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Protein

Toll-like receptor 6

Gene

Tlr6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Participates in the innate immune response to Gram-positive bacteria and fungi. Specifically recognizes diacylated and, to a lesser extent, triacylated lipopeptides (PubMed:19931471). 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 (PubMed:20037584, PubMed:23812099).3 Publications

GO - Molecular functioni

  • diacyl lipopeptide binding Source: MGI
  • lipopeptide binding Source: UniProtKB
  • protein heterodimerization activity Source: MGI
  • Toll-like receptor 2 binding Source: MGI
  • transmembrane signaling receptor activity Source: GO_Central

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 6
Alternative name(s):
CD_antigen: CD286
Gene namesi
Name:Tlr6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1341296. Tlr6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 584ExtracellularSequence analysisAdd BLAST557
Transmembranei585 – 605HelicalSequence analysisAdd BLAST21
Topological domaini606 – 795CytoplasmicSequence analysisAdd BLAST190

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Animals with a double knockout of APOE and TLR6, fed a Western diet for 12 weeks, have less aortic plaque formation than single APOE knockout mice. They also show lower serum concentrations of IL1A, ILB and IL18.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi680P → H: Dominant negative mutant, blocks response to Gram-positive pathogens. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3137289.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000003473228 – 795Toll-like receptor 6Add BLAST768

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi42N-linked (GlcNAc...)Sequence analysis1
Glycosylationi114N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi117 ↔ 1391 Publication
Glycosylationi144N-linked (GlcNAc...)1 Publication1
Glycosylationi195N-linked (GlcNAc...)1 Publication1
Glycosylationi214N-linked (GlcNAc...)1 Publication1
Disulfide bondi235 ↔ 2651 Publication
Glycosylationi253N-linked (GlcNAc...)1 Publication1
Glycosylationi285N-linked (GlcNAc...)1
Disulfide bondi348 ↔ 3731 Publication
Glycosylationi359N-linked (GlcNAc...)1 Publication1
Glycosylationi401N-linked (GlcNAc...)1 Publication1
Disulfide bondi424 ↔ 4471 Publication
Glycosylationi434N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9EPW9.
PRIDEiQ9EPW9.

PTM databases

iPTMnetiQ9EPW9.
PhosphoSitePlusiQ9EPW9.

Expressioni

Tissue specificityi

Detected in thymus, spleen, ovary and lung. Expressed in macrohpages.1 Publication

Gene expression databases

BgeeiENSMUSG00000051498.
CleanExiMM_TLR6.

Interactioni

Subunit structurei

Heterodimer with TLR2 via their respective extracellular domains (PubMed:19931471). Binds MYD88 via their respective TIR domains (Probable). 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).By similarityCurated1 Publication

GO - Molecular functioni

  • protein heterodimerization activity Source: MGI
  • Toll-like receptor 2 binding Source: MGI

Protein-protein interaction databases

IntActiQ9EPW9. 1 interactor.
STRINGi10090.ENSMUSP00000062096.

Structurei

Secondary structure

1795
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 37Combined sources3
Beta strandi56 – 58Combined sources3
Helixi69 – 71Combined sources3
Turni72 – 74Combined sources3
Beta strandi80 – 82Combined sources3
Turni93 – 98Combined sources6
Beta strandi104 – 106Combined sources3
Beta strandi124 – 127Combined sources4
Helixi140 – 144Combined sources5
Beta strandi150 – 154Combined sources5
Turni160 – 163Combined sources4
Helixi164 – 166Combined sources3
Beta strandi171 – 180Combined sources10
Beta strandi185 – 187Combined sources3
Beta strandi190 – 193Combined sources4
Beta strandi196 – 203Combined sources8
Beta strandi205 – 207Combined sources3
Beta strandi214 – 229Combined sources16
Helixi235 – 246Combined sources12
Beta strandi252 – 261Combined sources10
Helixi263 – 273Combined sources11
Beta strandi276 – 288Combined sources13
Beta strandi306 – 314Combined sources9
Helixi321 – 329Combined sources9
Beta strandi334 – 341Combined sources8
Beta strandi357 – 359Combined sources3
Turni367 – 372Combined sources6
Beta strandi381 – 383Combined sources3
Helixi394 – 397Combined sources4
Turni398 – 401Combined sources4
Beta strandi407 – 409Combined sources3
Beta strandi432 – 434Combined sources3
Helixi442 – 445Combined sources4
Beta strandi453 – 456Combined sources4
Turni467 – 470Combined sources4
Beta strandi476 – 479Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A79X-ray2.90B1-482[»]
ProteinModelPortaliQ9EPW9.
SMRiQ9EPW9.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9EPW9.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati54 – 77LRR 11 PublicationAdd BLAST24
Repeati78 – 101LRR 21 PublicationAdd BLAST24
Repeati102 – 125LRR 31 PublicationAdd BLAST24
Repeati126 – 150LRR 41 PublicationAdd BLAST25
Repeati151 – 175LRR 51 PublicationAdd BLAST25
Repeati176 – 199LRR 61 PublicationAdd BLAST24
Repeati200 – 223LRR 71 PublicationAdd BLAST24
Repeati224 – 250LRR 81 PublicationAdd BLAST27
Repeati251 – 278LRR 91 PublicationAdd BLAST28
Repeati279 – 308LRR 101 PublicationAdd BLAST30
Repeati309 – 337LRR 111 PublicationAdd BLAST29
Repeati338 – 361LRR 121 PublicationAdd BLAST24
Repeati362 – 388LRR 131 PublicationAdd BLAST27
Repeati389 – 414LRR 141 PublicationAdd BLAST26
Repeati415 – 437LRR 151 PublicationAdd BLAST23
Repeati438 – 457LRR 161 PublicationAdd BLAST20
Repeati458 – 478LRR 171 PublicationAdd BLAST21
Repeati479 – 500LRR 181 PublicationAdd BLAST22
Repeati501 – 524LRR 191 PublicationAdd BLAST24
Domaini525 – 576LRRCTAdd BLAST52
Domaini640 – 784TIRPROSITE-ProRule annotationAdd BLAST145

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated
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.
HOVERGENiHBG023180.
InParanoidiQ9EPW9.
KOiK10169.
PhylomeDBiQ9EPW9.

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.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027187. TLR6.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERiPTHR24365:SF23. PTHR24365:SF23. 1 hit.
PfamiPF12799. LRR_4. 1 hit.
PF13855. LRR_8. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037595. Toll-like_receptor. 1 hit.
SMARTiSM00369. LRR_TYP. 4 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.

Q9EPW9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSQDRKPIVG SFHFVCALAL IVGSMTPFSN ELESMVDYSN RNLTHVPKDL
60 70 80 90 100
PPRTKALSLS QNSISELRMP DISFLSELRV LRLSHNRIRS LDFHVFLFNQ
110 120 130 140 150
DLEYLDVSHN RLQNISCCPM ASLRHLDLSF NDFDVLPVCK EFGNLTKLTF
160 170 180 190 200
LGLSAAKFRQ LDLLPVAHLH LSCILLDLVS YHIKGGETES LQIPNTTVLH
210 220 230 240 250
LVFHPNSLFS VQVNMSVNAL GHLQLSNIKL NDENCQRLMT FLSELTRGPT
260 270 280 290 300
LLNVTLQHIE TTWKCSVKLF QFFWPRPVEY LNIYNLTITE RIDREEFTYS
310 320 330 340 350
ETALKSLMIE HVKNQVFLFS KEALYSVFAE MNIKMLSISD TPFIHMVCPP
360 370 380 390 400
SPSSFTFLNF TQNVFTDSVF QGCSTLKRLQ TLILQRNGLK NFFKVALMTK
410 420 430 440 450
NMSSLETLDV SLNSLNSHAY DRTCAWAESI LVLNLSSNML TGSVFRCLPP
460 470 480 490 500
KVKVLDLHNN RIMSIPKDVT HLQALQELNV ASNSLTDLPG CGAFSSLSVL
510 520 530 540 550
VIDHNSVSHP SEDFFQSCQN IRSLTAGNNP FQCTCELRDF VKNIGWVARE
560 570 580 590 600
VVEGWPDSYR CDYPESSKGT ALRDFHMSPL SCDTVLLTVT IGATMLVLAV
610 620 630 640 650
TGAFLCLYFD LPWYVRMLCQ WTQTRHRARH IPLEELQRNL QFHAFVSYSE
660 670 680 690 700
HDSAWVKNEL LPNLEKDDIR VCLHERNFVP GKSIVENIIN FIEKSYKAIF
710 720 730 740 750
VLSPHFIQSE WCHYELYFAH HNLFHEGSDN LILILLEPIL QNNIPSRYHK
760 770 780 790
LRALMAQRTY LEWPTEKGKR GLFWANLRAS FIMKLALVNE DDVKT
Length:795
Mass (Da):91,116
Last modified:January 31, 2002 - v2
Checksum:i34D8BD175A26C233
GO

Sequence cautioni

The sequence AAG38563 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAA78632 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti181Y → H in BAA78632 (PubMed:10231569).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020808 mRNA. Translation: BAA78632.1. Different initiation.
AF314636 mRNA. Translation: AAG38563.1. Different initiation.
RefSeqiNP_035734.3. NM_011604.3.
XP_006503920.1. XM_006503857.2.
XP_006503921.1. XM_006503858.3.
XP_006503922.1. XM_006503859.3.
XP_006503923.1. XM_006503860.1.
UniGeneiMm.42146.

Genome annotation databases

GeneIDi21899.
KEGGimmu:21899.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020808 mRNA. Translation: BAA78632.1. Different initiation.
AF314636 mRNA. Translation: AAG38563.1. Different initiation.
RefSeqiNP_035734.3. NM_011604.3.
XP_006503920.1. XM_006503857.2.
XP_006503921.1. XM_006503858.3.
XP_006503922.1. XM_006503859.3.
XP_006503923.1. XM_006503860.1.
UniGeneiMm.42146.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A79X-ray2.90B1-482[»]
ProteinModelPortaliQ9EPW9.
SMRiQ9EPW9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9EPW9. 1 interactor.
STRINGi10090.ENSMUSP00000062096.

Chemistry databases

ChEMBLiCHEMBL3137289.

PTM databases

iPTMnetiQ9EPW9.
PhosphoSitePlusiQ9EPW9.

Proteomic databases

PaxDbiQ9EPW9.
PRIDEiQ9EPW9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi21899.
KEGGimmu:21899.

Organism-specific databases

CTDi10333.
MGIiMGI:1341296. Tlr6.

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
HOVERGENiHBG023180.
InParanoidiQ9EPW9.
KOiK10169.
PhylomeDBiQ9EPW9.

Miscellaneous databases

EvolutionaryTraceiQ9EPW9.
PROiQ9EPW9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000051498.
CleanExiMM_TLR6.

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.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027187. TLR6.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERiPTHR24365:SF23. PTHR24365:SF23. 1 hit.
PfamiPF12799. LRR_4. 1 hit.
PF13855. LRR_8. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037595. Toll-like_receptor. 1 hit.
SMARTiSM00369. LRR_TYP. 4 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_MOUSE
AccessioniPrimary (citable) accession number: Q9EPW9
Secondary accession number(s): Q9WTQ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 31, 2002
Last modified: November 2, 2016
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.