Description: Homo sapiens toll-like receptor 6 (TLR6), mRNA. RefSeq Summary (NM_006068): 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 receptor functionally interacts with toll-like receptor 2 to mediate cellular response to bacterial lipoproteins. A Ser249Pro polymorphism in the extracellular domain of the encoded protein may be associated with an increased of asthma is some populations.[provided by RefSeq, Jan 2011]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Transcript (Including UTRs) Position: hg19 chr4:38,825,329-38,858,438 Size: 33,110 Total Exon Count: 2 Strand: - Coding Region Position: hg19 chr4:38,828,704-38,831,094 Size: 2,391 Coding Exon Count: 1
ID:TLR6_HUMAN DESCRIPTION: RecName: Full=Toll-like receptor 6; AltName: CD_antigen=CD286; Flags: Precursor; FUNCTION: Participates in the innate immune response to Gram- positive bacteria and fungi. 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. SUBUNIT: Binds TLR2 via their respective extracellular domains. Binds MYD88 via their respective TIR domains (By similarity). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein (By similarity). Cytoplasmic vesicle, phagosome membrane; Single-pass type I membrane protein (By similarity). TISSUE SPECIFICITY: Detected in monocytes, CD11c+ immature dendritic cells, plasmacytoid pre-dendritic cells and dermal microvessel endothelial cells. SIMILARITY: Belongs to the Toll-like receptor family. SIMILARITY: Contains 12 LRR (leucine-rich) repeats. SIMILARITY: Contains 1 LRRCT domain. SIMILARITY: Contains 1 TIR domain.
Arthritis, Rheumatoid|Rheumatoid Arthritis|Anti-TNF Response Potter C et al. 2010, Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NF{kappa}B signalling pathways., Annals of the rheumatic diseases 69(7) : 1315-20 2010.
[PubMed 20448286]
Several SNPs mapping to the TLR and NFkappaB signalling systems demonstrated association with anti-TNF response as a whole and, in particular, with response to etanercept. Validation of these findings in an independent cohort is now warranted.
aspergillosis Kesh, S. et al. 2005, TLR1 and TLR6 Polymorphisms Are Associated with Susceptibility to Invasive Aspergillosis after Allogeneic Stem Cell Transplantation, Ann N Y Acad Sci 2005 1062 95-103.
[PubMed 16461792]
Hemoglobins Qiong Yang et al. BMC medical genetics 2007, Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903294]
Using genome-wide association methodology, we have successfully identified a SNP in complete LD with a sequence variant previously shown to be strongly associated with factor VII, providing proof of principle for this approach. Further study of additional strongly associated SNPs and linked regions may identify novel variants that influence the inter-individual variability in hemostatic factors and hematological phenotypes.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 52047 - RNI-like 52058 - L domain-like 52075 - Outer arm dynein light chain 1 52200 - Toll/Interleukin receptor TIR domain
ModBase Predicted Comparative 3D Structure on Q9Y2C9
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
JD179042 - Sequence 160066 from Patent EP1572962. JD421430 - Sequence 402454 from Patent EP1572962. JD179041 - Sequence 160065 from Patent EP1572962. JD199439 - Sequence 180463 from Patent EP1572962. JD325408 - Sequence 306432 from Patent EP1572962. JD350212 - Sequence 331236 from Patent EP1572962. JD168580 - Sequence 149604 from Patent EP1572962. JD208753 - Sequence 189777 from Patent EP1572962. AB020807 - Homo sapiens mRNA for TLR6, complete cds. JD082102 - Sequence 63126 from Patent EP1572962. JD147965 - Sequence 128989 from Patent EP1572962. JD104380 - Sequence 85404 from Patent EP1572962. BC111755 - Homo sapiens toll-like receptor 6, mRNA (cDNA clone MGC:133029 IMAGE:40007924), complete cds. AB445652 - Homo sapiens TLR6 mRNA for toll-like receptor 6, complete cds. AK313618 - Homo sapiens cDNA, FLJ94188, highly similar to Homo sapiens toll-like receptor 6 (TLR6), mRNA. KJ902091 - Synthetic construct Homo sapiens clone ccsbBroadEn_11485 TLR6 gene, encodes complete protein. KR711814 - Synthetic construct Homo sapiens clone CCSBHm_00031157 TLR6 (TLR6) mRNA, encodes complete protein. KR711815 - Synthetic construct Homo sapiens clone CCSBHm_00031159 TLR6 (TLR6) mRNA, encodes complete protein.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04620 - Toll-like receptor signaling pathway hsa05142 - Chagas disease
Reactome (by CSHL, EBI, and GO)
Protein Q9Y2C9 (Reactome details) participates in the following event(s):
R-HSA-168950 TLR6:TLR2 is recruited to ligand:CD14:CD36 R-HSA-8869667 oxLDL:CD36 binds TLR4:TLR6 R-HSA-2201316 Activated TLR2/4 interacts with MAL(TIRAP) R-HSA-166072 MyD88 forms a complex with MAL:activated TLR2/4 R-HSA-2201322 MAL is phosphorylated by BTK R-HSA-2559414 Activated TLR2/4:MAL interacts with BTK R-HSA-937079 MyD88 oligomerization within the complex of activated TLR:Mal:MyD88 R-HSA-166082 IRAK4 binds to the activated TLR receptor:Mal:MyD88 complex R-HSA-937022 IRAK4 autophosphorylation in the complex with activated TLR:MyD88:Mal R-HSA-166091 IRAK1 or IRAK2 binds to the activated IRAK4 :activated TLR:MyD88:Mal complex R-HSA-166362 Dissociation of hp-IRAK1:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex R-HSA-2262775 Dissociation of p-IRAK2:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex R-HSA-166286 Multiple IRAK1 autophosphorylation steps R-HSA-166284 Second phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal R-HSA-166119 First phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal R-HSA-166363 TRAF6 binds to hp- IRAK1 R-HSA-937059 Phosphorylation of IRAK2 bound to the activated IRAK4:MyD88 oligomer:Mal:activated TLR complex R-HSA-2262777 TRAF6 binds to p-IRAK2 R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade R-HSA-5686938 Regulation of TLR by endogenous ligand R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade R-HSA-168898 Toll-Like Receptors Cascades R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane R-HSA-168249 Innate Immune System R-HSA-5602498 MyD88 deficiency (TLR2/4) R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade R-HSA-168256 Immune System R-HSA-5603041 IRAK4 deficiency (TLR2/4) R-HSA-5602358 Diseases associated with the TLR signaling cascade R-HSA-5260271 Diseases of Immune System R-HSA-1643685 Disease
US Server
