYISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWF KPLSSLTFLNLLGNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELE IDASDLQSYEPKSLKSIQNVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFS ELSTGETNSLIKKFTFRNVKITDESLFQVMKLLNQISGLLELEFDDCTLNGVGNFRASDN DRVIDPGKVETLTIRRLHIPRFYLFYDLSTLYSLTERVKRITVENSKVFLVPCLLSQHLK SLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQNHLASLEKTGETLLTLKNLTNIDI SKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDVSNNNLNLFSLNLPQLK ELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAGGNNFICSCE FLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGMCCALFL LILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVENLMV QELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFS HFRLFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRA AIKS |
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| Function |
Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. 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. 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. 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. MAPK activation in response to bacterial peptidoglycan also occurs via this receptor. 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. M. tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression. Recognizes M. tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse). 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. Required for normal uptake of M. tuberculosis, a process that is inhibited by M. tuberculosis LppM. Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components.
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| KEGG Pathway |
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| Reactome Pathway | |||||
Molecular Interaction Atlas (MIA) of This DTT
| Molecular Interaction Atlas (MIA) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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6 Clinical Trial Drug(s) Targeting This DTT
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1 Discontinued Drug(s) Targeting This DTT
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2 Investigative Drug(s) Targeting This DTT
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Molecular Expression Atlas (MEA) of This DTT
References
| 1 | Trial Watch: Experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology. 2012 August 1; 1(5): 699-716. | ||||
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| 2 | The novel arthritis-drug substance MCS-18 attenuates the antibody production in vivo. Acta Microbiol Immunol Hung. 2008 Mar;55(1):15-31. | ||||
| 3 | Treatment with OPN-305, a humanized anti-Toll-Like receptor-2 antibody, reduces myocardial ischemia/reperfusion injury in pigs. Circ Cardiovasc Interv. 2012 Apr;5(2):279-87. | ||||
| 4 | Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccha... J Biol Chem. 2003 May 2;278(18):15587-94. | ||||
| 5 | Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2. Microbes Infect. 2011 Apr;13(4):350-8. | ||||
| 6 | Phase I study of OM-174, a lipid A analogue, with assessment of immunological response, in patients with refractory solid tumors. BMC Cancer. 2013 Apr 2;13:172. | ||||
| 7 | Stability and CTL-activity of P40/ELA melanoma vaccine candidate. Biologicals. 2001 Sep-Dec;29(3-4):293-8. | ||||
| 8 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1752). | ||||
| 9 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||