Target General Infomation
Target ID
T52037
Former ID
TTDI02192
Target Name
Toll-like receptor 6
Gene Name
TLR6
Synonyms
CD286; TLR6
Target Type
Clinical Trial
Disease Pancreatic cancer [ICD9: 140-199, 140-229, 157, 210-229; ICD10: C25]
Function
Participates in the innate immune response to Gram- positive bacteria and fungi. Specifically recognizes diacylated and, to a lesser extent, triacylated lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. 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 TLR2. In complex with TLR4, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion.
BioChemical Class
Toll-like receptor family
UniProt ID
Sequence
MTKDKEPIVKSFHFVCLMIIIVGTRIQFSDGNEFAVDKSKRGLIHVPKDLPLKTKVLDMS
QNYIAELQVSDMSFLSELTVLRLSHNRIQLLDLSVFKFNQDLEYLDLSHNQLQKISCHPI
VSFRHLDLSFNDFKALPICKEFGNLSQLNFLGLSAMKLQKLDLLPIAHLHLSYILLDLRN
YYIKENETESLQILNAKTLHLVFHPTSLFAIQVNISVNTLGCLQLTNIKLNDDNCQVFIK
FLSELTRGSTLLNFTLNHIETTWKCLVRVFQFLWPKPVEYLNIYNLTIIESIREEDFTYS
KTTLKALTIEHITNQVFLFSQTALYTVFSEMNIMMLTISDTPFIHMLCPHAPSTFKFLNF
TQNVFTDSIFEKCSTLVKLETLILQKNGLKDLFKVGLMTKDMPSLEILDVSWNSLESGRH
KENCTWVESIVVLNLSSNMLTDSVFRCLPPRIKVLDLHSNKIKSVPKQVVKLEALQELNV
AFNSLTDLPGCGSFSSLSVLIIDHNSVSHPSADFFQSCQKMRSIKAGDNPFQCTCELREF
VKNIDQVSSEVLEGWPDSYKCDYPESYRGSPLKDFHMSELSCNITLLIVTIGATMLVLAV
TVTSLCIYLDLPWYLRMVCQWTQTRRRARNIPLEELQRNLQFHAFISYSEHDSAWVKSEL
VPYLEKEDIQICLHERNFVPGKSIVENIINCIEKSYKSIFVLSPNFVQSEWCHYELYFAH
HNLFHEGSNNLILILLEPIPQNSIPNKYHKLKALMTQRTYLQWPKEKSKRGLFWANIRAA
FNMKLTLVTENNDVKS
Drugs and Mode of Action
Drug(s) MALP-2S Drug Info Phase 1/2 Pancreatic cancer [528971]
Modulator MALP-2S Drug Info [531307]
Pathways
KEGG Pathway Phagosome
Toll-like receptor signaling pathway
Chagas disease (American trypanosomiasis)
Tuberculosis
NetPath Pathway IL5 Signaling Pathway
IL2 Signaling Pathway
TCR Signaling Pathway
PANTHER Pathway Toll receptor signaling pathway
Pathway Interaction Database Endogenous TLR signaling
Reactome Mal cascade initiated on plasma membrane
TLR2 Cascade
MyD88 deficiency (TLR2/4)
IRAK4 deficiency (TLR2/4)
WikiPathways Toll-like receptor signaling pathway
Toll-Like Receptors Cascades
Mal cascade initiated on plasma membrane
Regulation of toll-like receptor signaling pathway
References
Ref 528971Intratumoural injection of the toll-like receptor-2/6 agonist 'macrophage-activating lipopeptide-2' in patients with pancreatic carcinoma: a phase I/II trial. Br J Cancer. 2007 Sep 3;97(5):598-604. Epub 2007 Jul 31.
Ref 531307Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2. Microbes Infect. 2011 Apr;13(4):350-8.

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