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Protein

Toll-like receptor 6

Gene

TLR6

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Participates in the innate immune response to Gram-positive bacteria and fungi. Specifically recognizes diacylated and, to a lesser extent, triacylated lipopeptides. In response to diacylated lipopeptides, forms the activation cluster TLR2:TLR6:CD14:CD36, this cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway. 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.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 6Imported
Alternative name(s):
CD_antigen: CD286By similarity
Gene namesi
Name:TLR6Imported
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein Sequence analysis
  • Cytoplasmic vesiclephagosome membrane By similarity; Single-pass type I membrane protein Sequence analysis
  • Membrane raft By similarity
  • Golgi apparatus By similarity

  • Note: Upon complex formation with CD36 and TLR4, internalized through dynamin-dependent endocytosis. Does not reside in lipid rafts before stimulation but accumulates increasingly in the raft upon the presence of the microbial ligand. In response to diacylated lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid rafts, this recruitment determine the intracellular targeting to the Golgi apparatus.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 584ExtracellularSequence analysisAdd BLAST561
Transmembranei585 – 605HelicalSequence analysisAdd BLAST21
Topological domaini606 – 793CytoplasmicSequence analysisAdd BLAST188

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000039467024 – 793Toll-like receptor 6Sequence analysisAdd BLAST770

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi63N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi117 ↔ 140By similarity
Glycosylationi145N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi235 ↔ 265By similarity
Glycosylationi253N-linked (GlcNAc...)Sequence analysis1
Glycosylationi285N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi348 ↔ 373By similarity
Glycosylationi359N-linked (GlcNAc...)Sequence analysis1
Glycosylationi423N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi424 ↔ 447By similarity
Glycosylationi434N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ704V6.

Expressioni

Tissue specificityi

Highest expression levels seen in blood and lymph node, intermediate expression seen in spleen and lowest expression seen in the liver, lung and udder cistern.1 Publication

Interactioni

Subunit structurei

Heterodimer with TLR2 via their respective extracellular domains. Binds MYD88 via their respective TIR domains (By similarity). Interacts with CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer with TLR4. The trimeric complex is internalized and triggers inflammatory response. LYN kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation (By similarity). The heterodimer TLR2:TLR6 interacts with CD14 and CD36 in response to triacylated lipopeptides.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000035880.

Structurei

3D structure databases

ProteinModelPortaliQ704V6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati54 – 77LRR 1Add BLAST24
Repeati78 – 101LRR 2Add BLAST24
Repeati102 – 122LRR 3Add BLAST21
Repeati123 – 147LRR 4Add BLAST25
Repeati148 – 168LRR 5Add BLAST21
Repeati169 – 196LRR 6Add BLAST28
Repeati197 – 219LRR 7Add BLAST23
Repeati220 – 250LRR 8Add BLAST31
Repeati251 – 277LRR 9Add BLAST27
Repeati278 – 303LRR 10Add BLAST26
Repeati304 – 330LRR 11Add BLAST27
Repeati331 – 354LRR 12Add BLAST24
Repeati355 – 378LRR 13Add BLAST24
Repeati379 – 404LRR 14Add BLAST26
Repeati405 – 428LRR 15Add BLAST24
Repeati429 – 449LRR 16Add BLAST21
Repeati450 – 473LRR 17Add BLAST24
Repeati474 – 495LRR 18Add BLAST22
Repeati496 – 519LRR 19Add BLAST24
Domaini520 – 575LRRCTAdd BLAST56
Domaini640 – 784TIRPROSITE-ProRule annotationAdd BLAST145

Sequence similaritiesi

Belongs to the Toll-like receptor family.Sequence analysis
Contains 19 LRR (leucine-rich) repeats.Curated
Contains 1 LRRCT domain.Curated
Contains 1 TIR domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
HOGENOMiHOG000008676.
HOVERGENiHBG023180.
InParanoidiQ704V6.
KOiK10169.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 2 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027187. TLR6.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERiPTHR24365:SF23. PTHR24365:SF23. 1 hit.
PfamiPF13855. LRR_8. 1 hit.
PF01463. LRRCT. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037595. Toll-like_receptor. 1 hit.
SMARTiSM00369. LRR_TYP. 5 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 10 hits.
PS50104. TIR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q704V6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIKDKESPIR SCHFVYIVAL VFGTIIQFSD ESEFVVDMSK TSLIHVPKDL
60 70 80 90 100
PPKTKVLDLS QNNISELHLS DISFLSGLRV LRLSHNRIQG LDISIFKFNH
110 120 130 140 150
DLEYLDLSHN QLQKISCHPI TTTLKHLDLS FNDFDALPIC KEFGNLTQLN
160 170 180 190 200
FLGLSATKLQ QLDLLPIAHL HLSCILLDLE DYMKENKKES LQILNTKKLH
210 220 230 240 250
LVFHPNSFFS VQVDISANSL GCLQLTNIKL NDYNCQVLLK FLSGLTGGPT
260 270 280 290 300
LLNFTLNHVE TTWKCLVKVF QFLWPKPIEY LNIYNLTIVE SIDEEVFTYY
310 320 330 340 350
KTTLKALKIE HITNKVFIFS QTALYTVFSE MNILMLTISD TRFIHMLCPQ
360 370 380 390 400
EPSTFKFLNF TQNSFTDSVF QNCDTLARLE TLILQKNELK DLFKTSLMTK
410 420 430 440 450
DMLSLETLDV SWNSLEYDRS NGNCSWVGSI VVLNLSSNAL TDSVFRCLPP
460 470 480 490 500
RIKVLDLHNN RIRSIPKDVT GLETLQELNL ASNSLAHLPG CGIFSSLSIL
510 520 530 540 550
IIEHNSISNP SADFFQSCQK IRSLKAGNNP FQCSCELRDF IQSVGQVSSD
560 570 580 590 600
VVEGWPESYK CDYPESYKGT PLKDFQVSEL SCNTALLIIT IVVPGLVLAV
610 620 630 640 650
AVTVLCIYLD LPWYLRMVCQ WTQTRRRARN VPLEELQRTL QFHAFISYSE
660 670 680 690 700
HDSAWVKNEL IPNLEKEDIR ICLHERNFVA GKSIVENIIN CIEKSYKSIF
710 720 730 740 750
VLSPNFVQSE WCHYELYFAH HNLFHEGSDN LILILLDPIP QYSIPSSYHK
760 770 780 790
LRALMAQRTY LEWPKEKSKH GLFWANLRAS INIKLMEKAA EIH
Length:793
Mass (Da):90,927
Last modified:July 5, 2004 - v1
Checksum:iC11C26009F8E3668
GO

Sequence cautioni

The sequence CAJ35083 differs from that shown. Reason: Frameshift at position 414.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti221G → A in CAF02015 (PubMed:16701904).Curated1
Sequence conflicti221G → A in AAY40896 (PubMed:16701904).Curated1
Sequence conflicti259V → M in ACH92795 (PubMed:18639626).Curated1
Sequence conflicti259V → M in ACH92799 (PubMed:18639626).Curated1
Sequence conflicti259V → M in ACH92800 (PubMed:18639626).Curated1
Sequence conflicti259V → M in ACH92798 (PubMed:18639626).Curated1
Sequence conflicti259V → M in CAJ35083 (PubMed:16950576).Curated1
Sequence conflicti503 – 504EH → DY in ACH92795 (PubMed:18639626).Curated2
Sequence conflicti503 – 504EH → DY in ACH92799 (PubMed:18639626).Curated2
Sequence conflicti503 – 504EH → DY in ACH92800 (PubMed:18639626).Curated2
Sequence conflicti503 – 504EH → DY in ACH92798 (PubMed:18639626).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti214D → N in strain: Angus, Charolais, Holstein and Limousin. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY487803 mRNA. Translation: AAY40896.1.
EU746466 Genomic DNA. Translation: ACH92795.1.
EU746469 Genomic DNA. Translation: ACH92798.1.
EU746470 Genomic DNA. Translation: ACH92799.1.
EU746471 Genomic DNA. Translation: ACH92800.1.
AJ618974 mRNA. Translation: CAF02015.1.
AJ620670 Genomic DNA. Translation: CAF06197.1.
AM113851 mRNA. Translation: CAJ35083.1. Frameshift.
RefSeqiNP_001001159.1. NM_001001159.1.
UniGeneiBt.45021.

Genome annotation databases

GeneIDi407237.
KEGGibta:407237.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY487803 mRNA. Translation: AAY40896.1.
EU746466 Genomic DNA. Translation: ACH92795.1.
EU746469 Genomic DNA. Translation: ACH92798.1.
EU746470 Genomic DNA. Translation: ACH92799.1.
EU746471 Genomic DNA. Translation: ACH92800.1.
AJ618974 mRNA. Translation: CAF02015.1.
AJ620670 Genomic DNA. Translation: CAF06197.1.
AM113851 mRNA. Translation: CAJ35083.1. Frameshift.
RefSeqiNP_001001159.1. NM_001001159.1.
UniGeneiBt.45021.

3D structure databases

ProteinModelPortaliQ704V6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000035880.

Proteomic databases

PaxDbiQ704V6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi407237.
KEGGibta:407237.

Organism-specific databases

CTDi10333.

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
HOGENOMiHOG000008676.
HOVERGENiHBG023180.
InParanoidiQ704V6.
KOiK10169.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 2 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027187. TLR6.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERiPTHR24365:SF23. PTHR24365:SF23. 1 hit.
PfamiPF13855. LRR_8. 1 hit.
PF01463. LRRCT. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037595. Toll-like_receptor. 1 hit.
SMARTiSM00369. LRR_TYP. 5 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 10 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTLR6_BOVIN
AccessioniPrimary (citable) accession number: Q704V6
Secondary accession number(s): B5T272
, B5T275, B5T276, Q3BK20, Q706D2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 15, 2010
Last sequence update: July 5, 2004
Last modified: October 5, 2016
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.